FDA Orders Black-Box Warning for Botox (4/30/09)

Many in our local support group use Botox to treat blepharospasm (closing of the eyelids), drooling, painful joint contractures, dystonia, and rigid muscles. The FDA issued an order today requiring a black-box warning on Botox and its newly-approved competitor Dysport. Such “drugs must carry warning labels explaining that the material has the potential to spread from the injection site to distant parts of the body — with the risk of serious difficulties, like problems with swallowing or breathing.”

www.nytimes.com/2009/05/01/business/01botox.html

F.D.A. Orders Warning Label for Botox
By Natasha Singer
Published: April 30, 2009
New York Times

Botox and other similar antiwrinkle drugs must now carry the most stringent kind of warning label, the Food and Drug Administration said Thursday.

The F.D.A. issued that order the day after the agency approved a new drug, Dysport, that is expected to be the first real challenger to Botox in the United States. Like Botox, Dysport is an injectable drug derived from the paralytic agent botulinum toxin.

The F.D.A. said such drugs must carry warning labels explaining that the material has the potential to spread from the injection site to distant parts of the body — with the risk of serious difficulties, like problems with swallowing or breathing.

Requiring a drug to carry a box with bold-face risk information — a so-called black-box warning — is one of the strongest safety actions the F.D.A. can take. Black boxes are typically reserved for medications known to have serious or life-threatening risks. Antidepressants, for example, carry black boxes warning of the increased danger of suicidal thoughts and actions.

The F.D.A. said it would also require makers of injectable toxins to send doctors letters warning of their risks and to produce a medication guide to be given to patients at the time of injection.

In a conference call with reporters on Thursday, an F.D.A. official said that the problems had occurred mainly in patients who received overdoses of the drug for unapproved treatments, like limb spasticity in children with cerebral palsy.

Botulinum toxins are safe when administered for approved uses at approved doses, said Dr. Ellis F. Unger, an official at the agency’s office of new drugs.

The agency’s approval of Dysport, manufactured by Ipsen, based in Paris, portends a fierce competition in the United States toxin market of a sort that has been raging in Europe for years.

Last year, Botox had worldwide sales of about $1.3 billion, according to its maker, Allergan. Dysport had sales of $189 million, according to an earnings statement from Ipsen.

In the absence of serious competition, Allergan has been able to raise the drug’s price annually. But Dysport, which in Europe has been priced lower than Botox, has the potential to capture up to 20 percent of the market in this country, said David M. Steinberg, an analyst at Deutsche Bank.

“Many doctors have been clamoring for another option,” Mr. Steinberg said.

Injectable botulinum toxins are purified forms of the bacterial poison that causes botulism, a paralyzing disease that can be fatal. The drugs temporarily reduce or halt muscle activity.

In the last 20 years, the F.D.A. has approved Botox to treat crossed eyes, eyelid spasms, severe underarm sweating, and cervical dystonia, a neck problem that can cause severe pain and abnormal head position. Under the name Botox Cosmetic, the drug is also approved to treat frown lines.

In 2000, the agency approved a different type of the toxin, Myobloc, to treat cervical dystonia.

On Wednesday, the agency approved Dysport for frown lines and cervical dystonia.

Medicis Pharmaceutical, a company in Scottsdale, Ariz., that has the rights to sell Dysport for frown lines in the United States, said it planned to bring the drug to market within 60 days. Ipsen will market the drug in this country for the neck problem.

The new F.D.A. requirement for a black-box warning on such drugs comes 15 months after the agency received a petition from Public Citizen, a public advocacy group, calling for more substantial warnings.

In its petition, the group said that the F.D.A. had received reports of 180 serious health problems and 16 deaths connected to the injections. In a response sent to the group on Thursday, the agency said it had identified even more reports of complications, including 225 reports of problems caused by the drug spreading from the injection site to distant parts of the body.

“There would have been fewer problems caused if they had put this out a year ago,” said Dr. Sidney M. Wolfe, the director of the health research group at Public Citizen.

Allergan shares fell 1.3 percent to $46.66 on Thursday, while shares of Medicis rose more than 18 percent, to $16.07.

“Corticobasal degeneration” (Current Treatment Options)

This great overview of CBD was recently published. The lead author is Stephen Reich, MD, a neurologist at the University of Maryland in Baltimore. He was the chair of the CurePSP Board.

Here’s the abstract (or “Opinion statement,” as it’s called in the article):

Current Treatment Options in Neurology. 2009 May;11(3):179-85.
Corticobasal degeneration.
Reich SG, Grill SE.

Corticobasal degeneration (CBD) is a neurodegenerative disorder characterized clinically by a combination of cortical and basal ganglia signs. Pathologically, it is classified as a tauopathy. The most distinctive clinical feature is its unilateral or markedly asymmetric presentation; among parkinsonian syndromes, with rare exceptions, only Parkinson’s disease presents with such asymmetry. The most common presenting cortical features include apraxia (patients often complain of a “useless” limb), aphasia (usually nonfluent), parietal lobe sensory signs (agraphesthesia, extinction, astereognosis), frontal dementia, or myoclonus. Basal ganglia signs include rigidity, akinesia, limb dystonia, and postural instability.

The diagnosis is often challenging for three reasons: 1) The full complement of findings are rarely seen at presentation; 2) If CBD is not suspected, subtle but relevant findings (eg, extinction, language impairment, myoclonus, or apraxia) may not be searched for or appreciated; 3) The clinical picture of CBD has substantial overlap with a variety of other parkinsonian and dementing illnesses. The differential diagnosis includes Parkinson’s disease, progressive supranuclear palsy, frontotemporal dementia, primary progressive aphasia, and Alzheimer’s disease. The clinical diagnosis is not confirmed pathologically in up to half of cases, so the term corticobasal syndrome is often preferred during life, reserving the term corticobasal degeneration for pathologically verified cases.

Treatment of CBD is primarily supportive, and most patients die within 10 years of onset. Parkinsonian signs may improve to a modest degree with levodopa, clonazepam can suppress myoclonus, and botulinum toxin can relieve dystonia. Early speech therapy, physical therapy, and occupational therapy, as well as assist devices such as a rolling walker may improve functioning and reduce complications such as aspiration pneumonia and falls. With time, however, most patients lose their independence and mobility. Throughout the course of the illness (particularly when it is advanced), caring for the caregiver is as important as caring for the patient.

PubMed ID#: 19364452 (see pubmed.gov for this abstract only)

You may be in need of some definitions, as I was:
* apraxia: loss of the ability to execute or carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements (wikipedia)
* aphasia: loss of speech (or difficulty with speech); might also include loss of the ability to write (or difficulty writing)
* agraphesthesia: Inability to recognize letters or numbers drawn by the examiner on skin. The patients’ eyes are closed if this is done on skin visible to them. (wordinfo.com)
* extinction: when the conditional response no longer occurs i.e. salivating to the sound of a bell alone. (gerardkeegan.co.uk)
* astereognosis: a loss of the ability to recognize objects by handling them (wordnet.princeton.edu)
* akinesia: no movement or lack of movement

After reading the article, here are some new points for me:

* “…Togasaki and Tanner estimated that CBD accounts for about 5% of all cases of parkinsonism. The estimated incidence rate is 0.62 to 0.92 per 100,000 per year, with an estimated prevalence of 4.9 to 7.3 per 100,000, suggesting that about 20,000 people in the United States have CBD.”

* “Several reports have suggested that CBD may be more common in women.”

* “Other than PD, almost all other parkinsonian syndromes begin bilaterally, although not always symmetrically. In the typical onset of CBD, a limb (usually upper) gradually becomes “useless” or clumsy.”

* “One fourth of cases presented with difficulty walking. In our experience, this group represents a greater diagnostic challenge; it is not unusual for these patients to undergo unsuccessful shunting for presumed normal pressure hydrocephalus before more typical features of CBD either emerge or are tested for.”

* “…other challenging presentations include dementia (often confused with Alzheimer’s disease or frontotemporal dementia) and aphasia resembling progressive, nonfluent aphasia or apraxia of speech. Murray et al. demonstrated a typical cognitive profile of CBD: ‘…a characteristic impairment of gestural, executive, social, language, and visuospatial functioning but…normal recall and recognition memory even late in the course of the disease.’ The relative sparing of memory may help to distinguish CBD from frontotemporal dementia and Alzheimer’s disease.”

* “Rinne et al. emphasized the ‘striking rigidity, akinesia and apraxia of the affected limbs,’ and the dystonic postures were often accompanied by myoclonic jerks. Few other disorders have the distinctive picture of unilateral ‘jerky dystonia’.”

* “Almost half of the patients in this series demonstrated another feature of CBD, an alien limb. Such a limb is often described as ‘having a mind of its own,’ moving uncontrollably or seeming ‘foreign.’ Similarly, a limb in CBD may levitate, but levitation is not as specific for CBD as is the alien limb.”

* “Vidailhet et al. had previously demonstrated that there is no actual paralysis of vertical saccades in CBD, as occurs in PSP along with saccadic slowing; instead, patients with CBD demonstrate a prolonged latency prior to initiating a saccade. Thus, some patients with CBD may be mistakenly thought to have ophthalmoplegia if not given sufficient time or stimulation to generate a saccade. Unequivocal slowing of vertical saccades (often best demonstrated by testing optokinetic nystagmus) or vertical supranuclear ophthalmoplegia early in the course suggests PSP rather than CBD.”

* “It is often assumed that parkinsonian syndromes like CBD ‘don’t respond’ to levodopa, but this is not entirely accurate, as there may be some improvement early in the disease course. Kompoliti et al. reported a modest benefit with levodopa in up to 24% of patients. There is a report of an autopsy-confirmed CBD patient who developed dyskinesias on levodopa, but in general, levodopa dyskinesias are rarely seen except in Parkinson’s disease and (less frequently) in multiple system atrophy.”

The full article can be purchased for $35 here:
http://www.treatment-options.com/home_j … urnalID=NE

Robin

“PSP and PT” article in physical therapy newsletter

There is a good article in TodayinPT (todayinpt.com), a newsletter for physical therapists, about Cris Zampieri’s research (described in detail in a March 2009 post).

This article for the PT community is easy reading compared to the medical journal article!  It’s wonderful this research into PSP is reaching a broader PT community.  It’s one of the most hopeful pieces of research I’ve read on PSP!

At the bottom of the TodayinPT article, there’s a short comparison of PSP and PD, taken from NINDS (ninds.nih.gov).

Robin

———————————

news.todayinpt.com/article/20090330/TODAYINPT0104/90327004

PSP and PT
A Rare Disease Responds To Therapy
By Mark Cantrell
TodayinPT, Monday March 30, 2009

PTs who have never treated a patient with progressive supranuclear palsy are not alone. The disease is so rare that only now are clinical studies emerging that prove the benefit of physical therapy intervention for the population. Whereas more than half a million Americans are diagnosed with Parkinson disease, PSP is much less common, affecting 20,000 people nationwide.

PSP is a Parkinson-like condition that affects walking, balance, mobility, vision, speech, and swallowing. Affected individuals first notice balance difficulties that can cause spontaneous dizziness and sudden falls, and often experience problems with their vision, especially an inability to look downward.

“We don’t know why that happens,” says Cris Zampieri, PT, PhD, a postdoctoral fellow at the Neurological Science Institute at Oregon Health and Science University in Portland. “There is an area in the brain stem that controls eye movement, and when those neurons degenerate, it affects vision. But no one knows if it’s environmental, familial, or genetic.”

PSP is caused by a slowly progressive degeneration of brainstem nuclei with a typical onset in late middle age. Although PSP is not directly life-threatening, individuals with PSP are more susceptible to head injuries and fractures from unexpected falls, and pneumonia from impaired swallowing.

A Visionary Study

Because little research had been done on the subject, Zampieri and her colleague and mentor Richard Di Fabio, PT, PhD, developed a small clinical study that combined treatment for both eye movement and balance problems in people with PSP. Nineteen moderate-stage patients took part in the survey, with roughly half in a balance-only group and the other half given exercises for both balance and eye movement deficits. “The exercises included going from sitting to standing, walking in tandem, abduction exercises, and so on, along with eye movement exercises,” Zampieri notes.

Because there were no guidelines in the literature for developing such a program, the team had to be creative in constructing the study. “We pulled together information from other populations and studies as to what they had found effective to develop our protocol,” Zampieri says. “No one had integrated eye movement with gait and posture studies, yet it’s a normal neuromechanism that we all need in order to function.”

Moderate to large improvements in gait and eye movement was seen in the dual-therapy group, with only small benefits for the balance-only cohort, she reports: “It was a preliminary study that involved just a small group of subjects, but I think the main message is that when you associate eye movement training with balance training, you get more benefits than with balance training alone.” A larger study involving more subjects is in the planning stages.

Benefits in the Balance

At the University of Texas Medical Branch School of Health Professions in Galveston, Elizabeth J. Protas, PT, PhD, FACSM, created her own pilot study of PSP and balance problems. Protas, professor and chair of the department of physical therapy, was impressed with the Zampieri-Di Fabio trial due to its scope. “I really must compliment them, because getting 19 [patients with] PSP together is almost a miracle,” she says.

Protas became interested in studying balance when a nursing home resident with PSP came to her program after experiencing frequent falls. “His wife wanted to keep him safe, but I failed; I couldn’t help this guy, even though I tried everything I could think of to make him more stable. I found that walkers aren’t the answer for these people, because even while using one they fall over sideways or backward.”

Protas’ study concentrated on exercises to prevent falls, a symptom that, unlike PD, manifests itself early in the course of the disease. There are other differences as well, Protas says. “[With] PSP, [a] patient’s walk is entirely different than with Parkinson’s,” she explains. “They exhibit something called a cavalier gait: almost a kind of swagger, usually followed by a fall. Someone with Parkinson’s walks with very small steps, is very slow, and doesn’t have a lot of trunk and arm movement, whereas the person with PSP has an arm swing and a regular walking stride, but no postural responses.”

For the study, Protas’ nursing home resident was given 1 1/2 hours of exercise three days per week for eight weeks, using walk training, balance perturbation, and step training on a treadmill while strapped into a body support harness for safety reasons. “It took us about three to four weeks before we saw noticeable improvement,” Protas says. “When I saw the data, I could hardly believe it, because I had come to the point where I didn’t think we’d ever be able to help. I never would have predicted we could have helped him and made that much change. It was one of those wonderful moments in clinical science.”

Ongoing Gains

At Concordia University in Mequon, Wis., professor of physical therapy Teresa Steffen, PT, PhD, had a patient with PSP of her own who suffered from frequent falls. After reading Protas’ paper, she set up a treadmill training regimen for the patient, a 72-year-old former dentist who was six years post-diagnosis. The sessions lasted for 2 1/2 years, and during that time he also participated in an exercise group for patients with PD.

The outcome was a success, Steffen reports. The patient’s incidence of falls has decreased markedly, and today he is still ambulating with the aid of a walker, lives at home with his wife, and is very involved in his community. Now 75, he has continued his exercise regimen twice per week since the study ended.

Steffen stresses the importance of a long-term, ongoing exercise program for patients with PSP. “It’s not something you can do for a while and quit and be better,” she says. “It’s forever or forget it. To get this motor learning, patients really have to practice.”

Mark Cantrell is a medical writer for the Gannett Healthcare Group. To comment, e-mail [email protected]

More Info – PSP vs. PD
Due to its similarity to other neurodegenerative conditions, PSP is often misdiagnosed, usually as PD, which can lead to inappropriate treatment.
Patients with PSP
• Tend to stand straight or with heads tilted slightly back; tend to fall backward
• “Cavalier” swaggering gait pattern; normal trunk movement and arm swing
• Speech and swallowing problems more severe, starting earlier
• Eye movement abnormal, blurred vision
• Tremor rare
• Respond poorly to levodopa
Patients with PD
• Usually bend forward
• Slow, shuffling gait pattern; little trunk movement or arm swing
• Speech and swallowing problems less severe, starting later
• Eye movement close to normal
• Tremor common
• Respond well to levodopa
Source: NIH, NINDS: www.ninds.nih.gov.

More Info – Resources
• Steffen TM, Boeve BF, Mollinger-Riemann LA, Petersen CM. Long-term locomotor training for gait and balance in a patient with mixed progressive supranuclear palsy and corticobasal degeneration. Phys Ther. 2007; 87(8): 1078-1087.
• Suteerawattananon M, MacNeill B, Protas EJ. Supported treadmill training for gait and balance in a patient with progressive supranuclear palsy. Phys Ther. 2002; 82(5): 485-495.
• Zampieri C, Di Fabio RP. Balance and eye movement training to improve gait in people with progressive supranuclear palsy: quasi-randomized clinical trial. Phys Ther. 2008; 88(12): 1460-1473.

 

Hypersexuality and PSP?

I received this question via email today:

Did you find or have you heard anything about heightened sexuality with PSP patients, for older and more challenged patients, specifically women who find a need to masturbate?

My answer is:

As I’m pretty sure I’ve discussed elsewhere on the Forum, my father did grab CNAs and private caregivers we had hired in inappropriate places (breasts, crotch). This was not in keeping with his past prudish/modest/respectful behavior. Because PSP can affect the frontal lobe, society’s rules are somewhat out the window. There is a lack of inhibition. And certainly hypersexuality is possible.

You may have luck treating this with a mood stabilizer. But it’s likely refractory to medication. Well, you can sedate the person but this is typically unacceptable to many.

Dementia and suicidal behavior (literature review)

This may be of passing interest to those dealing with dementia.

This abstract is about a literature review of any evidence for an association between dementia and suicide. The British authors state: “Overall, the risk of suicide in dementia appears to be the same or less than that of the age-matched general population but is increased soon after diagnosis, in patients diagnosed with dementia during hospitalization and in Huntington’s disease. Putative risk factors for suicide in dementia include depression, hopelessness, mild cognitive impairment, preserved insight, younger age and failure to respond to anti-dementia drugs.” The authors note that more research is needed on this topic.

Robin

International Psychogeriatrics. 2009 Apr 16:1-14. [Epub ahead of print]

Dementia and suicidal behavior: a review of the literature.

Haw C, Harwood D, Hawton K.
St Andrew’s Hospital, Northampton, U.K.

ABSTRACT

Background: While dementia is more common in older people and suicide rates in many countries are higher among the elderly, there is some doubt about the association between these two phenomena.

Methods: A search of the major relevant databases was carried out to examine the evidence for this possible association.

Results: The association between dementia and suicide and also non-fatal self-harm did not appear strong but many studies have significant methodological limitations and there are few studies of suicide or self-harm in vascular, frontotemporal, Lewy body and HIV dementia where such behavior might be expected to be more common. Rates of self-harm may be increased in mild dementia and are higher before than after predictive testing for Huntington’s disease. Overall, the risk of suicide in dementia appears to be the same or less than that of the age-matched general population but is increased soon after diagnosis, in patients diagnosed with dementia during hospitalization and in Huntington’s disease. Putative risk factors for suicide in dementia include depression, hopelessness, mild cognitive impairment, preserved insight, younger age and failure to respond to anti-dementia drugs. Large, good quality prospective studies are needed to confirm these findings.

Conclusions: Further research should be undertaken to examine how rates of suicide and self-harm change during the course of the illness and vary according to the specific sub-type of dementia.

PubMed ID#: 19368760 (see pubmed.gov for this abstract only)

“Things are not right since he/she left hospital”

The National Parkinson Foundation (parkinson.org) has a good online forum where you can ask MDs questions. Most of the questions are about PD. Occasionally people ask questions about PSP or CBD.

Recently, someone on the NPF Forum asked about the use of general anesthesia during spinal surgery. Dr. Michael Okun (from the University of Florida) indicates that anesthesia in PD is being studied now, and there is concern that symptoms worsen by surgery. The rest of the MD’s answer is an excerpt from a document on hospitalization and PD. I copied the parts of the excerpt that deal with people having worsened motor symptoms or worsened confusion after being in the hospital. There’s also a small paragraph on anesthesia.

http://forum.parkinson.org/forum/viewtopic.php?t=6996

Anonymous
Posted: Mon Mar 09, 2009 5:06 am
Post subject: General Anesthesia

I have spinal stenosis… My orthopedic surgeon wants to do a laminectomy… My neurologist tells me that “the Parkinson brain does not do well under general anesthesia. It can cause cognitive impairment.” … What have you heard and what is your opinion regarding general anesthesia and the Parkinson Brain?…

Dr. Okun
Posted: Fri Mar 13, 2009 7:07 am

Thanks for the nice message. Cate Price at University of Florida has a NPF funded research project in this area. Indeed we are worried about worsening with any type of surgery with PD and we need a better understanding of how to do surgery and anaesthesia for patient safety, because people need these operations!

Here is some information we have written over the years on PD and surgery that may be helpful. …

Be aware that for unclear reasons some symptoms worsen following general or local anesthesia, and some patients have even reported feeling as if they never return to their baseline. In general, local anesthesia is thought to be safer than general anesthesia, and if you have problems with thinking and memory, they should be evaluated prior to surgery as they may also worsen (Chou 2007).

My mother has Parkinson disease and was recently hospitalized. However, she seems to be moving much worse in the hospital than at home. Why is that?

Several explanations are possible. When patients with Parkinson’s disease have an infection of some kind, whether it is the common cold, pneumonia, or a urinary tract infection, they often feel like their symptoms worsen. Increased tremor or more difficulty walking may be noted. When the infection is treated and resolves, the symptoms generally return to baseline. Another symptom that may worsen when patients with Parkinson’s disease have an infection is swallowing. When swallowing is impaired and patients are weak, the food may go down into the lungs, causing an “aspiration pneumonia”, which in turn, may further impair swallowing ability. In these situations, a speech pathology consultation can be useful to formally assess swallowing and make dietary recommendations. In addition, a respiratory therapist consultation for “chest PT” may be helpful. Chest PT consists of several minutes of chest clapping to help mobilize the sputum and make it easier to cough.

Another possibility is – new medication. Common offenders include antipsychotic drugs or anti-nausea drugs. Haloperidol (Haldol) is a common antipsychotic drug that is used in hospital settings. This drug blocks dopamine receptors and worsens Parkinson’s disease. Other commonly used antipsychotics include risperidone (Risperdal), olanzapine (Zyprexa), and aripiprazole (Abilify). The only antipsychotics that can be used safely in PD patients are clozapine (Clozaril) and quetiapine (Seroquel). Common anti-nausea medications that can worsen symptoms of Parkinson disease include prochlorperazine (Compazine), promethazine (Phenergan), and metoclopramide (Reglan). These medications have similar structures to the antipsychotics and should not be used. Trimethobenzamide (Tigan) and ondansetron (Zofran) are suitable alternatives that can be used without fear of worsening symptoms.

Regardless of the cause, all patients with Parkinson disease should be as active as possible while in the hospital. Moving around not only tones muscle, it allows faster recovery and prevents decomposition of the skin, which can happen when staying in one position for too long. Depending upon your condition, however, you may not have a choice and your doctor may order you to bed rest. In that case, physical therapy should be ordered as soon as possible. Some patients may also need rehabilitation at a rehabilitation hospital or a nursing facility before being discharged to home.

There are multiple explanations for worsening of Parkinson disease while in the hospital. Infections should be sought and treated. Drugs that block dopamine, like haloperidol and certain anti-nausea drugs, should be avoided. Chest PT, speech pathology, and physical therapy may all be useful in the recovery process (Chou 2007).

My husband has Parkinson’s disease and became confused in the hospital last time he was there. How can I prevent this?

Many things happen in the hospital that can contribute to confusion. Any infection in a patient with Parkinson’s disease can be enough to tip a patient “over the edge” mentally. Similarly, infections can adversely affect motor function as we discussed above. The introduction of new medications frequently results in disorientation and memory problems, especially pain medications. Lack of sleep while in the hospital can also contribute to a confusional state. Continuous alarms from IV machines and hallway lights can all result in frequent awakening. Nurses also may regularly enter the room overnight to take vital signs, give medications, or to check on a patient. In some patients, especially in the elderly with intermittent confusion at home, just the fact that they are placed in a different and unfamiliar environment may tip them into a delirious state. Finally, confusion is commonly seen following a surgical procedure. The combined effects of anesthesia and medications to treat surgical incision pain are contributing factors in this situation.

Confusion will often disappear once the underlying cause is treated, whether it is addressing the infection or withdrawing the offending medications. Diagnostic testing is rarely necessary. Frequent reassurance, support and comfort may be all that is needed to assist the patient through this period. However, sometimes confusion can lead to behavioral problems, such as aggression, refusal to take pills, and even hallucinations or delusions. In these cases, physical restraints are sometimes necessary to prevent self-injury. Some hospitals have bed or wheelchair alarms to alert nurses when patients attempt to wander, while other hospitals may use a sitter to promote safety. If there are psychotic symptoms, such as visual hallucinations, antipsychotics may be used. Remember in nearly all cases, clozapine (Clozaril) and quetiapine (Seroquel) are the only antipsychotics that should be used in patients with Parkinson disease. Occasionally, lorazepam (Ativan) or diazepam (Valium) can be helpful. These drugs, by themselves, may worsen confusion, but they also can calm the patient. These medications are only temporary and may be discontinued when the confusion resolves.

In very severe cases of confusion with hallucinations and behavioral changes, it may be necessary to temporarily discontinue dopamine agonists, MAO inhibitors, amantadine, benzodiazepines, and pain medications if possible. Treatment with carbidopa/levodopa and either clozapine or quetiapine will usually result in improvement. Later, once patients are stable, they may be slowly titrated back onto previous doses if tolerated (Chou 2007).

Infection and medications are common causes of confusion in the hospital, and when the underlying cause is addressed it usually improves dramatically. …

Michael S. Okun, M.D.

“A Life Worth Living” – Radio Interview and Book

Sadly, the loved ones of five local support group members died in March; one support group member (caregiver) died too. At least one group member was involved in end-of-life treatment decisions, and relied on her husband’s written wishes when he was no longer able to communicate.

Along these lines, I heard a book author interviewed today (Thursday 4/2/09) on NPR’s “Fresh Air” program, and wanted to pass the info along to all of you. The book is “A Life Worth Living,” and the author is Robert Martensen, MD. Dr. Martensen was an ER and ICU MD for many years; he’s also a bioethicist.

In his book he talks about his father’s hospital death, and “argues that safeguarding the quality of a patient’s life sometimes trumps the urge to sustain life at all cost.” He also addresses his father’s death in the “Fresh Air” interview as well as his mother’s impending death. His mother lives in Santa Cruz. In the story about his mother, he describes one of his mother’s first MDs in these final weeks who wanted to place a pacemaker. Dr. Martensen worries that it’s only because he is an MD that he was able to know the right questions to ask the treating physician. Ultimately, he’s very fortunate that both of his parents had given such clear advance directives about what sort of treatment they wanted, given certain circumstances. He contrasts his mother with another elderly woman also suffering from dementia.

I would recommend listening to the 40-minute “Fresh Air” interview. You can find it online here:

The interview is titled “The Ethical Way To Heal American Health Care,” which doesn’t really capture the interview.

“Treating an Illness Is One Thing. What About a Patient With Many?”

This is a good article in a recent New York Times (nytimes.com) about patients with many illnesses, not just one.  A key problem is that these patients end up on many medications.  Here’s an excerpt:

“Doctors know that it’s not right for someone to be on 15, 18, 20 medications,” said Dr. Tinetti, the Yale geriatrician. “But they’re being told that that’s what’s necessary in order to treat each of the diseases that the patients in front of them have.”

Here’s a link to the full article:

http://www.nytimes.com/2009/03/31/health/31sick.html

Treating an Illness Is One Thing. What About a Patient With Many?
Brendan Smialowski
The New York Times
March 30, 2009

Thanks to online friend Joe Blanc for making me aware of this article.

Robin

 

 

Progression of dysarthria + dysphagia in PSP, CBD, etc

I’ve posted some of the info in this article previously and the PubMed ID# but have never posted these excerpts.

This 2001 study is of dysarthria and dysphagia in autopsy-confirmed cases of DLB, CBD, MSA, PSP, and PD. According to the article, all atypical parkinsonism patients develop either dysarthria or dysphagia within one year of disease onset. (I thought dysarthria meant slurred speech. But, according to this article, it can also mean hypophonic speech or monotonic speech.)

Here’s the citation and abstract:

Archives of Neurology. 2001 Feb;58(2):259-64.

Progression of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders.

Muller J, Wenning GK, Verny M, McKee A, Chaudhuri KR, Jellinger K, Poewe W, Litvan I.
Cognitive Neuropharmacology Unit, Bethesda, MD

BACKGROUND: Dysarthria and dysphagia are known to occur in parkinsonian syndromes such as Parkinson disease (PD), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Differences in the evolution of these symptoms have not been studied systematically in postmortem-confirmed cases.

OBJECTIVE: To study differences in the evolution of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders.

PATIENTS AND METHODS: Eighty-three pathologically confirmed cases (PD, n = 17; MSA, n = 15; DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis for a multicenter clinicopathological study organized by the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Cases with enough clinicopathological documentation for the purpose of the study were selected from research and neuropathological files of 7 medical centers in 4 countries (Austria, France, England, and the United States).

RESULTS: Median dysarthria latencies were short in PSP and MSA (24 months each), intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months). Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months), and long in PD (130 months). Dysarthria or dysphagia within 1 year of disease onset was a distinguishing feature for atypical parkinsonian disorders (APDs) (specificity, 100%) but failed to further distinguish among the APDs. Survival time after onset of a complaint of dysphagia was similar in PD, MSA, and PSP (15 to 24 months, P =.7) and latency to a complaint of dysphagia was highly correlated with total survival time (rho = 0.88; P<.001) in all disorders.

CONCLUSIONS: Latency to onset of dysarthria and dysphagia clearly differentiated PD from the APDs, but did not help distinguish different APDs. Survival after onset of dysphagia was similarly poor among all parkinsonian disorders. Evaluation and adequate treatment of patients with PD who complain of dysphagia might prevent or delay complications such as aspiration pneumonia, which in turn may improve quality of life and increase survival time.

PubMed ID#: 11176964

These results were the most interesting (and depressing):

“Dysarthria or dysphagia within 1 year of disease onset was a distinguishing feature for atypical parkinsonian disorders (APDs).”

“Median dysarthria latencies were short in PSP and MSA (24 months each), intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months).”

“Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months), and long in PD (130 months).”

“Survival time after onset of a complaint of dysphagia was similar in PD, MSA, and PSP (15 to 24 months).”

On this last point, here are the CBD and PSP data from the article:

Survival Time After Onset of Dysphagia, months
CBD 49 (25-89…..including a single patient with dysphagia but without dysarthria)
PSP 18 (6-96)

Here are some excerpts from the article’s Comment section:

“(Early) dysarthria and perceived swallowing dysfunction are not features of PD.”

“Dysarthria) as a presenting symptom has been described in clinical series of CBD, MSA, and PSP. In PD and DLB, hypphonic/monotonous speech represented the most frequent type of dysarthria, whereas imprecise or slurred articulation predominated in CBD, MSA, and PSP.”

“In a clinical study of CBD, Rinne et al described dysarthria as one of the initial symptoms in 11% of the patients, which is close to our findings. At follow-up, on average 5.2 years, dysarthria was diagnosed in 70% of the patients… According to our findings, dysarthria occurred in almost every patient with CBD.”

“In both PSP and MSA, progressive dysarthria is believed to represent a manifestation of brainstem and cerebellar involvement. In fact, PET studies revealed marked hypometabolism in the cerebellum and brainstem of patients with MSA, which correlated with dysarthria.”

“In our study, dysphagia was associated with concomitant dysarthria in all parkinsonian patients except one. This sequence of dysphagia following dysarthria has also been reported in clinical studies of PD, MSA, and PSP.”

“…Golbe et al reported dysphagia after a median of 1 year after the onset of dysarthria in PSP.”

In all these disorders, “bronchopneumonia has been reported as a leading cause of death, which may be subsequent to silent aspiration resulting from dysphagia.”

“Most of our patients with MSA and PSP complained of a swallowing dysfunction, in contrast to patients with PD, CBD, and DLB… Impaired lingual proprioception is hypothesized to contribute to the unawareness of swallowing difficulties in PD and might in part explain significantly longer latencies to dysphagia in our PD cases. In contrast, patients with PSP were reported to be keenly aware of swallowing problems, including those with cognitive impairment.”

“(The) similarly short remaining survival time in PD and PSP after the onset of perceived dysphagia suggests that this symptom represents a reliable marker for the onset of functionally relevant swallowing abnormalities in both disorders.”

Robin