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Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Par
Friday, December 05, 2008
Monday, 04 August 2008) - Contributed by David A. Sun et al.
Journal of Neurosurgery August 2008 Volume 109, Number 2
Deep
brain stimulation (DBS) of the subthalamic nucleus (STN) is a
clinically effective neurosurgical treatment for Parkinson disease.
Tissue reaction to chronic DBS therapy and the definitive location of
active stimulation contacts are best studied on a postmortem basis in
patients who have undergone DBS. The authors report the postmortem
analysis of STN DBS following 5 years and 11 months of effective
chronic stimulation including the histologically verified location of
the active contacts associated with bilateral implants. They also
describe tissue response to intraoperative test passes with recording
microelectrodes and stimulating semimacroelectrodes. The results
indicated that 1) the neural tissue surrounding active and nonactive
contacts responds similarly, with a thin glial capsule and foreign-body
giant cell reaction surrounding the leads as well as piloid gliosis,
hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal
fibers; 2) there was evidence of separate tracts in the adjacent tissue
for intraoperative microelectrode and semimacroelectrode passes
together with reactive gliosis, microcystic degeneration, and scattered
hemosiderin deposition; and 3) the active contacts used for ~ 6 years
of effective bilateral DBS therapy lie in the zona incerta, just dorsal
to the rostral STN. To the authors' knowledge, the period of STN DBS
therapy herein described for Parkinson disease and subjected to
postmortem analysis is the longest to date.
When a Parkinson’s disease patient starts to hallucinate
Friday, December 05, 2008
(Tuesday, 22 July 2008) - Contributed by W. Poewe
Practical Neurology 2008;8:238-241
ABSTRACT
Visual
hallucinations are a typical feature of Lewy body parkinsonism and
occur in some 40% of patients with Parkinson’s disease. Age and
cognitive decline are the most important intrinsic risk factors, but
hallucinosis is often triggered by comorbid conditions such as
infection and dehydration. The single most important trigger, however,
is exposure to CNS drugs, in particular antiparkinsonian agents. While
hallucinosis and psychosis can be triggered by amantadine and
anticholinergics, they are more commonly experienced after changes in
dopaminergic medication. Dopamine
agonists have greater potential
to induce hallucinosis compared with L-dopa. Attempting to reduce
antiparkinsonian drugs is an important part in the management of these
patients, but atypical neuroleptics like clozapine or quetiapine are
frequently necessary. Visual hallucinations in Parkinson’s disease
patients with dementia can also be improved by treatment with the
cholinesterase inhibitor rivastigmine.
Thorough QT/QTc Study in Patients With Advanced Parkinson's Disease: Cardiac Safety of Rotigotine
Friday, December 05, 2008
(Monday, 28 July 2008) - Contributed by M Malik et al.
The
potential effects of the dopamine agonist rotigotine on cardiac
repolarization were studied in patients with Parkinson's disease, which
affects electrocardiogram (ECG) quality. The parallel-group trial was
double-blind and placebo- and positive (moxifloxacin 400
mg)-controlled. After two 24-h baseline ECGs, patients were randomized
to rotigotine (n = 66) or placebo (n = 64). Twenty four–hour ECGs were
recorded on days 14/15, 21/22, 28/29, 35/36, and 42/43 of a regimen
involving weekly dose escalations of 4 mg/24 h (4 mg/24 h–24 mg/24 h).
In 10-s ECGs (n = 357,948)
selected from 24-h records, QT
measurements were manually verified and individually rate-corrected
(QTc). Assay sensitivity showed maximum mean 13.5 ms QTc prolongation
after moxifloxacin with 95% confidence interval (CI) 11.8–15.2 ms.
Rotigotine vs. placebo differences in time-matched changes from
baseline (54 data points/24 h) showed
mean effects close to zero
with upper one-sided 95% CI <5 ms. Accurate, thorough QTc studies
are possible even in patients with diseases that profoundly affect ECG
quality. Rotigotine in supra- and therapeutic doses was shown not to
affect cardiac repolarization.Clinical Pharmacology & Therapeutics
advance online publication 23 July
Issues of Hope
Friday, December 05, 2008
In the waiting room the older girl cares for her red- haired sister.
The younger shines behind a fringe of bangs, her longer hair sweeps
into a curl someone has taken the time to induce. She is not yet two
and wears a pink dress. Her sister wears a white t-shirt with black
graphics and her long pony tail hangs down her back. They are waiting
for their mom. I am waiting for Parkinson's patients. We are still
waiting an hour and twenty minutes later. They've found the bathroom
and changed diapers. The younger has eaten cookies, torn pages from a
magazine, crawled around the floor, peered through the glass window,
giggled, fainted repeatedly into her sister's open arms, shrieked,
cried, run out of the area provoking a chase, and tried to persuade her
sister into taking off her bright pink belt, pointing to it, saying
"Off. Mine."
Their mother appears suddenly in a motorized wheel
chair. Though her face is glazed, I hear her say, 'shots in the back
for pain' as her left hand motions to her spine and the older girl
nods, concern in her features as she picks up the diaper bag, and scans
the seats as they leave.
The PD patient arrives at last. He
asks whether his wife may accompany him. She has an unlikely Spanish
name. They have been married fifty years. I learn this in a tense
moment between them when the doctor asks a question and they both
volunteer information. He is from Spain, and his tone is sharp towards
his spouse. His head and gesture of hand accentuate his request for her
to let him speak. They were not born married, how old can they be?
He
is fit and walks upright. They have come with questions and down loads
from the internet about a doctor in Valencia, Spain who stumbled upon
an apparent way to treat PD with an acupuncture needle in the ear; a
non- invasive approach. This sets the doctor on a tangent about how he
used to refer patients to an acupuncturist for tremor, but found
patients were not greatly improved and how he works with a physician
who used to be a neurosurgeon in China. Though he now works with rats,
the Chinese doctor described a very special type of acupuncture in
which a needle is inserted through the base of the skull into the
brain; it has been used to cure blindness. In this country we call that
neurosurgery, the doctor tells us.
The couple wants
information. Fetal cell transplants, newer drugs? It has been a year
since they were here. What about stem cells? In Santo Domingo they are
giving PD patients infusions of stem cells, the patient tells the
clinician.
"These are issues of hope." The doctor replies. If
money is not an issue the doctor advocates 1200mg/ day of coenzyme Q10.
Studies have shown some protective effects, but the pills are expensive
and not covered by insurance. Azilect in place of selegiline will also
improve slowing of the illness. Exercise is beneficial. The couple
plans to travel to Valencia where they can obtain the Neupro patch in
8mg strength. The patch will also improve symptoms as the drug bypasses
the digestive system and gets delivered through the skin continuously,
avoiding pulsatile stimulation of dopaminergic neurons.
Though
there is a patient in the room, the feeling is upbeat, healthy and
striving. The disease has not settled in, and that is good.
Falling into Open Arms
Friday, December 05, 2008
It seems the patient needs little provocation to fall. He fell three
times on Labor Day and twice this past weekend. The wife hesitates to
let him use a walker. She fears the tip- toeing will escalate with
wheels in front of him; the increased velocity will drive him into a
more traumatic accident. Occasionally he'll use a cane to get around,
though mostly he just loses them, his wife relates.
Six
months ago the patient's blood pressure was dangerously low. He
appeared today wearing compressive socks, a former suggestion they
implemented. The spouse relays they are focusing on adding salt to the
diet, and she's concerned about the thirty pounds he has lost since
January. She wonders whether the action of sinemet varies with weight
and the doctor shakes his head no, as he asks the patient to copy his
movements with his own hands.
The doctor opens the left palm
of his hand, with the right he pats the palm then flips the hand over
and pats with the back of the right hand. Quickly he flips the right
hand down and over, down and over onto the left palm. The patient
extends his left palm as well, and with the right he makes a downward
chop motion. The doctor asks whether he sees a difference in what their
hands are doing. The patient concedes the doctor is doing something
different and amends the chopping motion with a slap. The new action
resembles slightly more of what the doctor is performing.
'There's an apraxia here.. It’s indicative of problems with thought..'
The wife comments she has begun to shave her husband's face. 'He's losing independent function…'
In
a chair opposite her husband, the wife in a shirt of pale pink exhales
and shrinks into herself, apologizing as an emotional wave passes and
she sobs into her clenched hand. Wanting an unbiased opinion, she
sought the advice of a social worker at the VA who informed her there
are 2 total care nursing homes in Hernando County, and three more in
West Pasco. The patient is considered 70% disabled, so the VA system
should pick up the entire bill.
Frustration in her voice, the
wife related the patient was into everything. Drawers, cabinets,
closets; he turns the contents out, inspecting it all, reading the
smallest print on a shredded discarded napkin. It's hard when you are
the only one making all the decisions, she admits. She recalls seeing
her husband standing in front of the chest of drawers, then abruptly
going down and she was running to catch him. The force of his body hit
her and they both fell on the floor.
The doctor faces her and
tells her she must guard her own health; consider taking
antidepressants as well, because they can help, even though she has
appropriate reasons to feel as she does. The doctor leans back in his
chair. Two things I can suggest, he holds his thumb and index finger
erect. Physical therapy may help with gait and balance, though he will
not learn anything new, and will retain little. Seroquel, at night will
dampen the hallucinations, paranoia and delusions. During the day a
smaller dose will diminish odd behaviors. As they leave the room the
wife takes her husband by the hand, leading him slowly with his
shuffling steps.
Patients Old and Young
Thursday, December 04, 2008
The patient wears her straight white hair short like a flapper from the
thirties. While she moves randomly in her chair, her face is mobile and
her dynamic presence engages all in the room.
"I don't like to
think of myself as having Parkinson's Disease"- she tells the medical
student. She uses no term to describe her dyskinesias- she simply says,
"When I am like this"- gesturing towards her body. The doctor is unsure
whether the movements are due to levodopa levels peaking or subsiding.
He encourages the woman to keep a medication journal for several days
and to bring it when she visits again. With a week's worth of hourly
details listing medications and her physical symptoms, he will be
better educated to tweak her drugs and reduce the unwanted movements.
In a restaurant no one wants to sit next to her; the movements are
embarrassing. She describes her children's response to her initial
session with a physician; they thought she was cured. Levodopa quieted
everything.
Now balance and freezing become problematic. She takes
no antidepressants. She sleeps well, with one Vesicare she wakes only
once to use the toilet. The doctor recommends physical therapy, as
freezing can be a source of falling incidents. Sun City- a retirement
community south of Tampa is her home for the winter half of the year,
by April 30th she returns to New York.
"Try and get an appointment in April, I'd like to see you before you leave."
The medical student has long golden hair, hanging loose and straight
down her back. Beneath her white lab coat, she is curvy but tall. She
reports on another regular patient providing key issues of his visit.
The second student, still an undergraduate, is dark, slender and
intense. Thick black thick hair comes low on his forehead. When he is
not commenting, he takes notes. His assertive voice and commanding
attitude give him an authoritative air.
Diagnosed in his late
thirties, the patient has had PD for ten years. He notes he feels weak
in the legs sometimes, as if lacking the muscle strength to hold his
body erect. Dramatizing this he hops from the examination table,
performing several steps with bent knees. The doctor nods but has no
comment.
The wife notes when very happy or sad, the medications
seem to have no affect. Neither the doctor nor students provide any
explanation. The physician takes the patient's arm, testing for cogging
in the wrist or elbow and comments on the patient's muscle tone, noting
he must be active. The client concedes he cuts the lawn, but maintains
his bicep with fishing.
The edges of the man's mouth droop
slightly at the corners, making him appear sad. Describing his
experience with Amantadine, he saw the ceiling slant downward at an
angle and the floor slant upward. He felt space would compress him. His
hands felt enormous and his body barely fit through the doorway.
Addressing the cost of medications, Mirapex in particular, the doctor
suggests switching to Bromocriptine. Used during the seventies, it is
an alternative generic option. Expressing doubt about whether it will
be as effective as Mirapex, the doctor leaves the room, returning with
a white bag of sample bottles.
It is four o'clock. The patient
swallows a pill as the doctor explains to his wife, which cold
medications may combine safely with the drugs he is taking. Soon after,
the patient freezes in the hallway. He turns his wide shoulders
sideways performing a maneuver he hopes will unlock his frozen feet.
Functional balance performance in patients with Parkinson's disease after long-term treatment...
Tuesday, December 02, 2008
(Monday, 30 June 2008) - Contributed by M.H. Nilssona, b, , , G.-B. Jarnlob and S. Rehncrona
Abstract
The
aim was to investigate if functional balance performance in patients
with Parkinson's disease (PD) was affected by long-term (3 years)
treatment with bilateral subthalamic nucleus (STN) high-frequency
stimulation. Thirty-five patients were consecutively included, and 28
patients completed the study (mean age 62 years, SD 6.5). The Berg
Balance Scale (BBS) was assessed preoperatively and 1 and 3 years
postoperatively (with and without anti-PD medication and with the STN
stimulation turned OFF or ON). Although the balance performance of
patients with PD decreased over time, the functional balance
performance was still positively affected by STN stimulation alone 3
years after surgery.
Parkinsonism & Related Disorders
Volume 14, Issue 4, May 2008, Pages 291-297
A pilot study into the effect of vocal exercises and singing on dysarthric speech
Tuesday, December 02, 2008
(Friday, 13 June 2008) - Contributed by Jeanette Tamplin
Abstract
This
pilot study aimed to investigate the effects of vocal exercises and
singing on intelligibility and speech naturalness for subjects with
acquired dysarthria following traumatic brain injury or stroke. A
multiple case study design was used, involving pre, mid, and
post-treatment assessments of intelligibility, rate, naturalness, and
pause time for four subjects with dysarthria. Each subject participated
in 24 individual music therapy sessions over eight weeks involving oral
motor
respiratory exercises, rhythmic and melodic articulation
exercises, rhythmic speech cuing, vocal intonation therapy, and
therapeutic singing using familiar songs. Results were measured using a
standardized dysarthric speech assessment – the Sentence
Intelligibility Test, waveform analysis, and ratings of speech
naturalness. Statistically significant improvements in functional
speech intelligibility were achieved but improvements in rate of speech
were not significant. Speech naturalness improved post-treatment and a
reduction in the number and length of pauses was verified via waveform
analysis. Preliminary findings suggest that a program of vocal
exercises and singing may facilitate more normative speech production
for people with acquired dysarthria and support the need for further
research in this area.
NeuroRehab. V. 23 N.3 2008
A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease
Tuesday, December 02, 2008
(Friday, 20 June 2008) - Contributed by Spiridon Papapetropoulos et al.
Hallucinations occur in 20-40% of PD patients and have been associated with unfavorable clinical outcomes (i.e., nursing
home
placement, increased mortality). Hallucinations, like other non-motor
features of PD, are not well recognized in routine primary/secondary
clinical practice.
So far, there has been no instrument for
uniform characterization of hallucinations in PD. To this end, we
developed the University of Miami Parkinson's disease Hallucinations
Questionnaire (UM-PDHQ) that allows comprehensive assessment of
hallucinations in clinical or research settings.
Methods: The
UM-PDHQ is composed of 6 quantitative and 14 qualitative items. For our
study PD patients of all ages and in all stages of the disease were
recruited over an 18-month period.
The UPDRS, MMSE, and Beck
Depression and Anxiety Inventories were used for comparisons. Results
and Discussion: Seventy consecutive PD patients were included in the
analyses.
Thirty-one (44.3%) were classified as hallucinators
and 39 as non-hallucinators. No significant group differences were
observed in terms of demographics, disease characteristics, stage,
education, depressive/anxiety scores or cognitive functioning (MMSE)
between hallucinators and non-hallucinators.
Single mode
hallucinations were reported in 20/31 (visual/14, auditory/4,
olfactory/2) whereas multiple modalities were reported in 11/31
patients. The most common hallucinatory experience was a whole person
followed by small animals, insects and reptiles.
Conclusions: Using the UM-PDHQ, we were able to define the key characteristics of hallucinations in PD in our cohort.
Future
directions include the validation of the quantitative part of the
questionnaire than will serve as a rating scale for severity of
hallucinations.
Author: Spiridon Papapetropoulos, Heather Katzen, Anette Schrag, Carlos Singer, Blake K Scanlon, Daniel Nation,
AlexandraGuevara and Bonnie Levin
Credits/Source: BMC Neurology 2008, 8:21
Metatarsal fracture as a consequence of foot dystonia in Parkinson's disease
Tuesday, December 02, 2008
(Monday, 30 June 2008) - Contributed by Eric McDade, a, , William J. Weinera and Lisa M. Shulman
Abstract
We
report a 45-year-old man with a 4-year history of Parkinson's disease
complicated by the development of left-foot dystonia resulting in a
fracture of the fifth metatarsal. Orthopedic injuries are common in
Parkinson's disease, but they are usually secondary to falls. Although
drug-induced dystonia is a common side effect of pharmacological
treatment of Parkinson's disease, this is the first report of a
fracture related to these abnormal movements.
Parkinsonism & Related Disorders
Volume 14, Issue 4, May 2008, Pages 353-355.
Nonmotor symptoms of Parkinson's disease: Prevalence and awareness of patients and families
Tuesday, December 02, 2008
(Monday, 30 June 2008) - Contributed by Sang-Myung Cheona, Min-Soo Hab, Min Jeong Parka and Jae Woo Kima
Abstract
The
aim of this study was to explore the prevalence of nonmotor symptoms in
Parkinson's disease (PD) and the patients’ and family members’
awareness of these symptoms. We evaluated 74 parkinsonian patients and
54 family members.
Seventy-three patients had more than one
symptom (12.4±5.5 out of 30 symptoms on average). Nocturia was the most
common in men and feeling sad in women. The average number of symptoms
which patients knew to be related to PD was 5.2±6.8 and to family
members 7.7±6.5. Twenty-eight patients and five family members were
unaware of the
relationship between any of these symptoms and PD.
For PD to be properly managed, nonmotor symptoms should be
comprehensively assessed and patients and families informed that these
are associated with PD.
Parkinsonism & Related Disorders
Volume 14, Issue 4, May 2008, Pages 286-290.
Fatigue in Parkinson's disease is not related to excessive sleepiness or quality of sleep
Tuesday, December 02, 2008
(Wednesday, 18 June 2008) - Contributed by Eva Havlikovaa et al.
Abstract
Objectives
Many
patients with Parkinson's disease (PD) suffer from non-motor symptoms
like sleep disturbances, excessive daytime sleepiness and fatigue. The
aim of our research was to explore whether fatigue is related to
sleepiness and sleep problems, depression and functional status,
controlled for age, gender and disease duration.
Methods
The
sample consisted of 78 PD patients from Eastern Slovakia (52% males,
mean age 68.8 ± 8.7, mean disease duration 7.2 ± 6.8). The
Multidimensional Fatigue Inventory (5 dimensions), the Epworth
Sleepiness Scale, the Pittsburgh Sleep Quality Index, Hospital Anxiety
and Depression Scale and the Unified Parkinson's Disease Rating Scale
were used. Demographic data were obtained in a structured interview.
Multiple linear regression was used to analyse the data.
Results
Sleepiness
did not show significant association with fatigue in any of the fatigue
domains; neither did quality of sleep. Depression was significantly
associated with all domains of fatigue, the strongest being the
relationship with general fatigue (2 .42), reduced motivation (2 .39),
mental fatigue (2 .35) (p < .001), and physical fatigue (2 .31) (p
< .01), while the relationship with reduced activity was less strong
(2 .22) (p < .05). Worse functional status was significantly related
to
reduced activity (2 .50), general fatigue (2 .35), physical fatigue (2 .35), and mental fatigue (2 .35) (p < .001).
Conclusion
Fatigue
is not related to daytime sleepiness or night-time sleep dysfunction.
Fatigue is more strongly influenced by the presence of depression and
worse functional status.
Journal of the Neurological Sciences
Volume 270, Issues 1-2, 15 July 2008, Pages 107-113
Efficacy of long-term continuous subcutaneousapomorphine infusion in advanced Parkinson's disease
Tuesday, December 02, 2008
(Monday, 16 June 2008) - Contributed by Pedro J. Garci´a Ruiz MD et al.
Continuous
subcutaneous apomorphine infusion (CSAI) is, at present, an alternative
option for advanced Parkinson's disease (PD) with motor fluctuations.
We studied the evolution of patients with PD and severe motor
fluctuations long- term treated with CSAI. We reviewed data from 82
patients with PD (mean age, 67 ± 11.07; disease duration, 14.39 ± 5.7
years) and severe motor fluctuations referred to 35 tertiary hospitals
in Spain. These patients were long-term treated (for at least 3 months)
with CSAI and tolerated the procedure without serious side effects. We
compared the baseline data of these 82 patients (before CSAI) with
those obtained from the last follow-up visit of each patient. The mean
follow-up of CSAI was 19.93 ± 16.3 months. Mean daily dose of CSAI was
72.00 ± 21.38 mg run over 14.05 ± 1.81 hours. We found a statistically
significant reduction in off-hours, according to self-scoring diaries
(6.64 ± 3.09 vs. 1.36 ± 1.42 hours/day, P < 0.0001), total and motor
UPDRS scores (P < 0.0001), dyskinesia severity (P < 0.0006), and
equivalent dose of antiparkinsonian therapy (1,405 ± 536.7 vs. 800.1 ±
472.9 mg of levodopa equivalent units P < 0.0001). CSAI is an
effective option for patients with PD and severe fluctuations, poorly
controlled by conventional oral drug treatment.
Treadmill walking in Parkinson's disease patients: Adaptation and generalization effect
Tuesday, December 02, 2008
(Monday, 16 June 2008) - Contributed by Olalla Bello BSc, Jose A.Sanchez PhD, Miguel Fernandez-del-Olmo PhD
We
examined the adaptation and generalization effect of one
familiarization treadmill walking session on gait in patients with
Parkinson's disease (PD) with different degrees of disease severity.
Eight moderate PD patients (Hoehn and Yahr stage 2-2.5), eight advanced
PD patients (Hoehn and Yahr 3), and eight matched control subjects
participated in this study. Subjects first walked overground on a 10-m
walkway at a self-selected speed (pretreadmill). They then performed a
20-min treadmill training session, followed by three trials of
overground walking (Post1, Post2, Post3). Cadence, step length, speed,
and coefficient of variation of stride time (CV) were recorded. During
the treadmill session the advanced PD patients significantly decreased
their cadence (t = 3.9, P 0.01) and increased their step length (t =
4.27, P 0.01) compared with pretreadmill walking. After the treadmill,
all subjects walked overground significantly faster (F = 16.51 P 0.001)
and with a larger step length (F = 13.03 P 0.01) than pretreadmill
walking. The present study shows a specific adaptation to walk over the
treadmill for the advanced PD patients. Moreover, this confirms the
potential therapeutic use of the treadmill for PD gait rehabilitation
since a single familiarization session lead to an increase in the step
length and thus to the improvement of the main gait impairment in PD.
Frailty in Parkinson's disease and its clinical implications
Tuesday, December 02, 2008
(Monday, 30 June 2008) - Contributed by Nasiya N. Ahmeda, c, , , Scott J. Shermanb and David VanWyck
Abstract
The
purpose of our study was to determine the prevalence of frailty in
Parkinson's disease (PD) patients and the relationship between
individual frailty criteria and the severity of PD. We measured the
five components of frailty (Fried et al.) and the severity of PD
(unified Parkinson's disease rating scale (UPDRS)) in 50 optimally
treated PD patients. Frailty was more prevalent in PD patients. While
UPDRS scores differed between frail and non-frail participants
(44.8±15.8 vs. 31.4±12.7, P<0.002), higher scores were not
indicative of frailty. Weekly caloric expenditure bestpredicted frailty
status (OR=22.0 [4.5,107.8]). Frailty and PD bear distinct therapeutic
and prognostic significance; however, their clinical picture may
overlap and screening PD patients for frailty may be warranted.
Parkinsonism & Related Disorders
Volume 14, Issue 4, May 2008, Pages 334-337.
Rotigotine transdermal system for the treatment of Parkinson's disease
Tuesday, December 02, 2008
(Wednesday, 09 July 2008) - Contributed by David Q. Pham and Anna Nogid
Abstract
Background:
Levodopa has been the cornerstone of the treatment of Parkinson's
disease (PD) for >30 years, but long-term levodopa therapy is
associated with development of such motor complications as motor
fluctuations, dyskinesias, and drug-induced involuntary movements.
Rotigotine is a dopamine agonist with high affinity for the D2
receptor. Rotigotine transdermal system, the first such system approved
by the US Food and Drug Administration for the management of PD, has
been formulated to deliver a consistent concentration of drug to the
bloodstream with the goal of minimizing the complications associated
with pulsatile dosing.
Objective: This article reviews the
clinical pharmacology, pharmacokinetic and pharmacodynamic properties,
tolerability, and efficacy of rotigotine transdermal system in the
treatment of PD.
Methods: MEDLINE (1966-April 2008) and
International Pharmaceutical Abstracts (1971-April 2008) were searched
using the term rotigotine. All prospective, randomized clinical
efficacy trials in humans were included. The reference lists of the
identified articles were reviewed for additional publications.
Results:
In clinical trials, rotigotine transdermal system at doses ranging from
4.5 to 67 mg/d was associated with significant clinical benefit in
patients with early and advanced PD. In 4 randomized, doubleblind,
placebo-controlled trials of 6 months' duration, patients receiving
rotigotine transdermal system had significant improvements on the
Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of
daily living) that ranged from -0.3 to -4.2, compared with +0.92 to -2
for placebo (P < 0.001, rotigotine transdermal system vs placebo).
In one trial that included pramipexole as an active comparator, the
change in UPDRS II at 6 months was -4.2 in the rotigotine transdermal
system group and -4.6 in the pramipexole group (P = NS, rotigotine
transdermal system vs pramipexole). Changes on the UPDRS III (motor
examination)
at 6 months ranged from -3.58 to -8.7 with rotigotine transdermal
system, compared with +0.38 to -4.3 in the placebo group and -10.3 in
the pramipexole group (P < 0.001 vs placebo; P = NS vs pramipexole).
The change in “off” time at 6 months ranged from -2.1 to -2.7 hours
with rotigotine transdermal system, compared with -0.9 hour with
placebo and -2.8 hours with pramipexole (P < 0.001 vs placebo; P =
NS vs pramipexole). The proportion of patients achieving a >30%
reduction in “off” time ranged from 55.1% to 59.7% of patients
receiving rotigotine transdermal system, compared with 34.5% to 35.0%
of patients receiving placebo and 67.0% of patients receiving
pramipexole (P<0.001 vs placebo; P = NS vs pramipexole). The most
commonly reported adverse event was application-site reaction,
occurring in 9% to 46% of patients receiving rotigotine transdermal
system, compared with 5% to 13% of patients receiving placebo. Other
adverse events occurring in >20% of patients receiving rotigotine
transdermal systemweresomnolence(8% 2-33%)and nausea(12%-49%). Less
than 5% of patients assigned to rotigotine transdermal system
discontinued study medication
because of an adverse drug event.
Conclusions:
The available evidence suggests that rotigotine transdermal system was
effective compared with placebo in decreasing morbidity in patients
with early and advanced PD. The most commonly reported adverse events
associated with rotigotine transdermal system were application-site
reaction, nausea, and somnolence. Additional clinical trials are needed
to determine the long-term tolerability profile of rotigotine
transdermal system and its clinical efficacy and tolerability compared
with oral dopamine agonists.
David Q. Pham PharmD, BCPS and Anna Nogid PharmD, BCPS
1Western University of Health Sciences, College of Pharmacy, Pomona, California
2Fountain Valley Regional Hospital, Fountain Valley, California
3Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York
4Brookdale University Hospital & Medical Center, Brooklyn, New York
Accepted 7 April 2008.
Available online 13 June 2008
Health Literacy not Race Predicts End-of-Life Care Preferences
Tuesday, December 02, 2008
(Wednesday, 09 July 2008) - Contributed by Angelo E. Volandes MD et al.
Journal of Palliative Medicine V.11 N.5 2008
Prevalence of dementia after age 90. Results from The 90+ Study
Tuesday, December 02, 2008
(Wednesday, 09 July 2008) - Contributed by M. M. Corrada et al.
M. M. Corrada ScD*,
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