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Related Abstracts Authored or Co-authored by Dr. W.C. Koller 2009
1. Eur J Neurol. 2009 Apr;16(4):493-7.
Subthalamic deep brain stimulation and impulse control in Parkinson's disease.
Hälbig TD, Tse W, Frisina PG, Baker BR, Hollander E, Shapiro H, Tagliati M,
Koller WC, Olanow CW.
Fédération de Neurologie, Centre Hospitalier Universitaire Pitié-Salpêtrière,
Paris, France. halbig.psl@gmail.com
Comment in:
Eur J Neurol. 2009 Apr;16(4):440-1.
BACKGROUND AND PURPOSE: Experimental studies suggest that deep brain stimulation
(DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with
Parkinson's disease (PD). The purpose of this study was to assess various
measures of impulse control in PD patients with STN DBS in comparison to patients
receiving medical therapy. METHODS: In a cross-sectional evaluation, 53
consecutively eligible patients were assessed for impulsivity with the Barratt
Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota
Impulsive Disorders Interview, and for obsessive-compulsive symptoms using the
Maudsley Obsessional-Compulsive Inventory. RESULTS: Independent samples t-tests
revealed that compulsivity scores were not different between DBS patients and
patients without DBS. However, impulsivity scores were significantly higher in
DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and
in 3 of 37 (8%) medically treated patients. No association was found between the
use of dopamine agonists and impulsivity in DBS patients. CONCLUSIONS: Our data
suggest that screening for impulsivity and ICDs should be performed prior to DBS,
and that patients should be monitored for these problems during follow-up.
Prospective trials are needed to confirm the findings of this exploratory study
and to elucidate the reasons of a possible induction of impulsivity by STN DBS.
PMID: 19236471 [PubMed - indexed for MEDLINE]
2. Mov Disord. 2009 Mar 15;24(4):564-73.
Long-term outcome of early versus delayed rasagiline treatment in early
Parkinson's disease.
Hauser RA, Lew MF, Hurtig HI, Ondo WG, Wojcieszek J, Fitzer-Attas CJ; TEMPO
Open-label Study Group.
Collaborators: Marshall F, Gardiner IF, Pearson N, Berry D, Shannon K, Jaglin JA,
Ondo W, Hunter C, Anderson CR, LeWitt PA, Kaminski P, Miller D, DeAngelis M,
Miyasaki J, So J, Johnston L, Tanner C, Stewart T, Tagg L, Everett S, Germain G,
Welsh M, McCollister M, Mann LL, Singer C, Koller WC, Weiner WJ, Bateman D,
Mendis T, Moterson M, Alcorn-Costa C, Haas K, Gray P, Mohtat D, Mendis N,
Sutherland L, Hurtig H, Lloyd M, Mathews M, Gauger L, Dyches P, Newcomb C, Hubble
J, Betcher K, Weeks CC, Kostyk S, Rajput AH, Gerow M, Klassen L, Ewanishin M,
Golbe LI, Patterson V, Caputo D, Seuffert P, Pahwa R, Gales T, Jenkins LJ,
Parsons A, Crader S, Wellinghoff JN, Coe S, Lew MF, Armstrong C, Kawai C,
Hawthorne KB, Gelles K, Lu X, Schuman SW, Cooper C, Marek K, Fussell B, Caplan K,
Barnabei E, Karen Stavris K, Sethi KD, Carpenter JG, Osborne J Jr, Narayan S,
Ligon KM, Molho E, Evans S, Nash J, Brown D, Stacy M, Williamson K, Novak P,
Feldman RG, Thomas C, Martin W, King P, McInnes G, Caouette S, Wojcieszek J,
Belden J, Feigin A, Ayan J, Shannon B, Adler CH, Newman S, Radam T, Schear M,
Santoni N, Wortzel S, Satou N, Tuite P, Rolandelli S, Lowery J, Ebbitt BJ,
Baranauskas A, Aminoff MJ, DiMinno M, Roth J, Borst T, Hevezi J, Deloa C, Tam T,
Lopez A, Bertoni JM, Skrypnik LI, Peterson C, Gordon MF, Winnick R, Parness S,
Hamann J, Calabrese V, Roberge P, Atchison PR, Allen CW, Rolli S, Kang UJ,
Richman J, Uy S.
Parkinsons's Disease and Movement Disorders Center, University of South Florida,
5 Tampa General Circle, Tampa, FL 33606, USA. rhauser@health.usf.edu
The purpose of this study to compare the long-term clinical outcome of early
versus delayed rasagiline treatment in early Parkinson's disease (PD). Subjects
(N = 404) were randomly assigned to initial treatment with rasagiline
(early-start group) or placebo for 6 months followed by rasagiline (delayed-start
group) in the TEMPO study. Subjects who chose to participate in an open-label
extension (N = 306) continued to receive rasagiline as well as other PD
medications as needed. Average (+/-SD) duration in the study was 3.6 +/- 2.1
years; 177 subjects received rasagiline for > or =5.0 years. Over the entire
6.5-year follow-up period, the adjusted mean difference in change from baseline
in total UPDRS scores was 2.5 units (SE 1.1; P = 0.021) or 16% (SE 5.7; P =
0.006) in favor of the early-start versus delayed-start rasagiline group.
Although the interaction between treatment and time was significant, values for
the early-start group were better than the delayed-start group across all time
points. Significantly less worsening (percent change) in total UPDRS scores was
observed in the early-start group at the time points 0.5, 1.5, 2.0, 3.0, 4.5,
5.0, and 5.5 years (P < 0.05). Compared to delayed start, early initiation of
rasagiline provided long-term clinical benefit, even in the face of treatment
with other dopaminergic agents. This might reflect enduring benefits due to
neuroprotection or effects on compensatory mechanisms in early PD.
PMID: 19086083 [PubMed - indexed for MEDLINE]
3. J Am Med Dir Assoc. 2008 Nov;9(9):670-5. Epub 2008 Sep 25.
The effects of withdrawal of dopaminergic medication in nursing home patients
with advanced parkinsonism.
Tse W, Frisina PG, Hälbig TD, Gracies JM, Liang L, Tarshish C, Lesser G, Neufeld
R, Koller WC, Libow LS.
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
OBJECTIVE: To determine the effects of dopaminergic medication withdrawal in an
elderly, demented and minimally ambulatory nursing home population with
parkinsonism in New York City. METHODS: In our double-blind, randomized study, 11
patients (7 males, 4 females) were randomized into 2 groups: one group underwent
levodopa medication withdrawal (experimental group) and the other group continued
on their levodopa (control group). Patients were evaluated weekly over the course
of a month with a neurologic examination and a series of assessment tools,
including the motor UPDRS (Unified Parkinson's disease rating scale), Hoehn and
Yahr staging scale, the Mini-Mental State Examination (MMSE) and the Nursing
Assistant Behavioral Detection Form. SETTING: An academic nursing home in New
York City. RESULTS: The patients had a mean age of 82.00 +/- 10.14 years, with a
mean MMSE score of 9.50 +/- 6.60 out of 30.00 maximum. The control and
experimental groups did not differ significantly with respect to age (P = .52),
dementia severity (P = .35), nor severity of PD symptoms as measured by the UPDRS
(P = .22) and Hoehn and Yahr staging (P = .65). Overall, no significant changes
were observed between the control and experimental groups in cognitive,
behavioral, and motor function across each time period. Of interest, 2 of the
drug withdrawal patients showed modest improvements in cognitive function as
measured by the MMSE. CONCLUSION: Our findings suggest that in patients with
advanced parkinsonism and dementia, dopaminergic medication withdrawal may be a
feasible way to reduce polypharmacy and potential medication-related side
effects, with a minimal risk of worsening motor deterioration. Therefore, our
findings may have potential implications for a medication intervention that could
prevent potential deleterious side effects and improve health-related quality of
life in this frail population.
PMID: 18992700 [PubMed - indexed for MEDLINE]
4. Handb Clin Neurol. 2007;84:31-72.
Levodopa.
Hälbig TD, Koller WC.
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
PMID: 18808941 [PubMed - in process]
5. Handb Clin Neurol. 2007;84:IX.
Preface.
Koller WC, Melamed E.
PMID: 18808937 [PubMed - in process]
6. Handb Clin Neurol. 2007;83:IX.
Preface.
Koller WC, Melamed E.
PMID: 18808906 [PubMed - in process]
7. Parkinsonism Relat Disord. 1997 Dec;3(4):207-9.
A comparison of Parkinson's disease symptoms and self-reported functioning and
well being.
Lyons KE, Pahwa R, Troster AI, Koller WC.
University of Kansas Medical Center, Department of Neurology, 3901 Rainbow Blvd.,
Kansas City, KS 66160-7314 U.S.A.
This study was designed to determine if the presence of tremor, rigidity,
bradykinesia and postural instability and gait abnormalities differentially
influence Parkinson's disease patients' ratings of quality of life as measured by
the Parkinson's Disease Questionnaire (PDQ-39). A regression analysis indicated
that the presence of postural instability and gait abnormalities and bradykinesia
were strongly predictive of PDQ-39 quality of life scores. The presence of tremor
and rigidity had little effect on patients' ratings of quality of life.
PMID: 18591077 [PubMed - in process]
8. Arch Gerontol Geriatr. 2008 May-Jun;46(3):359-66. Epub 2007 Jun 26.
Prevalence of movement disorders in an elderly nursing home population.
Tse W, Libow LS, Neufeld R, Lesser G, Frank J, Dolan S, Tarshish C, Gracies JM,
Olanow CW, Koller WC, Hälbig TD.
Department of Neurology, Mount Sinai Medical Center, One Gustave L. Levy Place,
Box 1052, New York, NY 10029, USA. winona.tse@mssm.edu
We studied the prevalence of movement disorders in a large nursing home
population (397 patients, mean age 86 years) in New York City. Patients were
first evaluated by specially trained research coordinators and final clinical
diagnoses were confirmed by a movement disorder specialist. A movement disorder
was identified in 21% of patients (83/397). The most frequent movement disorders
were essential tremor (ET) (8.8%) and parkinsonism (7.1%). Only half of those
admitted with a diagnosis of parkinsonism were confirmed in their diagnosis by
the movement disorder specialists. Three percent of patients exhibited
drug-induced tremor, 1.3% had dystonia, 0.5% had myoclonus and 0.3% had
generalized dyskinesias. Overall, our findings underline the high frequency of
movement disorders in a nursing home population. The discrepancy between our
findings and the prevalence rates for parkinsonism reported on the initial
transfer diagnosis emphasizes the difficulty of accurate diagnosis of movement
disorders and in particular parkinsonism.
PMID: 17597235 [PubMed - indexed for MEDLINE]
9. J Neurol Sci. 2007 Jul 15;258(1-2):137-43. Epub 2007 Apr 27.
Subcutaneous apomorphine in patients with advanced Parkinson's disease: a
dose-escalation study with randomized, double-blind, placebo-controlled crossover
evaluation of a single dose.
Pahwa R, Koller WC, Trosch RM, Sherry JH; APO303 Study Investigators.
University of Kansas Medical Center, 3599 Rainbow Blvd, Kansas City, KS 66160,
USA. rpahwa@kumc.edu
OBJECTIVE: To further explore the efficacy and safety of subcutaneous apomorphine
(APO) in treating off episodes in APO-naïve patients with advanced Parkinson's
disease (PD). METHODS: 56 patients receiving optimized oral anti-PD medication
were evaluated on separate days for response to single increasing doses of APO.
Acute response to oral anti-PD medication and APO dose escalation (2-10 mg) was
evaluated under unblinded conditions. At the 4 mg APO dose, placebo was randomly
introduced under double-blind crossover conditions. RESULTS: Mean changes from
pre-dose in Unified Parkinson's Disease Rating Scale motor scores indicated
significant improvement following APO 4 mg versus placebo at 20 min (p=0.0002),
40 min (p<0.0001; maximum improvement) and 90 min (p=0.0229). Improvements showed
significant dose-response at 20 min, 40 min (both p<0.0001) and 90 min
(p=0.0049). Adverse events were more common with APO than placebo, and also
showed significant dose-response (p<0.0001). Common adverse events associated
with APO included yawning, dizziness, nausea, somnolence and dyskinesias, and
were generally mild to moderate. There were no significant differences between
APO and placebo in the incidence of hypotension associated with a postural change
from a sitting to standing position. CONCLUSIONS: Subcutaneous APO provided
rapid, effective relief of off episodes associated with advanced PD.
PMID: 17466338 [PubMed - indexed for MEDLINE]
10. J Neurol Sci. 2006 Oct 25;248(1-2):62-7.
Absence of the apolipoprotein E epsilon4 allele is associated with working memory
impairment in Parkinson's disease.
Tröster AI, Fields JA, Paolo AM, Koller WC.
Department of Neurology, University of North Carolina School of Medicine, Chapel
Hill, NC 27599, USA. trostera@neurology.unc.edu
The apolipoprotein E (APOE) epsilon4 allele has been associated with an increased
risk of Alzheimer's disease (AD) and weaker episodic memory among elderly.
Although this APOE allele has been linked to earlier onset of Parkinson's disease
(PD), an association with dementia in PD has been only inconsistently
demonstrated. Given the heterogeneity of cognitive impairment patterns in PD,
this study sought to determine whether an association exists between APOE
genotype and specific cognitive deficits in PD. The neuropsychological test
performance of 42 PD patients without an epsilon4 allele (PD-Non4) and of 20 with
at least one epsilon4 allele (PD-epsilon4) was compared to that of 146 elderly
control subjects (NC). The PD groups were comparable in overall severity of
cognitive impairment and disease duration, but the PD-epsilon4 group was younger,
had an earlier disease onset, and contained a higher proportion of persons with
dementia. Both PD groups showed wide-ranging cognitive impairments relative to
NC. Once age differences between groups were controlled for, the PD groups
generally did not differ from each other in cognitive performance. However, only
the PD-Non4 group demonstrated working memory/attention impairments (digit span,
visual span, Trailmaking test) relative to the NC group. Results suggest that the
APOE genotype may influence the cognitive phenotype of PD, and specifically that
absence of the epsilon4 allele is associated with working memory impairment.
Additionally, results are consistent with prior findings showing an association
between the epsilon4 allele and earlier onset of PD and presence of dementia.
PMID: 16769085 [PubMed - indexed for MEDLINE]
11. Neurology. 2006 Mar 14;66(5):672-7. Epub 2006 Jan 25.
Topiramate in essential tremor: a double-blind, placebo-controlled trial.
Ondo WG, Jankovic J, Connor GS, Pahwa R, Elble R, Stacy MA, Koller WC, Schwarzman
L, Wu SC, Hulihan JF; Topiramate Essential Tremor Study Investigators.
Baylor College of Medicine, Houston, TX 77030, USA. wondo@bc.tmc.edu
BACKGROUND: Essential tremor is most prevalent and most disabling in older
patients. Additional therapies are required for patients with an inadequate
response or intolerable side effects. In small trials, topiramate appeared to be
beneficial in essential tremor. METHODS: In this multicenter, double-blind,
placebo-controlled, parallel-design trial, patients with moderate to severe
essential tremor of the upper limbs were randomized to 24 weeks of treatment with
placebo or topiramate (target dose, 400 mg/day) as monotherapy or as an adjunct
to one antitremor medication. The primary efficacy variable was the final visit
tremor score based on the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS:
The intent-to-treat population was 208 patients (topiramate, 108; placebo, 100).
The final visit score (last observation carried forward) was lower in the
topiramate group than with placebo (p < 0.001). Mean percentage improvement in
overall TRS scores was 29% with topiramate at a mean final dose of 292 mg/day and
16% with placebo (p < 0.001). Topiramate was associated with greater improvement
in function and disability (p = 0.001). A between-group difference (p < 0.001)
was observed at the first on-treatment visit at 4 weeks when the target
topiramate dose was 100 mg/day (mean achieved dose, 62 +/- 9 mg/day). The most
common treatment-limiting adverse events in topiramate-treated patients were
paresthesia (5%), nausea (3%), concentration/attention difficulty (3%), and
somnolence (3%). Adverse events were treatment limiting in 31.9% of topiramate
patients and 9.5% of placebo patients. CONCLUSIONS: Topiramate was effective in
the treatment of moderate to severe essential tremor. Tremor reduction was
accompanied by functional improvements, such as in motor tasks, writing, and
speaking.
PMID: 16436648 [PubMed - indexed for MEDLINE]
12. Neurotoxicology. 2006 May;27(3):340-6. Epub 2005 Dec 1.
The diagnosis of manganese-induced parkinsonism.
Cersosimo MG, Koller WC.
Program of Parkinson's disease and Movement Disorders, Hospital de Clinicas, and
Department of Neurology, University of Buenos Aires, Buenos Aires, Peña 2225 5 C
(1126), Argentina. mgracersosimo@arnet.com.ar
Parkinsonism is a clinical syndrome consisting of tremor, bradykinesia, rigidity,
gait, balance problems, in addition to various non-motor symptoms. There are many
causes of parkinsonism such as neurodegenerative disease, drugs, vascular causes,
structural lesions, infections, and toxicants. Parkinson's disease, or idiopathic
parkinsonism, is the most common form of parkinsonism observed in the clinic.
There is degeneration of the substantia nigra, pars compacta, which results in
loss of striatal dopamine. Parkinson's disease is a slowly progressive condition
in which there is a dramatic and sustained responsiveness to levodopa therapy.
Manganese is an essential trace element that can be associated with
neurotoxicity. Hypermanganism can occur in a variety of clinical settings. The
clinical symptoms of manganese intoxication include non-specific complaints,
neurobehavioral changes, parkinsonism, and dystonia. Although the globus pallidus
is the main structure of damage, other basal ganglia areas can also be involved.
MRI scans may show globus pallidus changes during (and for a short period after)
exposure. Fluorodopa PET scans that assess the integrity of the substantia nigra
dopaminergic system are abnormal in Parkinson's disease. However, these scans
re-reported to be normal in a few cases studied with manganese-induced
parkinsonism. The parkinsonism due to manganese may have some clinical features
that occur less commonly in Parkinson's disease, such as kinetic tremor,
dystonia, specific gait disturbances, and early mental, balance and speech
changes. The clinical signs tend to be bilateral whereas Parkinson's disease
begins on one side of the body. Patients with manganese-induced parkinsonism may
be younger at the onset of the disease than with Parkinson's disease. Lastly,
there appears to be a lack of response to levodopa therapy in manganese-induced
parkinsonism. In summary it may be possible to differentiate manganese-induced
parkinsonism from Parkinson's disease using clinical and imaging studies.
PMID: 16325915 [PubMed - indexed for MEDLINE]
13. Parkinsonism Relat Disord. 2005 Aug;11(5):317-21.
Clinical usefulness of the Parkinson's disease sleep scale.
Tse W, Liu Y, Barthlen GM, Hälbig TD, Tolgyesi SV, Gracies JM, Olanow CW, Koller
WC.
Department of Neurology, The Mount Sinai School of Medicine, One Gustave L. Levy
Place, New York, NY 10029, USA. winona.tse@mssm.edu
OBJECTIVE: To test the usefulness of the Parkinson's disease sleep scale (PDSS)
in identifying sleep disorders in the clinical practice setting. METHODS:
Sixty-two PD patients were evaluated with the PDSS and the Epworth sleepiness
scale (ESS). A cut-off of less than five for each PDSS item as an indicator of
substantial sleep disturbance was chosen. If the ESS was equal to or greater than
eight, patients were referred to a sleep disorder specialist and possible
polysomnography. RESULTS: The mean total PDSS score was 104.7+/-21.5,which
correlated with the mean Hoehn and Yahr score (1.9+/-0.9) as well as the mean ESS
score (9.7+/-4.7). A significant correlation was also found between the ESS score
and several items of the PDSS. CONCLUSIONS: The PDSS was useful in identifying
sleep disturbances which were not previously diagnosed, such as sleep maintenance
insomnia and excessive daytime sleepiness. Problems with the PDSS include
ambiguities of some questions, lack of quantification and an inability to
identify specific sleep disturbances such as sleep apnea.
PMID: 15882956 [PubMed - indexed for MEDLINE]
14. Neurology. 2004 Oct 12;63(7 Suppl 2):S2-6.
A novel formulation of selegiline for the treatment of Parkinson's disease.
Tetrud JW, Koller WC.
The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, CA 94089, USA.
PMID: 15477582 [PubMed - indexed for MEDLINE]
15. J Neurosurg. 2004 Jul;101(1):36-42.
Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a
double-blind 12-month evaluation study.
Germano IM, Gracies JM, Weisz DJ, Tse W, Koller WC, Olanow CW.
Department of Neurosurgery, The Mount Sinai School of Medicine, New York, New
York 10029-6574, USA. isabelle.germano@msnyuhealth.org
OBJECT: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN)
has been established as an effective treatment for Parkinson disease (PD).
Nevertheless, bilateral surgical procedures can be associated with frequent and
severe complications. The aim in the present study was to assess the safety and
efficacy of unilateral STN stimulation, and the need for a second procedure.
METHODS: Twelve patients with PD underwent unilateral DBS of the STN and were
followed up for 12 months. Patients were assessed at baseline and at each visit
in a double-blind fashion by analyzing the Unified PD Rating Scale (UPDRS),
ambulation speed, and home diaries. Levodopa-off/stimulation-on UPDRS motor
scores were improved by 26 +/- 8% (p < 0.05, mean +/- standard deviation [SD])
compared with the baseline levodopa-off score; there was a 50% improvement in
contralateral features, a 17% improvement ipsilaterally, and a 36% improvement in
axial features. The mean ambulation speed increased by 83 +/- 44% (p < 0.01, mean
+/- SD). The medication-on time with dyskinesias was significantly reduced (p <
0.01) and the daily levodopa dose was reduced by 19 +/- 6% (p < 0.05, mean +/-
SD). There were no clinically significant side effects. CONCLUSIONS: Unilateral
DBS of the STN is safe and well tolerated, and may provide sufficient benefit so
that additional surgery is not required.
PMID: 15255249 [PubMed - indexed for MEDLINE]
16. Curr Neurol Neurosci Rep. 2004 Jul;4(4):277-83.
Neuroprotection in Parkinson's disease: an elusive goal.
Koller WC, Cersosimo MG.
Department of Neurology, The Mount Sinai Medical Center, One Gustave L. Levy
Place, Annenberg 1494/Box 1137, New York, NY 10029-6574, USA.
william.koller@mssm.edu
Parkinson's disease is a chronic progressive condition that causes disability and
reduction of quality of life. Symptomatic treatments are effective in the early
disease; however, with time, most patients develop motor complications.
Neuroprotective therapies are those that can slow disease progression;
unfortunately, these agents are not available. Advances in the knowledge of the
possible pathogenic events that can lead to nigral cell death have increased
dramatically. These mechanisms include oxidative stress, mitochondrial
dysfunction, inflammation, excitotoxicity, alterations in protein degradation,
and ultimately apoptosis. Based on these laboratory scientific findings, a number
of agents have been studied in clinical trials. However, how to assess disease
evolution and establish reliable endpoints is still an unresolved issue. The
monoamine oxidase inhibitors selegiline and rasagiline have been shown to be
neuroprotective in vitro and in animal models, but so far this property was not
demonstrated in clinical trials. Other agents have been studied and still others
are undergoing clinical investigation. These include antiexcitotoxicity drugs
like riluzole, the bioenergetic agent coenzyme Q10, trophic factors, and
antiapoptotic drugs. Laboratory and clinical data suggest that dopamine agonists
may have a neuroprotective action, but this has yet to be proven. However, as our
basic and clinical knowledge on Parkinson's disease increases, it is likely that
a neuroprotective drug will be found.
PMID: 15217541 [PubMed - indexed for MEDLINE]
17. Neurology. 2004 Jun 8;62(11):2005-9.
Apolipoprotein E controls the risk and age at onset of Parkinson disease.
Li YJ, Hauser MA, Scott WK, Martin ER, Booze MW, Qin XJ, Walter JW, Nance MA,
Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Goetz CG, Small
GW, Mastaglia F, Haines JL, Pericak-Vance MA, Vance JM.
Department of Medicine and Center for Human Genetics, Duke University Medical
Center, Durham, NC 27710, USA. yiju.li@duke.edu
BACKGROUND: Similarities between Alzheimer disease (AD) and Parkinson disease
(PD) suggest a possible role for apolipoprotein E (APOE) in PD. Most previous
studies seeking to establish such a link used case-control datasets and results
have been inconsistent. OBJECTIVE: To investigate APOE's role in PD using
family-based association analyses. METHODS: APOE functional polymorphisms were
genotyped for 658 PD affected families, including 282 multiplex and 376 singleton
families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used
to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the
effect of APOE on age at onset of PD. RESULTS: APOE was significantly associated
with risk of developing PD. Stratified analysis revealed that APOE was most
strongly associated with families with a positive PD family history (global p =
0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele
decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a
negative association of APOE-4 (p = 0.015) with age at onset in PD. CONCLUSIONS:
The APOE-4 allele increases risk and decreases age at onset of PD, an association
that may not be dependent upon cognitive impairment.
PMID: 15184605 [PubMed - indexed for MEDLINE]
18. Drugs Today (Barc). 1998 Feb;34(2):95-105.
Advances in the treatment of Parkinson's disease.
Pahwa R, Koller WC.
Department of Neurology, The University of Kansas Medical Center, Kansas City
66160-7314, USA.
Pharmacological treatment of Parkinson's disease has been advanced by a better
understanding of how to use currently existing drugs as well as by the
introduction of newer drugs. Three new dopaminergic agonists, ropinirole,
pramipexole and cabergoline, have been introduced recently for the treatment of
Parkinson's disease. A new class of drugs, COMT inhibitors, such as tolcapone,
also have been introduced into clinical practice. These drugs extend the effect
of levodopa therapy. The results of clinical trials such as the 5-year Sinemet
study indicate that low-dose levo-dopa therapy can control motor symptoms up to 5
years with the minimal prevalence of adverse reactions. Pharmacology, efficacy
and adverse reactions of these compounds will be discussed as well as their place
in the treatment of Parkinson's disease. (c) 1998 Prous Science. All rights
reserved.
PMID: 15094867 [PubMed]
19. Neurology. 2004 Mar 9;62(5):730-3.
Effect of levodopa treatment for parkinsonism in welders: A double-blind study.
Koller WC, Lyons KE, Truly W.
Department of Neurology, The Mount Sinai School of Medicine, New York, NY, USA.
william.koller@mssm.edu
Comment in:
Neurology. 2004 Oct 26;63(8):1541; author reply 1541.
BACKGROUND: Manganese is known to cause a parkinsonian syndrome similar
clinically to Parkinson disease (PD). L-Dopa responsiveness is a hallmark of PD;
however, L-dopa's effect on manganese-induced parkinsonism is not well defined.
OBJECTIVE: To access the efficacy and safety of L-dopa therapy in a double-blind,
randomized, placebo-controlled trial. METHODS: Thirteen patients with
manganese-induced parkinsonism were evaluated in a cross-over study with a
modified Unified PD Rating Scale (UPDRS), timed walk test, tapping, and global
clinical impression scores. Adverse reactions were assessed. RESULTS: There was
no significant difference between placebo and L-dopa for any measure: motor
UPDRS, 27.4 vs 28.8; walk time, 16.6 seconds vs 17.7 seconds; tapping right hand,
69.5 vs 64.7; and tapping left hand, 66.8 vs 64.4. There were no differences in
the global impression scores. Adverse reactions occurred similarly in the two
groups, including headaches, drowsiness, and diarrhea. CONCLUSIONS: L-Dopa
therapy is not effective for the management of parkinsonism in welders. L-dopa
unresponsiveness may be useful to distinguish manganese-induced parkinsonism from
Parkinson disease.
PMID: 15007122 [PubMed - indexed for MEDLINE]
20. Stereotact Funct Neurosurg. 2003;80(1-4):43-7.
Effect of motor improvement on quality of life following subthalamic stimulation
is mediated by changes in depressive symptomatology.
Tröster AI, Fields JA, Wilkinson S, Pahwa R, Koller WC, Lyons KE.
Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
trostera@glial.med.unc.edu
BACKGROUND/AIMS: Subthalamic deep brain stimulation (STN-DBS) for Parkinson's
disease (PD) improves motor symptoms and quality of life (QOL). Because
depression is a potent correlate of QOL, and STN-DBS may be associated with
changes in mood, this study sought to determine whether QOL improvement is a
direct or indirect consequence of motor improvement. METHODS: 26 patients with
PD, free of dementia and major depression, who consecutively underwent bilateral,
microelectrode-guided STN-DBS, underwent preoperative and 3-month postoperative
neuropsychological evaluation, including measures of QOL (PD Questionnaire -39)
and depressive symptoms (Beck Depression Inventory). RESULTS: Motor score in the
Unified Parkinson's Disease Rating Scale (UPDRS Part III) improved significantly
with STN-DBS relative to preoperative 'on' and 'off' scores, as did QOL and
depressive symptoms. Extent of QOL improvement tended to be associated with
improvement in motor score from presurgical on to postsurgical on stimulation and
on medication state. QOL improvement was significantly related to amelioration of
depressive symptoms. Partial correlations revealed that the association between
QOL improvement and depression remained significant when influence of motor
improvement on QOL and depression was controlled for. The motor-QOL association
was no longer significant when effects of depression were controlled for.
CONCLUSIONS: Significant QOL improvements after STN-DBS are associated with
improved motor 'on' state and depressive symptoms. The influence of motor
improvement on QOL may be largely indirect by reducing depression. Copyright 2003
S. Karger AG, Basel
PMID: 14745208 [PubMed - indexed for MEDLINE]
21. Neurology. 2004 Jan 13;62(1 Suppl 1):S1-8.
Unmet medical needs in Parkinson's disease.
Koller WC, Tse W.
Department of Neurology, Mt. Sinai School of Medicine, New York, NY 10029, USA.
Levodopa, introduced in the late 1960s, was the first highly effective drug for
the symptomatic treatment of Parkinson's disease (PD) and remains the mainstay of
pharmacologic treatment. However, long-term treatment has important limitations.
The disease continues to progress despite treatment with levodopa, and a
neuroprotective therapy is urgently required. In addition, motor complications
associated with chronic levodopa therapy are an important source of disability.
Treatment of these complications forms a major focus of modern PD management, and
it is in this area that recent advances in our knowledge offer the best
opportunity for therapeutic gain. In the search for improved therapies, suitable
outcome measures to better assess overall disability in PD and disease
progression are essential.
PMID: 14718675 [PubMed - indexed for MEDLINE]
22. Hum Mol Genet. 2003 Dec 15;12(24):3259-67. Epub 2003 Oct 21.
Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and
Parkinson disease.
Li YJ, Oliveira SA, Xu P, Martin ER, Stenger JE, Scherzer CR, Hauser MA, Scott
WK, Small GW, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner
BC, Jankovic J, Goetz CG, Mastaglia F, Middleton LT, Roses AD, Saunders AM,
Schmechel DE, Gullans SR, Haines JL, Gilbert JR, Vance JM, Pericak-Vance MA,
Hulette C, Welsh-Bohmer KA.
Department of Medicine, Center for Human Genetics, Institute for Genome Science
and Policy, Duke University Medical Center, Box 3445, Durham, NC 27710, USA.
yiju.li@duke.edu
Erratum in:
Hum Mol Genet. 2004 Mar 1;13(5):573.
We previously reported genetic linkage of loci controlling age-at-onset in
Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on
chromosome 10q. Given the large number of genes in this initial starting region,
we applied the process of 'genomic convergence' to prioritize and reduce the
number of candidate genes for further analysis. As our second convergence factor
we performed gene expression studies on hippocampus obtained from AD patients and
controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase;
NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and
glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their
expression between AD and controls and mapped to the 10q age-at-onset linkage
region, the first convergence factor. Using 2814 samples from our AD dataset
(1773 AD patients) and 1362 samples from our PD dataset (635 PD patients),
allelic association studies for age-at-onset effects in AD and PD revealed no
association for three of the candidates, but a significant association was found
for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2
(P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well
understood, but recent data suggest that GSTO1 maybe involved in the
post-translational modification of the inflammatory cytokine interleukin-1beta.
This is provocative given reports of the possible role of inflammation in these
two neurodegenerative disorders.
PMID: 14570706 [PubMed - indexed for MEDLINE]
23. Arch Neurol. 2003 Jul;60(7):975-80.
Association study of Parkin gene polymorphisms with idiopathic Parkinson disease.
Oliveira SA, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons KE, Pahwa
R, Stern MB, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Scott BL, Goetz CG,
Small GW, Mastaglia FL, Stajich JM, Zhang F, Booze MW, Reaves JA, Middleton LT,
Haines JL, Pericak-Vance MA, Vance JM, Martin ER.
Department of Medicine and Center for Human Genetics, Institute for Genome
Sciences and Policy, Duke University Medical Center, Durham, NC.
BACKGROUND: Previously, we detected linkage of idiopathic Parkinson disease (PD)
to the region on chromosome 6 that contains the Parkin gene (D6S305; logarithm of
odds score, 5.47) in families with at least one individual with age at onset
younger than 40 years (families with early-onset disease). Further study
demonstrated the presence of Parkin mutations in this data set. However, previous
case-control studies have reported conflicting results regarding the role of more
common Parkin polymorphisms as susceptibility alleles for idiopathic PD.
OBJECTIVE: To investigate the association of 7 previously studied Parkin
single-nucleotide polymorphisms (SNPs) throughout the promoter and most of the
open reading frame with PD in a large cohort of patients with primarily
late-onset PD. METHODS: One promoter, 3 intronic, and 3 exonic Parkin SNPs were
genotyped in 1580 individuals belonging to 397 families, and their association
with PD was evaluated using family-based association tests. RESULTS: No
significant association (P>.05) between PD and any Parkin SNP allele or genotype
was detected. Haplotype analysis and stratification by age at onset or family
history also failed to produce significant results. CONCLUSIONS: These results
suggest that these common variants of Parkin are not associated with PD in white
patients, although Parkin mutations are known to cause early- and late-onset PD.
PMID: 12873854 [PubMed - indexed for MEDLINE]
24. Med Clin North Am. 2003 Jul;87(4):771-91, vii.
Movement disorders.
Cersosimo MG, Koller WC.
Movement Disorder Program, Hospital de Clinicas Jose de San Martin, University of
Buenos Aires, Buenos Aires, Argentina.
Movement disorders are commonly encountered in clinical practice. The diagnosis
of movement disorders relies on a focused history and neurologic examination.
Diagnostic steps include (1) identification of the phenomenology of the movements
(eg, tremor); (2) characterization of appropriate clinical syndromes; and (3)
differential diagnosis of specific disease entities. Accurate diagnosis is
essential because symptomatic treatment exists for most movement disorders.
PMID: 12834148 [PubMed - indexed for MEDLINE]
25. Drug Saf. 2003;26(7):461-81.
Benefits and risks of pharmacological treatments for essential tremor.
Lyons KE, Pahwa R, Comella CL, Eisa MS, Elble RJ, Fahn S, Jankovic J, Juncos JL,
Koller WC, Ondo WG, Sethi KD, Stern MB, Tanner CM, Tintner R, Watts RL.
University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Essential tremor can cause significant functional disability in some patients.
The arms are the most common body part affected and cause the most functional
disability. The treatment of essential tremor includes medications, surgical
options and other forms of therapy. Presently there is no cure for essential
tremor nor are there any medications that can slow the progression of tremor.
Treatment for essential tremor is recommended if the tremor causes functional
disability. If the tremor is disabling only during periods of stress and anxiety,
propranolol and benzodiazepines can be used during those periods when the tremor
causes functional disability. The currently available medications can improve
tremor in approximately 50% of the patients. If the tremor is disabling,
treatment should be initiated with either primidone or propranolol. If either
primidone or propranolol do not provide adequate control of the tremor, then the
medications can be used in combination. If patients experience adverse effects
with propranolol, occasionally other beta-adrenoceptor antagonists (such as
atenolol or metoprolol) can be used. If primidone and propranolol do not provide
adequate control of tremor, occasionally the use of benzodiazepines (such as
clonazepam) can provide benefit. Other medications that may be helpful include
gabapentin or topiramate. If a patient has disabling head or voice tremor,
botulinum toxin injections into the muscles may provide relief from the tremor.
Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand
weakness and is not widely used. There are other medications that have been tried
in essential tremor and have questionable efficacy. These drugs include carbonic
anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel
antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine.
If the patient still has disabling tremor after medication trials, surgical
options are usually considered. Surgical options include thalamotomy and deep
brain stimulation of the thalamus. These surgical options provide adequate tremor
control in approximately 90% of the patients. Surgical morbidity and mortality
for these procedures is low. Deep brain stimulation and thalamotomy have been
shown to have comparable efficacy but fewer complications have been reported with
deep brain stimulation. In patients undergoing bilateral procedures deep brain
stimulation of the thalamus is the procedure of choice to avoid adverse effects
seen with bilateral ablative procedures. The use of medication and/or surgery can
provide adequate tremor control in the majority of the patients.
PMID: 12735785 [PubMed - indexed for MEDLINE]
26. Ann Neurol. 2003 May;53(5):624-9.
Parkin mutations and susceptibility alleles in late-onset Parkinson's disease.
Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa
R, Stern MB, Hiner BC, Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW,
Mastaglia F, Stajich JM, Zhang F, Booze MW, Winn MP, Middleton LT, Haines JL,
Pericak-Vance MA, Vance JM.
Department of Medicine and Center for Human Genetics, Institute for Genome
Sciences and Policy, Duke University Medical Center, Durham, NC 27710, USA.
Comment in:
Ann Neurol. 2003 Sep;54(3):415-6; author reply 416-7.
Parkin, an E2-dependent ubiquitin protein ligase, carries pathogenic mutations in
patients with autosomal recessive juvenile parkinsonism, but its role in the
late-onset form of Parkinson's disease (PD) is not firmly established.
Previously, we detected linkage of idiopathic PD to the region on chromosome 6
containing the Parkin gene (D6S305, logarithm of odds score, 5.47) in families
with at least one subject with age at onset (AAO) younger than 40 years. Mutation
analysis of the Parkin gene in the 174 multiplex families from the genomic screen
and 133 additional PD families identified mutations in 18% of early-onset and 2%
of late-onset families (5% of total families screened). The AAO of patients with
Parkin mutations ranged from 12 to 71 years. Excluding exon 7 mutations, the mean
AAO of patients with Parkin mutations was 31.5 years. However, mutations in exon
7, the first RING finger (Cys253Trp, Arg256Cys, Arg275Trp, and Asp280Asn) were
observed primarily in heterozygous PD patients with a much later AAO (mean AAO,
49.2 years) but were not found in controls in this study or several previous
reports (920 chromosomes). These findings suggest that mutations in Parkin
contribute to the common form of PD and that heterozygous mutations, especially
those lying in exon 7, act as susceptibility alleles for late-onset form of
Parkinson disease.
PMID: 12730996 [PubMed - indexed for MEDLINE]
27. Neurology. 2003 Apr 8;60(7):1189-91.
Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's
disease.
van der Walt JM, Martin ER, Scott WK, Zhang F, Nance MA, Watts RL, Hubble JP,
Haines JL, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic
J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Mastaglia F, Roses AD, Stajich JM,
Booze MW, Fujiwara K, Gibson RA, Middleton LT, Scott BL, Pericak-Vance MA, Vance
JM.
Department of Medicine and Center for Human Genetics, Institute for Genome
Sciences and Policy, Duke University Medical Center, Durham, NC 27710, USA.
Recently, the authors demonstrated linkage in idiopathic PD to a region on
chromosome 8p that contains the N-acetyltransferase genes, NAT1 and NAT2. The
authors examined NAT1 and NAT2 for association with PD using family-based
association methods and single nucleotide polymorphisms (SNPs). The authors did
not find evidence for association with increased risk for PD between any
individual NAT1 or NAT2 SNP or acetylation haplotype (N = 397 families, 1,580
individuals).
PMID: 12682333 [PubMed - indexed for MEDLINE]
28. Am J Hum Genet. 2003 Apr;72(4):804-11. Epub 2003 Feb 28.
Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.
van der Walt JM, Nicodemus KK, Martin ER, Scott WK, Nance MA, Watts RL, Hubble
JP, Haines JL, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC,
Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Mastaglia F, Stajich JM,
McLaurin AC, Middleton LT, Scott BL, Schmechel DE, Pericak-Vance MA, Vance JM.
Department of Medicine, and Center for Human Genetics, Institute for Genome
Sciences and Policy, Duke University Medical Center, Durham, NC 27710, USA.
Mitochondrial (mt) impairment, particularly within complex I of the electron
transport system, has been implicated in the pathogenesis of Parkinson disease
(PD). More than half of mitochondrially encoded polypeptides form part of the
reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme.
To test the hypothesis that mtDNA variation contributes to PD expression, we
genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European
mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control
subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55;
95% confidence interval [CI] 0.34-0.91; P=.02) or K (OR 0.52; 95% CI 0.30-0.90;
P=.02) demonstrated a significant decrease in risk of PD versus individuals
carrying the most common haplogroup, H. Furthermore, a specific SNP that defines
these two haplogroups, 10398G, is strongly associated with this protective effect
(OR 0.53; 95% CI 0.39-0.73; P=.0001). SNP 10398G causes a nonconservative amino
acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of
complex I. After stratification by sex, this decrease in risk appeared stronger
in women than in men (OR 0.43; 95% CI 0.27-0.71; P=.0009). In addition, SNP 9055A
of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22-0.93;
P=.03). Our results suggest that ND3 is an important factor in PD susceptibility
among white individuals and could help explain the role of complex I in PD
expression.
PMCID: 1180345
PMID: 12618962 [PubMed - indexed for MEDLINE]
29. J Neurol Neurosurg Psychiatry. 2003 Mar;74(3):305-11.
Neuropsychological and quality of life outcomes 12 months after unilateral
thalamic stimulation for essential tremor.
Fields JA, Tröster AI, Woods SP, Higginson CI, Wilkinson SB, Lyons KE, Koller WC,
Pahwa R.
Department of Psychiatry and Behavioral Sciences, University of Washington School
of Medicine, Seattle 98195-6560, USA.
OBJECTIVES: To evaluate the one year cognitive, mood state, and quality of life
(QoL) outcomes of unilateral thalamic deep brain stimulation (DBS) for essential
tremor (ET). METHODS: 40 patients diagnosed with ET completed comprehensive
neuropsychological assessments about one month before and three and 12 months
after DBS electrode implantation. Data were subjected to multivariate analyses,
and significant results were further analysed using univariate techniques.
RESULTS: Analyses revealed statistically significant improvements on a cognitive
screening measure and in aspects of fine visuomotor and visuoperceptual
functions, verbal memory, mood state, and QoL. No group-wise declines in
cognition were observed, but more patients showed declines than improvements on
language and visual memory tests. Semantic verbal fluency declined significantly
in four (10%) of the patients. In these four patients, diminished lexical verbal
fluency was present at baseline. CONCLUSION: Cognitive, mood, and QoL outcomes
after one year of DBS for ET are favourable; there were no overall deleterious
effects on cognition, and DBS was accompanied by a significant reduction in
anxiety and improvements in quality of life. However, preoperative verbal fluency
diminution may predispose to further fluency declines after DBS.
PMCID: 1738322
PMID: 12588913 [PubMed - indexed for MEDLINE]
30. Adv Neurol. 2003;91:383-96.
Differential diagnosis of parkinsonism.
Facca AG, Koller WC.
Department of Neurology, University of Miami, School of Medicine, Miami, Florida,
USA.
PMID: 12442697 [PubMed - indexed for MEDLINE]
31. Ann Neurol. 2002 Oct;52(4):511-6.
An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype.
Poorkaj P, Muma NA, Zhukareva V, Cochran EJ, Shannon KM, Hurtig H, Koller WC,
Bird TD, Trojanowski JQ, Lee VM, Schellenberg GD.
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound
Health Care System, Seattle Division, Seattle, WA 98195, USA.
MAPT, the gene encoding tau, was screened for mutations in 96 progressive
supranuclear palsy subjects. A point mutation (R5L) was identified in a single
progressive supranuclear palsy subject that was not in the other progressive
supranuclear palsy subjects or in 96 controls. Functionally, this mutation alters
the ability of tau to promote microtubule assembly. Analysis of soluble tau from
different brain regions indicates that the mutation does not affect the ratio of
tau isoforms synthesized. Aggregated insoluble tau from subcortical regions was
predominantly four-repeat tau with no or one amino terminal insert (0N4R and
1N4R). Insoluble tau from cortical regions also contained 1N3R tau. Thus, the R5L
mutation causes a progressive supranuclear palsy phenotype, presumably by a
gain-of-function mechanism.
PMID: 12325083 [PubMed - indexed for MEDLINE]
32. Stereotact Funct Neurosurg. 2001;76(1):2-18.
Magnitude of microelectrode refinement in pallidotomy and thalamotomy.
Milligan BD, Wilkinson S, Overman J, Kirschman DL, Koller WC, Pahwa R, Lyons KE,
Batnitzky S, Gordon MA.
Imaging Resource Center, University of Kansas Medical Center, Kansas City 66160,
USA.
The relative accuracy of starting point algorithms in microelectrode-guided
stereotactic pallidotomy and thalamotomy was evaluated using postoperative
magnetic resonance imaging (MRI) data. Multiplanar reformations were performed to
align postoperative MRI in anterior-posterior, dorsal-ventral and mediolateral
planes. Three-dimensional distance and direction from the pallidal and thalamic
stereotactic starting points to the respective radiofrequency lesions were
measured. Similar magnitude of microelectrode refinement in pallidotomy and
thalamotomy suggested similar accuracy of algorithms used to set the stereotactic
starting point. Fewer microelectrode-recording tracts were required to identify
optimal lesioning sites in thalamotomy compared to pallidotomy. Lesions were
consistently localized anterior and superior to the starting point and a refined
starting point algorithm may reduce the number of microelectrode recording
tracts. Copyright 2002 S. Karger AG, Basel
PMID: 12007274 [PubMed - indexed for MEDLINE]
33. Mov Disord. 2002 Mar;17(2):404-7.
Thalamic stimulation for midbrain tremor after partial hemangioma resection.
Pahwa R, Lyons KE, Kempf L, Wilkinson SB, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas
66160, USA. rpahwa@kumc.edu
We describe a patient with disabling medication-resistant midbrain tremor
developed after partial hemangioma resection, who responded to deep brain
stimulation of the thalamus. Copyright 2002 Movement Disorder Society.
PMID: 11921133 [PubMed - indexed for MEDLINE]
34. Neurology. 2002 Feb 26;58(4 Suppl 1):S79-86.
Treatment of early Parkinson's disease.
Koller WC.
Department of Neurology, University of Miami School of Medicine, Miami, FL, USA.
wkoller@med.miami.edu
The early treatment of Parkinson's disease (PD) consists of nonpharmacologic
treatment, consideration of neuroprotective therapy, and initial symptomatic
treatment. Education for the patient and family, access to support groups,
regular exercise, and good nutrition are essential to the overall management of
PD. Disease-modifying therapies, such as agents that provide neurorescue or
neuroprotection, will provide a major advance in the treatment of PD.
Intervention at the genetic/environmental level or that affects the cascade of
pathophysiologic events, protein aggregation, or apoptosis could result in
neuroprotection. Many agents are now being investigated for neuroprotective
potential. A major paradigm shift has recently occurred because of the recent
basic and clinical data indicating that dopamine agonists, rather than levodopa,
should be the initial symptomatic therapy in PD. However, levodopa may be started
first in some patients because of patient age, cognitive status, or cost of
drugs.
PMID: 11909989 [PubMed - indexed for MEDLINE]
35. Eur J Neurol. 2002 Mar;9(2):143-51.
Neuropsychological deficits in essential tremor: an expression of
cerebello-thalamo-cortical pathophysiology?
Tröster AI, Woods SP, Fields JA, Lyons KE, Pahwa R, Higginson CI, Koller WC.
Department of Psychiatry and Behavioral Sciences, University of Washington School
of Medicine, Box 136560, Seattle, WA 98195-6560, USA. atroster@u.washington.edu
Few studies have been published regarding the neuropsychological characteristics
of patients with essential tremor (ET), but preliminary findings suggest that
mild attentional and executive dysfunction accompany the disorder. A consecutive
series of 101 patients with ET referred for thalamotomy and/or thalamic deep
brain stimulation candidacy work-up also underwent neuropsychological evaluation.
Average neuropsychological test scores were calculated, along with the
proportions of subjects whose scores fell within or more than one SD above or
below the mean (using demographically corrected normative data). Significantly
lower than average (T-score of 50) scores were evident on measures of complex
auditory attention, visual attention and response inhibition, recall of a word
list, verbal fluency, and visual confrontation naming. A significantly greater
proportion of patients (ranging from about 34 to 60%) than might be expected on
the basis of a normal distribution obtained scores more than one SD below the
normative mean on select measures of attention, verbal fluency, immediate word
list recall, semantic encoding, and facial matching. Consistent with prior
research, notable, albeit clinically subtle, deficits in attention and select
executive functions are evident in patients with ET. Although not specific to ET
or cerebellar dysfunction, the observed pattern of cognitive deficits is
consistent with cerebello-thalamo-cortical circuit dysfunction.
PMID: 11882055 [PubMed - indexed for MEDLINE]
36. Am J Hum Genet. 2002 Apr;70(4):985-93. Epub 2002 Mar 1.
Age at onset in two common neurodegenerative diseases is genetically controlled.
Li YJ, Scott WK, Hedges DJ, Zhang F, Gaskell PC, Nance MA, Watts RL, Hubble JP,
Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Allen FA Jr, Goetz CG,
Mastaglia F, Stajich JM, Gibson RA, Middleton LT, Saunders AM, Scott BL, Small
GW, Nicodemus KK, Reed AD, Schmechel DE, Welsh-Bohmer KA, Conneally PM, Roses AD,
Gilbert JR, Vance JM, Haines JL, Pericak-Vance MA.
Department of Medicine, Center for Human Genetics, Duke University Medical
Center, Durham, NC 27710, USA.
To identify genes influencing age at onset (AAO) in two common neurodegenerative
diseases, a genomic screen was performed for AAO in families with Alzheimer
disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between
40%--60% were found in both the AD and PD data sets. For PD, significant evidence
for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO
effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage
on chromosomes 6 and 10 was identified independently in both the AD and PD data
sets. Subsequent unified analyses of these regions identified a single peak on
chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62.
These data suggest that a common gene affects AAO in these two common complex
neurodegenerative diseases.
PMCID: 379130
PMID: 11875758 [PubMed - indexed for MEDLINE]
37. Neurology. 2002 Feb 12;58(3):402-10.
Thalamic stimulation reduces essential tremor but not the delayed antagonist
muscle timing.
Zackowski KM, Bastian AJ, Hakimian S, Mink JW, Perlmutter JS, Koller WC, Thach WT
Jr.
Program in Physical Therapy, Department of Anatomy and Neurobiology, Washington
University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA.
BACKGROUND: Electrical stimulation of the thalamus dramatically reduces essential
tremor (ET). It has been hypothesized that the cerebellum and inferior olive are
involved in the generation of ET, and thalamic stimulation is presumed to dampen
ET through interactions with cerebellar output to the thalamus. Evidence suggests
that abnormal timing of agonist and antagonist muscle responses contribute to
cerebellar tremor (CbT); however, this relationship has not been investigated for
ET. The mechanisms of the tremor and improvement are unknown. OBJECTIVE: To
measure the effect of ventral intermediate thalamic stimulation in controlling
the ET response to sudden stretch of an agonist muscle and to determine whether,
in ET, the timing relationships between the initial agonist and antagonist
electromyography (EMG) responses show abnormalities similar to those seen in CbT.
METHODS: The authors studied ET subjects (with implanted thalamic stimulators
turned off and on) and normal controls as they responded to mechanical torque
pulses given at the wrist joint. The wrist joint angle, wrist agonist, and
antagonist EMG were recorded. RESULTS: Like CbT, patients with ET showed delayed
onsets of antagonist EMG and excessive rebound. Thalamic stimulation reduced the
tremor but did not alter the antagonist delay or the rebound. CONCLUSIONS: In ET,
antagonist muscle responses to a torque pulse are similar to that in CbT.
However, benefit from thalamic stimulation did not alter these EMG responses;
therefore, suppression of tremor must be caused by mechanisms other than the
re-establishment of normal agonist-antagonist timing.
PMID: 11839839 [PubMed - indexed for MEDLINE]
38. Acta Neurochir (Wien). 2001 Dec;143(12):1273-7; discussion 1278.
Neuropsychological and quality of life changes following unilateral thalamic deep
brain stimulation in Parkinson's disease: a one-year follow-up.
Woods SP, Fields JA, Lyons KE, Koller WC, Wilkinson SB, Pahwa R, Tröster AI.
Department of Psychiatry & Behavioral Sciences, University of Washington School
of Medicine, Seattle, Washington 98195, USA.
BACKGROUND: The long-term neuropsychological and quality of life (QOL) outcomes
of unilateral thalamic deep brain stimulation (DBS) in patients with intractable
Parkinson's disease (PD) have not heretofore been described. METHOD: Six patients
diagnosed with PD underwent unilateral DBS implantation into a verified thalamic
VIM nucleus target. Participants completed presurgical neuropsychological
evaluation and follow-up assessment at approximately one year postsurgery.
FINDINGS: Compared to their presurgical scores, PD patients exhibited significant
improvement on measures of conceptualization, verbal memory, emotional
adjustment, and QOL at one-year follow-up. A few nominal declines were observed
across the battery of tests. INTERPRETATION: These data provide preliminary
support for the long-term neurocognitive safety and QOL improvements following
thalamic stimulation in patients with PD.
PMID: 11810392 [PubMed - indexed for MEDLINE]
39. JAMA. 2001 Nov 14;286(18):2245-50.
Association of single-nucleotide polymorphisms of the tau gene with late-onset
Parkinson disease.
Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R,
Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small
GW, Masterman D, Mastaglia F, Laing NG, Stajich JM, Ribble RC, Booze MW, Rogala
A, Hauser MA, Zhang F, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL,
Pericak-Vance MA, Vance JM.
Center for Human Genetics, Box 2903, Duke University Medical Center, Durham, NC
27710, USA.
Comment in:
JAMA. 2002 Feb 13;287(6):715-6.
CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules,
has been associated with several rare neurologic diseases that clinically include
parkinsonian features. We recently observed linkage in idiopathic Parkinson
disease (PD) to a region on chromosome 17q21 that contains the tau gene. These
factors make tau a good candidate for investigation as a susceptibility gene for
idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate
whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND
PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from
13 clinical centers in the United States and Australia and from a family
ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs)
within the tau gene for association with PD, using family-based tests of
association. Both affected (n = 426) and unaffected (n = 579) family members were
included; 51 individuals had unclear PD status. Analyses were conducted to test
individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE:
Family-based tests of association, calculated using asymptotic distributions.
RESULTS: Analysis of association between the SNPs and PD yielded significant
evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P
=.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant
association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of
association was found with haplotype analysis, with a positive association with
one haplotype (P =.009) and a negative association with another haplotype (P
=.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the
5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of
genetic linkage and positional association analyses implicates tau as a
susceptibility gene for idiopathic PD.
PMID: 11710889 [PubMed - indexed for MEDLINE]
40. JAMA. 2001 Nov 14;286(18):2239-44.
Complete genomic screen in Parkinson disease: evidence for multiple genes.
Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB,
Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW,
Masterman D, Mastaglia F, Laing NG, Stajich JM, Slotterbeck B, Booze MW, Ribble
RC, Rampersaud E, West SG, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott
BL, Vance JM, Pericak-Vance MA.
Center for Human Genetics, Box 3445, Duke University Medical Center, Durham, NC
27710, USA.
CONTEXT: The relative contribution of genes vs environment in idiopathic
Parkinson disease (PD) is controversial. Although genetic studies have identified
2 genes in which mutations cause rare single-gene variants of PD and
observational studies have suggested a genetic component, twin studies have
suggested that little genetic contribution exists in the common forms of PD.
OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING,
AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete
genomic screen (n = 344 markers) was performed in 174 families with multiple
individuals diagnosed as having idiopathic PD, identified through probands in 13
clinic populations in the continental United States and Australia. A total of 870
family members were studied: 378 diagnosed as having PD, 379 unaffected by PD,
and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod)
scores generated from parametric and nonparametric genetic linkage analysis.
RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint
nonparametric lod score (LOD) linkage analysis detected significant evidence for
linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD
= 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at
younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD =
2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with
late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both
levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data
suggest that the parkin gene is important in early-onset PD and that multiple
genetic factors may be important in the development of idiopathic late-onset PD.
PMID: 11710888 [PubMed - indexed for MEDLINE]
41. Neurology. 2001 Oct 23;57(8):1389-91.
Essential tremor in twins: an assessment of genetic vs environmental determinants
of etiology.
Tanner CM, Goldman SM, Lyons KE, Aston DA, Tetrud JW, Welsh MD, Langston JW,
Koller WC.
Parkinson's Institute, Sunnyvale, CA 94089, USA. ctanner@parkinsoninstitute.org
OBJECTIVE: To determine the relative contribution of genetics and environment to
essential tremor using a twin study method. METHODS: Twins with postural or
kinetic tremor were identified by movement disorders specialists during the
conduct of a study investigating PD in members of the National Academy of
Sciences and National Research Council World War II Veteran Twins Registry. The
diagnosis of essential tremor was made by consensus using established diagnostic
criteria. RESULTS: A total of 196 twins had postural or kinetic tremor on
examination. Of these, 137 had PD or had a twin with PD and were excluded from
this study. Thirty-three others were excluded because of incomplete data for
their twin. Sixteen twin pairs were identified in which at least one twin had
essential tremor. Pairwise concordance in monozygotic twins was approximately two
times that in dizygotic twins (0.60 monozygotic, 0.27 dizygotic). CONCLUSION:
This pattern is consistent with a genetic cause of essential tremor. Because
monozygotic concordance is not 100%, environmental factors may also play a role
in the cause of the disease.
PMID: 11673577 [PubMed - indexed for MEDLINE]
42. J Neurol Neurosurg Psychiatry. 2001 Nov;71(5):682-4.
Long term safety and efficacy of unilateral deep brain stimulation of the
thalamus for parkinsonian tremor.
Lyons KE, Koller WC, Wilkinson SB, Pahwa R.
University of Miami Medical Center, Department of Neurology, 1501 NW 9th Avenue,
Miami, Florida 33136, USA. lyons.kelly@worldnet.att.net
The objective was to investigate the long term safety and efficacy of unilateral
deep brain stimulation (DBS) of the VIM nucleus of the thalamus in Parkinson's
disease. Twelve patients with Parkinson's disease underwent unilateral DBS of the
thalamus for medication resistant tremor between 1994 and 1997. Patients were
evaluated with the motor section of the unified Parkinson's disease rating scale
(UPDRS) in the medication on state at baseline, 3 months, 12 months, and yearly
thereafter.Three patients were lost to follow up. Nine patients had follow up
evaluations greater than 24 months and were included in the analyses. The last
postsurgical follow up occurred on average 40.0 (SD 17.2) months after surgery.
Tremor scores were significantly improved with stimulation on at the long term
follow up compared with baseline. There was no significant change in UPDRS motor
scores at long term follow up compared with baseline. There was no significant
change in any stimulus parameters from 3 months to the long term follow up. Two
patients had asymptomatic intracerebral haemorrhages and one patient had a
subcutaneous haematoma over the implantable pulse generator site. Stimulus
related adverse reactions were mild and easily controlled with changes in
stimulus parameters. Two patients had replacement of the implantable pulse
generator due to normal battery depletion, one patient had lead repositioning due
to migration, and one patient had the lead extension wire replaced due to
erosion. In conclusion, unilateral DBS of the thalamus has long term efficacy for
treatment of tremor due to Parkinson's disease.
PMCID: 1737606
PMID: 11606685 [PubMed - indexed for MEDLINE]
43. Geriatrics. 2001 Aug;56(8):24-5, 29-30, 33-5.
Parkinson's disease. Update in diagnosis and symptom management.
Marjama-Lyons JM, Koller WC.
Department of Neurology, Parkinson's Center, University of Florida at Shands
Jacksonville, Jacksonville, FL, USA.
Parkinson's disease (PD) is a progressive neurodegenerative disorder with a high
burden of morbidity. Because no diagnostic test exists for PD, clinical knowledge
and skill are key to making an early, accurate diagnosis. Diagnostic criteria for
PD require at least two of three motor signs: tremor, rigidity, or bradykinesia.
Levodopa and the dopamine agonists are considered first-line drug therapy. Recent
studies have shown a lower incidence of dyskinesia in patients who began therapy
with a dopamine agonist, although levodopa may be better tolerated by patients
age 70 or older. Combinations of medications and rehabilitative, alternative, and
surgical therapies can often help patients achieve adequate control of PD motor
symptoms and maintain a high quality of independent living.
PMID: 11505857 [PubMed - indexed for MEDLINE]
44. Brain. 2001 Aug;124(Pt 8):1601-9.
Networks mediating the clinical effects of pallidal brain stimulation for
Parkinson's disease: a PET study of resting-state glucose metabolism.
Fukuda M, Mentis MJ, Ma Y, Dhawan V, Antonini A, Lang AE, Lozano AM, Hammerstad
J, Lyons K, Koller WC, Moeller JR, Eidelberg D.
Center for Neurosciences, North Shore-Long Island Jewish Research Institute,
Manhasset, New York 11030, USA.
Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that
stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's
disease causes resting metabolic changes in brain regions remote from the lesion
site. In this study we determined whether similar metabolic changes occur in
Parkinson's disease patients treated with deep brain stimulation (DBS) of the
GPi. We studied seven Parkinson's disease patients with FDG-PET to measure
resting regional cerebral glucose utilization on and off GPi stimulation. We used
statistical parametric mapping to identify significant changes in regional brain
metabolism that occurred with this intervention. We also quantified
stimulation-related changes in the expression of a specific abnormal Parkinson's
disease-related pattern of metabolic covariation (PDRP) that had been identified
in earlier FDG-PET studies. Metabolic changes with DBS were correlated with
clinical improvement as measured by changes in Unified Parkinson's Disease Rating
Scale (UPDRS) motor ratings off medication. GPi DBS improved UPDRS motor ratings
(36%, P < 0.001) and significantly increased regional glucose metabolism in the
premotor cortex ipsilateral to stimulation and in the cerebellum bilaterally. GPi
DBS also resulted in a significant (P < 0.01) decline in PDRP activity
ipsilateral to stimulation, which correlated significantly with clinical
improvement in UPDRS motor ratings (P < 0.03). Clinical improvement with GPi DBS
is associated with reduced expression of an abnormal Parkinson's disease-related
metabolic network involving elements of the
cortico-striato-pallido-thalamocortical and the cerebello-cortical motor loops.
PMID: 11459751 [PubMed - indexed for MEDLINE]
45. Neurology. 2001 Jun;56(11 Suppl 5):S1-S88.
An algorithm (decision tree) for the management of Parkinson's disease (2001):
treatment guidelines.
Olanow CW, Watts RL, Koller WC.
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
warren.olanow@mssm.edu
PMID: 11402154 [PubMed - indexed for MEDLINE]
46. Neurology. 2001 Jun 12;56(11):1523-8.
A randomized, double masked, controlled trial of botulinum toxin type A in
essential hand tremor.
Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, Dubinsky RM,
Friedman JH, Manyam BV, Matsumoto JY, Pullman SL, Rajput AH, Sethi KD, Tanner C,
Koller WC.
Department of Neurology, Columbia University, New York, NY, USA.
OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A
injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is
an effective treatment for dystonia, spasticity, and other movement disorders and
has been found to be useful in open-label studies and one double-masked study of
essential hand tremor. METHODS: One hundred thirty-three patients with essential
tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin
type A (Botox) or vehicle placebo treatment. Injections were made into the wrist
flexors and extensors. Patients were followed for 16 weeks. The effect of
treatment was assessed by clinical rating scales, measures of motor tasks and
functional disability, and global assessment of treatment. Hand strength was
evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of
botulinum toxin type A significantly reduced postural tremor on the clinical
rating scales after 4 to 16 weeks. However, kinetic tremor was significantly
reduced only at the 6-week examination. Measures of motor tasks and functional
disability were not consistently improved with botulinum toxin type A treatment.
Grip strength was reduced for the low- and high-dose botulinum toxin type A
groups as compared with the placebo group. Adverse reactions consisted mainly of
dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for
essential tremor of the hands resulted in significant improvement of postural,
but not kinetic, hand tremors and resulted in limited functional efficacy. Hand
weakness is a dose-dependent significant side effect of treatment at the doses
used in this study.
PMID: 11402109 [PubMed - indexed for MEDLINE]
47. Mov Disord. 2001 May;16(3):464-8.
Long-term safety and efficacy of unilateral deep brain stimulation of the
thalamus in essential tremor.
Koller WC, Lyons KE, Wilkinson SB, Troster AI, Pahwa R.
Department of Neurology, University of Miami Medical Center, 1501 NW 9th Ave.,
Miami, FL 33136, USA. wkoller@med.miami.edu
Our objective was to investigate the long-term safety and efficacy of unilateral
deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential
tremor. Forty-nine patients were evaluated for DBS between December 1993 and
March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and
then yearly. Three patients were not implanted, seven were explanted prior to 24
months, 11 were lost to long-term follow-up, and three died from unrelated
causes. Twenty-five patients were evaluated with follow-up greater than or equal
to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7
months after surgery. Tremor scores were significantly improved with stimulation
on at the long-term follow-up as compared to baseline. There was no change in
tremor scores from baseline to long-term follow-up with stimulation off. There
was no significant change in any stimulus parameters from 3 months to the
long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages
and one patient had postoperative seizures. Stimulus-related adverse reactions
were mild and easily controlled with changes in stimulus parameters.
Device-related complications were common and required repeated surgical
procedures. Unilateral DBS of the thalamus has long-term efficacy in some
patients for treatment of essential tremor. However, this therapy is compromised
by loss of efficacy in some patients and device complications which increase the
risk of additional surgical procedures. Copyright 2001 Movement Disorder Society.
PMID: 11391740 [PubMed - indexed for MEDLINE]
48. Mov Disord. 2001 May;16(3):459-63.
Transdermal dopaminergic D(2) receptor agonist therapy in Parkinson's disease
with N-0923 TDS: a double-blind, placebo-controlled study.
Hutton JT, Metman LV, Chase TN, Juncos JL, Koller WC, Pahwa R, LeWitt PA, Samii
A, Tsui JK, Calne DB, Waters CH, Calabrese VP, Bennett JP, Barrett R, Morris JL.
Neurology Research & Education Center, Covenant Medical Center-Lakeside, 4102
24th St., Lubbock, TX 79410, USA. nrec@hub.ofthe.net
N-0923 is a non-ergot, dopaminergic D(2) agonist designed to be transdermally
available. It has anti-parkinsonian effects when infused intravenously. An
adhesive matrix patch was developed to deliver N-0923 transdermally (N-0923 TDS).
In this phase II trial, we evaluated the effectiveness of various doses of N-0923
TDS at replacing levodopa. Eighty-five Parkinson's disease (PD) patients were
randomized to placebo or one of four doses of N-0923 TDS for 21 days. Change in
daily levodopa dose was the primary efficacy measure. Significantly greater
reductions in levodopa dose were achieved as compared to placebo for the two
highest doses of N-0923 TDS. Patients treated with 33.5 mg and 67 mg N-0923 TDS
decreased levodopa use by 26% and 28%, vs. 7% for placebo. N-0923 TDS was safe
and well tolerated. Copyright 2001 Movement Disorder Society.
PMID: 11391739 [PubMed - indexed for MEDLINE]
49. Clin Neuropharmacol. 2001 May-Jun;24(3):150-7.
The effects of different repeated doses of entacapone on the pharmacokinetics of
L-Dopa and on the clinical response to L-Dopa in Parkinson's disease.
Heikkinen H, Nutt JG, LeWitt PA, Koller WC, Gordin A.
Research Center, Orion Pharma, Orion Corporation, Espoo, Finland.
We performed a double-blind, placebo-controlled, randomized, crossover,
multiple-dose study on entacapone in 25 patients with Parkinson's disease with
levodopa (L-Dopa) treatment-related fluctuations. A run-in period was followed by
four 2-week treatment periods during which the patients took 4 to 6 daily doses
of L-Dopa concomitantly with 100, 200, or 400 mg of entacapone or with placebo.
The effects were assessed at the end of each period; the inhibition of soluble
catechol-O-methyltransferase (S-COMT) activity in red blood cells and the plasma
concentrations of entacapone, L-Dopa, and 3-O-methyldopa (3-OMD) were measured
and clinical effects assessed on an 18-hour home diary. Twenty-one patients
completed the study. Entacapone decreased the COMT activity from predose level:
100 mg by 25%, 200 mg by 33%, and 400 mg by 32% (p < 0.001 vs. placebo for each
dose). Correspondingly, the 3-OMD concentrations decreased by 39%, 54%, and 66%
with 100-, 200-, and 400-mg doses, respectively. The elimination half-life of
L-Dopa was prolonged by 23% (p < 0.05), 26% (p < 0.001), and 48% (p < 0.001), and
the area under the curve of L-Dopa increased by 17% (p < 0.05), 27% (p < 0.001),
and 37% (p < 0.001) with the increasing doses. Despite a significant decrease in
the daily dose of L-Dopa, entacapone decreased the proportion of daily "off"
time: 100 mg by 11%, 200 mg by 18%, and 400 mg by 20% compared with placebo.
However, this decrease was not statistically significant for any of the doses in
this small patient population. The dyskinetic "on" time did not increase with
different doses of entacapone. All doses were well tolerated, and no severe
adverse events were reported. The study showed that repeated dosing of entacapone
inhibits the COMT activity in a dose-dependent manner and thereby reduces the
loss of L-Dopa to 3-OMD. Therefore, the area under the curve of L-Dopa is
increased and the patient's clinical condition improved.
PMID: 11391126 [PubMed - indexed for MEDLINE]
50. Mov Disord. 2001 Jan;16(1):140-3.
Comparison of thalamotomy to deep brain stimulation of the thalamus in essential
tremor.
Pahwa R, Lyons KE, Wilkinson SB, Tröster AI, Overman J, Kieltyka J, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160,
USA.
OBJECTIVE: To compare outcome in Essential Tremor (ET) patients who have
undergone either thalamotomy or Deep Brain Stimulation (DBS) of the thalamus.
BACKGROUND: Although both thalamotomy and thalamic DBS are effective surgical
treatments of tremor, it is not known if one procedure is superior to the other.
DESIGN/METHODS: Thirty-five ET patients underwent thalamotomy between 1994-1998.
Data on 18 patients were excluded. The remaining 17 patients were matched for
age, sex, side of surgery, and tremor severity to 17 ET patients who underwent
thalamic DBS. There were nine men and eight women in each group. The mean age of
the thalamotomy group was 74.4 years and that of the thalamic DBS group was 73.1
years. RESULTS: There were no significant differences between any efficacy
outcome variables comparing thalamotomy to DBS of the thalamus at baseline or
follow-up visits. The surgical complications were higher for the thalamotomy
group as compared to the DBS group. However, a larger number of DBS patients
underwent repeat surgeries due to problems with the device and the leads.
CONCLUSION: Although the efficacy is similar for thalamotomy and DBS of the
thalamus for ET, thalamotomy is associated with a higher complication rate. DBS
of the thalamus should be the procedure of choice for the surgical treatment of
ET in most cases.
PMID: 11215575 [PubMed - indexed for MEDLINE]
51. Neurology. 2000;55(12 Suppl 6):S29-33.
Deep brain stimulation of the Vim nucleus of the thalamus for the treatment of
tremor.
Koller WC, Pahwa PR, Lyons KE, Wilkinson SB.
University of Miami Medical Center, Department of Neurology, Florida 33136, USA.
The surgical treatment of tremor has evolved considerably in the past few years.
Of the several conditions associated with severe tremor, the most common are
Parkinson's disease (PD) and essential tremor (ET). Levodopa therapy reduced
drastically the number of patients with PD who require surgery because of
inadequate control. However, there remains a small number of "tremor dominant" PD
patients for whom surgical treatment is often the best option. The ventralis
intermediate nucleus (Vim) of the thalamus has been the preferred surgical target
for the treatment of parkinsonian tremor for many years, but this is now
challenged by the subthalamic nucleus (STN). Deep brain stimulation (DBS) of
either target possesses high therapeutic efficacy against tremor in PD. ET may be
difficult to treat pharmacologically. Thalamotomy is an effective surgical
procedure for ameliorating ET but may be associated with persistent neurologic
deficits. DBS of the thalamus is also a highly effective means of reducing ET.
DBS appears to be safer than thalamotomy and is now the recommended surgical
procedure.
PMID: 11188972 [PubMed - indexed for MEDLINE]
52. Neurology. 2000;55(11 Suppl 4):S2-7; discussion S8-12.
Levodopa in the treatment of Parkinson's disease.
Koller WC.
University of Miami School of Medicine, FL 33136, USA.
Levodopa is the most effective drug available for the symptomatic treatment of
Parkinson's disease (PD) and is the gold standard with which other therapies must
be compared. Levodopa improves most parkinsonian symptoms and is associated with
an apparent decrease in mortality rate. However levodopa usage is also associated
with both acute and chronic side effects which compromise treatment. Levodopa is
metabolized by both decarboxylase and catechol-O-methyl transferase enzymes. It
is routinely administered in combination with a decarboxylase inhibitor to
prevent the peripheral accumulation of dopamine and associated side effects such
as nausea and vomiting. More recent studies suggest that combination of levodopa
with an inhibitor of catechol-O-methyl transferase prolongs the duration of
effect of the drug and can prolong the duration of motor response in fluctuating
patients. This article will review the safety and efficacy of levodopa treatment.
PMID: 11147506 [PubMed - indexed for MEDLINE]
53. Drugs Aging. 2000 Sep;17(3):165-81.
Early Parkinson's disease: what is the best approach to treatment.
Hristova AH, Koller WC.
Neurology Department, University of Miami Medical Center, Florida 33136, USA.
Early and correct diagnosis and treatment of Parkinson's disease (PD) are crucial
for the patient's well being. At the first visit, it is important to deal with
the patient's misconceptions of the disease and its course, to offer sources of
information and to suggest exercises. To make a correct initial diagnosis of PD
we need to assess the course of the initial levodopa responsiveness. The most
frequent challenges in diagnosing PD are the conditions of essential tremor and
multiple system atrophy. PD has 3 stages of development: (i) early--from the
onset of symptoms to the appearance of motor fluctuations; (ii) middle--from
motor fluctuations to the appearance of moderate-to-severe disability; and (iii)
advanced--when moderate-to-severe disability is present. The medical treatment of
early PD should be started when functional disability appears, which is a
different threshold for each patient. For patients below 65 years old, or above
65 years old but with preserved mental function and with no severe comorbidity,
initial monotherapy with a dopamine agonist is advisable. This approach appears
to delay the appearance and reduce the amount of late motor complications with
subsequent levodopa treatment. All dopamine agonists have similar efficacy, which
is less than that of levodopa. It is important to consider the adverse effect
profile when a choice for initial or adjunctive therapy is made. When levodopa
therapy is started as an adjunct in younger patients or as initial monotherapy in
older patients, sustained-release levodopa preparations are preferred. They have
a longer half-life and possibly stimulate the dopamine receptors more
continuously. Anticholinergic drugs are appropriate for younger patients with
tremor-dominant PD. Amantadine is mainly used for dyskinesia control.
Catechol-O-methyl-transferase inhibitors and neurosurgery are not treatments of
choice for early PD but can be very effective for more advanced disease. The
presence of presymptomatic markers of PD, such as changes in odour detection,
handwriting, speech, movement time of self-initiated motor acts, personality
traits, presence of antibodies against dopaminergic neurons, pattern of positron
emission tomography results, appearance of mitochondrial DNA mutation profiles,
etc., appear to be very important in the light of the emerging neuroprotective
therapies. Neuroprotection is aimed at slowing the rate of disease progression.
Selegiline has been shown to cause a mild delay in the need for levodopa,
possibly suggesting some protection. However, this initial benefit was not
sustained in long term studies. Currently, there is no neuroprotective drug for
PD.
PMID: 11043817 [PubMed - indexed for MEDLINE]
54. Clin Neuropharmacol. 2000 Jul-Aug;23(4):208-11.
Effect and time course of deep brain stimulation of the globus pallidus and
subthalamus on motor features of Parkinson's disease.
Hristova A, Lyons K, Tröster AI, Pahwa R, Wilkinson SB, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, USA.
We studied the effect and temporal profile of deep brain stimulation (DBS) of the
globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease
(PD). Four patients with bilateral deep brain stimulators of the globus pallidus
and four patients with bilateral deep brain stimulators of the subthalamus were
studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6
hours after turning stimulation on. An immediate (15 minutes) and sustained (6
hours) benefit was observed for all the motor manifestations of PD for both
stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus
is highly effective in reducing all the cardinal motor features of PD.
PMID: 11020125 [PubMed - indexed for MEDLINE]
55. J Clin Pharmacol. 2000 Jun;40(6):641-6.
Linear pharmacokinetic behavior of ropinirole during multiple dosing in patients
with Parkinson's disease.
Hubble J, Koller WC, Atchison P, Taylor AC, Citerone DR, Zussman BD, Friedman CJ,
Hawker N.
Ohio State University Parkinson's Disease Center, Columbus 43210, USA.
The objectives of this study were to measure the pharmacokinetics of ropinirole
at steady state when the drug is used as an adjunct to L-dopa and evaluate the
long-term tolerability of ropinirole in this indication. Twenty-four patients who
were taking L-dopa for Parkinson's disease and experiencing a lack of symptomatic
control were recruited. Patients received open-label adjunctive treatment with
ropinirole for up to 2 years. The starting dose was 0.5 mg bid, which could be
titrated to a maximum of 6.0 mg tid. Ropinirole demonstrated approximately
dose-linear pharmacokinetics at steady state; corresponding values were higher
during tid than bid dosing. A reduction in mean L-dopa dose was maintained
throughout the trial. The combination of L-dopa and ropinirole was generally well
tolerated, with only 1 patient withdrawing from treatment because of adverse
events. Thus, ropinirole shows approximately linear steady-state pharmacokinetics
and a good safety profile when administered with L-dopa.
PMID: 10868315 [PubMed - indexed for MEDLINE]
56. Neuroepidemiology. 2000 Jul-Aug;19(4):206-9.
Prevalence of Parkinson's disease in Bulgarian Gypsies.
Milanov I, Kmetski TS, Lyons KE, Koller WC.
University Neurological Hospital, Regional Polyclinic No. 28, Sofia, Bulgaria.
We studied the prevalence of Parkinson's disease (PD) in Gypsies and Caucasians
in Bulgaria. Cases were ascertained by examination in a clinic, a screening
questionnaire and a door-to-door survey in a region of Sofia, Bulgaria. The
prevalence of PD in the Gypsies was found to be 16/100,000 based on 1 case
compared to 137/100,000 for Caucasians with 119 cases. It is concluded that PD is
rare in Bulgarian Gypsies. Copyright 2000 S. Karger AG, Basel
PMID: 10859500 [PubMed - indexed for MEDLINE]
57. Neurology. 2000;54(11 Suppl 4):S39-44.
Surgical treatment of essential tremor.
Pahwa R, Lyons K, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas
66160, USA.
Surgical treatment for essential tremor (ET) has been used since the early 1950s.
Initially, different areas were targeted for tremor control. However, the optimal
target was eventually determined to be the ventralis intermedius (VIM) nucleus of
the thalamus. Thalamotomy improves contralateral tremor in more than 90% of
patients. Long-term studies of thalamotomy indicate that the benefits continue in
most patients. Persistent morbidity associated with thalamotomy, which occurs in
less than 10% of patients, includes dysarthria, dysequilibrium, weakness, and
cognitive impairment. Bilateral thalamotomy is associated with substantial
morbidity and is usually avoided. Studies demonstrate that chronic stimulation of
the VIM is safe and effective for tremor. Adverse effects of chronic stimulation
include paresthesia, dysarthria, dysequilibrium, and localized pain. In many
patients, bilateral thalamic stimulation is performed without a substantial
increase in morbidity. ET patients with disabling medication-resistant tremor are
reasonable candidates for these stereotactic procedures.
PMID: 10854351 [PubMed - indexed for MEDLINE]
58. Neurology. 2000;54(11 Suppl 4):S30-8.
Pharmacologic treatment of essential tremor.
Koller WC, Hristova A, Brin M.
Department of Neurology, University of Miami School of Medicine, Miami, Florida
33136, USA.
Essential tremor (ET) is a common movement disorder that often causes functional
disability, potentially leading to physical and emotional difficulties. The
paucity of data available regarding the underlying pathophysiologic mechanism of
ET hinders the development of innovative approaches to pharmacotherapeutic
treatments. Options for drug therapy include the use of primidone,
beta-adrenergic blockers, such as propranolol, alcohol, and other drugs, such as
benzodiazepines, gabapentin, carbonic anhydrase inhibitors, clozapine,
flunarizine, clonidine, and the methylxanthine derivative theophylline.
Chemodenervation with botulinum toxin type A may be a therapeutic option for
selected patients with ET. Each drug is classified as to the quality of evidence
for efficacy and the suggested strength of therapeutic recommendation. In general
clinical practice, primidone and propranolol have proven efficacy in ET.
PMID: 10854350 [PubMed - indexed for MEDLINE]
59. Neurology. 2000;54(11 Suppl 4):S7.
Criteria for the diagnosis of essential tremor.
Bain P, Brin M, Deuschl G, Elble R, Jankovic J, Findley L, Koller WC, Pahwa R.
PMID: 10854345 [PubMed - indexed for MEDLINE]
60. Neurology. 2000;54(11 Suppl 4):S1.
Introduction. Essential tremor.
Deuschl G, Koller WC.
PMID: 10854343 [PubMed - indexed for MEDLINE]
61. Mov Disord. 2000 May;15(3):511-5.
Motor initiation and execution in essential tremor and Parkinson's disease.
Montgomery EB Jr, Baker KB, Lyons K, Koller WC.
Department of Neurology, Lerner Research Institute, Cleveland Clinic Foundation,
Ohio 44195, USA.
Clinical differentiation of essential tremor (ET) from idiopathic Parkinson's
disease (iPD) is based on the lack of akinesia and bradykinesia. Nevertheless,
early tremor-predominant iPD often is difficult to distinguish from ET. Motor
initiation and execution in ET, iPD, and normal control (NC) subjects were
investigated. Individuals with iPD, ET and NC performed a reaction-time wrist
flexion and extension task. Motor performances were similar between ET and iPD
and both were different than normal control subjects. Both the patients with iPD
and ET had longer reaction times and slower movement velocities than NC subjects.
This may help to explain some of the difficulties in distinguishing patients with
these two diseases. The similarities of motor performance suggest that while ET
and iPD may be separate disease entities, they may share similar pathogenic motor
mechanisms from the perspective of an integrated motor system that drives the
motor cortex.
PMID: 10830417 [PubMed - indexed for MEDLINE]
62. Mov Disord. 2000 May;15(3):485-9.
Time course of loss of clinical benefit following withdrawal of
levodopa/carbidopa and bromocriptine in early Parkinson' s disease.
Hauser RA, Koller WC, Hubble JP, Malapira T, Busenbark K, Olanow CW.
Parkinson's Disease and Movement Disorders Center, University of South Florida,
Tampa 33606, USA.
Putative neuroprotective agents for Parkinson's disease can be assessed in
untreated patients using progression of clinical disability as an index of
disease progression. To avoid the confound associated with symptomatic therapy,
progression of the underlying disease can be assessed by evaluating the
progression of clinical disability from an untreated baseline to a final visit
following wash-out of symptomatic medication. In this type of analysis it is
critical to use a washout of sufficient duration to ensure elimination of
symptomatic effects. To assess the time course of resolution of symptomatic
effects, we evaluated 31 patients at days 1, 8, and 15 following discontinuation
of levodopa/carbidopa and bromocriptine. Mean total Unified Parkinson's Disease
Rating Scale scores (+/- standard error) increased (worsened) by 7.4+/-1.5 from
day 1 to day 15 (p <0.0001), 4.5+/-1.2 from day 1 to day 8 (p = 0.0009), and
2.9+/-1.0 from day 8 to day 15 (p = 0.01). We conclude that a wash-out of at
least 2 weeks is required to eliminate the symptomatic effects of
levodopa/carbidopa and bromocriptine in patients with early Parkinson's disease.
PMID: 10830413 [PubMed - indexed for MEDLINE]
63. Mov Disord. 2000 May;15(3):474-8.
Early detection of probable idiopathic Parkinson's disease: II. A prospective
application of a diagnostic test battery.
Montgomery EB Jr, Lyons K, Koller WC.
Department of Neurology, Lerner Research Institute, Cleveland Clinic Foundation,
Ohio 44195, USA.
We developed a battery of tests, incorporating motor function, olfaction, and
mood, that distinguishes between early mild, probable idiopathic Parkinson's
disease (iPD), and normal control subjects. Here, we determined the PD Battery's
ability to prospectively identify which patients with symptoms and signs
suggestive of, but not yet diagnostic of, iPD who would subsequently be diagnosed
as having iPD. Of 212 enrolled patients, 194 have been followed for at least 1
year. Among these 194, 59 were diagnosed with iPD, 40 as neurologically normal,
and the remaining 106 with other neurologic conditions such as essential tremor.
The test battery was 92% specific and 68% sensitive for iPD. The area under the
Receiver Operating Characteristics curve was 0.88 for predicting which
participants would subsequently be diagnosed as having iPD or as being
neurologically normal.
PMID: 10830411 [PubMed - indexed for MEDLINE]
64. Mov Disord. 2000 May;15(3):467-73.
Early detection of probable idiopathic Parkinson's disease: I. Development of a
diagnostic test battery.
Montgomery EB Jr, Koller WC, LaMantia TJ, Newman MC, Swanson-Hyland E, Kaszniak
AW, Lyons K.
Department of Neurology, Lerner Research Institute, Cleveland Clinic Foundation,
Ohio 44195, USA.
We developed a test battery as an inexpensive and objective aid for the early
diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses.
The test battery incorporates tests of motor function, olfaction, and mood. In
the motor task, a wrist flexion-and-extension task to different targets, movement
velocities were recorded. Olfaction was tested with the University of
Pennsylvania Smell Identification Test. Mood was assessed with the Beck
Depression Inventory. An initial regression model was developed from the results
of 19 normal control subjects and 18 patients with early, mild, probable iPD.
Prospective application to an independent validation set of 122 normal control
subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity
rate, with an area under the Receiver Operator Characteristic curve of 0.87.
PMID: 10830410 [PubMed - indexed for MEDLINE]
65. Brain Cogn. 2000 Apr;42(3):417-34.
The behavioral complications of pallidal stimulation: a case report.
Miyawaki E, Perlmutter JS, Tröster AI, Videen TO, Koller WC.
Department of Neurology, The University of Kansas Medical Center, Kansas City, KS
66160-7314, USA. emiyawak@kumc.edu
We report a case of recurrent manic episodes associated with chronic deep brain
stimulation (DBS) targeting globus pallidus (GP) in the treatment of Parkinson's
disease (PD). Cardinal PD symptoms and dyskinesia improved with DBS, and
neuropsychological testing found improvements in visuospatial measures associated
with left DBS and in verbal memory with right DBS when compared to the patient's
preoperative baseline. Under conditions of right, left, and bilateral DBS, the
patient experienced bouts of mania and hypomania lasting several days at a time.
Positron emission tomography (PET) with (15)O-labeled water was performed after
his first manic episode under four conditions: no stimulation, right DBS, left
DBS, and bilateral DBS. Although no manic switch occurred during the course of
the PET study, all three DBS conditions were associated with decreases in
regional flow in the left parahippocampus and hippocampus and right mid-cingulate
gyrus. Increases in flow in left inferior frontal area, bilateral insula,
dorsolateral prefrontal cortex, and cuneus were common to all DBS conditions. GP
stimulation in PD may be associated with behavioral and cognitive effects.
Distributed blood flow changes observed with pallidal DBS support a role for the
pallidum in cognition and affective regulation. Copyright 2000 Academic Press.
PMID: 10753488 [PubMed - indexed for MEDLINE]
66. Brain Cogn. 2000 Apr;42(3):399-416.
Health-related quality of life in Parkinson's disease after pallidotomy and deep
brain stimulation.
Straits-Tröster K, Fields JA, Wilkinson SB, Pahwa R, Lyons KE, Koller WC, Tröster
AI.
Department of Veterans Affairs Medical Center, Kansas City, USA.
troster@kansas-city.va.gov
This study explored the multidimensional outcome of three neurosurgical
interventions for Parkinson's disease (PD): pallidotomy (N = 23), pallidal deep
brain stimulation (DBS) (N = 9), and thalamic DBS (N = 7). All patients completed
the Sickness Impact Profile (SIP) and the Beck Depression Inventory. Pallidotomy
patients also completed the Profile of Mood States, the Beck Anxiety Inventory,
and a disease-specific quality of life (QOL) measure, the Parkinson's Disease
Questionnaire (PDQ-39). Three months after surgery, all neurosurgical groups
showed significant improvements in mood and function, including physical,
psychosocial, and overall functioning. Pallidal DBS and pallidotomy patients who
completed additional QOL measures reported decreased anxiety and tension,
increased vigor, improved mobility and ability to perform activities of daily
living, and decreased perceived stigma. Psychosocial dysfunction scores from the
SIP were related to depressed mood both at baseline (r = .42) and at followup (r
= .45), but the physical dysfunction subscale was not related to mood at either
time point, suggesting that disruption of social relationships due to PD may have
more impact on affective distress than physical symptoms alone. Results suggest
that neurosurgical interventions for PD improve disabling PD motor symptoms and
also improve several domains of quality of life. Copyright 2000 Academic Press.
PMID: 10753487 [PubMed - indexed for MEDLINE]
67. Neurosurgery. 2000 Mar;46(3):613-22; discussion 622-4.
Pallidotomy microelectrode targeting: neurophysiology-based target refinement.
Kirschman DL, Milligan B, Wilkinson S, Overman J, Wetzel L, Batnitzky S, Lyons K,
Pahwah R, Koller WC, Gordon MA.
Department of Surgery, University of Kansas Medical Center, Kansas City 66103,
USA.
Comment in:
Neurosurgery. 2000 Dec;47(6):1472-3.
OBJECTIVE: Microelectrode recording can refine targeting for stereotactic
radiofrequency lesioning of the globus pallidus to treat Parkinson's disease.
Multiple intraoperative microelectrode recording/stimulating tracks are searched
and assessed for neuronal activity, presence of tremor cells, visual responses,
and responses to kinesthetic input. These physiological data are then correlated
with atlas-based anatomic data to approximate electrode location. On the basis of
these physiological properties, one or more tracks are selected for lesioning.
This study analyzes the track physiological factors that seem most significant in
determining the microelectrode recording track(s) that will be chosen for
pallidal lesioning. METHODS: Thirty-six patients with Parkinson's disease
underwent microelectrode-guided pallidotomy. Between one and five microelectrode
recording tracks were made per patient. Usually, one (n = 23) or two (n = 12) of
these tracks were lesioned. Electrode positions in the x (mediolateral) and y
(anteroposterior) axes were recorded and related to track neurophysiological
findings and final lesion location. The stereotactic location and sequence of
microelectrode tracks were recorded and plotted to illustrate individual search
patterns. These patterns were then compared with those noted in other patients.
Neurophysiological data obtained from recording tracks were analyzed. A
retrospective analysis of track electrophysiology was performed to determine the
track characteristics that seemed most important in the surgeon's choice of the
track to lesion. Track physiological properties included general cell spike
amplitude, tremor synchronous neuronal firing, kinesthetically responsive
neuronal firing, and optic track responses (either phosphenes reported by the
patient during track microstimulation or neuronal firing in response to light
stimulus into the patient's eyes). Orthogonally corrected postoperative magnetic
resonance images were used to confirm the anatomic lesion locations. RESULTS: In
patients who had a single mapped track lesioned, specific track
electrophysiological characteristics identified the track that would be lesioned
most of the time (20 of 24 patients). Tracks that exhibited a combination of
tremor synchronous firing, joint kinesthesia, and visual responsivity were
lesioned 17 (85%) of 20 times. Analysis of intraoperative electrode movement in
the x and y axes indicated a significant subset of moves but did not result in
microelectrode positioning closer to the subsequently lesioned track. Accuracy of
initial electrode movement in the x and y axes was most highly correlated with a
measure of first-track electrophysiological activity. The number of
microelectrode recording tracks did not correlate with clinical outcome. Anatomic
analysis, using postoperative magnetic resonance imaging, revealed that all
lesions were placed in the globus pallidus. Most patients (35 of 36) improved
after surgery. CONCLUSION: The level of electrophysiological activity in the
first track was the best predictive factor in determining whether the next
microelectrode move would be closer to the ultimately lesioned track. The
analysis of electrode track location and neurophysiological properties yields
useful information regarding the effectiveness of microelectrode searching in the
x and y axes. Within an institution, the application of this modeling method may
increase the efficiency of the microelectrode refinement process.
PMID: 10719858 [PubMed - indexed for MEDLINE]
68. Neurology. 1999 Nov 10;53(8):1774-80.
Neuropsychological and quality of life outcome after thalamic stimulation for
essential tremor.
Tröster AI, Fields JA, Pahwa R, Wilkinson SB, Strait-Tröster KA, Lyons K,
Kieltyka J, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain
stimulation (DBS) on cognition, mood state, and quality of life in patients with
essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are
effective in alleviating refractory tremor contralateral to the side of surgery.
Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable
surgical intervention given potential avoidance or reversibility of such
morbidity. Although unilateral thalamic DBS is cognitively safe and leads to
quality of life improvement in PD, its neurobehavioral effects in ET are unknown.
METHODS: Forty patients with ET were administered a broad neuropsychological test
battery, measures of mood state, and generic and disease-specific quality of life
measures approximately 1 month before and 3 months after surgery (left
hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with
significant improvements in tremor and dominant-hand fine visuomotor
coordination. Statistically significant but clinically modest gains were observed
on tasks of visuoperceptual and constructional ability, visual attention, delayed
word list recognition, and prose recall. Only lexical verbal fluency declined
significantly after surgery. Patients rated themselves as less anxious after
surgery, and they perceived their quality of life as improved significantly. In
particular, patients reported improved quality of life with respect to activities
of daily living, stigma, emotional well-being, and communication. CONCLUSIONS:
Unilateral thalamic DBS for ET is cognitively safe and associated with
improvements in anxiety and quality of life in the near term and in the absence
of operative complications. Patients were better able to carry out activities of
daily living after surgery, and they reported improvement in several psychosocial
domains of quality of life.
PMID: 10563627 [PubMed - indexed for MEDLINE]
69. J Clin Exp Neuropsychol. 1999 Aug;21(4):435-43.
Lexical, semantic, and action verbal fluency in Parkinson's disease with and
without dementia.
Piatt AL, Fields JA, Paolo AM, Koller WC, Tröster AI.
Department of Neurology, University of Kansas Medical Center, Kansas City, KS,
USA.
Previous research suggests that lexical and semantic verbal fluency are
differentially sensitive to the effects of cortical and subcortical dementias,
but little is known about action fluency performance in dementias. The present
study compared lexical, semantic, and action fluency in groups of patients with
Parkinson's disease (PD) with and without dementia and an elderly control group.
Findings revealed an interaction between fluency type and subject group. Although
the demented PD (PDD) group performed significantly more poorly than their
non-demented counterparts and normal controls on all three fluency tasks, a
disproportionate disparity in scores was noted on the action fluency task. The
findings suggest that action fluency may be particularly sensitive to
PD-associated dementia and may be an early indicator of the conversion from PD to
PDD. As reported elsewhere, PD without dementia was not associated with
significant impairment on any of the fluency tasks.
PMID: 10550804 [PubMed - indexed for MEDLINE]
70. Clin Neurol Neurosurg. 1999 Sep;101(3):182-8.
Cognitive outcome following staged bilateral pallidal stimulation for the
treatment of Parkinson's disease.
Fields JA, Tröster AI, Wilkinson SB, Pahwa R, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
As neurosurgical treatment of parkinsonian symptoms has become increasingly
popular, concern about the cognitive morbidity which may result from such
interventions has risen proportionately. Previous reports of cognitive
difficulties associated with pallidotomy and thalamotomy, especially in bilateral
cases, have provided the impetus for research into chronic electrical deep brain
stimulation procedures which are believed to be safer than ablation. Given the
lack of neurobehavioral research following bilateral deep brain stimulation
procedures, this preliminary study of six Parkinson's disease patients undergoing
staged bilateral pallidal stimulation was undertaken. A battery of tests
assessing attention, executive function, visuomotor coordination, language,
visuoperceptual function, learning memory and mood revealed no significant change
in overall level of cognitive functioning after either unilateral or bilateral
pallidal deep brain stimulation. No significant declines were observed about
three months following bilateral stimulation, and in fact, significant gains in
delayed recall and relief of anxiety symptoms were noted. It was concluded from
this preliminary data that bilateral pallidal stimulation for the treatment of
Parkinson's disease, at least in the absence of operative complications, offers a
cognitively safe alternative to ablation.
PMID: 10536904 [PubMed - indexed for MEDLINE]
71. Neurology. 1999 Oct 22;53(7):1447-50.
Bilateral thalamic stimulation for the treatment of essential tremor.
Pahwa R, Lyons KL, Wilkinson SB, Carpenter MA, Tröster AI, Searl JP, Overman J,
Pickering S, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160,
USA. rpahwa@kumc.edu
OBJECTIVE: To determine the safety and efficacy of bilateral thalamic stimulation
in the treatment of essential tremor (ET). METHODS: Nine ET patients with
disabling tremor refractory to pharmacotherapy underwent bilateral staged
implants. Tremor was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale at
baseline 1 (before first implant), baseline 2 (before second implant), and at
6-month and 1-year follow-up. Blinded evaluations were performed at 3 months.
Associated changes in speech were evaluated in six patients. There were seven men
and two women with a mean age of 73.8 years. RESULTS: There was a significant
improvement in the mean total tremor score from a baseline of 66.1+/-11.6 to
28.4+/-12.8 12 months after the second surgery. Similarly, the mean motor tremor
subscore was 20.1+/-5.0 before the first surgery and improved significantly to
14.1+/-3.6 before the second surgery. Motor tremor scores 6 months after the
second surgery (6.0+/-3.7) and 12 months after the second surgery (7.5+/-3.9)
also improved significantly relative to the preoperative scores. The mean
activities of daily living (ADL) subscore at baseline was 18.2+/-2.9 and improved
significantly before the second surgery to 9.0+/-3.2. These ADL scores further
improved 6 months (6.2+/-5.2) and 12 months (7.9+/-5.7) following the second
surgery, but these gains were not significant. Blinded evaluations also revealed
a similar degree of improvement. Complications were noted in five patients:
asymptomatic intracranial hematoma (1), postoperative seizures (1), a hematoma
over the implanted pulse generator (IPG) (1), lead repositioning (1), and IPG
malfunction (1). Adverse effects related to stimulation were mild and resolved
with adjustment of the stimulation parameters. Three of the six patients
demonstrated worsening of dysarthria with both stimulators on. CONCLUSIONS:
Bilateral thalamic stimulation is effective in reducing tremor and functional
disability in ET; however, dysarthria is a possible complication.
PMID: 10534249 [PubMed - indexed for MEDLINE]
72. J Neurol Sci. 1999 Aug 1;167(1):1-10.
Surgical treatment of Parkinson's disease.
Koller WC, Pahwa R, Lyons KE, Albanese A.
Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Blvd.,
Kansas City, KS 66160-7314, USA. wkoller@kumc.edu
Stereotaxtic surgery is an effective therapeutic maneuver in the management of
advanced Parkinson's disease (PD). Thalamotomy is an effective measure to control
tremor but other PD symptoms are not changed. Bilateral operations are associated
with a risk of severe speech impairment. Deep brain stimulation (DBS) of the
thalamus is as effective as thalamotomy and is associated with fewer side
effects. Pallidotomy is effective in reducing contralateral dyskinesias and the
cardinal symptoms of PD. Bilateral pallidotomy often results in cognitive
dysfunction. Deep brain stimulation of the pallidum replicates the positive
effects of pallidotomy and appears to be safer than ablative lesions. Subthalamic
DBS is currently under investigation. This procedure may control all PD symptoms,
and the dose of levodopa can often be dramatically reduced. Neurotransplantation
is a promising surgical approach to PD. However, further investigation is needed
to optimize this approach.
PMID: 10500254 [PubMed - indexed for MEDLINE]
73. Neurology. 1999 Sep 22;53(5):1012-9.
Immediate-release and controlled-release carbidopa/levodopa in PD: a 5-year
randomized multicenter study. Carbidopa/Levodopa Study Group.
Koller WC, Hutton JT, Tolosa E, Capilldeo R.
Department of Neurology, University of Miami, FL, USA.
Comment in:
Neurology. 2000 Jul 12;55(1):156-7.
OBJECTIVE: To compare effects of immediate-release (IR) and sustained-release
(CR) carbidopa/levodopa in levodopa-naive PD patients. BACKGROUND: It was
hypothesized that the long-acting preparation would be associated with fewer
long-term complications. METHODS: A total of 618 patients were studied in 36
centers worldwide in a blinded, randomized parallel study. Measures of efficacy
and adverse reactions were recorded at 3-month intervals for 5 years. Motor
fluctuations and dyskinesias were evaluated by a patient diary and a
physician-recorded questionnaire. The Nottingham Health Profile (NHP) was used to
evaluate quality of life. RESULTS: Approximately 60% of patients completed the
trial. After 5 years, the mean dose of IR was 426 mg/day, and the bioavailable
dose of CR was 510 mg/day (mean dose, 736 mg/day). After 5 years, 20.6% of the IR
group and 21.8% of the CR group had motor fluctuations or dyskinesia. Sixteen
percent of both groups had changes in motor response by the questionnaire's
definition. There was no significant difference between the two treatment groups.
Disability scores and the motor score of the Unified Parkinson Disease Rating
Scale (UPDRS) were highest at baseline, improved with therapy, and thereafter
worsened over time to reach baseline scoring at the end of 5 years. The CR group
was superior to IR for the Activities of Daily Living subsection of the UPDRS for
all 5 years and for emotional reactivity and social isolation on the NHP;
however, this may have resulted from higher doses of CR that were used.
CONCLUSION: Despite the progressive nature of PD, both the immediate-release and
sustained-release carbidopa/levodopa formulations maintained a similar level of
control in PD after 5 years compared with baseline. Additionally, the low
incidence of motor fluctuations or dyskinesia was not significantly different
between the treatment groups and may be partly attributed to the relatively low
doses of levodopa used throughout the 5-year study.
PMID: 10496260 [PubMed - indexed for MEDLINE]
74. Mov Disord. 1999 Sep;14(5):847-50.
Efficacy of unilateral deep brain stimulation of the VIM nucleus of the thalamus
for essential head tremor.
Koller WC, Lyons KE, Wilkinson SB, Pahwa R.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Essential tremor is a common movement disorder. Deep brain stimulation of the VIM
nucleus of the thalamus has been reported to be efficacious for reducing
essential hand tremor. The effect of deep brain stimulation of the thalamus on
essential head tremor has not been well studied. Therefore, we evaluated the
effect of DBS of the thalamus in 38 patients with essential head tremor. Head
tremor scores prior to surgery were compared with scores at 3, 6, and 12 months
postimplant with stimulation "on" and "off." The 3-month evaluations were blinded
for 24 patients and all others were open-label. There was a significant
improvement in head tremor at all postimplant evaluations compared with baseline.
Essential head tremor can be reduced with deep brain stimulation of the VIM
nucleus of the thalamus and, pending the results of other controlled trials,
should be considered as a treatment option for patients with disabling essential
head tremor unresponsive to medication.
PMID: 10495050 [PubMed - indexed for MEDLINE]
75. Stereotact Funct Neurosurg. 1998;71(4):164-72.
Lesion volume and clinical outcome in stereotactic pallidotomy and thalamotomy.
Goodman SH, Wilkinson S, Overman J, Koller WC, Tröster A, Pahwa R, Lyons K,
Kieltyka J, Burns J, Gordon M.
Imaging Resource Center, University of Kansas Medical Center, Kansas City, KS
66103, USA.
Postoperative lesion volume and clinical outcome were assessed in 19 Parkinson's
disease (PD) patients who received posteroventral pallidotomy, and in 14
essential tremor (ET) patients who received ventrolateral thalamotomy. Before and
after surgery, PD patients were evaluated using the Unified PD Rating Scale
(UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor
rating scale. Inner and total lesion volumes were determined with postoperative
MR imaging and three-dimensional data segmentation. Lesion volumes were compared
to percent improvement in UPDRS and FTM scores, using Spearman's rank-order
correlation test. No rank-order correlations were found between lesion volume and
clinical improvement in either the PD or the ET patients. In performing
stereotactic surgery for movement disorders, any lesion volume within a
prescribed range may be equally effective in relieving symptoms associated with
PD or ET.
PMID: 10461102 [PubMed - indexed for MEDLINE]
76. Stereotact Funct Neurosurg. 1998;71(3):131-44.
Comparative magnetic resonance image-based evaluation of thalamotomy and
pallidotomy lesion volumes.
Tollefson TT, Burns J, Wilkinson S, Overman J, Kieltyka J, Goodman SH, Koller WC,
Tröster A, Lyons K, Pahwa R, Batnitzky S, Wetzel L, Gordon M.
Imaging Resource Center, University of Kansas Medical Center, Kansas City, KS
66103, USA.
Acute thalamotomy and pallidotomy lesion volumes based on magnetic resonance (MR)
images were measured in 22 patients (11 thalamotomy and 11 pallidotomy patients).
Thalamotomy inner lesion volumes (0.06 +/- 0.04 ml; thermocoagulative zone) were
smaller than pallidotomy inner lesion volumes (0.14 +/- 0.08 ml) as determined
using T(1)-weighted 3D-MPRAGE (1.5-mm slice spacing). Similar results were found
using T(1)-weighted (6-mm slice spacing) image sets (0.09 +/- 0.05 ml,
thalamotomy; 0.13 +/- 0.05 ml, pallidotomy). No differences were found when
comparing thalamic or pallidal inner lesion volumes when the comparison was based
on T(2) weighted images. Thalamotomy total lesion volumes (thermocoagulative and
surrounding edematous zones) were less than pallidotomy total lesion volumes
independent of the MR protocol. The difference in thalamotomy and pallidotomy
lesion volumes is most likely based on the distance between each discrete lesion
placed along the lesioning tracts. In 7 of 11 thalamotomies, this distance was 1
mm with the remaining having 2 mm between each discrete lesion. All pallidotomy
discrete lesions were 2 mm apart. More overlap between discrete lesioning sites
for thalamotomies is likely to produce reduced lesion volumes.
PMID: 10420146 [PubMed - indexed for MEDLINE]
77. Adv Neurol. 1999;80:369-76.
Rare and unusual parkinsonian syndromes.
Wszolek ZK, Koller WC.
Department of Internal Medicine, University of Nebraska Medical Center, Omaha
68105, USA.
PMID: 10410743 [PubMed - indexed for MEDLINE]
78. Neurology. 1999 Mar 10;52(4):757-62.
Abnormal performance on the PD test battery by asymptomatic first-degree
relatives.
Montgomery EB Jr, Baker KB, Lyons K, Koller WC.
Department of Neurology, Lerner Research Institute, Cleveland Clinic Foundation,
OH 44195, USA.
OBJECTIVE: To determine whether a sensitive and specific battery of tests (PD
Battery) could identify a subset of asymptomatic first-degree relatives (FDRs) of
PD patients who were significantly more impaired than age-matched normal control
(NC) subjects. The PD Battery incorporates tests of motor function, olfaction,
and mood. In previous studies, it has shown high specificity and sensitivity in
distinguishing mildly affected PD patients from NC subjects. METHODS: The PD
Battery and regression analysis-derived scoring equations were applied to
asymptomatic FDRs. RESULTS: Eighty FDRs and 100 NC subjects were tested. Of the
FDRs, 22.5% scored in the abnormal range, and 9% of NC subjects had abnormal
scores. This difference was statistically significant. Further analysis
demonstrated that FDRs with abnormal scores on the PD Battery differed on all
three components of the test battery from FDRs who had normal scores. Among the
sons and daughters whose scores were abnormal, there was a much higher prevalence
of the affected parent being the father. CONCLUSIONS: The proportion of FDRs who
demonstrated abnormal performance on the PD Battery was greater than that of NC
subjects. Thus, the PD Battery may detect the asymptomatic carrier state or risk
for PD. Sons and daughters whose scores were in the abnormal range were more
likely to have fathers with PD.
PMID: 10078723 [PubMed - indexed for MEDLINE]
79. Stereotact Funct Neurosurg. 1998;71(1):1-19.
Comparison of actual pallidotomy lesion location with expected stereotactic
location.
Tsao K, Wilkinson S, Overman J, Kieltyka J, Tollefson T, Koller WC, Pahwa R,
Troster AI, Lyons KE, Batznitzky S, Wetzel L, Gordon MA.
Imaging Resource Center, Toxicology and Therapeutics, University of Kansas
Medical Center, Kansas City, Kans. 66103, USA.
Accuracy of pallidotomy lesion placement was assessed by comparing actual lesion
locations with expected pallidotomy lesion locations based on stereotaxy. Actual
and expected lesions were compared in anteroposterior, dorsoventral and lateral
axes. In 22 pallidotomies, actual lesion locations were determined using axial MR
images. Expected lesion locations were calculated using a starting point derived
from preoperative computerized tomography, displacements from the starting point
based on microelectrode-driven electrophysiological refinement, and the
trajectory angle of the lesioning tract relative to the anterior-posterior
commissural plane. On average, actual lesion locations were found 2.91 +/- 2.23
mm posterior, 3.22 +/- 2.49 mm ventral, and 0.05 +/- 1.80 mm lateral compared to
the expected lesion location. Discrepancies between the actual lesion and
expected lesion locations may be mostly accounted for by posterior and ventral
lesion spread from the exposed electrode tip, in-plane and volume averaging
effects associated with MR images, and possible brain shifting during surgery.
However, despite the remaining small differences between actual and expected
lesion location, good clinical outcome of reduced dyskinesias and 'off' time
along with UPDRS-based improvement in mentation, motor and activity of daily
living measures was observed.
PMID: 10072669 [PubMed - indexed for MEDLINE]
80. Brain Cogn. 1998 Nov;38(2):125-49.
Chronic electrical stimulation of the left ventrointermediate (Vim) thalamic
nucleus for the treatment of pharmacotherapy-resistant Parkinson's disease: a
differential impact on access to semantic and episodic memory?
Tröster AI, Wilkinson SB, Fields JA, Miyawaki K, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA. atroster@kumc.edu
Thalamotomy for medically refractory Parkinson's disease (PD) is considered to be
efficacious and relatively safe. Because a minority of patients experience
decrements in language and memory (often mild and transient) after thalamotomy,
chronic thalamic deep brain stimulation (DBS) might be a safer treatment given
its reversibility and the modifiability of stimulation parameters. Two
preliminary studies support the relative cognitive safety of unilateral DBS of
the ventral intermediate (Vim) thalamic nucleus, but it is unclear whether
possibly subtle changes in language and memory represent effects of
"microthalamotomy" or of stimulation per se. This report provides preliminary
data concerning effects of left thalamic stimulation on information processing
speed, semantic memory (verbal fluency and visual confrontation naming), and
verbal episodic memory in a patient with PD. In addition to being evaluated
before and 3 and 6 months after surgery, the patient was tested 18 months after
surgery either on or off medications and with the stimulator turned either on or
off (order counterbalanced across medication conditions). Test performance
differences between the stimulation conditions were attenuated "off" as compared
to "on" medication. Vim stimulation consistently, albeit subtly, improved
semantic verbal fluency but interfered with immediate recall of word lists.
Parallels to findings from acute, intraoperative thalamic stimulation studies are
explored. The hypothesis is offered that left Vim stimulation might facilitate
access to semantic memory, but interfere with episodic memory processes.
PMID: 9853093 [PubMed - indexed for MEDLINE]
81. Mov Disord. 1998;13 Suppl 3:90-100.
Pharmacologic treatment of tremor.
Wasielewski PG, Burns JM, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Tremor is a common neurologic symptom that can also be incapacitating to the
patient, so effective therapy is needed. The causes of tremor are heterogeneous.
Essential tremor (ET) and the tremor associated with Parkinson's disease (PD) are
the most common encountered in clinical practice. Beta-adrenergic blockers and
primidone remain the mainstay of treatment for ET, whereas carbidopa/levodopa and
anticholinergics are most beneficial in PD. However, the efficacy of various
other medications has been studied in ET and PD, and also in patients with tremor
resulting from other conditions, with varying results.
PMID: 9827602 [PubMed - indexed for MEDLINE]
82. Ann Neurol. 1998 Sep;44(3 Suppl 1):S155-9.
Neuroprotection for Parkinson's disease.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Levodopa is the most effective drug available for the treatment of Parkinson's
disease (PD). As a precursor of dopamine, levodopa causes an increase in brain
dopamine, which is depleted in PD. However, long-term levodopa therapy is
associated with complications such as dyskinesias, motor fluctuations, and mental
status changes. The treatment of these side effects is a major challenge for the
clinician.
PMID: 9749588 [PubMed - indexed for MEDLINE]
83. Neurosurgery. 1998 Sep;43(3):506-12; discussion 512-3.
Pallidotomy lesion locations: significance of microelectrode refinement.
Tsao K, Wilkinson S, Overman J, Koller WC, Batnitzky S, Gordon MA.
Imaging Resource Center, University of Kansas Medical Center, Kansas City 66103,
USA.
OBJECTIVE: To determine whether stereotactic pallidotomy requires refinement
using microelectrode recording to ensure proper lesion placement. METHODS: The
experiment approach was based on retrospective comparisons of
microelectrode-refined radiofrequency lesion locations with hypothetical
unrefined lesion positions. Actual and hypothetical pallidotomy lesions were
classified based on their lesion center (thermocoagulative zone) locations and
their total lesion areas (surrounding edematous zone) relative to the pallidal
target. Assessments were made using postoperative T2-weighted magnetic resonance
axial images, which showed both the lesion and globus pallidus (GP). The
magnitude of microelectrode refinement from an initial preoperative starting
point determined by computed tomography was calculated using stereotactic
coordinates and included corrections for the lesioning tract trajectory angle.
RESULTS: In all 25 patients, the center of the actual pallidotomy lesion was
within the GP. Without microelectrode refinement, 13 of 25 hypothetical lesion
positions would have been localized such that the lesion center would not have
remained in the GP. In eight cases, microelectrode refinement resulted in no
significant change in lesion location, but in one case, microelectrode refinement
resulted in lesion center placement away from the GP. CONCLUSION: Kinesthetically
driven microelectrode refinement in pallidotomy lesioning seems to be required to
ensure proper lesion location within the GP.
PMID: 9733306 [PubMed - indexed for MEDLINE]
84. Mov Disord. 1998 Jul;13(4):690-2.
Improvements in daily functioning after deep brain stimulation of the thalamus
for intractable tremor.
Lyons KE, Pahwa R, Busenbark KL, Tröster AI, Wilkinson S, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with
essential tremor (ET). However, few studies have determined the degree of
improvement in daily functioning associated with DBS. We developed a self-report
Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with
the stimulator turned on and off. Patients rated their performance on the 30
items of the TADLS with the stimulator turned off and then on. They also
performed 10 activities under the supervision of a clinician who rated their
functional ability with stimulation off and then on. There was a 58% improvement
in self-rated TADLS scores in patients with DBS with the stimulator on compared
with stimulation off. When activities were rated by the clinician, the average
improvement in functioning with the stimulator on was 54%. There were reasonably
high correlations between patient and clinician ratings of functioning. ET
patients have a marked improvement in daily functioning with thalamic DBS.
PMID: 9686776 [PubMed - indexed for MEDLINE]
85. Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8.
Mechanism of action of dopaminergic agents in Parkinson's disease.
Koller WC, Rueda MG.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
As the substantia nigra degenerates in Parkinson's disease (PD), the
nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD
symptoms. Although dopamine does not readily cross the blood-brain barrier, its
precursor, levodopa, does. Levodopa is absorbed in the small bowel and is rapidly
catabolized by aromatic-L-amino-acid decarboxylase (AADC) and
catechol-O-methyltransferase (COMT). Because gastric AADC and COMT degrade
levodopa, the drug is given with inhibitors of AADC (carbidopa or benserazide),
and inhibitors of COMT will also enter clinical use. Although the exact site of
decarboxylation of exogenous levodopa to dopamine in the brain is unknown, most
striatal AADC is located in nigrostriatal dopaminergic nerve terminals. Newly
synthesized dopamine is stored in the terminals and then released, stimulating
postsynaptic dopamine receptors and mediating the antiparkinsonian action of
levodopa. Dopamine agonists act directly on postsynaptic dopamine receptors, thus
obviating the need for metabolic conversion, storage, and release. How the
actions of dopaminergic drugs produce side effects and how these side effects
should be managed are discussed.
PMID: 9633680 [PubMed - indexed for MEDLINE]
86. Neurology. 1998 Jun;50(6 Suppl 6):S1.
Current and emerging drug therapies in the management of Parkinson's disease.
Koller WC, Tolosa E.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
PMID: 9633678 [PubMed - indexed for MEDLINE]
87. J Neurol. 1998 May;245 Suppl 1:S28-30.
Quality of life and Parkinson's disease: the CR FIRST Study.
Wasielewski PG, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, USA.
Quality of life is an important issue in the treatment of Parkinson's disease.
Both general and disease specific quality of life scales are now being used in
interventional trials. In the Sinemet CR First trial, the long-acting preparation
was found to be superior to the immediate release preparation in several measures
of the Nottingham Health Profile, a generic quality of life scale. In particular
social isolation and emotional reactivity was better with Sinemet CR. The long
acting drug was also superior for all five years of the study, for activities of
daily living subscale of the UPDRS. It is concluded the Sinemet CR may have
advantages over the immediate release preparation on Quality of life issues in
PD.
PMID: 9617720 [PubMed - indexed for MEDLINE]
88. Mov Disord. 1998 May;13(3):465-7.
Double-blind controlled trial of gabapentin in essential tremor.
Pahwa R, Lyons K, Hubble JP, Busenbark K, Rienerth JD, Pahwa A, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160,
USA.
Gabapentin has been reported to be effective for essential tremor (ET) based on
open-label trials. We studied gabapentin (1800 mg/day) and placebo in a
double-blind crossover design in 20 ET patients. Eighteen patients completed the
study and two patients dropped out as a result of adverse effects which resolved
when the medication was discontinued. Tremor was assessed at baseline and after 2
weeks of gabapentin and placebo treatment. One patient was mildly improved and
another was moderately improved with placebo. Similarly, one patient reported
mild improvement and another patient had marked improvement with gabapentin. All
the remaining patients either reported no change or were worse with both
treatment arms. There was no significant difference for total tremor score, hand
tremor score, handwriting scores, or pouring scores. Sickness Impact Profile
scores were no different between placebo and gabapentin. Our results suggest that
as an adjuvant therapy in ET, gabapentin has limited benefit.
PMID: 9613738 [PubMed - indexed for MEDLINE]
89. Mov Disord. 1998 May;13(3):377-82.
Clozapine use in Parkinson's disease: a retrospective analysis of a large
multicentered clinical experience.
Trosch RM, Friedman JH, Lannon MC, Pahwa R, Smith D, Seeberger LC, O'Brien CF,
LeWitt PA, Koller WC.
Department of Neurology, Wayne State University School of Medicine, Detroit,
Michigan, USA.
We conducted a multicentered, retrospective review of clozapine's (CZP) effects
on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in
Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared
with varying prescribing practices at participating sites. The medical records of
172 consecutive PD patients treated with CZP at four movement disorder clinics
were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety,
depression, hypersexuality, sleep disturbance, and akathisia. Tremor,
torticollis, limb dystonia, and pain showed modest rates of improvement.
Twenty-three percent of patients withdrew as a result of adverse events or
treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy,
or reduce adverse events or the withdrawal rate. Low-dose CZP in the outpatient
setting is generally an effective and well-tolerated treatment for many of the
psychiatric, sleep, motor, and sensory disturbances common to late-stage PD.
PMID: 9613725 [PubMed - indexed for MEDLINE]
90. Neuroepidemiology. 1998;17(2):96-104.
Gene-toxin interaction as a putative risk factor for Parkinson's disease with
dementia.
Hubble JP, Kurth JH, Glatt SL, Kurth MC, Schellenberg GD, Hassanein RE, Lieberman
A, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, USA.
We had previously examined environmental, sociodemographic and clinical variables
as predictors for Parkinson's disease with dementia (PD + D) and found that lower
educational attainment, greater motor impairment and advanced age at disease
onset were more common in PD + D than in subjects with Parkinson's disease
without dementia (PD-D). We now explore the hypothesis that genetic traits
coupled with nongenetic factors may raise the risk of development of PD + D. The
study cohort of 43 PD + D and 51 PD-D subjects was analyzed examining
environmental, sociodemographic and clinical variables along with 3 candidate
gene markers: poor debrisoquine metabolizer allele (CYP 2D6 29B+), monoamine
oxidase B allele 1, and apolipoprotein E epsilon 4 allele. Variables were
initially entered into a multivariate model singly. Again lower education, age at
onset and motor impairment appeared as predictors of PD + D while other variables
(including allele status) failed to emerge as significant individual risk factors
for dementia. We then examined environmental and genetic variables analyzed in
tandem to look for potential variable interactions. Subjects who had pesticide
exposure and at least 1 copy of the CYP 2D6 29B+ allele had 83% predicted
probability of PD + D (stepwise logistic regression model: p = 0.0491). This
case-control study provides preliminary evidence that a gene-toxin interaction
may play an etiological role in PD + D. Further assessment of the role of these
putative risk factors in incident dementia in PD is indicated.
PMID: 9592786 [PubMed - indexed for MEDLINE]
91. Clin Neuropharmacol. 1998 Mar-Apr;21(2):118-21.
Gender differences in Parkinson's disease.
Lyons KE, Hubble JP, Tröster AI, Pahwa R, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We examined data from 630 patients entered into the University of Kansas Medical
Center's Parkinson's Disease (PD) Registry to determine if gender differences
exist in terms of both cognitive and motor symptoms of PD. An analysis of the
Mini-Mental State Examination scores indicated slightly higher scores for women
relative to men. Although women had significantly better scores than did men on
the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), they
had a significantly greater prevalence of dyskinesias compared with men. These
motor differences were significant only in patients with PD of greater than 5
years duration. There were no gender differences for age of diagnosis, Hoehn and
Yahr Staging, Schwab and England Scale, or the mentation and activities of daily
living sections of the UPDRS. We conclude that as PD progresses, gender
differences emerge, with men exhibiting more severe parkinsonian motor features
and women experiencing more levodopa-induced dyskinesia.
PMID: 9579298 [PubMed - indexed for MEDLINE]
92. Neurosurg Clin N Am. 1998 Apr;9(2):295-306.
Surgical treatment options in Parkinson's disease.
Koller WC, Wilkinson S, Pahwa R, Miyawaki EK.
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas
66160-7314, USA.
Surgical treatment of Parkinson's disease has become an important mode of therapy
for advanced disease. Both ablative lesions and, more recently, deep brain
stimulation have been employed. Various brain areas, including the thalamus,
globus pallidus, and subthalamus, have been target sites.
PMID: 9495892 [PubMed - indexed for MEDLINE]
93. Neurology. 1998 Mar;50(3 Suppl 3):S1-57.
An algorithm (decision tree) for the management of Parkinson's disease: treatment
guidelines. American Academy of Neurology.
Olanow CW, Koller WC.
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
PMID: 9524552 [PubMed - indexed for MEDLINE]
94. Neurology. 1998 Mar;50(3):796-8.
Reduction in voice tremor under thalamic stimulation.
Carpenter MA, Pahwa R, Miyawaki KL, Wilkinson SB, Searl JP, Koller WC.
Hearing and Speech Department, University of Kansas Medical Center, Kansas City
66160-7605, USA.
We studied the effect of deep brain stimulation (DBS) of the ventral intermediate
thalamic nucleus on voice symptoms in seven patients with essential tremor. All
had undergone DBS for management of hand tremor. Five of the patients had
received unilateral implants; two were treated bilaterally. Each reported
improvement in hand tremor with thalamic stimulation (a 1-to-3-point change on a
5-point severity scale). Voice tremor was evaluated with and without stimulation
using patient and clinician severity ratings, and acoustic measures (rate and
amplitude). Four of the seven patients showed reductions in voice symptoms in at
least two of these measures, although degree of change differed (e.g., from 1 to
3 points on the 5-point severity scale). Voice gains typically were restricted to
those patients with the more severe symptoms and did not parallel improvements in
the upper extremities. It appears that reduced voice tremor may be an additional
benefit of DBS for some individuals.
PMID: 9521280 [PubMed - indexed for MEDLINE]
95. Arch Neurol. 1998 Mar;55(3):360-5.
Diagnostic validity of the dementia questionnaire for Alzheimer disease.
Ellis RJ, Jan K, Kawas C, Koller WC, Lyons KE, Jeste DV, Hansen LA, Thal LJ.
Department of Neurosciences, University of California, San Diego, La Jolla
92093-0948, USA. roellis@ucsd.edu
OBJECTIVE: To determine the sensitivity and specificity of postmortem dementia
diagnoses based on a retrospective informant interview by comparison with
criterion standard neuropathological diagnoses and the results of previous
clinical examinations. SETTING: Three university-based academic research centers.
SUBJECTS: Fifty-four deceased elderly persons with Alzheimer disease, another
dementing disorder, a neurologic disease resulting in functional impairment but
no dementia, or no neurologic disorder. METHODS: Blinded nonclinician
interviewers administered the Dementia Questionnaire (DQ) by telephone to
informants, typically close relatives, who were familiar with the intellectual
and functional status of the subjects before death. Two senior clinicians (LJ.T.
and C.K.) rated each DQ for the presence or absence of a dementia syndrome during
life and for the specific disorders causing the dementia, if present. Raters were
blinded to the neuropathological findings and based their assessments only on
data provided by responses to the DQ. Comparison was made with diagnoses based on
neuropathological assessment. In most cases, the results of antemortem clinical
examinations were also available as a check on the clinical diagnosis of the
dementia syndrome. Sensitivity and specificity of the DQ diagnoses were computed,
and chance-corrected agreement measures were calculated for the 2 independent DQ
raters (LJ.T. and C.K.). RESULTS: Compared with antemortem clinical diagnosis,
the average sensitivity of the DQ for the clinical syndrome of dementia was
92.8%, the specificity was 89.5%, and the interrater agreement was 98% (kappa =
0.96). Among 7 subjects with mild dementia (Mini-Mental State Examination score >
or = 24 at the last clinical examination), 5 (71%) were correctly identified
using the DQ. The DQ correctly indicated the absence of dementia in 8 (80%) of 10
subjects with other neurologic disorders causing functional impairment. Compared
with the neuropathological diagnoses, the DQ differentiated Alzheimer disease
from other primary causes of dementia with a sensitivity of 89% and a specificity
of 72%. The interrater agreement was 93.8% (kappa = 0.85). CONCLUSIONS: Compared
with the results of the antemortem clinical examinations, the DQ was sensitive to
the presence of dementia, detected most cases of mild dementia, and discriminated
dementia from other neurologic disorders causing functional impairment. Compared
with the neuropathological diagnoses, the ability of the DQ to differentiate
Alzheimer disease from other dementing disorders indicates that it may be useful
as a research tool.
PMID: 9520010 [PubMed - indexed for MEDLINE]
96. Clin Neuropharmacol. 1997 Dec;20(6):523-30.
Motor complications of chronic levodopa therapy in Parkinson's disease.
Miyawaki E, Lyons K, Pahwa R, Tröster AI, Hubble J, Smith D, Busenbark K, McGuire
D, Michalek D, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We report on motor complications of chronic levodopa therapy among 811
levodopa-responsive patients with idiopathic Parkinson's disease (PD), stratified
by duration after diagnosis. Predictable "offs" were noted in 20.2% of patients
in the first 5 years, in 58.3% after 15 years. Unpredictable or sudden offs and
early morning dystonia were less common. Longer duration was associated with
greater percentages of patients with off periods or dyskinesias (up to 70% after
15 years), although patients with 6-15 years' duration saw relatively little
increase in frequency of those complications, and a minority of patients
(approximately 30%) with duration into the second decade did not experience off
periods or dyskinesia. Across groups, mean Hoehn and Yahr stage and daily
levodopa dosage progressively increase (and mean Schwab and England disability
ratings decrease), but more conservatively than in prior reports in the
postlevodopa era. We note that with advancing PD duration, levodopa complications
are more common, but in many cases there appear to be relatively stable periods
in terms of levodopa dosage and disease severity, and a minority of patients will
be relatively free of motor complications into the second decade of their
disease.
PMID: 9403226 [PubMed - indexed for MEDLINE]
97. Neurosurgery. 1997 Dec;41(6):1303-16; discussion 1316-8.
Analysis of pallidotomy lesion positions using three-dimensional reconstruction
of pallidal lesions, the basal ganglia, and the optic tract.
Burns JM, Wilkinson S, Kieltyka J, Overman J, Lundsgaarde T, Tollefson T, Koller
WC, Pahwa R, Troster AI, Lyons KE, Batnitzky S, Wetzel L, Gordon MA.
Imaging Resource Center, University of Kansas Medical Center, Kansas City, USA.
OBJECTIVE: To assess the position of radiofrequency pallidotomy lesions placed
using microelectrode stimulation and cellular recordings in relation to a
stereotactically defined starting point. Radiofrequency lesion locations were
also evaluated in relation to the putamen, posterior limb of the internal
capsule, and optic tract. METHODS: Magnetic resonance images obtained from 23
patients with Parkinson's disease who underwent pallidotomy at the University of
Kansas Medical Center were analyzed. Using computerized techniques, lesion
positions in relation to the midcommissural point and a hypothetical starting
point were determined. Data segmentation and three-dimensional reconstruction of
pallidal lesions, the internal capsule, and the optic tract allowed assessment of
lesion position in relation to internal anatomy. Clinical outcome of pallidotomy
was assessed using both the Unified Parkinson's Disease Rating Scale and the
Dementia Rating Scale. RESULTS: Pallidal lesions were usually placed anterior and
dorsal to the stereotactically defined starting point. The position of pallidal
lesions in the men were observed, in four trials, to be significantly more dorsal
than the lesions in the women. The outer zone of the lesion was usually adjacent
to the internal capsule and the putamen and relatively close to the optic tract.
The inner zone of the lesion was usually several millimeters removed from
anatomic boundaries of the putamen, internal capsule, and optic tract. Patients
achieved favorable outcomes, with reduced dyskinesias and "off" time and
improvement of their Parkinsonian symptoms, as evidenced by clinical assessment,
the Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale.
CONCLUSION: Microelectrode stimulation and cellular recordings usually led to a
final pallidotomy lesion position that deviated from the stereotactically defined
starting point. The pallidotomy lesions in the men were observed to be more
dorsal than the lesions in the women. Clinical outcomes were not correlated with
either lesion location relative to the starting point or distances between the
pallidal lesion and the putamen, internal capsule, or optic tract.
Kinesthetically responsive cells may be localized generally more anterior and
dorsal to the starting point (within the globus pallidus) and may be grouped
variably from patient to patient in relation to other basal ganglia structures.
Although the primary lesion site is most likely within the sensorimotor region of
the globus pallidus internus, the more dorsal locations of responsive cell groups
may indicate that some lesion sites may be localized within the globus pallidus
externus.
PMID: 9402582 [PubMed - indexed for MEDLINE]
98. Mov Disord. 1997 Nov;12(6):969-72.
Clinical expression of essential tremor: effects of gender and age.
Hubble JP, Busenbark KL, Pahwa R, Lyons K, Koller WC.
Department of Neurology, Ohio State University, Columbus, USA.
Essential tremor (ET) is considered to be a monosymptomatic disorder consisting
primarily of postural hand tremor. Nevertheless, clinical expression can vary
based on the body region affected by tremor and the coexistence of other
neurologic signs, such as tandem gait disturbance. We conducted a two-part study
to test the hypothesis that variability in ET clinical expression is influenced
by gender and age. In part 1, we examined a large ET clinical database (n = 450),
comparing ratings of postural hand and head/voice tremor based on gender.
Head/voice tremor was significantly more frequent and more severe among female ET
patients; men had more severe postural hand tremor. In part 2, ET patients (n =
40) had significantly more missteps when tandem walking in comparison to
age-matched controls. Poor tandem walk in ET cases was associated with more
advanced age, but not gender, disease duration, or ratings of postural hand or
head/voice tremor. We conclude that gender influences the body region most
affected by ET possibly through the effects of the sex chromosomes or hormones.
Ataxia (tandem gait difficulty) is common in ET and may be an accentuation of
cerebellar dysfunction due to aging.
PMID: 9399222 [PubMed - indexed for MEDLINE]
99. Mov Disord. 1997 Nov;12(6):841.
Essential tremor: the beginning of a new era.
Koller WC.
Comment on:
Mov Disord. 1997 Nov;12(6):865-70.
PMID: 9399204 [PubMed - indexed for MEDLINE]
100. J Clin Psychol. 1997 Nov;53(7):713-22.
Comparison of NART and Barona demographic equation premorbid IQ estimates in
Alzheimer's disease.
Paolo AM, Tröster AI, Ryan JJ, Koller WC.
University of Kansas Medical Center, Kansas City 66160, USA.
Two methods of estimating premorbid WAIS-R intelligence were compared in matched
samples of normal and AD persons. The NART and Barona 1984 demographic equations
accurately predicted the IQs of the normal group and overestimated the IQs of the
AD subjects. When the AD group was divided into mild and moderately impaired
subgroups, the more severely demented subjects displayed lower WAIS-R IQs and
NART estimated IQs, revealing that NART performance is sensitive to dementia
severity. However, the NART estimated IQs for the mild and moderately impaired AD
subgroups were larger than the WAIS-R IQs, suggesting that while the NART is
sensitive to dementia severity, it may still provide relevant clinical
information.
PMID: 9356900 [PubMed - indexed for MEDLINE]
101. Neurology. 1997 Oct;49(4):1078-83.
Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral
functioning before and 3 months after electrode implantation.
Tröster AI, Fields JA, Wilkinson SB, Pahwa R, Miyawaki E, Lyons KE, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Unilateral pallidotomy is thought to have a low risk for cognitive morbidity.
Nonetheless, recent research suggests that some patients experience declines in
memory and language and that pallidal stimulation might be a safer treatment for
Parkinson's disease (PD). We investigated the neurobehavioral effects of
unilateral pallidal stimulation. Nine consecutive PD patients undergoing
unilateral deep brain-stimulating electrode implantation in the globus pallidus
interna were evaluated with a neuropsychological test battery approximately 1
month before and 3 months after surgery. Patients reported significantly fewer
symptoms of anxiety and greater vigor after surgery. There was a trend toward
fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test
scores declined significantly after surgery. However, among five patients showing
declines in semantic verbal fluency, only one patient's score declined by more
than 2 SD. No patient showed significant decline or improvement in the overall
level of cognitive functioning. This study supports the relative safety, in terms
of cognitive function, of unilateral pallidal stimulation in PD.
PMID: 9339693 [PubMed - indexed for MEDLINE]
102. Mov Disord. 1997 Sep;12(5):677-81.
Comparison of standard carbidopa-levodopa and sustained-release
carbidopa-levodopa in Parkinson's disease: pharmacokinetic and quality-of-life
measures.
Pahwa R, Lyons K, McGuire D, Silverstein P, Zwiebel F, Robischon M, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160,
USA.
We compared clinical, pharmacokinetic, and quality-of-life measures in patients
with Parkinson's disease (PD) who were on standard carbidopa-levodopa (Std-L) and
after conversion to sustained-release carbidopa-levodopa 50/200 (L-CR). A total
of 20 PD patients with motor fluctuations participated in the study and 18
completed it. There were 10 women and eight men, with a mean age of 67.5 years
and a mean disease duration of 9.9 years. All patients underwent 10-h
pharmacokinetic and clinical evaluations while on Std-L and again while on L-CR.
The patients maintained diaries for 2 days before the 10-h evaluations and
completed a sickness impact profile (SIP) while on Std-L and again while on L-CR.
The total daily levodopa intake was significantly greater with L-CR because of
the reduced bioavailability of the L-CR. The mean daily levodopa dosage was 569
mg for Std-L compared with 751 mg for L-CR. The patients performed better in
walking time, Unified Parkinson's Disease Rating Scale (motor score), and tapping
total with L-CR, although the improvement was not statistically significant.
There was no significant difference in dyskinesias between the two preparations.
The plasma levodopa levels and the areas under the curve were significantly
greater with L-CR. "On" time as measured by patient diaries was significantly
greater for L-CR. There was no significant difference in the total SIP scores for
patients on the two preparations, but patients had significantly better home
management and mobility while on L-CR. In conclusion, L-CR resulted in more "on"
time with greater plasma levodopa levels, which resulted in better home
management and mobility.
PMID: 9380047 [PubMed - indexed for MEDLINE]
103. Clin Neuropharmacol. 1997 Aug;20(4):300-10.
Serotonin, dopamine, and motor effects in Parkinson's disease.
Miyawaki E, Meah Y, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We review recent reports suggesting that use of selective serotonergic agents
that either inhibit synaptic reuptake or have specific serotonin receptor
affinities may benefit a variety of motor disturbances in Parkinson's disease.
The complex, mixed motoric effects of these agents in Parkinson's disease have
not allowed for a consistent view on the interrelationship between dopamine and
serotonin (5HT) in motor control but may speak to the nature of dysregulated
neurotransmission in the disease.
PMID: 9260728 [PubMed - indexed for MEDLINE]
104. Neurology. 1997 Jul;49(1 Suppl 1):S10-25.
Issues in the early diagnosis of Parkinson's disease.
Koller WC, Montgomery EB.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
The clinical diagnosis of Parkinson's disease (PD) is most difficult early in the
disease when the signs and symptoms are most subtle. The differential diagnosis
of PD includes a number of movement disorders with similar symptomatology (e.g.,
essential tremor, multiple system atrophy, vascular parkinsonism). In most
published studies of PD, the disease is diagnosed simply by the presence of two
of the three cardinal motor signs-tremor, rigidity, and bradykinesia-or by the
presence of three of the four motor signs: tremor, rigidity, bradykinesia, and
postural instability. However, there is an obvious need for better diagnostic
criteria. Until discrete biologic markers are developed, the use of exclusion
criteria may improve the accuracy of the presumptive diagnosis of PD.
PMID: 9222271 [PubMed - indexed for MEDLINE]
105. Neurology. 1997 Jul;49(1):249-53.
High-frequency stimulation of the globus pallidus for the treatment of
Parkinson's disease.
Pahwa R, Wilkinson S, Smith D, Lyons K, Miyawaki E, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160,
USA.
Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by
the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy
can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed
chronic stimulation of the globus pallidus (CSGP) to duplicate the positive
results of pallidotomy with reduced risk of permanent neurologic deficit in
patients with advanced PD. The lead for CSGP was stereotactically implanted with
the aid of microelectrode recordings in the globus pallidus pars interna. An
electrical pulse generator was implanted in the subclavicular region. Stimulation
settings were adjusted by computer. Five PD patients (four men, one woman) with
disabling symptoms were enrolled. Three of the patients had bilateral implants.
At 3 months following the last implant, four patients rated themselves as
markedly improved, and one patient was moderately improved. The amount of time in
the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p <
0.05). There was a significant improvement in all subscales of the UPDRS (p <
0.05). One patient had an asymptomatic intracranial bleed, one patient had
transient hemiparesis during surgery with stimulation, and one patient required
surgical repositioning of the lead. Adverse effects caused by stimulation were
minimal. CSGP is a safe and effective procedure in PD patients with motor
fluctuations and dyskinesias.
PMID: 9222199 [PubMed - indexed for MEDLINE]
106. Mov Disord. 1997 May;12(3):337-41.
Effects of thalamic deep brain stimulation based on tremor type and diagnosis.
Hubble JP, Busenbark KL, Wilkinson S, Pahwa R, Paulson GW, Lyons K, Koller WC.
Department of Neurology, Ohio State University, Columbus, USA.
It has been suggested that deep brain stimulation (DBS) is less effective in
alleviating proximal than distal postural arm tremor reduction is said to be less
in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded
rater's tremor scores and subjects' disability ratings at 3-month follow-up to
examine the effects of DBS based on tremor type (rest, kinetic, distal postural,
proximal postural) and diagnosis (ET, PD). An independent examiner provided
tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at
baseline and at follow-up with DBS "on." Subjects provided self-ratings of
disability at baseline and at follow-up. Comparisons of baseline and follow-up
tremor scores and disability ratings were made using the Mann-Whitney U and
Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank
order correlation test. There were significant and essentially equal improvements
in tremor scores of test, kinetic, distal postural, and proximal postural tremor
at follow-up. Only one subject had no improvement in tremor. Tremor improved
significantly and to the same extent in ET and PD subjects in each position
except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects
did not differ in the extent of disability improvement. Improved disability
correlated only with improved postural tremor scores; proximal postural and
distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in
alleviating tremor and disability in both ET and PD. Resting, kinetic, distal
postural, and proximal postural tremor can be reduced to an equal degree.
However, DBS produces the greatest improvement in disability in association with
improved postural tremor in both ET and PD.
PMID: 9159728 [PubMed - indexed for MEDLINE]
107. Neurology. 1997 Apr;48(4):1077-81.
Benztropine versus clozapine for the treatment of tremor in Parkinson's disease.
Friedman JH, Koller WC, Lannon MC, Busenbark K, Swanson-Hyland E, Smith D.
Memorial Hospital of Rhode Island, Department of Clinical Neurosciences,
Pawtucket 02860, USA.
Four open-label studies have reported beneficial effects of clozapine on the
tremor of idiopathic Parkinson's disease (PD). We performed a double-blind
crossover trial with a 2-week washout, comparing low-dose clozapine to
benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and
19 completed the study. Benztropine and clozapine were equally effective in
improving tremor and the motor score of the United Parkinson's Disease Rating
Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse
events were experienced with each drug, but leukopenia was not encountered. We
conclude that the atypical antipsychotic drug clozapine is helpful in the
treatment of tremor in PD and should be considered when all other drug therapies
fail.
PMID: 9109903 [PubMed - indexed for MEDLINE]
108. Neurosurg Focus. 1997 Mar 15;2(3):e3.
Magnetic resonance image evaluation of pallidotomy lesions: a volumetric and
shape analysis.
Burns JM, Wilkinson S, Overman J, Kieltyka J, Lundsgaarde T, Tollefson T, Koller
WC, Pahwa R, Tröster AI, Lyons KE, Batnitzky S, Wetzel L, Gordon MA.
Imaging Resource Center and Department of Surgery (Division of Neurosurgery),
University of Kansas Medical Center, Kansas City, Kansas 66103, USA.
Determination of acute pallidotomy-produced lesion volumes, pre- and
postpallidotomy globus pallidus (GP) volumes, and assessment of lesion shape
using magnetic resonance (MR) imaging-based computerized segmentation
(contouring) and three-dimensional rendering was made in 19 patients. Magnetic
resonance image slice thickness (1.5 mm or 6 mm) was not found to be a
significant factor influencing contour-based pallidotomy lesion volume estimates.
Previously reported lesion volumes produced by pallidotomy have often been
estimated using the ellipsoid volume formula. Using 1.5-mm-thick MR sections,
contour-based pallidotomy-produced lesion volumes were significantly different
from those volumes estimated by the ellipsoid formula. Globus pallidus volumes,
estimated by contouring T2-weighted MR images, were bilaterally similar (2.4 +/-
0.37 ml [right]; 2.2 +/- 0.45 ml [left]). Postoperative GP volumes were found on
the contralateral, unlesioned side to be 2 +/- 0.45 ml and on the lesioned side
to be 1.25 +/- 0.45 ml. Using the contralateral, unlesioned side as a reference
volume, approximately 39 +/- 14% of the GP was visibly affected on the lesioned
side. Seventeen of 18 patients had a favorable outcome with reduced dyskinesias
and "off" time with improvement in parkinsonian symptoms. Analysis of
computerized three-dimensional rendering of pallidotomy-produced lesions based on
MR images showed no relationship between lesioning technique and resulting lesion
shape. Important factors in the volumetric analysis of pallidotomy lesions are
identified and allow reasonable assessment of the pallidotomy lesion volume and
shape and the extent of the affected GP.
PMID: 15096011 [PubMed]
109. Exp Neurol. 1997 Mar;144(1):24-8.
Neuroprotective therapy for Parkinson's disease.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
The concept of neuroprotection relates to the fact that intervention may be able
to interfere with the pathogenesis of neuronal cell death. Neuroprotective
therapy may make it possible to delay disease progression or prevent the disease
altogether. The pathophysiological mechanism of cell death in Parkinson's disease
is unknown; however, hypotheses have been developed. The discovery that the toxin
MPTP can cause Parkinson's disease both in humans and in animals strengthened the
hypothesis that either exogenous or endogenous toxins may be involved in the
mechanism of cell death in Parkinson's disease. The mechanism of MPTP toxicity
has been elucidated, lending several possible mechanisms for therapeutic
intervention in Parkinson's disease. Current data suggest that oxidative stress
may play a prominent role in the pathogenesis of Parkinson's disease. It is
possible that the generation of free radicals leads to neuronal cell death. There
is also evidence that mitochondrial damage may play a role in the pathogenesis of
Parkinson's disease. Other theories of possible pathogenesis include
excitotoxicity, disturbances of calcium homeostasis, immunological mechanisms,
and infectious etiologies. The first agent to be tested as a candidate for
neuroprotection was the MAO-B inhibitor deprenyl. Evidence is reviewed for and
against the theory that this drug is neuroprotective.
PMID: 9126147 [PubMed - indexed for MEDLINE]
110. J Clin Exp Neuropsychol. 1996 Dec;18(6):892-7.
Utility of a Wisconsin Card Sorting Test short form in persons with Alzheimer's
and Parkinson's disease.
Paolo AM, Axelrod BN, Tröster AI, Blackwell KT, Koller WC.
University of Kansas Medical Center, USA.
The utility of administering only the first deck of 64 cards from the Wisconsin
Card Sorting Test (WCST-64) in persons with Alzheimer's (AD) and Parkinson's
disease (PD) was evaluated. There were 35 elderly subjects matched for gender,
age, and education in each of four groups: controls, PD without dementia (PDN),
PD with dementia (PDD), and AD. Additionally, the control and PDN subjects were
matched for level of cognitive functioning as were the PDD and AD groups. Results
revealed that demented persons performed significantly worse than nondemented
subjects. The WCST-64 was also sensitive to the subtle executive deficits
demonstrated by persons with PD without dementia. The findings support the use of
the WCST-64 in elderly persons with AD and PD.
PMID: 9157112 [PubMed - indexed for MEDLINE]
111. Neurology. 1996 Dec;47(6 Suppl 3):S196-9.
Selegiline monotherapy in the treatment of Parkinson's disease.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
PMID: 8959988 [PubMed - indexed for MEDLINE]
112. Neurology. 1996 Nov;47(5):1331-2.
Methazolamide for essential voice tremor.
Busenbark K, Ramig L, Dromey C, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We studied the safety and efficacy of methazolamide (average dose 168 mg/day) in
a placebo-controlled blinded investigation in nine patients with essential voice
tremor. There were no significant differences for physician or patient clinical
rating scores. Digital audio tape recordings showed no difference for amplitude
modulation, but frequency modulation was significantly altered by methazolamide.
Side effects were common with the drug. We conclude that methazolamide has
limited usefulness in the treatment of essential voice tremor.
PMID: 8909454 [PubMed - indexed for MEDLINE]
113. Mov Disord. 1996 Jul;11(4):427-30.
Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a
single-dose study.
Pahwa R, Marjama J, McGuire D, Lyons K, Zwiebel F, Silverstein P, Ward R, Koller
WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We compared the pharmacokinetic and motor responses of Sinemet and Atamet
(generic carbidopa/levodopa) in patients with Parkinson's disease. Thirty
Parkinson's disease patients (10 previously untreated, 10 with early disease, and
10 with motor fluctuations/dyskinesia) participated in a single-dose double-blind
study. Following administration of an equivalent oral dose of Sinemet and Atamet
on two separate days, we compared the peak plasma concentration, time to peak
plasma concentration, area under the curve, total motor score, tapping score, and
walking time. The mean time to peak plasma concentrations was 49 min with Sinemet
and 47 min with Atamet, the mean peak plasma concentration was 1,273 ng/ml with
Sinemet and 1,153 ng/ml with Atamet, and the mean area under the curve was 2,295
micrograms/ml/h with Sinemet and 2,330 micrograms/ml/h with Atamet. Similarly,
there was no significant difference between total motor score, tapping score, or
walking time. In this single-dose study, there were no significant differences in
pharmacokinetic and motor responses between Sinemet and Atamet.
PMID: 8813223 [PubMed - indexed for MEDLINE]
114. Neurology. 1996 Jul;47(1):264-5.
Accuracy of reported family histories of essential tremor.
Busenbark K, Barnes P, Lyons K, Ince D, Villagra F, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We studied the accuracy of reported family histories of essential tremor (ET) by
questioning the patients in our clinic and subsequently by mail and phone. For
individuals who continued to report a negative family history, we mailed a
screening questionnaire to their first-degree relatives to further ascertain the
presence of ET. On initial assessment, 67.7% of patients reported a positive
family history of ET, but following all assessments, 96.0% of patients had a
positive family history. We conclude that a negative family history of ET is
often inaccurate, and that ET is primarily a hereditary disease.
PMID: 8710092 [PubMed - indexed for MEDLINE]
115. Drug Saf. 1996 Jun;14(6):365-74.
Methods of managing levodopa-induced dyskinesias.
Giron LT Jr, Koller WC.
Neurology Service, Department of Veterans Affairs Medical Center, Kansas City,
Missouri, USA. GIRON.LOUIS_T+@KANSAS-CITY.VA.GOV
Levodopa-induced dyskinesias result in considerable functional impairment for
patients and formidable therapeutic challenges for physicians. A practical method
of treating such dyskinesias is first to classify the levodopa dyskinesias
according to their temporal profile after drug administration, namely, into
predictable (interdose, biphasic and 'off-period') and unpredictable ('on-off')
dyskinesias. Treatment of each type of dyskinesia requires a different and
relatively specific therapeutic strategy. With progression of Parkinson's
disease, the threshold for interdose dyskinesia lowers, while the threshold for
antiparkinsonian efficacy is unchanged; therefore, the strategy is to maintain
levodopa concentrations between these 2 thresholds and avoid high concentrations.
Frequent small doses of liquid levodopa preparations may be indicated. Clozapine
appears to increase the threshold for dyskinesia. However, its usefulness is
limited primarily by dose-related sedation and by dose-unrelated agranulocytosis.
Buspirone and fluoxetine may have specific antidyskinetic benefit. Surgical
treatment may aid selected patients, although criteria for selection are not
fully established. The biphasic dyskinesias occur just before and just after an
oral dose of levodopa. They result when levodopa concentrations fall below or
rise above the threshold for therapeutic efficacy; therefore, the strategy is to
maintain concentrations as nearly constant as possible above that threshold.
Dopamine agonists such as subcutaneous apomorphine combined with domperidone may
be particularly helpful. Thalamic stimulation can also benefit selected patients.
'Off-period' dyskinesias occur at times of predicted low concentrations of
levodopa. The treatment strategy is to provide sufficient levodopa or
dopaminergic stimulation during those intervals. Dopamine agonists (e.g.
bromocriptine at night) may help the characteristic early foot dystonia.
Anticholinergic agents may also help. The unpredictable ('on-off') dyskinesias
are first analysed to establish a pattern of response. Then, on the basis of that
pattern, they are treated by maintaining levodopa concentrations or dopaminergic
tone during the periods that would ordinarily be 'off.' Administration of liquid
levodopa preparations, addition of dopaminergic agents, restriction of treatment
during the morning hours as well as restriction of the majority of dietary
protein in the evening meal may provide a period of predictable good function
early in the day. Clozapine, even early in treatment, appears to reduce the
incidence of these dyskinesias. Rescue with apomorphine during a malignant
prolonged 'off' phase is particularly valuable.
PMID: 8828014 [PubMed - indexed for MEDLINE]
116. Neurology. 1996 Apr;46(4):1156-7.
Normal distribution of apolipoprotein E alleles in progressive supranuclear
palsy.
Anouti A, Schmidt K, Lyons KE, Hubble JP, Schellenberg G, Golbe LI, Lang AE,
Galvez-Jimenez N, Hershey L, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Apolipoprotein E (Apo E) genotype is a genetic risk factor influencing the
development of Alzheimer's disease (AD). Progressive supranuclear palsy (PSP),
like AD, is a dementing illness with neurofibrillary tangles. We determined the
frequencies of Apo E alleles in 52 PSP patients and 52 age- and gender-matched
controls. The distribution of Apo E allele frequencies and genotypes showed no
difference between PSP and controls. Apo E allele status does not influence the
development of PSP.
PMID: 8780111 [PubMed - indexed for MEDLINE]
117. Neurology. 1996 Apr;46(4):1150-3.
Deep brain stimulation for essential tremor.
Hubble JP, Busenbark KL, Wilkinson S, Penn RD, Lyons K, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, USA.
We examined the effects and safety of deep brain stimulation (DBS) as a treatment
for essential tremor (ET). Ten ET patients with disabling medication-refractory
tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic
nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and
disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up.
There were significant improvements in dressing, drinking, eating, bathing, and
handwriting as reported by the subjects. Tremor severity, writing, pouring, and
spiral and line drawing were significantly improved as rated by the examiner.
Improvements persisted through the 6-month follow-up period. Although global
disability significantly lessened in the group as a whole, one subject with
hand-finger tremor accentuated by writing had no change in disability status. In
this 6-month open-label study, DBS was effective and safe in reducing tremor and
functional disability in ET.
PMID: 8780109 [PubMed - indexed for MEDLINE]
118. Neurology. 1996 Apr;46(4):1062-5.
Multicenter, placebo-controlled trial of cabergoline taken once daily in the
treatment of Parkinson's disease.
Hutton JT, Koller WC, Ahlskog JE, Pahwa R, Hurtig HI, Stern MB, Hiner BC,
Lieberman A, Pfeiffer RF, Rodnitzky RL, Waters CH, Muenter MD, Adler CH, Morris
JL.
Neurology Research and Education Center, St. Mary of the Plains Hospital,
Lubbock, TX 79410, USA.
Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and
much longer-acting than other dopamine agonists. We conducted a randomized,
placebo-controlled, double-blind study of cabergoline in 188
levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's
disease (PD). The cabergoline patients had significantly better Activities of
Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the
conclusion of the trial compared with the placebo group. The daily levodopa dose
for the cabergoline patients decreased 18% compared with a 3% reduction for the
placebo group (p < 0.001). The amount of time in the "on" state increased more in
the cabergoline group (p = 0.022). The side-effect was similar to that seen with
other dopamine agonists, and cabergoline was generally well tolerated. We
conclude that cabergoline is an effective adjunct to levodopa for the treatment
of PD.
PMID: 8780092 [PubMed - indexed for MEDLINE]
119. Neurology. 1996 Apr;46(4):1059-62.
Early morning akinesia in Parkinson's disease: effect of standard
carbidopa/levodopa and sustained-release carbidopa/levodopa.
Pahwa R, Lyons K, McGuire D, Dubinsky R, Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We examined the effects of supplemental standard carbidopa/levodopa (Std-L) on
early morning akinesia in patients with Parkinson's disease (PD) who were being
treated with sustained-release carbidopa/levodopa (L-CR). We compared plasma dopa
levels and clinical response in 15 PD patients after a dose of Std-L and L-CR (2
hours later) and after a dose of L-CR and placebo in a double-blind,
placebo-controlled, crossover study. Plasma dopa levels, total motor score,
walking time, and finger tapping time were assessed every 15 minutes for the
first 2 hours and then every 30 minutes for the next 3 hours. The time of onset
in clinical benefit was significantly earlier with Std-L (47 minutes, range 15 to
75 minutes) as the first dose as compared with L-CR (58 minutes, range 30 to 105
minutes). Similarly, there was a significant difference in the peak plasma dopa
levels (Cmax) and the time to reach peak plasma dopa levels (Tmax) with
administration of Std-L (Tmax 36 minutes; Cmax 1,501 micrograms/ml) as compared
with L-CR (Tmax 111 minutes, Cmax 1,260 micrograms/ml). There was no significant
difference in dyskinesias between the two treatment arms. An initial morning dose
of Std-L alleviates the problem of delayed-onset clinical response that commonly
occurs with L-CR.
PMID: 8780091 [PubMed - indexed for MEDLINE]
120. Neurol Clin. 1996 Feb;14(1):169-82.
Diagnostic testing in movement disorders.
Anouti A, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, USA.
The diagnosis of movement disorders is essentially clinical. Work-up depends on
patient age, part of the body affected, drug response, and presence of other
systemic or neurologic symptoms and signs. Typical Parkinson's disease, essential
tremor, and tics need only minimal work-up if any. Brain magnetic resonance
imaging/computed tomography, positron emission tomography and single photon
emission computed tomography, and DNA studies are promising diagnostic tools.
Exclusion of Wilson's disease and neuroacanthocytosis is emphasized in children
and young adults with movement disorders.
PMID: 8676842 [PubMed - indexed for MEDLINE]
121. Eur Neurol. 1996;36 Suppl 1:43-8.
Management of motor fluctuations in Parkinson's disease.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
A complication of chronic levodopa therapy is a shortening of benefit of each
dose. Peripheral pharmacokinetics, central pharmacokinetics, and central
pharmacodynamics are involved in the pathophysiology of motor fluctuations.
Strategies to improve 'wearing-off' fluctuations attempt to provide more constant
plasma levodopa levels or more continuous stimulation of dopamine receptors.
Controlled-release levodopa preparations are very effective for mild to moderate
fluctuations. The addition of direct-acting dopamine agonists or the MAO-B
inhibitor selegiline is helpful for short-term improvement. Liquid levodopa is
beneficial for some patients with severe fluctuations. Apomorphine injections
will provide immediate 'rescue' from 'off' states. Catechol-O-methyl transferase
inhibitors are a new class of drugs which appear to improve motor fluctuations.
Manipulations of dieting protein may reduce fluctuations in some patients. It is
possible that motor fluctuations may be delayed by the early use of sustained
release levodopa preparations or early combinations of levodopa with a dopamine
agonist.
PMID: 8791022 [PubMed - indexed for MEDLINE]
122. Neuroepidemiology. 1996 Jan-Feb;15(1):20-5.
Risk factors for dementia in Parkinson's disease: effect of education.
Glatt SL, Hubble JP, Lyons K, Paolo A, Tröster AI, Hassanein RE, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Cognitive deficits are common in Parkinson's disease (PD), but the
pathophysiology and relationship to Alzheimer's disease (AD) are not understood.
We used a case-control format to investigate putative risk factors for the
development of dementia in patients with Parkinson's disease. We compared 52
cognitively intact patients with PD to 43 PD patients with dementia with regard
to factors previously suggested as relevant to either AD or PD. Multiple logistic
regression yielded the following significant predictors of dementia in PD: lack
of education (less than a high school graduate) (OR 21); severity of motor
deficit (UPDRS total motor score greater than 20; OR 6.34), and PD onset at
greater than 60 years of age (OR 4.12). The predictive probability of dementia in
our subjects when all three variables were positive was 97.9%. We conclude that
education may modify the risk of cognitive decline in PD. Protective effects of
educational attainment, independent of dementia etiology, may be due to greater
functional brain reserve.
PMID: 8719045 [PubMed - indexed for MEDLINE]
123. Adv Neurol. 1996;69:487-91.
Treatment of Parkinson's disease with controlled-release Carbidopa/L-DOPA.
Pahwa R, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
PMID: 8615169 [PubMed - indexed for MEDLINE]
124. Arch Neurol. 1995 Dec;52(12):1164-9.
Neuropsychological impairment in Parkinson's disease with and without depression.
Tröster AI, Stalp LD, Paolo AM, Fields JA, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, USA.
OBJECTIVES: To compare quantitative and qualitative aspects of neuropsychological
test performance in patients with Parkinson's disease who currently had
depression (PDD) and those without depression (PDN) so as to evaluate the
influence of depression on cognition in Parkinson's disease. DESIGN:
Cross-sectional comparisons among PDN, PDD, and normal control (NC) groups. The
setting was a neurodegenerative disease research center in a teaching hospital.
Groups consisted of 44 patients with PDN and 44 patients with PDD matched for
age, education, gender, age at onset of disease, disease duration, and disease
severity; a group of 44 NC subjects matched for age, education, and gender; and a
second set of comparisons between 15 patients with PDN and 15 patients with PDD
also matched for overall severity of cognitive impairment. MEASURES: The
neuropsychological measures used were the Mattis Dementia Rating Scale, Beck
Depression Inventory, Wisconsin Card Sorting Test, Controlled Oral Word
Association Test, Logical Memory subtest of the Wechsler Memory Scale-Revised,
Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised, and the
Boston Diagnostic Aphasia Examination's Animal Naming test and Boston Naming
Test. RESULTS: Relative to the NC group, both PDN and PDD groups demonstrated
impairments in immediate and delayed verbal recall, semantic fluency, and problem
solving. When PDN and PDD groups were matched for demographic and disease
variables, only the PDD group evidenced impairment relative to NC in visual
confrontation naming, and in lexical and semantic fluency. In addition,
impairments on immediate recall and semantic fluency in the PDD group were more
pronounced than those in the PDN group. However, when PDN and PDD groups were
also matched for overall severity of cognitive impairment, no significant
differences emerged among the two groups' neuropsychological test performances.
CONCLUSIONS: Depression exacerbates some memory and language impairments
associated with PD, even when the PDN and PDD groups are matched for demographic
and disease variables. However, the extent and pattern of cognitive impairment is
similar in PDN and PDD when the groups are also matched also for overall severity
of cognitive impairment. Depression influences the quantity rather than the
quality of cognitive impairment associated with Parkinson's disease.
PMID: 7492290 [PubMed - indexed for MEDLINE]
125. Arch Clin Neuropsychol. 1995 Oct;10(5):463-73.
Construct validity of the WCST in normal elderly and persons with Parkinson's
disease.
Paolo AM, Tröster AI, Axelrod BN, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City,
66160-7314, USA.
Separate principle component analyses of the WCST were conducted on 187 normal
elderly and 181 persons with Parkinson's disease (PD). Adequate construct
validity was found for "conceptualization/problem solving" and "failure to
maintain set" factors in both groups. Perseverative and nonperseverative errors
were related for the normal group, but not for the PD subjects. This may reflect
the frontal systems deficit observed in PD. Additional principle component
analyses were conducted with the WCST and measures of memory and attention. In
neither the normal nor the PD group did the WCST significantly load with the
memory and attention measures. This suggests that the WCST provides information
about problem solving relatively independent of memory and attention functions
for elderly persons.
PMID: 14588903 [PubMed]
126. J Clin Microbiol. 1995 Oct;33(10):2768-9.
Nocardia species as an etiologic agent in Parkinson's disease: serological
testing in a case-control study.
Hubble JP, Cao T, Kjelstrom JA, Koller WC, Beaman BL.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
To test the hypothesis that Nocardia spp. may be an etiologic factor in
Parkinson's disease (PD), we used a serodiagnostic panel to determine if PD
patients had antibodies specific for Nocardia spp. To validate the serological
test panel, sera from healthy volunteers and from patients with culture-proven
nocardiosis (n = 307) were compared in part 1 of the study. The sensitivity of
the panel was 88% for detection of culture-proven nocardial infections, and
specificity was 85% (excluding cross-reactive leprosy cases). In part 2, no
difference in seropositivity was found when PD patients were compared with their
age- and gender-matched controls (n = 140). We found a high exposure rate of
humans to nocardial antigens, especially among men and older individuals. Our
results offer no support to the hypothesis that Nocardia spp. are causative in
PD; however, it is possible that serological testing may not be optimal for
detection of nocardial central nervous system infection.
PMCID: 228573
PMID: 8567923 [PubMed - indexed for MEDLINE]
127. Neurology. 1995 Oct;45(10):1903-6.
Erythrocyte thiolmethyltransferase: another failed marker for Alzheimer's and
Parkinson's diseases.
Hurwitz A, Hubble JP, Glatt SL, Koller WC, Pollack J.
Department of Medicine, University of Kansas Medical Center, Kansas City
66160-7320, USA.
Comment in:
Neurology. 1996 Sep;47(3):849-50.
There are reports that patients with Parkinson's disease (PD) and Alzheimer's
disease (AD) have reduced levels of thiolmethyltransferase (TMT) in erythrocyte
membranes. TMT methylates thiols and thiocarbamates, thereby reducing their
toxicity. We examined TMT levels in erythrocytes from patients with PD and AD and
from age-matched controls. Specific activities of TMT were 564 +/- 199 U/mg
protein in PD (n = 32), 513 +/- 118 in AD (n = 13), and 565 +/- 183 in controls
(n = 35). There was no difference between any of the groups (p = 0.64). We failed
to confirm TMT as a marker for neurodegenerative diseases or for this metabolic
defect predisposing to susceptibility to neurotoxins.
PMID: 7477990 [PubMed - indexed for MEDLINE]
128. J Am Diet Assoc. 1995 Sep;95(9):979-83.
Weight change and body composition in patients with Parkinson's disease.
Beyer PL, Palarino MY, Michalek D, Busenbark K, Koller WC.
Department of Dietetics and Nutrition, University of Kansas Medical Center,
Kansas City 66160-7250, USA.
OBJECTIVE: To compare reports of weight loss and actual measures of body
composition to predict nutritional risk in patients with Parkinson's disease and
matched control subjects. DESIGN: Patients and control subjects were asked to
record prior changes in weight and activity. Body composition was then compared
in both groups using percentage ideal body weight (IBW), body mass index (BMI),
triceps skinfold (TSF) thickness, midarm muscle circumference, and percentage
body fat (BF) as determined by bioelectrical impedance. SUBJECTS: Fifty-one
free-living patients with Parkinson's disease and 49 matched control subjects
were recruited from the neurology clinic and the surrounding area. MAIN OUTCOME
MEASURES: We anticipated that reported weight loss would be greater and actual
measures of body composition would show greater nutritional risk in the patients
with Parkinson's disease. STATISTICAL ANALYSES PERFORMED: chi 2 Analysis was used
to determine differences in the ratio of patients and control subjects who lost
weight. Paired t tests were used to compare amount of weight change and measures
of body composition. Correlations were performed among measures of weight change,
body composition, and associated disease factors. RESULTS: Patients with
Parkinson's disease were four times more likely to report weight loss greater
than 10 lb than the matched control subjects (odds ratio > 4.2). Patients
reported a mean (+/- standard deviation) weight loss of 7.2 +/- 2.9 lb and
control subjects reported a mean weight gain of 2.1 +/- 1.6 lb (P < .01).
Percentage IBW (P < .02), BMI (P < .009), TSF thickness (P < .005), and
percentage BF (P < .022) were lower in patients. Significant correlations (P <
.01) were found between reported weight change and percentage IBW, BMI, TSF,
percentage BF, and stage of the disease. CONCLUSIONS/APPLICATION: Patients with
Parkinson's disease appear to be at greater nutritional risk than a matched
population. Simple screening and assessment tools can be used to detect
nutritional risk.
PMID: 7657912 [PubMed - indexed for MEDLINE]
129. Clin Neuropharmacol. 1995 Aug;18(4):338-47.
Pramipexole in patients with early Parkinson's disease.
Hubble JP, Koller WC, Cutler NR, Sramek JJ, Friedman J, Goetz C, Ranhosky A,
Korts D, Elvin A.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
We evaluated the efficacy, safety, tolerability, and pharmacokinetics of
pramipexole, a novel dopamine D2 receptor agonist, in early Parkinson's disease
(PD). The study design was a parallel, placebo-controlled trial using an
ascending dose of 4.5 mg/day pramipexole maximum. All subjects received
selegiline (10 mg/day) but were not treated with levodopa. Of the 55 subjects who
received at least one dose of the study medication, all but one, in the placebo
group, completed the trial, which was 9 weeks in duration. The primary efficacy
endpoints were changes in scores from baseline to final measurement on the
Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. The
pramipexole group had a significantly greater improvement (p = 0.002) than the
placebo group on UPDRS Part II (Activities of Daily Living). The change in score
from baseline to final measurement on UPDRS Part III (Motor Examination) was not
significantly different (p = 0.10) between the pramipexole and placebo groups,
although the trend favoured the pramipexole group. All subjects in both the
pramipexole and the placebo groups experienced one or more episodes of
asymptomatic orthostatic hypotension; there was no significant difference between
the pramipexole and the placebo groups in the number of subjects experiencing
symptomatic orthostatic hypotension. The adverse events profile of pramipexole
was similar, in general, to that of other dopamine receptor agonists. Plasma
pramipexole levels increased linearly with dose. Pramipexole appears to be
promising agent in the treatment of early PD.
PMID: 8665547 [PubMed - indexed for MEDLINE]
130. Arch Neurol. 1995 Aug;52(8):802-10.
Psychogenic parkinsonism.
Lang AE, Koller WC, Fahn S.
Department of Medicine (Neurology), University of Toronto, Ontario.
BACKGROUND: Parkinsonism resulting from a primary psychiatric disorder has not
been well characterized previously. We had been impressed that this was a rare
but definite cause of parkinsonism in patients presenting to our subspecialty
movement disorders clinics. OBJECTIVE: To define the clinical characteristics of
"psychogenic parkinsonism" to assist in the differentiation of these patients
from those with "organic" parkinsonian disorders. DESIGN: Retrospective chart
reviews of patients seen at three large movement disorders centers. PATIENTS:
Seven men and seven women were diagnosed as having "documented" or "clinically
established" psychogenic parkinsonism after repeated assessments. RESULTS: Tremor
(12 patients) was present at rest but continued without the usual transient
dampening on taking up a posture and persisted with action. Tremor frequency and
rhythmicity varied markedly. Tremor could often be entrained to the frequency of
other movements or subsided with distraction. Rigidity (six patients) had
features of voluntary resistance, often decreasing with distraction and/or
activating synkinetic movements in opposite limbs. Arm swing was usually
diminished or absent on the affected side; however, the arm could be held tightly
to the side or cradled in front of the patient. Slowness of movement (all 14
patients) usually lacked the typical decrementing amplitude feature of
bradykinesia. The slowness, ambulatory abnormalities, and postural instability
(12 patients) often had bizarre, inconsistent, or incongruous features.
Functional "give-way" weakness and nonorganic sensory disturbances were common
(10 patients). Spontaneous remissions and remissions with placebo treatment or
psychotherapy and response fluctuations related to unusual interventions were
occasionally seen (five patients). Underlying psychological factors varied
considerably. Most patients had been seen by several physicians and had undergone
multiple unrevealing investigations. Fluorodopa F 18 (F-dopa) positron emission
tomographic scanning yielded normal findings in three patients. Abnormal positron
emission tomographic scanning results in a fourth patient, whose signs and
symptoms had improved with psychotherapy and haloperidol therapy, emphasizes the
possibility that prominent psychogenic features may be superimposed on organic
parkinsonism in some patients. CONCLUSION: Psychogenic parkinsonism occurs
rarely. It is a diagnosis of exclusion that should be made only by physicians
with considerable experience in the care and treatment of patients with
parkinsonism.
PMID: 7639632 [PubMed - indexed for MEDLINE]
131. Cleve Clin J Med. 1995 Jul-Aug;62(4):212-7.
Dopamine agonists in the treatment of Parkinson's disease.
Pahwa R, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160,
USA.
Bromocriptine or pergolide can be used as initial monotherapy in Parkinson's
disease. When used as an adjuvant to levodopa therapy, these drugs can result in
clinical improvement and a decreased levodopa requirement. To avoid side effects,
the starting dosage should be low (1.25 mg per day of bromocriptine or 0.05 mg of
pergolide) and should be increased slowly. The standard daily dose of
bromocriptine ranges from 7.5 to 60 mg, and of pergolide, from 0.75 to 4 mg.
Combination therapy with low dosages of levodopa and a dopamine agonist may also
decrease the incidence of side effects of both agents.
PMID: 7641388 [PubMed - indexed for MEDLINE]
132. J Geriatr Psychiatry Neurol. 1995 Jul;8(3):184-8.
Differentiation of the dementias of Alzheimer's and Parkinson's disease with the
dementia rating scale.
Paolo AM, Tröster AI, Glatt SL, Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
The Mattis Dementia Rating Scale (DRS) was used to distinguish between 50
dementia of the Alzheimer's type (DAT) and 50 Parkinson's disease (PD) subjects
matched for age, education, and DRS total score. Despite a similar level of
overall cognitive impairment, the DAT group earned significantly lower scores
than did the PD group on the Memory subscale, while the PD group displayed lower
scores than did the DAT subjects on the Construction subscale. Ajackknifed,
stepwise, linear discriminant function using the five DRS subscales revealed that
the Memory, Construction, and Initiation subtests significantly distinguished the
groups. These results suggest qualitative differences in the dementias of DAT and
PD patients and reveal that such differences can emerge on brief mental status
examinations.
PMID: 7576044 [PubMed - indexed for MEDLINE]
133. Mov Disord. 1995 Jul;10(4):527-8.
The core assessment program for intracerebral transplantation.
Lang AE, Benabid AL, Koller WC, Lozano AM, Obeso JA, Olanow CW, Pollak P.
Comment in:
Mov Disord. 1997 Jan;12(1):127-8.
Comment on:
Mov Disord. 1994 Jul;9(4):390-4.
PMID: 7565843 [PubMed - indexed for MEDLINE]
134. West J Med. 1995 Jun;162(6):510-3.
Tremor disorders. Diagnosis and management.
Anouti A, Koller WC.
Department of Neurology, School of Medicine, University of Kansas Medical Center,
Kansas City 66160-7314, USA.
Tremor is commonly encountered in medical practice, but can be difficult to
diagnose and manage. It is an involuntary rhythmic oscillation of a body part
produced by reciprocally innervated antagonist muscles. Tremors vary in frequency
and amplitude and are influenced by physiologic and psychological factors and
drugs. Categorization is based on position, posture, and the movement necessary
to elicit the tremor. A resting tremor occurs when the body part is in repose. A
postural tremor occurs with maintained posture and kinetic tremor with movement.
Various pathologic conditions are associated with tremors. Essential tremor,
which is the most common, is postural and kinetic, with a frequency between 4 and
8 Hz, and involves mainly the upper extremities and head. Essential tremor
responds to treatment with primidone, beta-blockers, and benzodiazepines.
Parkinson's disease causes a 4- to 6-Hz resting tremor in the arms and legs that
responds to the use of anticholinergics and a combination of carbidopa and
levodopa. Tremor can also be a manifestation of Wilson's disease, lesions of the
cerebellum and midbrain, peripheral neuropathy, trauma, alcohol, and conversion
disorders. Treatment should be directed to the underlying condition. Stereotactic
thalamotomy of thalamic stimulation is a last resort.
PMCID: 1022828
PMID: 7618310 [PubMed - indexed for MEDLINE]
135. Neurol Clin. 1995 May;13(2):283-97.
Psychogenic movement disorders.
Marjama J, Tröster AI, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
The diagnosis of PMDs is by no means a simple task. Organic movement disorders
are more often misdiagnosed as psychogenic rather than the reverse. The degree to
which psychological factors underlie movement disorders may range from being the
exclusive cause to being a reaction to the movement disorder. The most common
psychiatric illnesses associated with PMDs are depression, conversion reactions,
and anxiety disorders. Although the diagnosis of psychogenicity may seem elusive,
the definitions and diagnostic criteria of PMDs outlined in this article serve as
useful guidelines for obtaining a more accurate diagnosis. The emphasis on a
multidisciplinary approach with a strong alliance of neurologist and psychologist
or psychiatrist is essential to assure proper diagnoses and treatment.
PMID: 7643826 [PubMed - indexed for MEDLINE]
136. Neurology. 1995 Apr;45(4):822-4.
Botulinum toxin treatment of essential head tremor.
Pahwa R, Busenbark K, Swanson-Hyland EF, Dubinsky RM, Hubble JP, Gray C, Koller
WC.
Department of Neurology, University of Kansas, Medical Center, Kansas City 66160,
USA.
We examined in a double-blind, placebo-controlled study the effects of botulinum
toxin in 10 patients with essential head tremor. Each subject received two
treatments approximately 3 months apart, one with botulinum toxin injections and
another with normal saline injections into the sternocleidomastoid and splenius
capitis muscles. The subjects were assessed before each treatment and at 2, 4,
and 8 weeks after injections. There was moderate to marked improvement in
clinical ratings in five subjects after botulinum toxin injections and in one
subject after placebo. There was moderate to marked subjective improvement in
five patients with botulinum toxin as compared with three subjects with placebo.
Side effects were mild and transient. We conclude that botulinum toxin may be
useful for patients with essential head tremor who have failed to benefit from
oral medications.
PMID: 7723978 [PubMed - indexed for MEDLINE]
137. Neurology. 1995 Apr;45(4):672-6.
The influence of depression on cognition in Parkinson's disease: a pattern of
impairment distinguishable from Alzheimer's disease.
Tröster AI, Paolo AM, Lyons KE, Glatt SL, Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Conflicting reports about the effects of depression on cognition in Parkinson's
disease (PD) are difficult to interpret because they are based on small sample
sizes and confound depression with other variables. We found that a sample of 45
PD patients with current depression was cognitively more impaired than a sample
of 45 PD patients without current depression matched for age, education, gender,
age at disease onset, disease duration, and disease severity. The domains of
cognition impaired in the two PD groups (compared with 45 age-, education-, and
gender-matched controls) overlapped considerably, but only the depressed PD group
had impaired memory relative to the control group. Our comparison of 22 depressed
PD patients and 22 Alzheimer's disease (AD) patients matched for over-all
severity of cognitive impairment, age, education, and gender indicated that the
depressed PD group performed significantly worse on visuoconstructive tasks and
marginally worse on conceptualization tasks. In contrast, the AD group performed
significantly worse than the depressed PD group on memory tasks. Together, our
results suggest that depression has a negative impact on cognition (and, in
particular, memory) in PD, and that the pattern of this cognitive impairment is
distinguishable from that associated with AD.
PMID: 7723954 [PubMed - indexed for MEDLINE]
138. Ann Neurol. 1995 Feb;37(2):242-5.
Apolipoprotein E genotypes in Parkinson's disease with and without dementia.
Koller WC, Glatt SL, Hubble JP, Paolo A, Tröster AI, Handler MS, Horvat RT,
Martin C, Schmidt K, Karst A, et al.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor
influencing the development and age of onset of Alzheimer's disease. Because
Parkinson's disease shares many characteristics of Alzheimer's disease, we
studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease
patients with dementia and 61 patients without dementia. Dementia was determined
per National Institute of Neurological and Communicative Disorders and Stroke
criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was
defined as DRS > 132. Apo E genotype and allele frequencies did not differ
between demented and nondemented parkinsonian patients. Neither group's genotype
and allele frequencies differed from that of a nondemented population of 78
controls. We conclude that the Apo E epsilon 4 allele influences neither the
development of Parkinson's disease nor the dementia associated with Parkinson's
disease.
PMID: 7847865 [PubMed - indexed for MEDLINE]
139. Adv Neurol. 1995;65:43-8.
The parkinsonian personality.
Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
PMID: 7872151 [PubMed - indexed for MEDLINE]
140. J Geriatr Psychiatry Neurol. 1995 Jan;8(1):38-41.
Influence of demographic variables on the Dementia Rating Scale.
Paolo AM, Tröster AI, Glatt SL, Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314, USA.
Demographic characteristics influence many cognitive assessment tools. We
evaluated the impact of age, education, and gender on the Dementia Rating Scale
(DRS) in a sample of 212 normal people. Separate regression analyses revealed
that age was the most potent demographic factor, whereas education and gender had
little impact. However, the amount of variance accounted for by age was small
(less than 20%). Clinical utility of age-adjusted DRS total score cut-offs was
investigated in samples of Alzheimer's and Parkinson's disease patients. Hit rate
analysis revealed greater sensitivity for a single cut-off value than
age-corrected cut-off scores. Overall, these findings revealed the lack of a
clinically meaningful relationship between demographic characteristics and DRS
scores, suggesting that age, education, and gender can be ignored for
interpretative purposes based on cut-off scores.
PMID: 7710645 [PubMed - indexed for MEDLINE]
141. Neurology. 1994 Dec;44(12 Suppl 10):S1-52.
An algorithm for the management of Parkinson's disease.
Koller WC, Silver DE, Lieberman A.
Comment in:
Neurology. 1995 Dec;45(12):2301-2.
PMID: 7854513 [PubMed - indexed for MEDLINE]
142. Mov Disord. 1994 Nov;9(6):679-86.
Case 2, 1994: parkinsonism and cognitive impairment.
Gordon MF, Weiner WJ, Koller WC, Rao TH, Chehebar V, Dickson DW.
Department of Neurology, Long Island Jewish Medical Center, New Hyde Park, NY
11042.
PMID: 7845411 [PubMed - indexed for MEDLINE]
143. Neurology. 1994 Jul;44(7 Suppl 6):S23-8.
Treating motor fluctuations with controlled-release levodopa preparations.
Koller WC, Pahwa R.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
A major problem in the long-term treatment of Parkinson's disease with chronic,
intermittent levodopa therapy is fluctuations in motor response. Both peripheral
and central pharmacokinetic properties of levodopa are important in determining
the duration of response. The "wearing-off" phenomenon or "end-of-dose"
deterioration is related directly to the level of plasma levodopa. Therefore, a
principal strategy for the treatment of motor fluctuations has been the attempt
to prolong levodopa plasma levels with the use of long-acting, controlled-release
levodopa preparations. This paper reviews the available data on the two compounds
that are commercially available: benserazide-levodopa hydrodynamically balanced
system (Madopar HBS) and controlled-release carbidopa-levodopa (Sinemet CR).
PMID: 8047257 [PubMed - indexed for MEDLINE]
144. Ann Neurol. 1994 Jun;35(6):717-23.
The relationship of essential tremor to other movement disorders: report on 678
patients. Essential Tremor Study Group.
Koller WC, Busenbark K, Miner K.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
We examined 678 essential tremor patients in specialty, university, and private
practice clinics. The mean age of patients was 65.2 years with a similar number
of men and women. Six percent of patients were left-handed. A positive family
history of tremor was reported in more than 60% of patients. Alcohol ingestion
was reported to decrease tremor in 74% of patients who were cognizant of the
effect of alcohol on tremor. Mean age at tremor onset was 45.3 years. An earlier
onset of tremor was observed in those patients having a positive family history
of tremor. Tremor affected the hands in 90% of patients, head in 50%, voice in
30%, and legs and chin in 15%. Functional disability was common and impairment at
work occurred in 18%. Propranolol and primidone were the most frequently used
drugs and were effective in 40% of patients. Six and one-tenth percent of
essential tremor patients had concomitant Parkinson's disease, 6.9% had a
coexisting dystonia, and 1.8% had myoclonus. It is concluded that the frequency
of Parkinson's disease in essential tremor is more than would be reported in the
general population and that other movement disorders are infrequently observed in
essential tremor.
PMID: 8210229 [PubMed - indexed for MEDLINE]
145. Neurology. 1994 Mar;44(3 Suppl 1):S8-11.
Individualizing therapy in patients with disabling Parkinson's disease symptoms.
Calne DB, Duvoisin RC, Koller WC.
PMID: 8121579 [PubMed - indexed for MEDLINE]
146. Neurology. 1993 Nov;43(11):2382-4.
Essential tremor and dystonia.
Dubinsky RM, Gray CS, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
We reviewed the database of the Dystonia Clinic at the University of Kansas
Medical Center for patients with dystonia and tremor. Of 296 patients with
idiopathic dystonia, 24 had dystonic tremor, 20 with cervical dystonia had an
isolated head-nodding tremor, two patients with writer's cramp had ipsilateral
hand tremor, and two patients with generalized dystonia had arm tremor. Eight
patients, all with cervical dystonia, had essential tremor that preceded the
onset of their dystonia.
PMID: 8232962 [PubMed - indexed for MEDLINE]
147. J Nerv Ment Dis. 1993 Nov;181(11):657-62.
Personality and depression in Parkinson's disease.
Hubble JP, Venkatesh R, Hassanein RE, Gray C, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
The Parkinson's disease (PD) patient has been characterized as having a
distinctive personality with introverted features. These personality traits are
said to predate motor symptoms and are theorized to serve as a subtle clue to
latent PD. To examine this hypothesis, we compared remote and current personality
features in 35 PD subjects and 35 controls. Subjects' spouses completed a
personality inventory (PI) characterizing patients' premorbid and current status.
The premorbid PI of PD subjects differed from that of controls in being more
"quiet," "generous," "cautious," and "even-tempered," and less "flexible." The
characterization of the PD subjects' current personality differed greatly from
reported premorbid personality features, i.e., significant change in 13 of 24 PI
items. Personality inventory responses regarding both the PD subjects' premorbid
and current personality correlated to symptoms of depression and disease
severity. Cognition, tobacco use, alcohol consumption, and rural versus urban
residency did not correlate with PI responses. We conclude that PD patients are
apt to be viewed as introverts premorbidly, and, with disease onset, more
striking personality changes are recognized. These perceptions appear to be
closely linked to depressed affect and correlate with motor impairment to a
lesser extent.
PMID: 8228945 [PubMed - indexed for MEDLINE]
148. Neurology. 1993 Sep;43(9):1693-7.
Risk factors for Parkinson's disease.
Hubble JP, Cao T, Hassanein RE, Neuberger JS, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
Comment in:
Neurology. 1993 Sep;43(9):1641-3. Neurology. 1994 Aug;44(8):1557-8.
Parkinson's disease (PD) has been associated with rural living, well-water
consumption, and pesticide exposure; however, the individual risk contribution of
these variables has not been established. We examined social and medical
histories of predominantly rural populations to determine relative risk factors
for PD. Patients and controls were surveyed regarding residency, occupation,
medical history, and social and dietary habits. An initial multiple logistic
regression model was confounded by excessive variable colinearity. Principal
factor analysis yielded three factors: rural living (including years of rural
residency and ground-water use), pesticide use, and male lifestyle (male gender,
head trauma, male-dominated occupations). Other variables did not load in factor
analysis and were entered separately, with the three factor scores, in a second
multiple logistic regression model. Significant predictors of PD emerged (in
order of strength): pesticide use, family history of neurologic disease, and
history of depression. The predicted probability of PD was 92.3% (odds ratio =
12.0) with all three predictors positive. Pesticide use (distinguishable from
rural living) can be considered a risk factor for the development of PD, with
family history of neurologic disease and history of depression serving as weaker
predictors of PD.
PMID: 8414014 [PubMed - indexed for MEDLINE]
149. Mov Disord. 1993 Jul;8(3):380-2.
Interactive video conferencing: a means of providing interim care to Parkinson's
disease patients.
Hubble JP, Pahwa R, Michalek DK, Thomas C, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
Inequity in health care delivery is attributable to a variety of factors
including geographic isolation. Patients living far from major urban centers have
limited access to medical specialists. In the instance of Parkinson's disease
(PD), optimal assessment and care may depend upon availability of specialty
health care providers. In order to broaden health care access, interactive video
conference (IVC) units are being developed for medical use. IVC allows a patient
at a distant site to be "seen and heard" by a hospital-based physician;
simultaneously, the patient can "see and hear" the doctor. To establish the
validity of this technology in the evaluation of PD, nine patients were
independently examined and scored (UPDRS) by two movement disorder specialists.
One examination was performed in-person by the usual physician. The other
examination was performed on the same day via IVC over a distance of 350 miles by
an examiner previously unfamiliar with the patients. Individual patient scores
did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS
total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A
standardized exit interview was conducted to assess patients' perceptions of this
application of video technology. Responses were favorable and virtually all
patients viewed this as a means of accessing better health care. We conclude that
valid motor assessments of PD patients can be made via IVC.
PMID: 8341308 [PubMed - indexed for MEDLINE]
150. Neurology. 1993 Jun;43(6):1159-61.
Identical twins with similar onset of Parkinson's disease: a case report.
Pahwa R, Busenbark K, Gray C, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66160.
The role of heredity in Parkinson's disease (PD) is controversial. We report a
pair of monozygotic twins (confirmed by DNA fingerprints) concordant for PD.
Their disease began when they were 62 and 63 years old. Both patients presented
with left-side bradykinesia. One of the twins had a long history of depression.
Both patients had typical manifestations of PD, which were responsive to
dopaminergic therapy. The similar age of onset along with the similar clinical
characteristics of these twins suggests that hereditary or genetic susceptibility
may be important in the etiology of PD.
PMID: 8170561 [PubMed - indexed for MEDLINE]
151. Neurology. 1993 Apr;43(4):677-81.
Clinical experience with controlled-release carbidopa/levodopa in Parkinson's
disease.
Pahwa R, Busenbark K, Huber SJ, Michalek D, Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
Comment in:
Neurology. 1993 Dec;43(12):2728-9.
We converted 158 Parkinson's disease (PD) patients on stable doses of standard
carbidopa/levodopa (Std-L) to controlled-release carbidopa/levodopa (L-CR). Of
the 141 patients who completed the study, 103 (73%) preferred L-CR, 26 (18.5%)
preferred Std-L, and 12 (8.5%) had no preference. One hundred fourteen patients
elected to continue L-CR, and we performed the primary data analysis on this
group. Following conversion to L-CR, patients reported an increase in length of
benefit from each dose and an increased "kick-in" time. There was a decrease in
the total number of doses, "off" periods, sleep interruptions per night, dose
failures, and sleep disturbances. Conversion to L-CR resulted in a significant
increase in total levodopa dose. There was no significant change in the
dyskinesias. However, early-morning dystonia resolved in eight of 14 patients.
Our findings suggest that L-CR is particularly effective in decreasing motor
fluctuations, reducing nocturnal problems, and minimizing levodopa dose failures
in PD.
PMID: 8469321 [PubMed - indexed for MEDLINE]
152. Clin Neuropharmacol. 1993 Feb;16(1):83-7.
Effects of selegiline dosing on motor fluctuations in Parkinson's disease.
Hubble JP, Koller WC, Waters C.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
To examine selegiline's dosing effects, we studied 16 Parkinson disease patients
with motor fluctuations in a double-blind, crossover trial of selegiline at 0, 5,
and 10 mg daily. Patients' motor diaries, disability scores, and walking speed
were marginally improved, with no advantage of 10 mg over 5 mg found. We conclude
that in patients with motor fluctuations, selegiline provides modest symptomatic
effects, with daily dosing of 5 mg being indistinguishable from 10 mg.
PMID: 8422661 [PubMed - indexed for MEDLINE]
153. Clin Neuropharmacol. 1993 Feb;16(1):30-5.
Is there a relationship between Parkinson's disease and essential tremor?
Pahwa R, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
The issue of whether there is a relationship between essential tremor (ET) and
Parkinson's disease (PD) is controversial partly due to the confusion regarding
the accurate diagnosis of these conditions. The presence of postural tremor,
which often occurs in PD, by itself is insufficient for the diagnosis of ET. Most
epidemiological studies have shown that there is no association between these two
conditions. Some studies, but not others have found a higher prevalence of tremor
in family members of PD patients. Clinical, positron emission tomography scan,
and neuropathological data have failed to show any relationship between these two
conditions. It is concluded that there is no relationship between ET and PD and
that when these two conditions are seen in the same patient, this represents a
chance occurrence of two common diseases.
PMID: 8422655 [PubMed - indexed for MEDLINE]
154. Mov Disord. 1992 Oct;7(4):370-2.
Hemiballism and tremor due to ependymal cyst.
Bejar JM, Kepes J, Koller WC.
Neurology Service, Colmery-O'Neil VA Medical Center, Topeka, Kansas 66622.
A 21-year-old woman was admitted with right hemiballism and tremor. She had
tremor since the age of 6 years. At age 12, an intracerebral, left
paraventricular space-occupying lesion was found and treated with 4,500 rads.
Increasing tremor was associated with mass enlargement. By age 20, there was
insidious presentation of right hemiballism. At age 21, she had craniotomy and a
large septate cyst was opened and drained. Biopsy of the cyst wall revealed that
it was consistent with ependymal cyst. Postoperatively the hemiballism resolved
and the tremor improved. This case is unusual due to the presentation of
hemiballism caused by ependymal cyst.
PMID: 1484535 [PubMed - indexed for MEDLINE]
155. Neurology. 1992 Sep;42(9):1807-8.
Metabolism of glucurolactone to glucarate in Parkinson's disease.
Koller WC, Rope SD, Huber SJ, Blumenthal DC, Blumenthal HJ.
Department of Neurology, University of Kansas Medical Center, Kansas City
66160-7314.
The metabolism of oral glucurolactone to serum D-glucarate by the hepatic
cytochrome P450 enzyme system was no different in 20 untreated Parkinson's
disease (PD) patients as compared with 20 age- and sex-matched controls. There
was no evidence for a deficit in hepatic enzymes in PD.
PMID: 1513472 [PubMed - indexed for MEDLINE]
156. Neurology. 1992 Aug;42(8):1631-2.
Olfactory function in essential tremor.
Busenbark KL, Huber SJ, Greer G, Pahwa R, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Olfactory function, assessed by the University of Pennsylvania Smell
Identification Test, was normal in essential tremor (ET) patients and
significantly reduced in patients with Parkinson's disease (PD). This finding
further supports a lack of association between ET and PD.
PMID: 1641163 [PubMed - indexed for MEDLINE]
157. Curr Opin Neurol Neurosurg. 1992 Jun;5(3):321-3.
Non-parkinsonian tremor.
Hopfensperger K, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City.
Tremor may be seen not only in association with Parkinson's disease but also as
an idiopathic disorder or in association with a variety of neurologic diseases.
Our knowledge of these associations and of effective treatments for various types
of tremor has increased.
PMID: 1623258 [PubMed - indexed for MEDLINE]
158. Clin Neuropharmacol. 1992 Apr;15(2):81-7.
Classification of essential tremor.
Koller WC, Busenbark K, Gray C, Hassanein RS, Dubinsky R.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Classification of essential tremor was attempted using tremor frequency; tremor
duration; family history of tremor; responsiveness to alcohol, propranolol, and
primidone; muscle contraction pattern; and long-latency reflexes. Sixty-one
patients were evaluated. The majority of patients had a tremor frequency less
than 7.0 Hz, a positive family history, and a positive response to alcohol.
Approximately 46% of patients had a beneficial response with propranolol and 71%
with primidone. Tremor frequency was inversely correlated with age and directly
correlated with an antagonist pattern of muscle contraction. Enhanced
long-latency reflexes were not found. Other characteristics of essential tremor
were not significantly correlated. It is concluded that essential tremor can not
be classified into subtypes.
PMID: 1591741 [PubMed - indexed for MEDLINE]
159. Neurology. 1992 Apr;42(4 Suppl 4):27-31; discussion 41-8.
When does Parkinson's disease begin?
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
A long preclinical or asymptomatic period may occur in Parkinson's disease (PD).
Many long-latency parkinsonian syndromes exist. The presence of early-life risk
factors is consistent with a long prodromal period. Marked degeneration of the
substantia nigra and loss of striatal dopamine are necessary before clinical
symptoms develop. Lewy bodies, the histological hallmark of PD, occur in 10% of
normal individuals over age 50. Clinical symptoms develop slowly and are often
intermittent in early PD. Nonmotor signs, eg, depression or sensory changes,
often precede motor signs by many years. Reduction of striatal dopamine can be
detected with PET in "at-risk" asymptomatic individuals. Individual sensitivity
to drug-induced parkinsonism also suggests a preclinical state. Biologic markers
may eventually be able to detect preclinical PD.
PMID: 1350072 [PubMed - indexed for MEDLINE]
160. Neurology. 1992 Jan;42(1 Suppl 1):6-16; discussion 57-60.
How accurately can Parkinson's disease be diagnosed?
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
The clinical picture of Parkinson's disease (PD) can be so varied that absolute
clinical diagnosis may not always be possible. Several diverse entities
(including toxins, pharmacologic agents, and multisystem atrophies and other
degenerative diseases) can produce clinical syndromes almost indistinguishable
from those of PD. Nevertheless, a sufficient number of guiding criteria--such as
the presence of at least two of three motor signs (tremor, bradykinesia, and
rigidity), persistence of these signs for several years, and responsiveness to
levodopa--may serve to clarify and specify diagnosis, at least until such time as
a biologic marker of PD is discovered. However, currently the clinical diagnosis
of PD remains difficult.
PMID: 1549203 [PubMed - indexed for MEDLINE]
161. Neurology. 1992 Jan;42(1 Suppl 1):4-5; discussion 57-60.
Controlled-release carbidopa-levodopa: old drug--new drug. Introduction.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 1549200 [PubMed - indexed for MEDLINE]
162. Neurology. 1992 Jan;42(1 Suppl 1):33-8; discussion 57-60.
Initiating treatment of Parkinson's disease.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City, KS
66103.
Treatment of Parkinson's disease (PD) can be divided into two categories:
symptomatic therapy (restoring dopamine levels toward normal and reversing
functional disability) and preventive therapy (interfering with the
pathophysiologic mechanism of PD to prevent or decrease the rate of progression
of the disease). Regarding symptomatic treatment, although anticholinergic
preparations generally are considered effective for the symptoms of tremor and
rigidity without altering bradykinesia, their effectiveness is limited and
adverse reactions are common; their role should be restricted to use as adjuvants
to levodopa therapy. Amantadine has been shown to be as effective as
anticholinergics, but it lacks long-term efficacy. Dopamine
agonists--bromocriptine, pergolide mesylate and lisuride in Europe--are not as
effective as levodopa and therefore rarely are used as initial therapy; their
proposed role, too, is as adjuvants to levodopa therapy. Levodopa is the most
effective drug presently available for the treatment of PD; its introduction is
accompanied by rapid and dramatic reduction of symptoms and signs. Initial
adverse reactions are not usually a major problem; and although there is
speculation that initiation of therapy should be delayed because of possible
long-term complications, clinically distinguishing these from problems related to
disease progression itself is difficult. The possibility that nigral cell death
is mediated by oxidative mechanisms provides the basis for considering
antioxidant therapy as protective treatment; selegiline, an antioxidant, has been
found to delay the need for symptomatic therapy. It is suggested that initial
treatment of Parkinson's disease begin with both preventive therapy with
selegiline and symptomatic treatment with the sustained-release preparation of
levodopa, which may be associated with fewer long-term complications.
PMID: 1347909 [PubMed - indexed for MEDLINE]
163. Neurology. 1991 Dec;41(12):1982-3.
Is essential tremor benign?
Busenbark KL, Nash J, Nash S, Hubble JP, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
We analyzed the results of the Sickness Impact Profile, a self-reporting measure
of sickness-related dysfunction in 753 essential tremor (ET) patients, 87
controls from the general population, and 145 patients with Parkinson's disease
(PD). Compared with the general population, ET patients had significantly greater
dysfunction in all but one category. Communication, Work, Emotional Behavior,
Home Management, and Recreation and Pastimes were particularly impaired in ET.
The PD patients had significantly higher dysfunction in all categories as
compared with ET patients. We conclude that significant disability can occur in
ET and, compared with PD, ET tends to be less severe but causes relatively
greater psychosocial dysfunction.
PMID: 1745359 [PubMed - indexed for MEDLINE]
164. Neurology. 1991 Nov;41(11):1719-22.
United Parkinson Foundation Neurotransplantation Registry on adrenal medullary
transplants: presurgical, and 1- and 2-year follow-up.
Goetz CG, Stebbins GT 3rd, Klawans HL, Koller WC, Grossman RG, Bakay RA, Penn RD.
Rush University.
Thirteen centers participated in a multicenter database with systematic
evaluation of US and Canadian patients who had adrenal medullary transplantation
for Parkinson's disease. This voluntary registry collected demographic, safety,
and efficacy data using the same scoring measures over a 2-year follow-up period.
Baseline data on 61 patients and 2-year follow-up data on 56 patients were
compared. Eighteen percent died during the study period, and one-half of these
deaths were related or questionably related to the surgery. Of the remaining 45
patients with data, global improvement, defined as an improved summed score of
the "on" and "off" motor and activities of daily living functions from the
Unified Parkinson's Disease Rating Scale, occurred in 32% of the patients at 2
years after surgery. At follow-up, significant group improvement persisted in the
amount of daily "on" time and the quality of "off" function, but other measures
were no better than baseline. When the global improvement calculation was based
on the total sample and included deaths and patients lost to follow-up as "not
improved," only 19% were improved 2 years after surgery. Twenty-two percent of
survivors had persistent psychiatric morbidity not present prior to surgery.
These data document a modest group improvement in "off" function after
neurotransplantation, but a serious level of mortality and morbidity.
PMID: 1944898 [PubMed - indexed for MEDLINE]
165. Mayo Clin Proc. 1991 Oct;66(10):1085-7.
A new drug for treatment of essential tremor? Time will tell.
Koller WC.
Comment on:
Mayo Clin Proc. 1991 Oct;66(10):991-7.
PMID: 1921492 [PubMed - indexed for MEDLINE]
166. Clin Neuropharmacol. 1991 Aug;14(4):322-9.
Effect of MK-458 (HPMC) in Parkinson's disease previously untreated with
dopaminergic drugs. A double-blind, placebo-controlled multicenter study.
Koller WC, Block GA, Ahlskog JE, Ahrens S, Cedarbaum JM, Cyhan G, Goetz CG,
LeWitt PA, Liss C, McLean L, et al.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Ninety-four patients with early Parkinson's disease were investigated in a
double-blind, placebo-controlled evaluation of MK-458 [hydroxypropyl
methylcellulose/lactose matrix (HPMC)], a sustained release formulation of a
novel naphthoxazine compound with selective D-2 dopamine receptor agonism.
Patients were previously untreated with dopaminergic drugs. Efficacy was assessed
by clinical rating scales and by patient self-evaluation. MK-458 (HPMC) caused a
significant decrease in most parkinsonian symptoms. Though disability rating
scores were lowered by the drug, the scores did not differ significantly from
placebo. However, statistically significant improvement occurred with MK-458
(HPMC) on both the physician and the patient global assessments. Adverse
reactions such as nausea and vomiting, sedation, confusion, and hallucinations
occurred more with MK-458 (HPMC) than with placebo. MK-458 (HPMC) possesses
antiparkinsonian efficacy in early Parkinson's disease; however, side-effects are
frequently associated with its use. Selective D-2 receptor agonists, such as
MK-458 (HPMC), may not be the ideal treatment as monotherapy for Parkinson's
disease.
PMID: 1913699 [PubMed - indexed for MEDLINE]
167. Geriatrics. 1991 Aug;46 Suppl 1:8-15.
Does a long preclinical period occur in Parkinson's disease?
Koller WC, Langston JW, Hubble JP, Irwin I, Zack M, Golbe L, Forno L, Ellenberg
J, Kurland L, Ruttenber AJ, et al.
Department of Neurology, University of Kansas Medical Center, Kansas City.
PMID: 1894149 [PubMed - indexed for MEDLINE]
168. Geriatrics. 1991 Aug;46 Suppl 1:5-7.
Preclinical detection of Parkinson's disease. The next frontier: presymptomatic
detection. Introduction.
Langston JW, Koller WC.
California Parkinson's Foundation, San Jose.
PMID: 1894146 [PubMed - indexed for MEDLINE]
169. Postgrad Med. 1991 Jul;90(1):49-50, 55-6, 59.
Recognizing early Parkinson's disease.
Hopfensperger K, Koller WC.
University of Kansas School of Medicine, Department of Neurology, Kansas City,
66103.
Differential diagnosis of Parkinson's disease should cover not only the classic
disorder described by James Parkinson in 1817 (paralysis agitans) but also
numerous other idiopathic and secondary disorders that have varying degrees of
parkinsonian features. Because treatment options can vary greatly among mimicking
disorders and differ from those effective for Parkinson's disease, a prompt,
accurate diagnosis is essential. Physicians can distinguish between these
often-overlapping disorders by differentiating primary from secondary
parkinsonism and by classifying primary syndromes into disorders with prominent
tremor and those without.
PMID: 2062763 [PubMed - indexed for MEDLINE]
170. Clin Neuropharmacol. 1991 Jun;14(3):262-7.
Electromyographic guidance of botulinum toxin treatment in cervical dystonia.
Dubinsky RM, Gray CS, Vetere-Overfield B, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
We report the results of electromyographic (EMG) guidance in the treatment of
cervical dystonia with botulinum toxin. Eight-four patients received a total of
225 injection sessions. Overall there was moderate objective improvement in
78.7%. The mean dose of toxin was 269 +/- 39 mouse lethal units and the mean
duration of maximum effect was 107 +/- 49 days. Complications included excessive
neck weakness in 16.0% and dysphagia in 11.1% of the injection sessions. We
conclude that EMG guidance is a safe and effective method of administering
botulinum toxin in the treatment of cervical dystonia.
PMID: 2070367 [PubMed - indexed for MEDLINE]
171. Neurology. 1991 May;41(5 Suppl 2):8-13.
Does a long preclinical period occur in Parkinson's disease?
Koller WC, Langston JW, Hubble JP, Irwin I, Zack M, Golbe L, Forno L, Ellenberg
J, Kurland L, Ruttenber AJ, et al.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 2041599 [PubMed - indexed for MEDLINE]
172. Neurology. 1991 May;41(5 Suppl 2):5-7.
The next frontier in Parkinson's disease: presymptomatic detection.
Langston JW, Koller WC.
California Parkinson's Foundation, San Jose 95128.
PMID: 2041592 [PubMed - indexed for MEDLINE]
173. Neurology. 1991 Apr;41(4):517-20.
Driving in Parkinson's disease.
Dubinsky RM, Gray C, Husted D, Busenbark K, Vetere-Overfield B, Wiltfong D,
Parrish D, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Altered motor or mental skills in Parkinson's disease (PD) could adversely affect
driving ability. We interviewed 150 patients regarding their driving habits and
compared them with 100 controls. Thirty patients had stopped driving because of
PD. PD patients had no more lifetime accidents than controls. With increased
disability, however, there was a smaller percentage of patients still driving
with fewer miles traveled and with proportionately more accidents occurring.
Though disability scores did not correlate well with driving ability, there were
significantly more accidents in subjects with more severe PD. The presence of
cognitive impairment was associated with an increased accident rate. We conclude
that driving in PD may be a public health problem and that some PD patients
should not drive.
PMID: 2011249 [PubMed - indexed for MEDLINE]
174. Arch Neurol. 1991 Mar;48(3):287-9.
Environmental risk factors in siblings with Parkinson's disease.
Wong GF, Gray CS, Hassanein RS, Koller WC.
Department of Neurology, Kansas City 66103.
To investigate possible risk factors in Parkinson's disease, we conducted a
case-controlled study of 19 families having two or more siblings with Parkinson's
disease. Demographic data were collected, including lifetime histories of places
of residence; sources of drinking water; occupations, such as farming; and
exposure to herbicides and pesticides. Rural living and drinking well water, but
not farming and herbicide exposure, were significantly increased in 38
parkinsonians compared with 38 normal control subjects. A comparison of
parkinsonian siblings with siblings with essential tremor revealed no differences
in any risk factors for the years of shared environment. These data suggest that
living in a rural environment and drinking well water are risk factors for
Parkinson's disease and that the total life exposure to an environmental toxin
may be more important than exposure in early life.
PMID: 2001187 [PubMed - indexed for MEDLINE]
175. Arch Neurol. 1991 Feb;48(2):221-3.
Posttraumatic torticollis.
Truong DD, Dubinsky R, Hermanowicz N, Olson WL, Silverman B, Koller WC.
Department of Neurology, University of California, Irvine, Orange 92668.
We report six cases of torticollis precipitated by neck trauma. The dystonia
began 1 to 4 days after the trauma and differed clinically from idiopathic
torticollis by marked limitation of range of motion, lack of improvement after
sleep ("honeymoon period"), and absence of geste antagonistique. Worsening with
action was not present; nor was there improvement with support as seen with
idiopathic torticollis. Onset of pain immediately after the trauma and marked
spasms of the paracervical muscles were other predominant features.
Anticholinergic therapy was without benefit; however, some improvement occurred
with botulinum toxin injection. It is concluded that torticollis can be caused by
peripheral trauma and that it has unique clinical characteristics.
PMID: 1993013 [PubMed - indexed for MEDLINE]
176. Crit Care Med. 1991 Feb;19(2):181-6.
High incidence of cardiopulmonary complications associated with implantation of
adrenal medullary tissue into the caudate nucleus in patients with advanced
neurologic disease.
Waxman MJ, Morantz RA, Koller WC, Paone DB, Nelson PW.
Kansas City Pulmonary Clinic, MO 64132.
OBJECTIVE: The purpose of our study was to examine the cardiopulmonary
complications of a group of patients who had undergone implantation of adrenal
medullary tissue into the caudate nucleus for treatment of neurologic disease.
DESIGN: Prospective study with partially matched historical controls. SETTING:
Tertiary care community medical center. PATIENTS AND METHODS: Seven patients with
advanced Parkinson's disease and three patients with progressive supranuclear
palsy underwent implantation of adrenal medullary tissue into the caudate
nucleus. These patients were compared with respect to their cardiopulmonary
complications with a control group who had undergone craniotomy and then compared
with a control group who had undergone only abdominal surgery. RESULTS: In the
study group, six patients developed major postoperative complications including
development of large pleural effusions, lobar atelectasis, pneumonia, upper
airway obstruction, and cardiac arrest. Three patients had minor complications
including development of small pleural effusions, subsegmental atelectasis,
purulent bronchitis, mild congestive heart failure, and atrial
flutter/fibrillation. One patient had an unremarkable postoperative course. The
first control group, whose only surgery was a craniotomy, had only one major
complication. The second control group, the abdominal surgery control group, had
one major and five minor complications. CONCLUSION: The particular neurologic
disease, its severity, and the type of surgery performed appear to be causative
factors in the high incidence of complications in the study group.
PMID: 1989756 [PubMed - indexed for MEDLINE]
177. Clin Neuropharmacol. 1990 Oct;13(5):461-3.
Sexual dysfunction in Parkinson's disease.
Koller WC, Vetere-Overfield B, Williamson A, Busenbark K, Nash J, Parrish D.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Sexual functioning was investigated in 50 parkinsonian male and female patients
using a questionnaire. A loss of sexual interest and functioning was reported in
a high percentage of patients. Depression was not prevalent but 70% had some
evidence of autonomic nervous system dysfunction that may be related to sexual
dysfunction. It is concluded that the sexual function is frequently impaired in
Parkinson's disease.
PMID: 2272026 [PubMed - indexed for MEDLINE]
178. Neurology. 1990 Oct;40(10 Suppl 3):suppl 40-7; discussion 47-9.
Levodopa therapy in Parkinson's disease.
Koller WC, Hubble JP.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 2215973 [PubMed - indexed for MEDLINE]
179. Neurology. 1990 Oct;40(10 Suppl 3):suppl 58-60.
Selegiline HC1: Selective MAO-type B inhibitor.
Koller WC, Giron LT Jr.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 2120616 [PubMed - indexed for MEDLINE]
180. Neurology. 1990 Jun;40(6):897-900.
Parkinsonism due to a basal ganglia lacunar state: clinicopathologic correlation.
Murrow RW, Schweiger GD, Kepes JJ, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
We report a patient with a clinical syndrome indistinguishable from Parkinson's
disease in which postmortem examination revealed extensive lacunar infarction of
the basal ganglia without evidence of coexistent Parkinson's disease. This case
provides pathologic confirmation of the concept of vascular parkinsonism.
PMID: 2345612 [PubMed - indexed for MEDLINE]
181. Hosp Pract (Off Ed). 1990 May 30;25(5A):23, 26-7, 30-1.
Evaluation of tremor disorders.
Koller WC.
Department of Neurology, University of Kansas School of Medicine, Kansas City.
PMID: 2111823 [PubMed - indexed for MEDLINE]
182. Prog Brain Res. 1990;82:611-7.
United Parkinson Foundation Neurotransplantation Registry: multicenter US and
Canadian data base, presurgical and 12 month follow-up.
Goetz CG, Stebbins GT 3rd, Klawans HL, Koller WC, Grossman RG, Bakay RA, Penn RD.
PMID: 2290962 [PubMed - indexed for MEDLINE]
183. Adv Neurol. 1990;53:559-65.
Adrenal neural transplants in Parkinson's disease.
Koller WC, Waxman M, Morantz R.
Department of Neurology, University of Kansas Medical Center, Kansas City.
PMID: 2239496 [PubMed - indexed for MEDLINE]
184. Adv Neurol. 1990;53:271-5.
Psychogenic tremors.
Koller WC, Findley LJ.
Deparment of Neurology, University of Kansas Medical Center, Kansas City, 66103.
PMID: 2239465 [PubMed - indexed for MEDLINE]
185. Neurology. 1990 Jan;40(1):62-6.
Post-traumatic midbrain tremors.
Samie MR, Selhorst JB, Koller WC.
Department of Neurology, University of Buffalo, State University of New York.
We report 3 patients with post-traumatic tremor and describe the characteristics
of the tremor and accompanying neurologic signs. Radiographic and pathologic
examination indicated a contralateral midbrain localization of the lesion. The
tremor responded to anticholinergic or dopaminergic therapy.
PMID: 1967492 [PubMed - indexed for MEDLINE]
186. Clin Neuropharmacol. 1989 Dec;12(6):453-82.
Essential tremor.
Hubble JP, Busenbark KL, Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 2691068 [PubMed - indexed for MEDLINE]
187. Neurology. 1989 Dec;39(12):1587-8.
Acute and chronic effects of propranolol and primidone in essential tremor.
Koller WC, Vetere-Overfield B.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
We studied the acute and chronic effects of propranolol and primidone in
essential tremor by administering long-acting propranolol (80 to 160 mg/d) and
primidone (50 to 250 mg/d) to 50 patients. We evaluated patients at 1, 3, 6, 9,
and 12 months after treatment and assessed tremor by subjective rating by
patients, clinical scoring, and thermographic (accelerometer) recordings. Acute
adverse reactions occurred in 8% with propranolol and 32% with primidone.
Propranolol was without therapeutic effect in 30%, and 32% had no benefit from
primidone. Significant chronic side effects occurred in 17% taking propranolol
and in 0% with primidone. Tolerance to drug effect occurred with chronic
treatment in 12.5% of patients with propranolol and 13.0% with primidone. We
conclude that propranolol and primidone are effective long-term treatment for
some patients with essential tremor. Acute adverse reactions with primidone and
side effects with chronic use of propranolol hamper therapy.
PMID: 2586774 [PubMed - indexed for MEDLINE]
188. Clin Neuropharmacol. 1989 Aug;12(4):293-7.
Tremors in early Parkinson's disease.
Koller WC, Vetere-Overfield B, Barter R.
Department of Neurology, University of Kansas Medical School, Kansas City.
We examined 50 untreated parkinsonian patients with a complaint of tremor for the
presence of a resting, postural, or kinetic tremor. Tremors were recorded by an
accelerometer to determine amplitude and frequency. A postural tremor was present
in 92% and a resting tremor in 76%. The amplitude of postural tremor was greater
than resting tremor in 50%, the same in 25%, and less in 25%. The average tremor
frequency of resting and postural tremor was not significantly different.
Carbidopa/levodopa reduced testing tremor in 58% and postural tremor in 46% of
patients. The dopamine agonist naxoglide (PHNO) reduced resting tremor in 77% and
postural tremor in 70% of patients. Postural tremor was not worsened by either
drug. It is concluded that tremors in both the resting and postural positions are
an integral part of the symptoms of Parkinson's disease and that both tremors
have a similar frequency and pharmacological responsiveness in the early phases
of the disease.
PMID: 2804993 [PubMed - indexed for MEDLINE]
189. Neurology. 1989 Aug;39(8):1066-8.
Autologous adrenal medullary transplant in progressive supranuclear palsy.
Koller WC, Morantz R, Vetere-Overfield B, Waxman M.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
We transplanted autologous adrenal medullary cells to the caudate nucleus in 3
patients with progressive supranuclear palsy, using the method Madrazo has
employed for neural transplantation in Parkinson's disease. Major and minor
complications occurred post-operatively from which the patients recovered. One
patient had a marked improvement in his postural stability and a decreased
incidence of falling. This change was evident at 1 month after surgery and has
remained for the 6 months of follow-up. Postural reflexes were not altered in the
other 2 patients. There was no change in extraocular movements, speech, or the
rigid-bradykinetic features of parkinsonism in any patient. Adrenal medullary
transplantation has only limited efficacy in progressive supranuclear palsy.
PMID: 2761701 [PubMed - indexed for MEDLINE]
190. Geriatrics. 1989 May;44(5):33-6, 41.
Tremor disorders of aging: diagnosis and management.
Koller WC, Huber SJ.
Department of Neurology, University of Kansas Medical Center, Kansas City.
Tremor disorders are commonly encountered in the elderly. Physiological tremor is
present in all of us and may be enhanced by drugs or other circumstances to cause
symptomatic dysfunction. Essential tremor consists of postural and kinetic
tremors which may involve the hands, head, and voice. Approximately 50% of cases
are hereditary. Significant disability may occur. Propranolol and primidone
provide effective treatment for some patients. The tremor of Parkinson's disease
occurs in resting and postural positions. Treatment with levodopa usually reduces
the tremor. Anticholinergics may also decrease tremor but often cause mental side
effects in the elderly. Disturbances of the cerebellum may cause a kinetic tremor
of the extremities or shakiness of the trunk. Tremors may also occur on a
psychogenic basis. Proper classification of tremor disorder will lead to
appropriate diagnosis and, often, effective treatment.
PMID: 2651214 [PubMed - indexed for MEDLINE]
191. Clin Neuropharmacol. 1989 Apr;12(2):98-105.
Falls and Parkinson's disease.
Koller WC, Glatt S, Vetere-Overfield B, Hassanein R.
Department of Neurology, Kansas University Medical Center, Kansas City 66103.
One hundred patients with Parkinson's disease (PD) and five patients with
progressive supranuclear palsy were questioned about the frequency,
circumstances, and consequences of falling. Parkinsonian symptoms were scored
using the unified rating scale. Thirty-eight percent of parkinsonian patients
fell, and 13% fell more than once a week. Broken bones (13%), hospitalization
(18%), confinement to wheelchair (3%), and fear of walking occurred. Postural
hypotension was uncommon and did not correlate to falling. Sensory loss,
dementia, heart disease, and the use of antihypertensive medications were not
related to falling. Falling did correlate with postural instability,
bradykinesia, and rigidity but not with tremor. Falling was also related to age
and duration of disease. The frequency of falling was correlated only to the
severity of one parkinsonian symptom, postural instability. Progressive
supranuclear palsy patients fell often and had marked postural instability.
Factor analysis of parkinsonian characteristics yielded three groups, with tremor
being an independent symptom. Frequent fallers and postural instability were not
changed by dopaminergic therapy. Some fallers with gait difficulties and
bradykinesia were improved with levodopa. Physical therapy was also of benefit to
some patients. It is concluded that falling is a common problem in PD and may
cause serious disability. Falling may be related to all the major motor signs
except for tremor. Frequent falling is caused by postural instability, which is
not reversible with dopaminergic therapy.
PMID: 2720700 [PubMed - indexed for MEDLINE]
192. Clin Neuropharmacol. 1989 Apr;12(2):134-7.
Tradozone in essential tremor. Probe of serotoninergic mechanisms.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 2655897 [PubMed - indexed for MEDLINE]
193. Neurology. 1989 Mar;39(3):457.
Task-specific dystonias.
Koller WC.
PMID: 2927668 [PubMed - indexed for MEDLINE]
194. N Engl J Med. 1989 Feb 9;320(6):337-41.
Multicenter study of autologous adrenal medullary transplantation to the corpus
striatum in patients with advanced Parkinson's disease.
Goetz CG, Olanow CW, Koller WC, Penn RD, Cahill D, Morantz R, Stebbins G, Tanner
CM, Klawans HL, Shannon KM.
Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center,
Chicago, IL 60612.
Comment in:
N Engl J Med. 1989 Aug 3;321(5):324-7.
In 19 patients with severe Parkinson's disease, we replicated the surgical
procedures developed by Madrazo et al. for transplantation of the adrenal medulla
to the striatum, and followed them for six months after operation. We monitored
their motor function with the use of standardized scales and determined the
amount and quality of "on" and "off" time (the hours of the waking day when the
antiparkinsonian medications were effective and ineffective, respectively). We
found significant improvement in focal areas of motor function. The mean
percentage of on time during the day increased from 47.6 percent to 75.0 percent
(P = 0.012); the mean percentage of on time without chorea increased from 26.6
percent to 59.2 percent (P = 0.006); the mean severity of off time decreased as
assessed by both the Activities of Daily Living subscale of the Unified
Parkinson's Disease Scale (P = 0.002) and the Schwab and England scale (P =
0.037). In contrast to the finding of Madrazo et al., however, the dosages of
antiparkinsonian medications could not be decreased and postoperative morbidity
was substantial. Despite cautious optimism, we conclude that the widespread use
of this procedure outside of research centers is premature, since the improvement
we found was slighter than in the previous cases.
PMID: 2643770 [PubMed - indexed for MEDLINE]
195. Neurology. 1989 Jan;39(1):149-50.
Usefulness of a writing aid in writer's cramp.
Koller WC, Vetere-Overfield B.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Comment in:
Neurology. 1989 Oct;39(10):1404-5.
PMID: 2909904 [PubMed - indexed for MEDLINE]
196. Mov Disord. 1989;4(2):153-6.
Volitional control of involuntary movements.
Koller WC, Biary NM.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
Voluntary suppressibility of abnormal movements is helpful in the classification
of movement disorders because this ability appears to be a common component of
tics. However, there has been no systematic study of voluntary suppressibility in
other movement disorders. We have therefore assessed 146 patients with tremors
and dyskinetic disorders as to their ability to suppress movements by mental
concentration. Patients were videotaped while trying to stop their movements, and
the length of time they could suppress their abnormal movements was recorded. One
hundred percent (10 of 10) of patients with tics could suppress movements for an
average of 2.5 min. Two percent (1 of 50) of essential tremor patients could
suppress the tremor, and the tremor of 24% (12 of 50) was made worse by mental
concentration. Eighty percent (4 of 5) of neuroleptic-induced tremor could be
improved mentally. Seventy percent (35 of 50) of patients with parkinsonian
tremor could voluntarily diminish their tremor for an average of 48 s. Fifty
percent (8 of 16) of chorea (tardive dyskinesia, Huntington's disease,
postencephalitic) was reduced. Dystonia was suppressible in 20% (3 of 15). It is
concluded that movement disorders besides tics can be voluntarily suppressed and
that suppressibility should not be used to classify movement disorders. Tics,
however, are easier to suppress and can be suppressed for a longer time.
PMID: 2733707 [PubMed - indexed for MEDLINE]
197. Mov Disord. 1989;4(1):20-36.
Posttraumatic movement disorders: a review.
Koller WC, Wong GF, Lang A.
Department of Neurology, University of Kansas Medical School, Kansas City.
PMID: 2648136 [PubMed - indexed for MEDLINE]
198. Clin Neuropharmacol. 1988 Jun;11(3):282-6.
Nicotine and tremor.
Zdonczyk D, Royse V, Koller WC.
Department of Neurology, Loyola-Hines Medical Center, Chicago, Illinois.
PMID: 3401862 [PubMed - indexed for MEDLINE]
199. Clin Neuropharmacol. 1988 Jun;11(3):221-31.
D1 and D2 dopamine receptor mechanisms in dopaminergic behaviors.
Koller WC, Herbster G.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
SKF 38393, a selective D1 dopamine receptor agonist, was investigated when
administered alone and in combination with dopaminergic agonists in animal models
of extrapyramidal behavior. SKF 38393 did not induce stereotypy in normal rats
but enhanced apomorphine-induced stereotypy in a dose-dependent manner. SKF 38393
also augmented and altered the stereotypic response of dopaminergic agonists
(+)-4-propylhydronaphthoxazine quinpirole, and ciladopa. The addition of SKF
38393 with ciladopa changed the behavioral response of ciladopa from a partial to
a full agonist. SKF 38393 did not alter locomotor behavior; however, it augmented
the stimulatory but not the inhibitory response of apomorphine on locomotion. In
unilateral 6-hydroxydopamine-lesioned animals, SKF 38393 caused contralateral
rotation that were similar to those of other dopaminergic agonists. The addition
of SKF 38393 to both mixed D1/D2 (levodopa, pergolide) and selective D2 (PHNO,
quinpirole) dopamine agonists resulted in a synergistic rather than an additive
effect. No changes in behavior were observed in rats challenged with apomorphine
after being treated 21 days with SKF 38393, PHNO, SKF 38393 plus PHNO, or saline.
D1 agonism is capable of augmenting and altering dopaminergic behavior of both
mixed D1/D2 and D2 dopamine receptor agonists. A combination of D1 and D2
dopamine agonists may represent optimal drug treatment for Parkinson's disease.
PMID: 3261198 [PubMed - indexed for MEDLINE]
200. Adv Neurol. 1988;49:177-83.
Idiopathic oral-facial dyskinesia.
Koller WC.
Department of Neurology, University of Kansas Medical Center, Kansas City 66103.
PMID: 3278540 [PubMed - indexed for MEDLINE]
TITLE: Tremor-predominant Parkinson's disease. Approaches
to treatment [In Process Citation]
AUTHORS: Marjama-Lyons J; Koller W
AUTHOR AFFILIATION: Department of Neurology, University of
Florida, Jacksonville, USA. jm.lyons@jax.ufl.edu
SOURCE: Drugs Aging 2000 Apr;16(4):273-8
[MEDLINE record in process]
CITATION IDS: PMID: 10874522 UI: 20332696
ABSTRACT: Parkinson's disease is a neurodegenerative disorder
that manifests clinically with variable degrees of tremor, muscle
rigidity, bradykinesia and postural instability.
Tremor-predominant Parkinson's disease is characterised by
prominent tremor of one or more limbs with a relative lack of
significant rigidity and bradykinesia. Despite the lack of other
disabling motor symptoms, the tremor of tremor-predominant
Parkinson's disease can be very disabling, especially if a
postural and kinetic component exists. A wide variety of
treatments for Parkinson's disease tremor are currently available
and include use of oral medications, injections with botulinum
toxin and neurosurgical procedures. Some of the first line
medications (levodopa, dopamine agonists, anticholinergics) are
very effective in controlling tremor. However, some patients with
Parkinson's disease tremors are unresponsive to first line drugs
and treatment with second line medications (clozapine,
amantadine, clonazepam, propranolol, neurontin) should be
attempted. In the small number of patients with disabling tremor
that is refractory to all medications, neurosurgical intervention
should be considered. Both thermocoagulation and deep brain
stimulation at several different neuroanatomical sites (thalamus,
globus pallidus, subthalamic nucleus) offer good to excellent
tremor control with relatively low risk to the patient.
2000/06
2000/30 11:00
--------------------------------------------------------------------------------
TITLE: Linear pharmacokinetic behavior of ropinirole
during multiple dosing in patients with Parkinson's disease [In
Process Citation]
AUTHORS: Hubble J; Koller WC; Atchison P; Taylor AC; Citerone DR;
Zussman BD; Friedman CJ; Hawker N
AUTHOR AFFILIATION: Ohio State University Parkinson's Disease
Center, Columbus 43210, USA.
SOURCE: J Clin Pharmacol 2000 Jun;40(6):641-6
[MEDLINE record in process]
CITATION IDS: PMID: 10868315 UI: 20326297
ABSTRACT: The objectives of this study were to measure the
pharmacokinetics of ropinirole at steady state when the drug is
used as an adjunct to L-dopa and evaluate the long-term
tolerability of ropinirole in this indication. Twenty-four
patients who were taking L-dopa for Parkinson's disease and
experiencing a lack of symptomatic control were recruited.
Patients received open-label adjunctive treatment with ropinirole
for up to 2 years. The starting dose was 0.5 mg bid, which could
be titrated to a maximum of 6.0 mg tid. Ropinirole demonstrated
approximately dose-linear pharmacokinetics at steady state;
corresponding values were higher during tid than bid dosing. A
reduction in mean L-dopa dose was maintained throughout the
trial. The combination of L-dopa and ropinirole was generally
well tolerated, with only 1 patient withdrawing from treatment
because of adverse events. Thus, ropinirole shows approximately
linear steady-state pharmacokinetics and a good safety profile
when administered with L-dopa.
2000/06
2000/27 11:00
--------------------------------------------------------------------------------
TITLE: Surgical treatment of essential tremor.
AUTHORS: Pahwa R; Lyons K; Koller WC
AUTHOR AFFILIATION: Department of Neurology, University of Kansas
Medical Center, Kansas City, Kansas 66160, USA.
SOURCE: Neurology 2000;54(11 Suppl 4):S39-44
CITATION IDS: PMID: 10854351 UI: 20312906
ABSTRACT: Surgical treatment for essential tremor (ET) has been
used since the early 1950s. Initially, different areas were
targeted for tremor control. However, the optimal target was
eventually determined to be the ventralis intermedius (VIM)
nucleus of the thalamus. Thalamotomy improves contralateral
tremor in more than 90% of patients. Long-term studies of
thalamotomy indicate that the benefits continue in most patients.
Persistent morbidity associated with thalamotomy, which occurs in
less than 10% of patients, includes dysarthria, dysequilibrium,
weakness, and cognitive impairment. Bilateral thalamotomy is
associated with substantial morbidity and is usually avoided.
Studies demonstrate that chronic stimulation of the VIM is safe
and effective for tremor. Adverse effects of chronic stimulation
include paresthesia, dysarthria, dysequilibrium, and localized
pain. In many patients, bilateral thalamic stimulation is
performed without a substantial increase in morbidity. ET
patients with disabling medication-resistant tremor are
reasonable candidates for these stereotactic procedures.
2000/07
2000/08 11:00
--------------------------------------------------------------------------------
TITLE: Pharmacologic treatment of essential tremor.
AUTHORS: Koller WC; Hristova A; Brin M
AUTHOR AFFILIATION: Department of Neurology, University of Miami
School of Medicine, Miami, Florida 33136, USA.
SOURCE: Neurology 2000;54(11 Suppl 4):S30-8
CITATION IDS: PMID: 10854350 UI: 20312905
ABSTRACT: Essential tremor (ET) is a common movement disorder
that often causes functional disability, potentially leading to
physical and emotional difficulties. The paucity of data
available regarding the underlying pathophysiologic mechanism of
ET hinders the development of innovative approaches to
pharmacotherapeutic treatments. Options for drug therapy include
the use of primidone, beta-adrenergic blockers, such as
propranolol, alcohol, and other drugs, such as benzodiazepines,
gabapentin, carbonic anhydrase inhibitors, clozapine,
flunarizine, clonidine, and the methylxanthine derivative
theophylline. Chemodenervation with botulinum toxin type A may be
a therapeutic option for selected patients with ET. Each drug is
classified as to the quality of evidence for efficacy and the
suggested strength of therapeutic recommendation. In general
clinical practice, primidone and propranolol have proven efficacy
in ET.
2000/07
2000/08 11:00
--------------------------------------------------------------------------------
TITLE: Essential tremor: clinical characteristics.
AUTHORS: Jankovic J
AUTHOR AFFILIATION: Department of Neurology, Baylor College of
Medicine, Houston, Texas 77030, USA.
SOURCE: Neurology 2000;54(11 Suppl 4):S21-5
CITATION IDS: PMID: 10854348 UI: 20312903
ABSTRACT: Essential tremor (ET) is the most common movement
disorder. However, only a small percentage of people affected by
this genetically transmitted neurologic disorder seek medical
attention. Lack of consensus on the diagnostic criteria for ET is
an impediment to accurate diagnosis and leads to difficulty in
accessing accurate prevalence data. Although a positive family
history, alcohol sensitivity, and propranolol responsiveness are
characteristic of ET, these factors should not be considered
necessary for the diagnosis of ET. ET can produce substantial
physical and psychosocial disabilities. The occasional
coexistence of ET and Parkinson's disease (PD) in the same
individual may present a diagnostic challenge.
2000/07
2000/08 11:00
--------------------------------------------------------------------------------
TITLE: Motor initiation and execution in essential tremor
and Parkinson's disease [In Process Citation]
AUTHORS: Montgomery EB Jr; Baker KB; Lyons K; Koller WC
AUTHOR AFFILIATION: Department of Neurology, Lerner Research
Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
SOURCE: Mov Disord 2000 May;15(3):511-5
[MEDLINE record in process]
CITATION IDS: PMID: 10830417 UI: 20289229
ABSTRACT: Clinical differentiation of essential tremor (ET) from
idiopathic Parkinson's disease (iPD) is based on the lack of
akinesia and bradykinesia. Nevertheless, early tremor-predominant
iPD often is difficult to distinguish from ET. Motor initiation
and execution in ET, iPD, and normal control (NC) subjects were
investigated. Individuals with iPD, ET and NC performed a
reaction-time wrist flexion and extension task. Motor
performances were similar between ET and iPD and both were
different than normal control subjects. Both the patients with
iPD and ET had longer reaction times and slower movement
velocities than NC subjects. This may help to explain some of the
difficulties in distinguishing patients with these two diseases.
The similarities of motor performance suggest that while ET and
iPD may be separate disease entities, they may share similar
pathogenic motor mechanisms from the perspective of an integrated
motor system that drives the motor cortex.
2000/06
2000/01 09:00
--------------------------------------------------------------------------------
TITLE: Time course of loss of clinical benefit following
withdrawal of levodopa/carbidopa and bromocriptine in early
Parkinson' s disease [In Process Citation]
AUTHORS: Hauser RA; Koller WC; Hubble JP; Malapira T; Busenbark
K; Olanow CW
AUTHOR AFFILIATION: Parkinson's Disease and Movement Disorders
Center, University of South Florida, Tampa 33606, USA.
SOURCE: Mov Disord 2000 May;15(3):485-9
[MEDLINE record in process]
CITATION IDS: PMID: 10830413 UI: 20289225
ABSTRACT: Putative neuroprotective agents for Parkinson's disease
can be assessed in untreated patients using progression of
clinical disability as an index of disease progression. To avoid
the confound associated with symptomatic therapy, progression of
the underlying disease can be assessed by evaluating the
progression of clinical disability from an untreated baseline to
a final visit following wash-out of symptomatic medication. In
this type of analysis it is critical to use a washout of
sufficient duration to ensure elimination of symptomatic effects.
To assess the time course of resolution of symptomatic effects,
we evaluated 31 patients at days 1, 8, and 15 following
discontinuation of levodopa/carbidopa and bromocriptine. Mean
total Unified Parkinson's Disease Rating Scale scores (+/-
standard error) increased (worsened) by 7.4+/-1.5 from day 1 to
day 15 (p <0.0001), 4.5+/-1.2 from day 1 to day 8 (p =
0.0009), and 2.9+/-1.0 from day 8 to day 15 (p = 0.01). We
conclude that a wash-out of at least 2 weeks is required to
eliminate the symptomatic effects of levodopa/carbidopa and
bromocriptine in patients with early Parkinson's disease.
2000/06
2000/01 09:00
--------------------------------------------------------------------------------
TITLE: The behavioral complications of pallidal
stimulation: a case report.
AUTHORS: Miyawaki E; Perlmutter JS; Troster AI; Videen TO; Koller
WC
AUTHOR AFFILIATION: Department of Neurology, The University of
Kansas Medical Center, Kansas City, KS 66160-7314, USA.
emiyawak@kumc.edu
SOURCE: Brain Cogn 2000 Apr;42(3):417-34
CITATION IDS: PMID: 10753488 UI: 20218810
ABSTRACT: We report a case of recurrent manic episodes associated
with chronic deep brain stimulation (DBS) targeting globus
pallidus (GP) in the treatment of Parkinson's disease (PD).
Cardinal PD symptoms and dyskinesia improved with DBS, and
neuropsychological testing found improvements in visuospatial
measures associated with left DBS and in verbal memory with right
DBS when compared to the patient's preoperative baseline. Under
conditions of right, left, and bilateral DBS, the patient
experienced bouts of mania and hypomania lasting several days at
a time. Positron emission tomography (PET) with (15)O-labeled
water was performed after his first manic episode under four
conditions: no stimulation, right DBS, left DBS, and bilateral
DBS. Although no manic switch occurred during the course of the
PET study, all three DBS conditions were associated with
decreases in regional flow in the left parahippocampus and
hippocampus and right mid-cingulate gyrus. Increases in flow in
left inferior frontal area, bilateral insula, dorsolateral
prefrontal cortex, and cuneus were common to all DBS conditions.
GP stimulation in PD may be associated with behavioral and
cognitive effects. Distributed blood flow changes observed with
pallidal DBS support a role for the pallidum in cognition and
affective regulation. Copyright 2000 Academic Press.
2000/06
2000/08 09:00
--------------------------------------------------------------------------------
TITLE: Health-related quality of life in Parkinson's
disease after pallidotomy and deep brain stimulation.
AUTHORS: Straits-Troster K; Fields JA; Wilkinson SB; Pahwa R;
Lyons KE; Koller WC; Troster AI
AUTHOR AFFILIATION: Department of Veterans Affairs Medical
Center, Kansas City, USA. troster@kansas-city.va.gov
SOURCE: Brain Cogn 2000 Apr;42(3):399-416
CITATION IDS: PMID: 10753487 UI: 20218809
ABSTRACT: This study explored the multidimensional outcome of
three neurosurgical interventions for Parkinson's disease (PD):
pallidotomy (N = 23), pallidal deep brain stimulation (DBS) (N =
9), and thalamic DBS (N = 7). All patients completed the Sickness
Impact Profile (SIP) and the Beck Depression Inventory.
Pallidotomy patients also completed the Profile of Mood States,
the Beck Anxiety Inventory, and a disease-specific quality of
life (QOL) measure, the Parkinson's Disease Questionnaire
(PDQ-39). Three months after surgery, all neurosurgical groups
showed significant improvements in mood and function, including
physical, psychosocial, and overall functioning. Pallidal DBS and
pallidotomy patients who completed additional QOL measures
reported decreased anxiety and tension, increased vigor, improved
mobility and ability to perform activities of daily living, and
decreased perceived stigma. Psychosocial dysfunction scores from
the SIP were related to depressed mood both at baseline (r = .42)
and at followup (r = .45), but the physical dysfunction subscale
was not related to mood at either time point, suggesting that
disruption of social relationships due to PD may have more impact
on affective distress than physical symptoms alone. Results
suggest that neurosurgical interventions for PD improve disabling
PD motor symptoms and also improve several domains of quality of
life. Copyright 2000 Academic Press.
2000/06
2000/08 09:00
Mov Disord 1999 Sep;14(5):847-50
Efficacy of unilateral deep brain stimulation of the VIM nucleus of the thalamus for essential head tremor.
Koller WC, Lyons KE, Wilkinson SB, Pahwa R
Department of Neurology, University of Kansas Medical Center, Kansas City 66160-7314, USA.
Essential tremor is a common movement disorder. Deep brain stimulation of the VIM nucleus of the thalamus has been reported to be efficacious for reducing essential hand tremor. The effect of deep brain stimulation of the thalamus on essential head tremor has not been well studied. Therefore, we evaluated the effect of DBS of the thalamus in 38 patients with essential head tremor. Head tremor scores prior to surgery were compared with scores at 3, 6, and 12 months postimplant with stimulation "on" and "off." The 3-month evaluations were blinded for 24 patients and all others were open-label. There was a significant improvement in head tremor at all postimplant evaluations compared with baseline. Essential head tremor can be reduced with deep brain stimulation of the VIM nucleus of the thalamus and, pending the results of other controlled trials, should be considered as a treatment option for patients with disabling essential head tremor unresponsive to medication.
PMID: 10495050, UI: 99423241
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