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.
Friday, December 5, 2008
Issues of Hope
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.
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.
Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Parkinson's
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.
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.
Thorough QT/QTc Study in Patients With Advanced Parkinson's Disease: Cardiac Safety of Rotigotine
(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
2008 Clinical Pharmacology & Therapeutics advance online publication
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
2008 Clinical Pharmacology & Therapeutics advance online publication
When a Parkinson’s disease patient starts to hallucinate
(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.
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.
Thursday, December 4, 2008
Patients Old and Young
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.
"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.
Tuesday, December 2, 2008
Health Literacy not Race Predicts End-of-Life Care Preferences
(Wednesday, 09 July 2008) - Contributed by Angelo E. Volandes MD et al.
Journal of Palliative Medicine V.11 N.5 2008
Journal of Palliative Medicine V.11 N.5 2008
Prevalence of dementia after age 90. Results from The 90+ Study
(Wednesday, 09 July 2008) - Contributed by M. M. Corrada et al.
M. M. Corrada ScD*,
M. M. Corrada ScD*,
Rotigotine transdermal system for the treatment of Parkinson's disease
(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
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
Metatarsal fracture as a consequence of foot dystonia in Parkinson's disease
(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.
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.
Frailty in Parkinson's disease and its clinical implications
(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.
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.
Nonmotor symptoms of Parkinson's disease: Prevalence and awareness of patients and families
(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.
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.
Functional balance performance in patients with Parkinson's disease after long-term treatment...
(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
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 questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease
(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
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
Fatigue in Parkinson's disease is not related to excessive sleepiness or quality of sleep
(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
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
(Monday, 16 June 2008) - Contributed by Pedro J. García 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.
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
(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.
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.
A pilot study into the effect of vocal exercises and singing on dysarthric speech
(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
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
Thursday, October 30, 2008
Read Weekly Journals
Read about patient concerns, family dilemmas, and the clinical dynamics of a weekly movement disorder clinic. Observe ways a movement disorder neurologist manages patient symptoms with medications, surgical referrals, physical therapy, and caregiver options.
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