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Welcome to the Parkinson's
Disease File
Patients all over the world
have used the information in The Parkinson's Disease File since
1992, when the Center for Current Research—one of the first
80 companies on the Internet—was founded. Our highly trained
researchers (all of whom hold Ph.D.s) have searched the advanced
medical database at the National Library of Medicine and compiled
a comprehensive collection of research descriptions on Parkinson's
Disease and its care.
As you will see, the following research descriptions detail the
findings published in the most respected journals in the field.
Because the research descriptions are written in medical terms,
most people will bring all or parts of the Parkinson's Disease
File to their doctor for further explanation and discussion.
Often your doctor will have access to full-text articles and
other information that could be useful in planning a successful
course of treatment and prevention. Note that the titles of the
journals are abbreviated according to the National Library of
Medicine's format; your doctor can provide the full title if
you need it.
Thank you for accessing the Parkinson's Disease File. We truly
hope the information fosters better health.
Sincerely,
Gregory A. Fraser, Ph.D.
Director of Research
Important Note: The following information
is provided for your education. It should not be relied upon for
personal diagnosis or treatment. If you believe that a
particular therapy applies to you or someone you care about, be
sure to consult a doctor before trying it.
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Previous Parkinson's
Research: 2002-2006
The
Parkinson's Disease File
also contains summaries of past
research that has shown promise and may still be standard
practice among many physicians.
To
download earlier
research findings on
Parkinson's Disease, click
HERE.
Latest Research on
Parkinson's Disease
J Med Chem. 2008 Aug 14;51(15):4581-8. Epub 2008 Jul 24.
Design, synthesis and biological evaluation of glutathione
peptidomimetics as components of anti-Parkinson prodrugs.
More SS, Vince R.
Department of Medicinal Chemistry, Center for Drug Design, Academic Health
Center, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
55455, USA.
Plethoras of CNS-active drugs fail to effect their pharmacologic response due to
their in vivo inability to cross the blood-brain barrier (BBB). The classical
prodrug approach to overcome this frailty involves lipophilic derivatives of the
polar drug, but we herein report a novel approach by which endogenous
transporters at BBB are exploited for brain drug delivery. The crucial role
played by glutathione in pathogenesis of Parkinson's and the presence of its
influx transporters at the basolateral membrane of BBB served as the basis for
our anti-Parkinson prodrug design strategy. A metabolically stable analogue of
glutathione is used as a carrier for delivery of dopamine and adamantamine. An
account of successful syntheses of these prodrugs along with their transport
characteristics and stability determination is discussed.
------
Hum Genet. 2008 Aug;124(1):95-9. Epub 2008 Jun 29.
Replication of association between ELAVL4 and Parkinson disease:
the GenePD study.
DeStefano AL, Latourelle J, Lew MF, Suchowersky O, Klein C, Golbe LI, Mark MH,
Growdon JH, Wooten GF, Watts R, Guttman M, Racette BA, Perlmutter JS, Marlor L,
Shill HA, Singer C, Goldwurm S, Pezzoli G, Saint-Hilaire MH, Hendricks AE, Gower
A, Williamson S, Nagle MW, Wilk JB, Massood T, Huskey KW, Baker KB, Itin I,
Litvan I, Nicholson G, Corbett A, Nance M, Drasby E, Isaacson S, Burn DJ,
Chinnery PF, Pramstaller PP, Al-Hinti J, Moller AT, Ostergaard K, Sherman SJ,
Roxburgh R, Snow B, Slevin JT, Cambi F, Gusella JF, Myers RH.
Department of Biostatistics, Boston University School of Public Health, 715
Albany Street, Crosstown Center, 3rd floor, Boston, MA 02118, USA. adestef@bu.edu
Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4
(ELAVL4) have been reported to be associated with onset age of Parkinson disease
(PD) or risk for PD affection in Caucasian populations. In the current study we
genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study
sample consisting of 712 PD patients and 312 unrelated controls from the GenePD
study. The minor allele of rs967582 was associated with increased risk of PD
(odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor
allele of rs967582 was also the risk allele for PD affection or earlier onset
age in the previously studied populations. This replication of association with
rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility
gene.
------
Hum Genet. 2008 Aug;124(1):89-94. Epub 2008 Jun 22.
Calbindin 1, fibroblast growth factor 20, and alpha-synuclein in
sporadic Parkinson's disease.
Mizuta I, Tsunoda T, Satake W, Nakabayashi Y, Watanabe M, Takeda A, Hasegawa K,
Nakashima K, Yamamoto M, Hattori N, Murata M, Toda T.
Division of Clinical Genetics, Department of Medical Genetics, Osaka University
Graduate School of Medicine, 2-2-B9 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Parkinson's disease (PD), one of the most common human neurodegenerative
disorders, is characterized by the loss of dopaminergic neurons in the
substantia nigra of the midbrain. Our recent case-control association study of
268 SNPs in 121 candidate genes identified alpha-synuclein (SNCA) as a
susceptibility gene for sporadic PD (P = 1.7 x 10(-11)). We also replicated the
association of fibroblast growth factor 20 (FGF20) with PD (P = 0.0089). To find
other susceptibility genes, we added 34 SNPs to the previous screen. Of 302 SNPs
in a total 137 genes, but excluding SNCA, SNPs in NDUFV2, FGF2, CALB1 and B2M
showed significant association (P < 0.01; 882 cases and 938 control subjects).
We replicated the association analysis for these SNPs in a second independent
sample set (521 cases and 1,003 control subjects). One SNP, rs1805874 in
calbindin 1 (CALB1), showed significance in both analyses (P = 7.1 x 10(-5);
recessive model). When the analysis was stratified relative to the SNCA
genotype, the odds ratio of CALB1 tended to increase according to the number of
protective alleles in SNCA. In contrast, FGF20 was significant only in the
subgroup of SNCA homozygote of risk allele. CALB1 is a calcium-binding protein
that widely is expressed in neurons. A relative sparing of CALB1-positive
dopaminergic neurons is observed in PD brains, compared with CALB1-negative
neurons. Our genetic analysis suggests that CALB1 is associated with PD
independently of SNCA, and that FGF20 is associated with PD synergistically with
SNCA.
------
Eur J Neurol. 2008 Jul;15(7):643-8.
Levodopa/DDCI and entacapone is the preferred treatment for
Parkinson's disease patients with motor fluctuations in routine practice: a
retrospective, observational analysis of a large French cohort.
Damier P, Viallet F, Ziegler M, Bourdeix I, Rerat K.
INSERM, CIC04, Nantes, France and CHU Nantes, Clinique Neurologique, Nantes,
France. philippe.damier@chu-nantes.fr
Levodopa is the gold standard drug for the symptomatic control of Parkinson's
disease (PD). However, long-term treatment with conventional formulations [levodopa
and a dopa decarboxylase inhibitor (DDCI)], is associated with re-emergence of
symptoms because of wearing-off and dyskinesia. Treatment with levodopa/DDCI and
entacapone extends the half-life of levodopa, avoiding deep troughs in levodopa
plasma levels and providing more continuous delivery of levodopa to the brain.
In this open-label, retrospective, observational study we investigated the
effects of levodopa/DDCI and entacapone therapy in 800 PD patients with motor
fluctuations. Levodopa/DDCI and entacapone treatment was assessed as good/very
good in improving motor fluctuations (64%) and activities of daily living (ADL;
62%). The therapeutic utility was considered to be good/very good in 70% of
cases. Moreover, there was a reduction in levodopa dose in 20% of patients.
Neurologists preferred levodopa/DDCI and entacapone compared with increasing
levodopa dosage, dose-fractionation or addition of a dopamine agonist (63%, 29%
and 23% of patients respectively). Reasons included achieving more continuous
dopaminergic stimulation (40%), reducing motor fluctuations (54%) and improving
ADL (41%). This analysis reveals the preference of neurologists for levodopa/DDCI
and entacapone over conventional levodopa-modification strategies for the
effective treatment of PD motor fluctuations in clinical practice.
------
J Neurosurg. 2008 Jul;109(1):133-9.
Motor cortex stimulation in patients with Parkinson disease:
12-month follow-up in 4 patients.
Arle JE, Apetauerova D, Zani J, Deletis DV, Penney DL, Hoit D, Gould C, Shils JL.
Department of Neurosurgery, Lahey Clinic, Burlington, Massachusetts 01805, USA.
jeffrey.arle@lahey.org
OBJECT: Since the initial 1991 report by Tsubokawa et al., stimulation of the M1
region of cortex has been used to treat chronic pain conditions and a variety of
movement disorders. METHODS: A Medline search of the literature published
between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex
stimulation (MCS) was used. Of these, 72 were related to a movement disorder.
More recently, up to 16 patients specifically with Parkinson disease were
treated with MCS, and a variety of results were reported. In this report the
authors describe 4 patients who were treated with extradural MCS. RESULTS:
Although there were benefits seen within the first 6 months in Unified
Parkinson's Disease Rating Scale Part III scores (decreased by 60%), tremor was
only modestly managed with MCS in this group, and most benefits seen initially
were lost by the end of 12 months. CONCLUSIONS: Although there have been some
positive findings using MCS for Parkinson disease, a larger study may be needed
to better determine if it should be pursued as an alternative surgical treatment
to DBS.
------
Neurogastroenterol Motil. 2008 Jul;20(7):741-9.
Parkinson's disease and the gut: a well known clinical
association in need of an effective cure and explanation.
Natale G, Pasquali L, Ruggieri S, Paparelli A, Fornai F.
Department of Human Morphology and Applied Biology, University of Pisa, Italy.
Parkinson's disease (PD) is a neurodegenerative disorder which leads to severe
movement impairment; however, Parkinsonian patients frequently suffer from
gastrointestinal (GI) problems which at present are poorly understood, scarcely
investigated, and lack an effective cure. Traditionally, PD is attributed to the
loss of mesencephalic dopamine-containing neurons; nonetheless, additional
nuclei, such as the dorsal motor nucleus of the vagus nerve and specific central
noradrenergic nuclei, are now identified as targets of PD. While the effects of
PD on the somatic motor systems are well characterized, the influence on the
digestive system still needs to be clarified. Recent findings demonstrate the
occurrence of pathological alterations within peripheral neuronal networks in
the GI tract of Parkinsonian patients. However, it remains unclear whether a
real cell loss occurs, and whether this happens specifically for a subclass of
autonomic neurons or if it reflects the sole loss of autonomic nerves. This
review summarizes the neurochemical and morphological changes which might be
responsible for impaired GI motility. Moreover, we focus on the experimental
models to reproduce the altered digestive system of Parkinsonian patients since
an experimental model able to mimic such features of PD is required. In the last
part of the manuscript, we suggest potential therapeutic targets.
------
Bull Soc Sci Med Grand Duche Luxemb. 2008;(2):217-57.
Brain repair how stem cells are changing neurology.
Modo M.
Centre for the Cellular Basis of Behaviour, Kings College London, Institute of
Psychiatry, London, UK. mike.modo@iop.kcl.ac.uk
The concept that everything can die, but nothing can regenerate in the brain has
been replaced with new hope that stem cells will provide avenues to repair the
damaged central nervous system (CNS). The treatment of brain damage has been
demonstrated preclinically using a variety of stem cell sources. The
prototypical cell that gives rise to the CNS is the neural stem cell (NSC). NSCs
differentiate into site-appropriate phenotypes when transplanted into the damage
brain and can recover lost functions. In some cases, cells can be
pre-differentiated into a particular neuronal phenotype, such as dopaminergic
cells, that can then be transplanted ectopically to promote behavioural
improvements in conditions like Parkinson's disease. Early clinical studies in
PD have demonstrated the proof of principle that this approach can improve
neurodegenerative disease. The current review will discuss the different sources
of stem cells in their preclinical and clinical application, as well as
providing an overview as to the issues that need to be addressed to ensure a
successful translation from bench to bedside.
------
Curr Clin Pharmacol. 2007 Sep;2(3):234-43.
The pharmacokinetics and pharmacodynamics of levodopa in the
treatment of Parkinson's disease.
Khor SP, Hsu A.
Clinical Pharmacokinetics and Pharmacodynamics, IMPAX Laboratories, Inc.
Hayward, CA, USA.
Levodopa, a prodrug of dopamine, remains to be one of the main drugs in the
treatment of Parkinson's disease. All current levodopa products are formulated
with aromatic amino acid decarboxylase inhibitors such as carbidopa or
benserazide to prevent the metabolism of levodopa in the gastrointestinal tract
and systemic circulation. Levodopa pharmacokinetic profiles remain unchanged
after multiple doses, and are similar between healthy volunteers and patients
and among patients at different stages of disease. Entacapone inhibits the
metabolism of levodopa therefore increases the area under the plasma
concentration-time profile of levodopa; however, it may decrease the initial
absorption rate of levodopa in some patients probably due to competitive
absorption. Food appears to affect the absorption of levodopa, but its effects
vary with formulations. The results of positron emission tomography study
suggest that a high protein diet may compete with the uptake of levodopa into
the brain, therefore, may result in reduced levodopa effects. Since infusion
studies demonstrated that it is beneficial to maintain stable plasma
concentrations of levodopa, controlled-release formulations have been designed
to provide prolonged absorption of levodopa. However, subsequent pharmacokinetic
and pharmacodynamic studies demonstrated that a threshold concentration of
levodopa appears to be necessary to switch patients "on". Once patients are
turned "on", the duration of levodopa effects may be correlated with plasma
concentration of levodopa. As such, more recent studies have demonstrated
significant clinical benefits such as shorter time to "on" and longer duration
of "on" when combining the immediate- and controlled-release levodopa products
as compared to controlled-release levodopa products. Given these findings, it is
important for physicians to understand the relationship between the
pharmacokinetics and pharmacodynamics of levodopa in order to provide dosage
regimens that meet patient needs. The pharmacokinetics and pharmacodynamics data
of levodopa reported in the literature are reviewed here.
------
Lancet Neurol. 2008 Apr 1 [Epub ahead of print]
Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated
virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: an
open-label, phase I trial.
Marks WJ Jr, Ostrem JL, Verhagen L, Starr PA, Larson PS, Bakay RA, Taylor R,
Cahn-Weiner DA, Stoessl AJ, Olanow CW, Bartus RT.
Department of Neurology, University of California, San Francisco, San Francisco,
CA, USA.
BACKGROUND: There is an urgent need for therapies that slow or reverse the
progression of Parkinson's disease (PD). Neurotrophic factors can improve the
function of degenerating neurons and protect against further neurodegeneration,
and gene transfer might be a means to deliver effectively these factors to the
brain. The aim of this study was to assess the safety, tolerability, and
potential efficacy of gene delivery of the neurotrophic factor neurturin.
METHODS: In this phase I, open-label clinical trial, 12 patients aged 35-75
years with a diagnosis of PD for at least 5 years in accordance with the UK
Brain Bank Criteria received bilateral, stereotactic, intraputaminal injections
of adeno-associated virus serotype 2-neurturin (CERE-120). The first six
patients received doses of 1.3x10(11) vector genomes (vg)/patient, and the next
six patients received 5.4x10(11) vg/patient. This trial is registered with
ClinicalTrials.gov, number NCT00252850. FINDINGS: The procedure was well
tolerated. Extensive safety monitoring in all patients revealed no clinically
significant adverse events at 1 year. Several secondary measures of motor
function showed improvement at 1 year; for example, a mean improvement in the
off-medication motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRS)
of 14 points (SD 8; p=0.000121 [36% mean increase; p=0.000123]) and a mean
increase of 2.3 h (2; 25% group mean increase; p=0.0250) in on time without
troublesome dyskinesia were seen. Improvements in several secondary measures
were not significant, including the timed walking test in the off condition
(p=0.053), the Purdue pegboard test of hand dexterity (p=0.318), the reduction
in off time (p=0.105), and the activities of daily living subscore (part II) of
the UPDRS (p=0.080). (18)F-levodopa-uptake PET did not change after treatment
with either dose of CERE-120. INTERPRETATION: The initial data support the
safety, tolerability, and potential efficacy of CERE-120 as a possible treatment
for PD; however, these results must be viewed as preliminary until data from
blinded, controlled clinical trials are available. FUNDING: Ceregene; Michael J
Fox Foundation for Parkinson's Research.
-----
Clin Neuropharmacol. 2008 Mar-Apr;31(2):63-73.
Enteral levodopa/carbidopa infusion in advanced Parkinson
disease: long-term exposure.
Nyholm D, Lewander T, Johansson A, Lewitt PA, Lundqvist C, Aquilonius SM.
Department of Neuroscience, Neurology, Uppsala University Hospital, Uppsala,
Sweden. dag.nyholm@neurologi.uu.se
OBJECTIVES: In patients with advanced Parkinson disease, levodopa/carbidopa
formulated as a gel suspension (Duodopa) permits continuous delivery into the
small intestine using a portable pump, resulting in less variability in levodopa
concentrations and fewer motor fluctuations and dyskinesias than with oral
levodopa administration. This is a retrospective analysis of the long-term
clinical experience with this agent. METHODS: All but 1 of the patients who had
received enteral levodopa infusion treatment between January 1, 1991, and June
30, 2002, consented to a review of their hospital charts. RESULTS: Of the 65
patients with initial testing of the treatment, 86% opted for continued
treatment via percutaneous endoscopic gastrostomy or gastrojejunostomy. Total
exposure to levodopa infusion was 216 patient-years (mean, 3.7 years). Maximum
treatment duration was 10.7 years. Fifty-two patients were treated for 1 year or
longer. The adverse effect profile of levodopa/carbidopa infusion was similar to
that observed with oral administration of levodopa. Seven deaths occurred, all
considered unrelated to the treatment. Intestinal tube problems, including
dislocation of the intestinal tube to the stomach, were the most common
technical problem, occurring in 69% of the patients during the first year. The
optimal daily dose of levodopa decreased by an average of 5% during follow-up.
CONCLUSIONS: The safety of enteral infusion of levodopa/carbidopa formulated as
a gel suspension was found acceptable. For most patients, the technical
challenges posed by the enteral infusion system were offset by the improvement
in motor fluctuations and dyskinesias offered by this technique.
-----
Gait Posture. 2008 Mar 29 [Epub ahead of print]
Tai Chi improves balance and mobility in people with Parkinson
disease.
Hackney ME, Earhart GM.
Program in Physical Therapy, Washington University School of Medicine, St.
Louis, MO 63108, United States.
This pilot study examines the effects of Tai Chi on balance, gait and mobility
in people with Parkinson disease (PD). Thirty-three people with PD were randomly
assigned to either a Tai Chi group or a control group. The Tai Chi group
participated in 20 1-h long training sessions completed within 10-13 weeks;
whereas, the control group had two testing sessions between 10 and 13 weeks
apart without interposed training. The Tai Chi group improved more than the
control group on the Berg Balance Scale, UPDRS, Timed Up and Go, tandem stance
test, six-minute walk, and backward walking. Neither group improved in forward
walking or the one leg stance test. All Tai Chi participants reported
satisfaction with the program and improvements in well-being. Tai Chi appears to
be an appropriate, safe and effective form of exercise for some individuals with
mild-moderately severe PD.
-----
Parkinsonism Relat Disord. 2008 Mar 26 [Epub ahead of print]
Effectiveness of tai chi for Parkinson's disease: A critical
review.
Lee MS, Lam P, Ernst E.
Complementary Medicine, Peninsula Medical School, Universities of Exeter &
Plymouth, 25 Victoria Park Road, Exeter, Devon EX2 4NT, UK.
The objective of this review is to assess the effectiveness of tai chi as a
treatment option for Parkinson's disease (PD). We have searched the literature
using 21 databases from their inceptions to January 2008, without language
restrictions. We included all types of clinical studies regardless of their
design. Their methodological quality was assessed using the modified Jadad
score. Of the seven studies included, one randomised clinical trial (RCT) found
tai chi to be superior to conventional exercise in terms of the Unified PD
Rating Scale (UPDRS) and prevention of falls. Another RCT found no effects of
tai chi on locomotor ability compared with qigong. The third RCT failed to show
effects of tai chi on the UPDRS and the PD Questionnaires compared with wait
list control. The remaining studies were either non-randomised (n=1) or
uncontrolled clinical trials (n=3). Collectively these data show that RCTs of
the tai chi for PD are feasible but scarce. Most investigations suffer from
methodological flaws such as inadequate study design, poor reporting of results,
small sample size, and publication without appropriate peer review process. In
conclusion, the evidence is insufficient to suggest tai chi is an effective
intervention for PD. Further research is required to investigate whether there
are specific benefits of tai chi for people with PD, such as its potential
effect on balance and on the frequency of falls.
-----
CNS Spectr. 2008 Mar;13(3 Suppl 4):26-33.
Course, prognosis, and management of psychosis in Parkinson's
disease: are current treatments really effective?
Zahodne LB, Fernandez HH.
Department of Clinical and Health Psychology, University of Florida,
Gainesville, FL, USA.
It is essential to recognize and treat psychosis in Parkinson's disease for
several reasons. Studies have shown that psychosis in Parkinson's disease
patients is a strong risk factor for nursing home placement. Psychosis may be
the greatest source of stress for caretakers of Parkinson's patients; it is
often persistent, and its presence markedly increases mortality. Treatment of
psychotic symptoms should occur only after potential medical and environmental
causes of delirium have been eliminated or addressed. Initial pharmacologic
changes should include limiting the patient's antiparkinsonian medications to
those that are necessary to preserve motor function. Should that fail, an
atypical antipsychotic is presently the treatment of choice. An emerging
treatment option is acetylcholinesterase inhibitors. This article reviews what
is currently known about the course, prognosis, and treatment strategies in
Parkinson's disease psychosis.
-----
CNS Spectr. 2008 Mar;13(3 Suppl 4):18-25.
Psychosis in Parkinson's disease: phenomenology, frequency, risk
factors, and current understanding of pathophysiologic mechanisms.
Fénelon G.
Department of Neurology, Henri-Mondor Hospital, Créteil, France. gilles.fenelon@hmn.aphp.fr
Psychosis in Parkinson's disease refers to a combination of hallucinations and
delusions occurring with a clear sensorium and a chronic course. Hallucinations
may involve several sensory modalities. Complex visual hallucinations are the
most common type. "Minor" hallucinatory phenomena are frequently present and
include visual illusions, passage hallucinations, and sense of presence. Insight
may be lost in patients with cognitive impairment. Delusions of a paranoid type
are more rare than hallucinations. Both hallucinations and delusions are more
frequent in Parkinson's disease patients with dementia. Pathogenesis involves
complex and probably multifactorial mechanisms, including pharmacologic (dopaminergic
treatment and others) and disease-related factors.
-----
Rev Neurol. 2008 Mar 1-15;46(5):257-60.
[Rotigotine in the treatment of Parkinson's disease. A study on a
sample of 150 patients]
[Article in Spanish]
Ruiz-Huete C, Bermejo PE, Terrón C, Anciones B.
Unidad de Trastornos del Movimiento, Servicio de Neurología, Sanatorio Nuestra
Señora del Rosario, Hospital de La Zarzuela, Madrid, España.
INTRODUCTION: Rotigotine is a non-ergot dopamine agonist that has become the
first treatment for Parkinson's disease formulated as a transdermal release
system. Its side effects are very similar to those of other dopamine agonists,
as well as those deriving from the site of application, while its advantages
include a once-daily administration, the absence of interactions with foods and
steady levels in plasma. AIM: To determine the frequency of and reasons for
withdrawing rotigotine in 150 consecutive patients diagnosed with Parkinson's
disease. PATIENTS AND METHODS: A retrospective analysis was carried out using
the database at our Movement Disorders Unit in order to identify the first 150
patients who were treated with rotigotine. Only patients with Parkinson's
disease who were free of intracranial lesions, psychiatric pathologies or
dementia were eligible for inclusion in the sample. Patients were evaluated
before and at two, four and six months after beginning treatment with rotigotine.
RESULTS: In all, 85 males and 65 females were identified. A total of 110 of them
had previously been treated with dopamine agonists. Although 12% of the patients
dropped out, 88% of them continued the treatment. The reasons for withdrawing
were worsening of the clinical condition (12 patients), lack of effectiveness
(three patients), drowsiness (two patients) and dyskinesias (one patient).
CONCLUSIONS: Rotigotine is safe and effective as medication in the treatment of
Parkinson's disease. The fact that most of the drop-outs were due to a worsening
of the clinical signs and symptoms after changing from another dopamine agonist
suggests the need for an equivalence between other agonists and rotigotine.
-----
Parkinsonism Relat Disord. 2008 Mar 12 [Epub ahead of print]
The persistent effects of unilateral pallidal and subthalamic
deep brain stimulation on force control in advanced Parkinson's patients.
Alberts JL, Okun MS, Vitek JL.
Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA;
Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA;
Cleveland FES Center, L. Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
The persistent effects of unilateral deep brain stimulation (DBS) of the globus
pallidus interna (GPi) or subthalamic nucleus (STN) on specific movement
parameters produced by Parkinson's disease (PD) patients are poorly understood.
The aim of this study was to determine the effects of unilateral GPi and STN DBS
on the force-producing capabilities of PD patients during maximal efforts and
functional bimanual dexterity. Clinical and biomechanical data were collected
from 14 unilaterally implanted patients (GPi=7; STN=7), at least 13months
post-DBS surgery, during On and Off stimulation in the absence of medication.
Unilateral DBS of either location produced a 33% improvement in UPDRS motor
scores. Significant gains in maximum force production were present in both limbs
during unimanual efforts. The greatest increase in maximum force, for both
limbs, was under bimanual conditions. Force in the contralateral limb increased
more than 30% during bimanual efforts while ipsilateral force increased by 25%.
Unilateral DBS improved grasping force control and consistency of digit
placement during the performance of a bimanual dexterity task. The clinical and
biomechanical data indicate that unilateral DBS of GPi or STN results in
persistent improvements in the control and coordination of grasping forces
during maximal efforts and functional dexterous actions. Unilateral DBS
implantation of either site should be considered an option for those patients in
which bilateral procedures are contraindicated.
-----
Neurosurg Focus. 2008;24(3-4):E6.
Recent advances in cell-based therapy for Parkinson disease.
Astradsson A, Cooper O, Vinuela A, Isacson O.
NINDS Udall Parkinson's Disease Research Center of Excellence, Harvard
University and McLean Hospital, Belmont, Massachusetts 02478, USA.
In this review, the authors discuss recent advances in the field of cell therapy
for Parkinson disease (PD). They compare and contrast recent clinical trials
using fetal dopaminergic neurons. They attribute differences in cell preparation
techniques, cell type specification, and immunosuppression as reasons for
variable outcome and for some of the side effects observed in these clinical
trials. To address ethical, practical, and technical issues related to the use
of fetal cell sources, alternative sources of therapeutic dopaminergic neurons
are being developed. The authors describe the progress in enrichment and
purification strategies of stem cell-derived dopaminergic midbrain neurons. They
conclude that recent advances in cell therapy for PD will create a viable
long-term treatment option for synaptic repair for this debilitating disease.
-----
Mov Disord. 2008 Jan 3 [Epub ahead of print]
Placebo influences on dyskinesia in Parkinson's disease.
Goetz CG, Laska E, Hicking C, Damier P, Müller T, Nutt J, Warren Olanow C,
Rascol O, Russ H.
Rush University Medical Center, Chicago, Illinois, USA.
Clinical features that are prognostic indicators of placebo response among
dyskinetic Parkinson's disease patients were determined. Placebo-associated
improvements occur in Parkinsonism, but responses in dyskinesia have not been
studied. Placebo data from two multicenter studies with identical design
comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan
(2 mg/day) failed to improve dyskinesia compared with placebo, but both
treatments improved dyskinesia compared with baseline. Stepwise regression
identified baseline characteristics that influenced dyskinesia response to
placebo, and these factors were entered into a logistic regression model to
quantify their influence on placebo-related dyskinesia improvements and
worsening. Because placebo-associated improvements in Parkinsonism have been
attributed to heightened dopaminergic activity, we also examined the association
between changes in Parkinsonism and dyskinesia. Four hundred eighty-four subject
s received placebo treatment; 178 met criteria for placebo-associated dyskinesia
improvement and 37 for dyskinesia worsening. Older age, lower baseline
Parkinsonism score, and lower total daily levodopa doses were associated with
placebo-associated improvement, whereas lower baseline dyskinesia score was
associated with placebo-associated worsening. Placebo-associated dyskinesia
changes were not correlated with Parkinsonism changes, and all effects in the
sarizotan group were statistically explained by the placebo-effect regression
model. Dyskinesias are affected by placebo treatment. The absence of correlation
between placebo-induced changes in dyskinesia and Parkinsonism argues against a
dopaminergic activation mechanism to explain placebo-associated improvements in
dyskinesia. The magnitude and variance of placebo-related changes and the
factors that influence them can be helpful in the design of future clinical
trials of antidyskinetic agents. (c) 2007 Movement Disorder
Society.
-----
Drug Saf. 2008;31(1):79-94.
Effects of rivastigmine on tremor and other motor symptoms in patients with
Parkinson's disease dementia : a retrospective analysis of a double-blind trial
and an open-label extension.
Oertel W, Poewe W, Wolters E, De Deyn PP, Emre M, Kirsch C, Hsu C, Tekin S, Lane
R.
Department of Neurology, Philipps University, Marburg, Germany.
BACKGROUND AND AIM: Rivastigmine is now widely approved for the treatment of
mild to moderately severe dementia in Parkinson's disease (PDD). However, since
anticholinergic drugs have a role in the management of tremor in patients with
Parkinson's disease (PD), concerns have been raised that the use of cholinergic
drugs might worsen PD. The current analyses were performed to examine the
potential of rivastigmine to affect tremor and other motor symptoms in patients
with PDD. METHODS: The safety profile of rivastigmine was evaluated using a
database from a 24-week, randomized, double-blind, placebo-controlled trial in
541 PDD patients (362 randomized to rivastigmine, 179 to placebo), and 334 PDD
patients who subsequently entered an open-label 24-week extension on
rivastigmine. RESULTS: During the double-blind trial, the adverse event (AE) of
emerging or worsening tremor was reported in 10.2% of patients in the
rivastigmine group, compared with 3.9% in the placebo group (p = 0.
012). Tremor was most frequently reported during the titration phase of
rivastigmine treatment, although this was not reflected in total motor Unified
Parkinson's Disease Rating Scale (UPDRS) part III scores. Dose dependence of
this AE was not observed. At the end of the double-blind phase, six (1.7%)
rivastigmine-treated patients had discontinued the study because of tremor. In
the open-label extension in which all patients received rivastigmine, tremor was
reported by 6.9% of patients: 3.8% and 12.2% of whom had previously received
double-blind rivastigmine and placebo, respectively (p = 0.006), suggesting that
first exposure to rivastigmine leads to a transient increase in tremor. Three
(0.9%) of the 334 patients who entered the open-label extension phase
discontinued because of tremor. Incidences of worsening parkinsonism,
bradykinesia and rigidity were all <5% in both treatment groups (all p-values
not statistically significant, rivastigmine vs placebo). In the 48-week
observation of rivastigmine treatment, there was no evidence of adverse
long-term motor outcomes. Post-hoc analysis showed that similar improvements in
the symptoms of dementia, including the ability to perform activities of daily
living, were seen regardless of whether exacerbation of tremor was reported
during the study. CONCLUSION: Rivastigmine did not induce clinically significant
exacerbation of motor dysfunction in patients with PDD. Rest tremor incidence as
an AE was a transient phenomenon during dose titration of rivastigmine. There
was no indication that exposure to long-term rivastigmine was associated with a
worsening of PD.
-----
J Neurol Phys Ther. 2007 Dec;31(4):173-9.
Effects of tango on functional mobility in Parkinson's disease: a preliminary
study.
Hackney ME, Kantorovich S, Levin R, Earhartm GM.
Program in Physical Therapy (M.E.H., R.L., G.M.E.), Department of Biology (S.K.),
Department of Anatomy and Neurobiology (G.M.E.), and Department of Neurology (G.M.E.),
Washington University School of Medicine, St. Louis, Missouri.
Recent research has shown that dance, specifically tango, may be an appropriate
and effective strategy for ameliorating functional mobility deficits in people
who are frail and elderly. Individuals with Parkinson's disease (PD) experience
declines in functional mobility that may be even more pronounced than those
experienced by frail elderly individuals without PD. The purpose of this study
was to compare the effects of two movement programs: tango classes or exercise
classes. Nineteen subjects with PD were randomly assigned to a tango group or a
group exercise class representative of the current classes offered in our
geographical area for individuals with PD. Subjects completed a total of 20
tango or exercise classes and were evaluated the week before and the week
following the intervention. Both groups showed significant improvements in
overall Unified Parkinson's Disease Rating Scale (UPDRS) score and
nonsignificant improvements in self-reported Freezing of Gait. In addition, the tango group showed significant improvements on the Berg Balance Scale.
The exercise group did not improve on this measure. Finally, the tango group
showed a trend toward improvement on the Timed Up and Go test that was not
observed in the exercise group. Future studies with a larger sample are needed
to confirm and extend our observation that tango may be an effective
intervention to target functional mobility deficits in individuals with PD.
-----
Exp Neurol. 2007 Nov 29 [Epub ahead of print]
Unilateral vs. bilateral STN DBS effects on working memory and motor function in
Parkinson disease.
Hershey T, Wu J, Weaver PM, Perantie DC, Karimi M, Tabbal SD, Perlmutter JS.
Department of Psychiatry, Washington University School of Medicine, St Louis,
MO, 63110, USA; Department of Neurology, Washington University School of
Medicine, St Louis, MO, 63110, USA; Department of Radiology, Washington
University School of Medicine, St Louis, MO, 63110, USA.
Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce
working memory while improving motor function in Parkinson disease (PD), but
findings are variable. One possible explanation for this variability is that the
effects of bilateral STN DBS on working memory function depend in part on
functional or disease asymmetry. The goal of this study was to determine the
relative contributions of unilateral DBS to the effects seen with bilateral DBS.
Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working
memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients
with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and
Both-on in a randomized, double-blind manner. Patients were off PD medications
overnight. Effects of unilateral DBS were compared to effects of bilateral STN
DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not
differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the
more affected side of the brain than in the less affected side of the brain
(p=.008). The effect of unilateral DBS on the more affected side on
contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS.
These results suggest that motor and working memory function respond to
unilateral STN DBS differentially depending on the asymmetry of motor symptoms.
-----
Mov Disord. 2007 Sep;22 Suppl 17:S385-91.
Future directions in the treatment of Parkinson's disease.
Schapira AH.
University Department of Clinical Neurosciences, Royal Free and University
College Medical School, University College London, London, UK.
a.schapira@medsch.ucl.ac.uk
The development of treatment for the symptoms of Parkinson's disease (PD) has
been one of the most notable successes of neurology. Dopaminergic therapies in
the form of levodopa, dopamine agonists, or monoamine oxidase B inhibitors
significantly improve the characteristic motor symptoms of bradykinesia and
rigidity, with a beneficial effect upon tremor in a proportion of patients.
Novel delivery of dopaminergic drugs whether in the form of once a day sustained
release preparations or transdermal applications ensures that they remain at the
forefront of PD treatment. The development of drugs to slow the progression of
PD has attracted considerable attention and there appears to be some measure of
success although additional studies need to be performed. A range of
nondopaminergic drugs including alpha 2-adrenergic antagonists, serotoninergics,
and adenosine A2a antagonists are in late-stage development for PD and offer
benefit for motor symptoms and motor complications.
-----
Mov Disord. 2007 Sep;22 Suppl 17:S379-84.
Management of motor complications in advanced Parkinson's disease.
Melamed E, Ziv I, Djaldetti R.
Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tikva,
Sackler School of Medicine, Tel Aviv University, Israel. emelamed@clalit.org.il
After several years of smooth and stable response to levodopa, many patients
develop motor fluctuations manifested by "on" and "off" phases. There are
various subtypes of motor fluctuations that have different underlying mechanisms
and therapeutical strategies. The "wearing off" phenomenon may be mainly due to
the loss of stratial dopamine storage capacity and short levodopa half-life. The
"delayed on" and "no-on" phenomena may be due to impaired absorption of oral
levodopa. Management include various combined approaches, such as administration
of small multiple daily doses of levodopa, controlled release, dispersible and
soluble levodopa formulations, oral dermal- patch and subcutaneous dopamine
agonists, MAO-B and COMT inhibitors, and surgical approaches, i.e., subthalamic
deep brain stimulation. Future strategies may include gene therapy (e.g.,
intrastriatal GDNF) or transplantation of stem cells that can either produce and
release dopamine or generate trophical factors.
-----
Neurologist. 2007 Sep;13(5):237-252.
Deep Brain Stimulation.
Kern DS, Kumar R.
From the *College of Medicine, University of Vermont, Burlington, Vermont;
†Department of Pediatrics, University of Colorado at Denver and Health Sciences
Center, Denver, Colorado; and ‡No academic institutional affiliation.
BACKGROUND:: Deep brain stimulation (DBS) for the treatment of neurologic
diseases has markedly increased in popularity over the past 15 years. This
review primarily focuses on movement disorder applications and efficacy of DBS,
but also briefly reviews other promising new and old uses of DBS. REVIEW
SUMMARY:: A multidisciplinary team consisting of a movement disorders
neurologist, a functional neurosurgeon, and a neuropsychologist optimally
selects patients for DBS. Patients must be significantly disabled despite
optimal medical therapy and be cognitively healthy without significant
psychiatric disorders. Although this surgery is elective, it should not be
withheld until the patient suffers marked loss of quality of life. Patients must
have support from caregivers and postoperatively multiple DBS programming visits
may be required. DBS of the subthalamic nucleus (STN) and the globus pallidus
pars interna (GPi) significantly improves motor performance, activities of daily
living, and quality of life in advanced Parkinson disease. In addition, STN DBS
allows for marked reductions of antiparkinson medication. Stimulation of the
ventralis intermedius nucleus of the thalamus is an effective treatment for
essential tremor with sustained long-term effects. The GPi may be the preferred
site of stimulation for dystonia with movement scores typically improved by 75%
in patients with primary dystonia. CONCLUSIONS:: DBS is an effective surgical
treatment for movement disorders with sustained long-term benefits. Further
research is ongoing to better understand the mechanism of DBS, refine the
hardware to improve efficacy and reduce adverse effects, and identify additional
applications and new anatomic targets.
-----
Exp Brain Res. 2007 Sep 8; [Epub ahead of print]
Locomotor response to levodopa in fluctuating Parkinson's
disease.
Moore ST, Macdougall HG, Gracies JM, Ondo WG.
Department of Neurology, Mount Sinai School of Medicine, Box 1135, 1 E 100th
St., New York, NY, 10029, USA, steven.moore@mssm.edu.
The aim of this study was to quantify the dynamic response of locomotion to the
first oral levodopa administration of the day in patients with fluctuating
Parkinson's disease (PD). Stride length, walking speed, cadence and gait
variability were measured with an ambulatory gait monitor in 13 PD patients (8
males) with a clinical history of motor fluctuations. The Unified Parkinson's
Disease Rating Scale (UPDRS) gait score (part 29) was also determined by a
movement disorders specialist from video recordings. Subjects arrived in the
morning in an 'off' state (no PD medication) and walked for a maximum length of
100 m. They then took their usual morning dose of oral levodopa and repeated the
walking task at 13 min intervals (on average) over a 90 min period. Changes in
stride length over time were fit with a Hill (Emax) function. Latency (time
until stride length increased 15% of the difference between baseline and maximum
response) and the Hill coefficient (shape of the 'off-on' transition) were
determined from the fitted curve. Latency varied from 4.7 to 53.3 min
post-administration [23.31 min (SD 14.9)], and was inversely correlated with age
at onset of PD (R = -0.83; P = 0.0004). The Hill coefficient (H) ranged from a
smooth hyperbolic curve (0.9) to an abrupt 'off-on' transition (16.9), with a
mean of 8.1 (SD 4.9). H correlated with disease duration (R = 0.67; P = 0.01)
and latency (R = 0.67; P = 0.01), and increased with Hoehn & Yahr stage in the
'off' state (P = 0.02) from 5.7 (SD 3.5) (H&Y III) to 11.9 (SD 4.7) (H&Y IV).
Walking speed correlated with changes in mean stride length, whereas cadence and
gait variability did not. UPDRS gait score also reflected improving gait in the
majority of subjects (8), providing clinical confirmation of the objective
measures of the locomotor response to levodopa. Increasing abruptness (H) of the
'off-on' transition with disease duration is consistent with results from
finger-tapping studies, and may reflect reduced buffering capacity of
pre-synaptic nigrostriatal dopaminergic neurons. Ambulatory monitoring of gait
objectively measures the dynamic locomotor response to levodopa, and this
information could be used to improve daily management of motor fluctuations.
-----
Eur Neurol. 2007 Sep 7;58(4):218-223 [Epub ahead of print]
Motor and Nonmotor Symptom Follow-Up in Parkinsonian Patients
after Deep Brain Stimulation of the Subthalamic Nucleus.
Zibetti M, Torre E, Cinquepalmi A, Rosso M, Ducati A, Bergamasco B, Lanotte M,
Lopiano L.
Department of Neuroscience, University of Turin, Turin, Italy.
Objective: To evaluate motor and nonmotor symptoms in patients with Parkinson's
disease undergoing bilateral deep brain stimulation of the subthalamic nucleus (STN
DBS). Methods: Thirty-six consecutive patients receiving bilateral STN
stimulation implants were evaluated preoperatively as well as 12 and 24 months
after surgery. Motor symptoms were assessed through the Unified Parkinson's
Disease Rating Scale (UPDRS). Data concerning nonmotor symptoms were collected
from items of the UPDRS and 2 additional questions from clinical charts
regarding constipation and urological dysfunction. Results: STN DBS was
effective in controlling motor symptoms; concerning nonmotor symptoms, sleep
quality and constipation improved after surgery as compared to baseline.
Salivation, swallowing and sensory complaints were ameliorated to a comparable
degree by the medication on state, whether preoperatively or postoperatively.
With a lower dose of dopaminergic medication, however, the medication
on state appeared to be a much larger percentage of the day postoperatively. No
significant variations were detected in intellectual impairment, depression,
thought disorders, motivation, falling unrelated to freezing, nausea,
orthostatic hypotension and urological dysfunction. Conclusions: STN DBS
effectively controls motor symptoms, while nonmotor features of advanced
Parkinson's disease patients are mostly unchanged after surgery, even though
some specific aspects, notably sleep complaints and constipation, are
ameliorated. Copyright (c) 2007 S. Karger AG, Basel.
-----
Parkinsonism Relat Disord. 2007 Sep 4; [Epub ahead of print]
Long-term outcome of 50 consecutive Parkinson disease patients
treated with subthalamic deep brain stimulation.
Wider C, Pollo C, Bloch J, Burkhard PR, Vingerhoets FJ.
Department of Neurology, CHUV, Rue du Bugnon, 1011 Lausanne, Switzerland.
OBJECTIVE: To describe the long-term outcome in 50 consecutive advanced
Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain
stimulation (STN-DBS). METHOD: Assessments were carried out at baseline, 6
months, 2 years, and 5 years postoperatively. RESULTS: Compared to baseline
scores without medication, we found a highly significant improvement of UPDRS
III with stimulation, maintained at 5 years (p<0.001). This improvement,
however, tended to diminish over time. Dyskinesia and off periods were also
improved (p<0.0001 for both). Seventeen patients died during follow-up, who
tended to be older at surgery (p<0.01). CONCLUSIONS: STN-DBS is an effective
treatment for advanced PD patients, and the beneficial effect is maintained at 5
years. However, worsening occurs over time due to disease progression.
-----
Parkinsonism Relat Disord. 2007 Sep 3; [Epub ahead of print]
Young onset parkinson's disease: Part 1. Practical management of
medical issues.
Calne SM, Kumar A.
Pacific Parkinson's Research Centre, University of Britsh Columbia, Vancouver,
BC, Canada V6T 2B5.
Young Onset Parkinson's disease (YOPD) is defined as Parkinson's disease
diagnosed between the ages of 21 and 40 years. Problems faced by this group are
different from those faced by older subjects because they face decades with the
illness. This article reviews current literature and offers suggestions for
intervention when appropriate and practical suggestions in the areas of drug
treatment, rehabilitation, nutrition, sexuality, pregnancy, menstruation and
menopause. The suggestions are not exclusively restricted to the management of
YOPD, but emphasis is placed on items where people with YOPD have either had
particular difficulties or where they can proactively self-manage their illness.
-----
Neurosurgery. 2007 Aug;61(2):297-304; discussion 304-5.
Exhaustive, one-year follow-up of subthalamic nucleus deep brain
stimulation in a large, single-center cohort of parkinsonian patients.
Tir M, Devos D, Blond S, Touzet G, Reyns N, Duhamel A, Cottencin O, Dujardin K,
Cassim F, Destée A, Defebvre L, Krystkowiak P.
Department of Neurology, Salengro Hospital, Lille University Medical Centre,
Lille, France.
OBJECTIVE: To prospectively assess the impact of subthalamic nucleus (STN) deep
brain stimulation (DBS) at 12 months after surgery in a series of 100
consecutive patients treated in a single center. The primary objective was to
describe the clinical outcome in terms of efficacy and tolerance in STN-DBS
patients. A secondary objective was to discuss presurgery clinical
characteristics a posteriori as a function of outcome. METHODS: One hundred and
three consecutive patients with severe Parkinson's disease received bilateral
STN-DBS in our clinic between May 1998 and March 2003. Clinical assessment was
performed before and 12 months after surgery and was based on the Unified
Parkinson's Disease Rating Scale, Parts II, III, and IV A; the Schwab and
England Scale; and cognitive evaluation. Patient-rated overall improvement was
also evaluated. RESULTS: Twelve months after surgery, the Unified Parkinson's
Disease Rating Scale Part III score decreased by 43%, the Unified Parkinson's
Disease Rating Scale Part II score (activities of daily living) fell by 34%, and
the severity of dyskinesia-related disability decreased by 61%. The main
surgical complications after STN-DBS were as follows: infection (n = 7),
intracerebral hematoma (n = 5), electrode fracture (n = 4), and incorrect lead
placement (n = 8). We observed cognitive decline and depression in 7.7 and 18%
of the patients, respectively. The mean patient-rated overall improvement score
was 70.7%. CONCLUSION: The efficacy and safety of STN-DBS in our center's large
cohort of Parkinsonian patients are generally similar to the results obtained by
other groups, albeit at the lower limit of the range of reported values. In
contrast to efficacy, the occurrence of adverse events cannot be predicted.
Younger patients with Parkinson's disease (i.e., those younger than 60 yr) often
show an excellent response to levodopa. However, in view of our data on overall
patient satisfaction and the occurrence of adverse events, we suggest that older
patients (but not those older than 70 yr) and less dopa-sensitive patients (but
not those with a response <50%) should still be offered the option of STN-DBS.
-----
Parkinsonism Relat Disord. 2007 Aug 16; [Epub ahead of print]
Deep brain stimulation and continuous dopaminergic stimulation in
advanced Parkinson's disease.
Ch Wolters E.
Department of Neurology, VU University Medical Center, Amsterdam, The
Netherlands.
Patients receiving oral levodopa, the standard treatment for Parkinson's disease
(PD), eventually develop motor fluctuations and dyskinesias. Treatment options
for patients with these symptoms include high-frequency deep brain stimulation
of the subthalamic nucleus (STN-DBS) or continuous dopaminergic stimulation
(CDS). STN-DBS is the prevalent surgical therapy for PD and has shown efficacy,
but behavioural disorders, including cognitive problems, depression and
suicidality have been reported. CDS can be achieved with oral dopamine agonists
with a long half-life, transdermal or subcutaneous delivery of dopamine
agonists, or intestinal levodopa infusion. Of these, duodenal levodopa infusion
appears to be the most promising option in terms of both efficacy and safety.
-----
Mov Disord. 2007 Aug 22; [Epub ahead of print]
Psychiatric and neuropsychiatric adverse events associated with
deep brain stimulation: A meta-analysis of ten years' experience.
Appleby BS, Duggan PS, Regenberg A, Rabins PV.
Department of Psychiatry, The Johns Hopkins Hospital, Baltimore, Maryland.
Deep brain stimulation (DBS) has been approved by the FDA for use in the
treatment of Parkinson's disease, essential tremor, and dystonia. Case reports
and case series have reported significant psychiatric side effects in some
individuals. The goal of this meta-analysis is to characterize the risks and
benefits of DBS and to assess its possible use within the psychiatric setting. A
search was conducted on PubMed, EBSCO, and PsycInfo in January 2006 that covered
the time period 1 Jan 1996-30 Dec 2005. All identified articles were reviewed
and those describing adverse events were further examined with a structured
instrument. The initial searches yielded 2667 citations; 808 articles met
inclusion criteria for the meta-analysis; 98.2% of studies that specifically
assessed motor function reported some level of improvement. Most reported side
effects were device or procedure related (e.g., infection and lead fracture).
The prevalence of depression was 2-4%, mania 0.9-1.7%, emotional changes
0.1-0.2%, and the prevalence of suicidal ideation/suicide attempt was 0.3-0.7%.
The completed suicide rate was 0.16-0.32%. In conclusion, DBS is an effective
treatment for Parkinson's disease, dystonia, and essential tremor, and case
reports suggest that major depression and OCD may also respond to DBS. Reported
rates of depression, cognitive impairment, mania, and behavior change are low,
but there is a high rate of suicide in patients treated with DBS, particularly
with thalamic and GPi stimulation. Because of the high suicide rate, patients
should be prescreened for suicide risk prior to DBS surgery. Additionally,
patients should be monitored closely for suicidal behavior post-operatively. (c)
2007 Movement Disorder Society.
-----
Parkinsonism Relat Disord. 2007 Aug 16; [Epub ahead of print]
Continuous dopaminergic stimulation-From theory to clinical
practice.
Antonini A.
Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy.
Patients with advanced Parkinson's disease (PD) experience worsening motor
fluctuations and dyskinesia. Management options include deep brain stimulation
of the subthalamic nucleus (STN-DBS), subcutaneous apomorphine (in combination
with oral levodopa) or continuous duodenal levodopa administration. We have used
all three therapies at our clinic in Milan and report our experience.
Apomorphine infusion reduced daily off time but did not improve dyskinesia;
long-term treatment was associated with impulse control disorders. STN-DBS
provided motor benefit, but was associated with behavioural changes including
attempted suicide. Duodenal levodopa produced significant clinical benefit
without behavioural changes and allowed patients to discontinue all other PD
medications. Duodenal levodopa should be considered in PD patients with advanced
disease.
-----
MMW Fortschr Med. 2007 May 21;149 Suppl 2:94-6.
[Diagnosis and treatment of tremor in Parkinson's disease and
essential tremor]
[Article in German]
Wolters A, Benecke R.
Klinik und Poliklinik für Neurologie, Universität Rostock. alexander.wolters@med.uni-rostock.de
For patients presenting predominantly or purely with tremor, the correct
diagnosis of tremor-dominant Parkinson's disease (PD) versus essential tremor
(ET) is very important for prognosis and effective therapy. ET tremor is usually
characterized by symmetric bilateral postural and kinetic tremor, which may
respond to low alcohol consumption. Many patients have a family history of ET
tremors. Medical treatment with primidone or beta-blockers effectively controls
ET tremor, but in many cases no treatment is needed at all. The typical tremor
form of PD is an asymmetric rest tremor, which is treated with dopaminergic
agents such as levodopa. Differential diagnosis of ET and PD may be difficult in
a subset of PD patients who present with additional postural and kinetic tremor
and in a minority of ET patients who show a clear asymmetry of their postural
and kinetic tremor. In some patients with ET, the tremor can later become severe
and even require treatment with deep brain stimulation.
-----
Mov Disord. 2007 May 7; [Epub ahead of print]
Is there seasonal variation in risk of Parkinson's disease?
Postuma RB, Wolfson C, Rajput A, Stoessl AJ, Martin WR, Suchowersky O, Chouinard
S, Panisset M, Jog MS, Grimes DA, Marras C, Lang AE.
Department of Neurology, McGill University, Montreal General Hospital, Montreal,
Quebec, Canada.
Recent studies suggest that, for many adult-onset neurological diseases, persons
born at a certain time of year are at higher risk of the disease. Small-scale
studies have suggested that persons born in the spring may be at higher risk of
developing Parkinson's disease (PD) late in life. There have also been
suggestions that there are clusters of PD birth dates in the years of major
influenza pandemics. To determine whether there is any seasonal variation in the
birth dates of PD patients, we examined birth dates of 8,168 PD patients
collected from subspecialty movement disorder clinics across Canada. Patterns of
seasonality of birth were examined and compared with the general Canadian
population. In addition, we compared counts of patients born in the years of
major influenza pandemics with the number born in the surrounding years. We
found no evidence of systematic seasonal variation in PD incidence by birth
date, or of clustering of birth dates during influenza pandemic years in PD
patients. (c) 2006 Movement Disorder Society.
-----
Eur J Nucl Med Mol Imaging. 2007 May 4; [Epub ahead of print]
Are there adaptive changes in the human brain of patients with
Parkinson's disease treated with long-term deep brain stimulation of the
subthalamic nucleus? A 4-year follow-up study with regional cerebral blood flow
SPECT.
Sestini S, Pupi A, Ammannati F, Silvia R, Sorbi S, Castagnoli A.
Department of Diagnostic Imaging, Nuclear Medicine Unit, Ospedale Misericordia e
Dolce, Piazza Ospedale 5, 59100, Prato, Italy, ssestini@usl4.toscana.it.
PURPOSE: The aim of this follow-up study was to assess persistent motor and
regional cerebral blood flow (rCBF) changes in patients with Parkinson's disease
(PD) treated with high-frequency deep brain stimulation (DBS) of the subthalamic
nucleus (STN). METHODS: Ten PD patients with STN-DBS underwent three rCBF SPECT
studies at rest, once preoperatively in the off-drug condition (T(0)), and twice
postoperatively in the off-drug/off-stimulation conditions at 5 +/- 2 (T(1)) and
42 +/- 7 months (T(2)). Patients were assessed using the UPDRS, H&Y and S&E
scales. SPM was used to investigate baseline rCBF changes from the preoperative
condition to the postoperative conditions and the relationship between rCBF and
UPDRS scores used as covariate of interest. RESULTS: Parkinsonian patients
showed a clinical improvement which was significant only on follow-up at 42
months. The main effect of treatment from T(0) to T(1) was to produce baseline
rCBF increases in the pre-supplementary motor area (pre-SMA), premotor cortex
and somatosensory association cortex. From T(1) to T(2) a further baseline rCBF
increase was detected in the pre-SMA (p < 0.0001). A correlation was detected
between the slight improvement in motor scores and the rCBF increase in the pre-SMA
(p < 0.0001), which is known to play a crucial role in clinical progression.
CONCLUSION: Our study suggests the presence of adaptive functional changes in
the human brain of PD patients treated with long-term STN-DBS. Such adaptive
processes seem to occur in the pre-SMA and to play only a slightly beneficial
role in terms of functional compensation of motor impairment.
-----
Expert Opin Pharmacother. 2007 May;8(7):1011-23.
Donepezil: an update.
Seltzer B.
V.A. Boston Healthcare System, Department of Neurology, Harvard Medical School,
Geriatric Research Center, Boston, MA 02130, USA. bseltzer@partners.org
Donepezil hydrochloride is the most widely prescribed drug for Alzheimer's
disease (AD). The main mechanism of action through which it influences cognition
and function is presumed to be the inhibition of acetylcholinesterase enzyme in
the brain; however, donepezil may also impact the pathophysiology of AD at
several other points. Officially approved for mild-to-moderate and severe AD,
donepezil has also been shown to be effective in early-stage AD, vascular
dementia, Parkinson's disease dementia/Lewy body disease and cognitive symptoms
associated with multiple sclerosis. In addition, one study suggested that
donepezil may delay the onset of AD in subjects with mild cognitive impairment,
a prodrome to AD. The pharmacokinetics, pharmacodynamics, safety/tolerability
profile and drug interaction properties of donepezil make it an easy and safe
agent to use. However, in general, the efficacy of donepezil is limited, and
ongoing studies are investigating other agents that may ultimately overtake its
present position as the mainstay of anti-AD therapy.
-----
Am J Speech Lang Pathol. 2007 May;16(2):95-107.
Effects of an extended version of the lee silverman voice
treatment on voice and speech in Parkinson's disease.
Spielman J, Ramig LO, Mahler L, Halpern A, Gavin WJ.
National Center for Voice and Speech, 1101 13th Street, Denver, CO 80204, USA.
jspielman@dcpa.org
PURPOSE: The present study examined vocal SPL, voice handicap, and speech
characteristics in Parkinson's disease (PD) following an extended version of the
Lee Silverman Voice Treatment (LSVT), to help determine whether current
treatment dosages can be altered without compromising clinical outcomes. METHOD:
Twelve participants with idiopathic PD received the extended treatment version (LSVT-X),
similar to LSVT except that it was administered twice a week in 1-hr sessions
over 8 weeks and required substantially more home practice. Recordings were made
in a sound-treated booth immediately before and after treatment, and again 6
months later. Vocal SPL was measured for 4 different tasks and compared with
data from a previous study, in which participants with PD received traditional
LSVT 4 times a week for 4 weeks. Listener ratings were conducted with audio
samples from both studies, using sentence pairs from a standard passage. LSVT-X
participants completed the Voice Handicap Index (VHI) before each set of
recordings. RESULTS: Participants receiving LSVT-X significantly increased vocal
SPL by 8 dB after treatment and maintained increased vocal SPL by 7.2 dB at 6
months. VHI scores improved for 25% of the LSVT-X participants following
treatment, and listener ratings indicated audible improvement in speech.
CONCLUSIONS: LSVT-X successfully increased vocal SPL (which was consistent with
improvements following traditional LSVT), decreased perceived voice handicap,
and improved functional speech in individuals with PD. Further large-scale
research is required to truly establish LSVT-X efficacy.
-----
Tenn Med. 2007 Apr;100(4):45-7.
Deep brain stimulation for Parkinson's disease: the Vanderbilt
University Medical Center experience, 1998-2004.
Gill CE, Konrad PE, Davis TL, Charles D.
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN
37232, USA.
Deep brain stimulation (DBS) has become increasingly popular to treat the
symptoms of Parkinson's disease (PD) that are no longer adequately controlled by
oral medications. This report summarizes safety and efficacy outcomes for 72
patients who underwent DBS surgery at Vanderbilt University Medical Center
between September 1998 and December 2004. Efficacy was measured by reduction in
anti-PD medications; patients saved an average of $2,292 per year after surgery.
The most common adverse event was intracranial hemorrhage (12.5 percent), which
led to permanent deficits in one patient (1.4 percent) and transient deficits in
five patients (6.9 percent). The next most common event was DBS lead infection
in seven patients (9.7 percent). Our experience provides further evidence that
DBS is one of the safest and most effective treatments for PD patients suffering
from motor complications.
-----
Mov Disord. 2007 Apr 27; [Epub ahead of print]
Deep brain stimulation and medication for parkinsonian tremor
during secondary tasks.
Sturman MM, Vaillancourt DE, Metman LV, Sierens DK, Bakay RA, Corcos DM.
Department of Movement Sciences, University of Illinois at Chicago, Chicago,
Illinois.
This study examined the efficacy of subthalamic nucleus (STN), deep brain
stimulation (DBS), and medication for resting tremor during performance of
secondary tasks. Hand tremor was recorded using accelerometry and
electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten
matched control subjects. The PD subjects were examined off treatment, on STN
DBS, on medication, and on STN DBS plus medication. In the first experiment,
tremor was recorded in a quiet condition and during a cognitive task designed to
enhance tremor. In the second experiment, tremor was recorded in a quiet
condition and during isometric finger flexion (motor task) with the
contralateral limb at 5% of the maximal voluntary contraction (MVC) that was
designed to suppress tremor. Results showed that: (1) STN DBS and medication
reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS
normalized tremor frequency in both the quiet and cognitive task conditions,
whereas tremor amplitude was only normalized in the quiet condition, (3) a
secondary motor task reduced tremor in a similar manner to STN DBS. These
findings demonstrate that STN DBS still suppresses tremor in the presence of a
cognitive task. Furthermore, a secondary motor task of the opposite limb
suppresses tremor to levels comparable to STN DBS. (c) 2007 Movement Disorder
Society.
-----
J Neurol Sci. 2007 Apr 25; [Epub ahead of print]
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.
OBJECTIVE: To further explore the efficacy and safety of subcutaneous
apomorphine (APO) in treating off episodes in APO-naive 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.
-----
Neurology. 2007 Apr 24;68(17):1356-63.
Quetiapine for agitation or psychosis in patients with dementia
and parkinsonism.
Kurlan R, Cummings J, Raman R, Thal L; Alzheimer's Disease Cooperative Study
Group.
Mt. Hope Professional Building, Rochester, NY 14620, USA. Roger_Kurlan@urmc.rochester.edu
OBJECTIVE: To assess the efficacy and tolerability of quetiapine for agitation
or psychosis in patients with dementia and parkinsonism. METHODS: Multicenter
randomized, double-blind, placebo-controlled parallel groups clinical trial
involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease
(PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n =
8). The main outcome measure for efficacy was change in the Brief Psychiatric
Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it
was change in the Unified PD Rating Scale (UPDRS) motor section over the same
time period. The trial was confounded by the need for a design change and
incomplete recruitment. RESULTS: No significant differences in the primary or
secondary outcome measures of efficacy were observed. An unexpectedly large
placebo effect, inadequate dosage (mean 120 mg/day), and inadequate power may
have contributed to lack of demonstrable benefit. Quetiapine was generally
well-tolerated and did not worsen parkinsonism, but was associated with a trend
toward a decline on a measure of daily functioning. CONCLUSIONS: Quetiapine was
well-tolerated and did not worsen parkinsonism. Although conclusions about
efficacy may be limited, the drug in the dosages used did not show demonstrable
benefit for treating agitation or psychosis in patients with dementia and
parkinsonism. These findings are in keeping with prior studies reporting limited
efficacy of various medications for reducing behavioral problems in demented
patients.
-----
Parkinsonism Relat Disord. 2007 Apr 17; [Epub ahead of print]
Dopamine replacement therapy does not restore the ability of
Parkinsonian patients to make rapid adjustments in motor strategies according to
changing sensorimotor contexts.
Tunik E, Feldman AG, Poizner H.
Department of Physical Therapy, New York University, New York, NY, USA.
The ability of dopamine replacement to restore rapid motor adjustments in
Parkinson's disease (PD) was investigated. Medicated and non-medicated patients
performed finger-to-nose movements while simultaneously bending the trunk
forward, without vision. Trunk motion was blocked unexpectedly, necessitating
rapid adjustments in arm trajectories. Patients exhibited irregular hand paths,
plateaus in hand velocity, and prolonged movement times, which were
significantly greater in perturbed trials. Medication improved kinematics but
perturbation-induced disturbances persisted and did not approximate the levels
of non-perturbed trials nor those of controls. Dopaminergic replenishment in PD
may therefore have limited restorative benefits for rapid context-specific motor
control.
-----
Mov Disord. 2007 Jan 17; [Epub ahead of print]
Effects of unilateral subthalamic and pallidal deep brain
stimulation on fine motor functions in Parkinson's disease.
Nakamura K, Christine CW, Starr PA, Marks WJ Jr.
Department of Neurology, University of California, San Francisco, California,
USA.
Deep brain stimulation (DBS) is an effective treatment for selected patients
with disabling Parkinson's disease (PD). The two main targets are the
subthalamic nucleus (STN) and the globus pallidus internus (GPi), although it
has not been established whether stimulation at one target is superior to the
other. This prospective randomized study assessed the effects of unilateral DBS
of the STN versus GPi on fine motor skills in 33 patients with advanced PD.
Stimulation of either the STN (18 subjects) or GPi (15 subjects) in the off
medication state significantly improved movement time and dexterity, but had
little or no effect on reaction time. Overall, the extent of improvement did not
differ between the two targets. The degree of improvement in movement time, but
not dexterity, was correlated with the extent of preoperative medication
responsiveness. Our findings suggest that DBS of the STN or GPi results in a
similar improvement in hand movements at short-term follow-up. Preoperative
medication responsiveness predicts improvement in some but not other motor
tasks. (c) 2006 Movement Disorder Society.
-----
Mov Disord. 2007 Jan 16; [Epub ahead of print]
Exercise improves efficacy of levodopa in patients with
Parkinson's disease.
Muhlack S, Welnic J, Woitalla D, Muller T.
Department of Neurology, St. Josef Hospital, Ruhr University Bochum,
Gudrunstrasse 56, Bochum 44791, Germany.
The objective was to investigate the impact of exercise on absorption and
efficacy of levodopa (LD) in patients with Parkinson's disease (PD). A soluble,
immediate release LD formulation was given followed by exercise near the aerobic
limit on one day to PD patients, who underwent the same procedure only at rest
on the second day. LD plasma behavior did not significantly differ between both
conditions, but the motor response was significantly better 120 and 150 min
after LD intake on the day with exercise than on the day with rest. Moderate
exercise increases clinical efficacy of LD. (c) 2007 Movement Disorder Society.
-----
Ther Umsch. 2007 Jan;64(1):29-33.
[Rehabilitation of parkinsonian patients.]
[Article in German]
Baronti F.
Klinik Bethesda / Neurorehabilitation, Parkinson-Zentrum, Epileptologie, Tschugg
(BE).
Although most parkinsonian patients greatly benefit from medical and/or surgical
treatment, their clinical management should not be limited to these two
interventions. Axial symptoms, freezing, postural instability, speech and
swallowing problems may be drug-resistant, and disability may persist in spite
of improvement of motor symptoms. A coordinate interdisciplinary approach
facilitates the clinical management of the disease. Physiotherapy, occupational
therapy and speech therapy may contribute to reduce impairment and improve
quality of life; a psychological and social support of patients and caregivers
helps them carrying the burden of the disease; counseling through a specialized
nurse may give practical solutions to problems like bladder incontinence,
symptomatic hypotension or hypersalivation. As sensory cueing may help patients
bypassing the disease-specific motor control deficits, it should be included in
training programs. Rehabilitatory interventions are part of the standards of
care of Parkinson's disease and their efficacy is supported by several
neurophysiological and clinical investigations. However, the poor methodological
quality of most clinical studies as compared with the standard of
pharmacological investigations fails to provide clear-cut evidence in favour of
rehabilitation.
-----
Ther Umsch. 2007 Jan;64(1):21-7.
[Surgery for Parkinson's disease.]
[Article in German]
Kaelin-Lang A, Stibal A.
Zentrum fur Bewegungsstorungen, Neurologische Klinik, Universitatsspital, Bern.
Surgery for Parkinson's Disease (PD) is being increasingly used. The main reason
for this renewal in surgical treatment for PD is the "deep brain stimulation"
(DBS) that replaced the previously used stereotactic lesions in most centers.
DBS allows a focal specific electrical stimulation of basal ganglia target
instead of an irreversible lesion. Mainly bilateral DBS of the nucleus
subthalamicus is now an established surgical treatment for PD. But DBS of the
Globus pallidus internus and of the thalamus should still be considered in
selected patients. DBS is an efficient treatment for motor complication of PD
that can no longer be controlled by drug treatment. Dyskinesia, bradykinesia,
tremor and rigor can be improved by DBS and the medication can be reduced. It is
still unclear, however, how the improvement in motor symptoms affects quality of
life in the long term. Furthermore, patients with severe cognitive and
psychiatric symptoms as well as patients with severe axial symptoms should not
be operated since these symptoms may worsen after surgery.
-----
Ann Pharmacother. 2007 Jan 9; [Epub ahead of print]
Rotigotine: Transdermal Dopamine Agonist Treatment of Parkinson's
Disease and Restless Legs Syndrome (February).
Splinter MY.
Department of Pharmacy: Clinical and Administrative Sciences, College of
Pharmacy, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma
City, OK 73190, fax 405/271-6430.
OBJECTIVE: To evaluate the pharmacology, pharmacokinetics, clinical efficacy,
and tolerability of rotigotine, a nonergoline D3/D2/D1 dopamine receptor agonist
in the treatment of Parkinson's disease and restless legs syndrome (RLS). DATA
SOURCES: A literature search was conducted using MEDLINE (1996-December 2006)
and International Pharmaceutical Abstracts, using the search terms rotigotine
and dopamine agonist. References cited in the articles were reviewed for
additional information. Information was also obtained from Schwarz Pharma.
Abstracts for posters at scientific conferences were accessed from conference
Web sites. STUDY SELECTION AND DATA EXTRACTION: English-language literature
reporting controlled animal and human clinical studies was reviewed to evaluate
the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of
rotigotine. Clinical trials selected for inclusion were limited to those with
human subjects; data from animal studies were included if human data were not
available. DATA SYNTHESIS: Rotigotine has been investigated in early Parkinson's
disease, as adjuvant therapy to levodopa in advanced Parkinson's disease, and in
RLS. It is administered transdermally, which provides the convenience of
once-daily dosing, constant drug delivery, and sustained stable plasma
concentrations. In clinical trials of patients with early Parkinson's disease,
rotigotine has decreased combined scores on the motor and activities of daily
living sections of the Unified Parkinson's Disease Rating Scale up to 85 weeks.
In patients with advanced Parkinson's disease, rotigotine reduced mean off-time
when used as an adjuvant to levodopa. Rotigotine has decreased the severity of
RLS in Phase III trials. Acute adverse events are similar to those of other
dopamine agonists and are most common during the titration phase.
Mild-to-moderate application site reactions are common. CONCLUSIONS: Longer
trials are required to determine whether transdermal rotigotine will reduce
development of dyskinesias and motor fluctuations in Parkinson's disease and
augmentation and rebound in RLS by preventing pulsatile dopamine stimulation
associated with levodopa and other dopamine agonists.
-----
J Neurol Phys Ther. 2006 Dec;30(4):195-200.
CSM 2007 Locomotor Control Platform Presentations: Effects of
Limb Load on Gait Initiation in Persons with Parkinson's Disease.
Diephuis T, Beuth S, McCloy M, Hilliard MJ, Martinez KM, Simuni T, Zhang
Y, Rogers MW.
Purpose/Hypothesis: Individuals with Parkinson's disease (PD) experience
difficulties with posture and locomotion. In gait initiation, anticipatory
postural adjustments (APAs) for lateral weight transfer are prolonged and
smaller in amplitude with delayed step onset. Persons with PD may show
abnormalities in load proprioception during stance and gait that may influence
the initiation timing and other step characteristics. The purpose of this study
was to examine whether external assistance with APAs through changes in limb
loading enhances posture and gait performance. Number of Subjects: 8 subjects
with mild to moderate PD tested while ON medication and 8 age and gender-matched
controls. Materials/Methods: Ground reaction forces and the net mediolateral
center of pressure (COP) were measured with two force platforms to determine APA
characteristics. Whole body kinematic data were recorded using a 6-camera
infrared motion analysis system to determine step parameters. Subjects performed
5 blocks of 6 trials of rapid, self-paced forward stepping. Following an initial
baseline walking condition with no platform manipulation, participants received
either an air-driven elevation or drop of the single stance limb support surface
(1.5 cm in 150 ms), with the order of presentation rotated between subjects. The
manipulations were externally triggered during the APA phase of gait initiation
when the vertical load was reduced by ~5% body weight under the stance limb. A
second baseline condition was followed by the converse elevation or drop, and
finally a third baseline condition. Data was analyzed using repeated measures
ANOVA (p< 0.05). Results: Group effects indicated longer APA duration and later
step onset (p< 0.01) for PD subjects. In both groups the drop condition resulted
in shorter APA duration (by 100 ms), larger APA amplitude (by 3 cm), and faster
step onset (by 93 ms) compared with other conditions (p< 0.001). Platform
elevation decreased APA amplitude (p< 0.05) and first step length (p< 0.05).
Conclusions: This study confirms previous findings that individuals with PD have
prolonged APA durations and delayed step onset compared to age-matched healthy
controls. These results indicated the capacity for persons with PD to acutely
improve their gait initiation with postural manipulations that assist the
transfer of body weight laterally. In contrast, when a postural manipulation
that mechanically opposed lateral weight transfer was applied by elevating the
impending stance limb to tilt the body towards the swing limb side, no
improvements or a decrement in APA amplitude were observed. Clinical Relevance:
This study suggests that a drop or unloading of the support surface on the
single stance side assisted the APA for lateral weight transfer and released an
earlier step onset. Posture assisted locomotion (PAL) training could be utilized
clinically to enhance gait function in patients with PD.
Previous Parkinson's
Research: 2002-2006
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