Recent developments in MSA (dementia?)

This looks like an important paper on MSA, written by Gregor Wenning, one of Europe’s authorities on MSA.

To me, the most interesting sentences were about whether dementia can occur in MSA.  The authors say:

“The revised consensus criteria regard dementia as a non-supportive feature of MSA [50]. However, recent evidence suggests that dementia can occur in some patients otherwise satisfying the MSA criteria [77]. Further studies are required to assess the frequency and profile of dementia in MSA. These data may support a broader phenotype of MSA that also includes cognitive dysfunction.”

In personal correspondence, Dr. Wenning confirmed that there are no post-mortem confirmed cases of MSA with dementia….so far.  He believes we need to “keep an open mind.”

I’ve copied the abstract below.

Robin

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Journal of Neurology. 2009 May 27. [Epub ahead of print]
Recent developments in multiple system atrophy.
Wenning GK, Stefanova N.
Section of Clinical Neurobiology, Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria,Gregor.Wenning@i-med.ac.at.

Multiple system atrophy (MSA) is a rare late onset neurodegenerative
disorder which presents with autonomic failure and a complicated motor syndrome including atypical parkinsonism, ataxia and pyramidal signs. MSA is a glial alpha-synucleinopathy with rapid progression and currently poor therapeutic management. This paper reviews the clinical features, natural history and novel diagnostic criteria for MSA as well as contemporary knowledge on pathogenesis based on evidence from neuropathological studies and experimental models. An outline of the rationale for managing symptomatic deterioration in MSA is provided together with a summary of novel experimental therapeutic approaches to decrease disease progression.

PubMed ID#: 19471850

 

Recall of Nitrofurantoin (Macrobid) Capsules

Nitrofurantoin is an antibiotic. (It is generic Macrobid.) My dad used it prophylactically to prevent UTIs. I read this news of the recall on an MSA-related online discussion group. Here are two very short articles on the recall, which is from a single manufacturer of this medication.

http://www.ashp.org/import/news/HealthS … px?id=3079

Ranbaxy Recalls All Lots of Nitrofurantoin
Cheryl A. Thompson
American Society of Health-System Pharmacists

BETHESDA, MD 05 May 2009—The U.S. subsidiary of Ranbaxy Laboratories Limited on May 2 announced a recall of all lots of nitrofurantoin 100-mg capsules because some do not conform to laboratory specifications.

Ranbaxy Pharmaceuticals Inc. said there is a “remote possibility” that capsules not conforming to the specifications may increase the occurrence of “local non-serious” adverse gastrointestinal events, such as nausea and vomiting, in patients using the product.

The company’s nitrofurantoin capsules, containing 25 mg of nitrofurantoin macrocrystals and 75 mg of nitrofurantoin monohydrate, are a therapeutic equivalent of Macrobid capsules, manufactured by Norwich Pharmaceuticals Inc. According to the FDA-approved labeling for Macrobid, the rate of possible or probable drug-related nausea under usual circumstances is 8%. Vomiting is described in the labeling as a symptom of acute overdosage.

Ranbaxy has advised patients who have any of the company’s nitrofurantoin capsules to consult their physician for “alternate and appropriate medication/treatment options.”

http://www.drugs.com/news/ranbaxy-volun … 17559.html

Ranbaxy Voluntarily Recalls Nitrofurantoin Capsules in the U.S.

PRINCETON, N.J., May 1 /PRNewswire/ — Ranbaxy Pharmaceuticals Inc. (RPI) announced today that it is conducting a voluntary recall of all lots of Nitrofurantoin (Monohydrate/Macrocrystals) Capsules, USP 100 mg currently on the market in the U.S.

Although certain lots of the product were determined to not be in conformity with the approved laboratory specifications, Ranbaxy decided to recall all the lots, as a matter of abundant caution, given its commitment to the health and safety of patients. Ranbaxy is continuing to look into the cause of such non-conformity.

The recall is being conducted in coordination with the FDA and will be a retail level recall. To the best of Ranbaxy’s knowledge, the recalled product is unlikely to produce any serious adverse health effects. However, there is a remote possibility that the non-conforming product may increase the incidence of local non-serious gastrointestinal adverse events such as nausea and vomiting. All patients presently consuming and/or prescribed this formulation should consult their physicians for alternate and appropriate medication/treatment options.

Ranbaxy Pharmaceuticals Inc. (RPI) based in Jacksonville, Florida, is a wholly owned subsidiary of Ranbaxy Laboratories Limited (RLL), India’s largest pharmaceutical company. RPI is engaged in the sale and distribution of generic and branded prescription products in the U.S. healthcare system.

Source: Ranbaxy Pharmaceuticals Inc.

16 patients with clinical DX of CBS (11 had CBD, 5 had AD)

This research by Mayo Rochester (including CBD expert Dr. Brad Boeve) was published a couple of days ago. In this study, 16 patients had a clinical diagnosis of CBS (corticobasal syndrome). After death, 11 were pathologically diagnosed with CBD (corticobasal degeneration) and 5 with Alzheimer’s Disease (AD). Here are the key differences in the two patient groups, after correlating the clinical record with the pathological results:

* “Patients with AD pathology had an earlier age of onset than patients with CBD pathology (58 vs. 68 years).”
* “Tremors were only present in CBD cases (73%)…”
* Interestingly, “myoclonus was more common in AD than CBD (80 vs. 18%).”
* “SPECT imaging demonstrated parietal hypoperfusion in AD patients and frontotemporal hypoperfusion in CBD patients.”

The authors conclude that: “Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD.”

We need more articles like this, with bigger patient numbers!

Robin

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Movement Disorders. 2009 May 7. [Epub ahead of print]

Alzheimer’s disease and corticobasal degeneration presenting as corticobasal syndrome.

Hu WT, Rippon GW, Boeve BF, Knopman DS, Petersen RC, Parisi JE, Josephs KA.
Department of Neurology, Mayo Clinic, Rochester, Minnesota.

The aim of this article is to compare patients with Alzheimer’s disease (AD) pathology and corticobasal degeneration pathology (CBD) presenting as corticobasal syndrome (CBS).

Clinicopathologic series was used. Five patients with AD and 11 patients with CBD were clinically diagnosed with CBS. Patients with AD pathology had an earlier age of onset than patients with CBD pathology (58 vs. 68 years, P = 0.004), but the two groups had similar disease duration and core features of CBS. Tremors were only present in CBD cases (73%, P = 0.026), but myoclonus was more common in AD than CBD (80 vs. 18%, P = 0.036). Neuropsychological testing showed similar degrees of memory impairment and attentional deficits. (99m)Tc-HMPAO SPECT imaging demonstrated parietal hypoperfusion in AD patients and frontotemporal hypoperfusion in CBD patients. AD patients with clinical CBS have similar characteristics to CBD patients. Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD.

PubMed ID#: 19425061 (see pubmed.gov for this abstract only; you can also link to the full article for which the publisher probably charges $30)

“The Alzheimer’s Project” (HBO and free online)

I received this announcement from the Alzheimer’s Association:

http://www.alz.org/news_and_events_16202.asp

The documentary that will change the way America thinks about Alzheimer’s disease.

On May 10, 11 and 12, tune into HBO’s “THE ALZHEIMER’S PROJECT” to take a look at the faces behind the disease – and the forces leading us to find a cure. This multi-platform series reveals groundbreaking Alzheimer discoveries and the effects this debilitating and fatal disease has on those with Alzheimer’s and their families.

As the leading voluntary health organization in Alzheimer’s care, support and research, the Alzheimer’s Association has been an active partner in “THE ALZHEIMER’S PROJECT,” providing expert insight and leading community engagement.

Air dates and times

Sunday, May 10 at 9 p.m. EST
“The Memory Loss Tapes”

Monday, May 11 at 7:30 p.m. and 8 p.m. EST
“Grandpa, Do You Know Who I Am? With Maria Shriver”
“Momentum in Science, Part 1”

Tuesday, May 12 at 7 p.m. and 8 p.m. EST
“Caregivers”
“Momentum in Science, Part 2”

For additional details, please visit hbo.com/alzheimers.

Be a part of something big.

HBO’s “THE ALZHEIMER’S PROJECT” will expose the Alzheimer crisis facing our nation and drive concerned citizens to take action.

“THE ALZHEIMER’S PROJECT” is a presentation of HBO Documentary Films and the National Institute on Aging at the National Institutes of Health in association with the Alzheimer’s Association, The Fidelity® Charitable Gift Fund and Geoffrey Beene Gives Back® Alzheimer’s Initiative.

All films will stream free of charge on www.hbo.com/alzheimers and will be offered for free on multiple platforms by participating television service providers.

Delirium (from hospitalization or illness) accelerates memory loss

This press release out of Beth Israel Deaconess Medical Center (bidmc.org) in Boston will be of interest to those dealing with dementia.

The press release reports on a study that:

“…confirms that an episode of delirium rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients. … Delirium often develops in elderly patients during hospitalization or serious illness, and this acute state of confusion and agitation has long been suspected of having ties to Alzheimer’s disease and other dementias.”

The press release is copied below.

Robin
_____________________________

www.bidmc.org/News/InResearch/2009/April/DeliriumandDementia.aspx

Delirium Accelerates Memory Loss in Patients With Alzheimer’s Disease
Acute state of confusion and disorientation often complicates hospitalizations for patients with dementia
Beth Israel Deaconess Medical Center, Boston, MA
Press Release
Date: 5/4/2009

BOSTON ­ Delirium often develops in elderly patients during hospitalization or serious illness, and this acute state of confusion and agitation has long been suspected of having ties to Alzheimer’s disease and other dementias. Now a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Hebrew Senior Life confirms that an episode of delirium rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients. The findings are reported in the May 5 issue of the journal Neurology.

“The cognitive rate of decline was found to be three times more rapid among those Alzheimer’s patients who had had an episode of delirium than among those who did not have such a setback,” according to lead author Tamara Fong, MD, a staff neurologist at BIDMC and Assistant Scientist at the Institute for Aging Research, Hebrew Senior Life. “In other words, the amount of decline you might expect to see in an Alzheimer’s patient over the course of 18 months would be accelerated to 12 months following an episode of delirium.”

Alzheimer’s disease is an irreversible, progressive form of dementia that gradually destroys a person’s ability to carry out even the simplest of tasks, and affects as many as 4.5 million individuals in the U.S. according to figures from the National Institute on Aging. There is currently no cure for Alzheimer’s disease.

Delirium, on the other hand, is a potentially preventable condition, which often develops following a medical disturbance, surgery or infection and is estimated to affect between 14 percent and 56 percent of all hospitalized elderly patients.

The investigators performed a secondary analysis of data gathered from 408 patients examined between 1991 and 2006 at the Massachusetts Alzheimer’s Disease Research Center (MADRC). Over this 15-year period, MADRC staff conducted a number of memory tests on patients. Testing was done on at least three occasions, separated by intervals of approximately six months. Seventy-two of the participants developed delirium during the course of the study.

In their final analysis, the authors found that among patients who developed delirium, the average decline on cognitive tests was 2.5 points per year at the beginning of the study; following an episode of delirium, decline nearly doubled to 4.9 points per year.

“Although each dementia patient declines at his or her own individual rate, the results of our study tell us that this rate can increase three-fold following an episode of delirium,” says Fong. “As an example, suppose an Alzheimer’s patient begins with mild symptoms, such as forgetting appointments or details of conversations, but over a period of the next 18 months, loses the ability to identify relatives, becomes lost while driving familiar routes, or can no longer balance a checkbook or manage financial transactions. This same patient, were he or she to experience an episode of delirium, might experience this same rate of decline in only 12 months.”

While further investigations are needed to determine the mechanism behind this turn-of-events, Fong explains that delirium may, in fact, be a key link in a chain of events that results in injury to brain cells. “Older patients may be at greater risk of developing delirium ­ particularly in the hospital setting ­ because they tend to have less ‘reserve’ or ability to compensate in settings of increased stress. Consequently, infections, new medications and other stressors put the patient at risk for delirium.”

All elderly patients, but particularly patients who have already been diagnosed with Alzheimer’s disease, can benefit from a number of preventive measures if they are hospitalized, notes Fong.

“As much as possible, it’s important to try and orient the patient to his or her surroundings [i.e. frequently remind the patient that he or she is in the hospital], to allow for as much uninterrupted sleep as possible by not waking patients to take vital signs or do blood draws at night, and to get patients out of bed and walking as soon as their medical condition allows,” notes Fong. Also, important, she adds, is to avoid use of unnecessary medications.

“Twenty percent of all elderly patients who develop delirium go on to experience complications, whether it’s a prolonged hospital stay, a move to a rehabilitation center or long-term care facility, or even death,” notes Fong. “Our current study now shows that delirium can also adversely impact the state of cognitive decline in patients with Alzheimer’s disease. Because up to 40 percent of delirium episodes can be prevented, taking steps to avoid delirium could result in significant improvements.”

This study was funded, in part, by grants from the Massachusetts Alzheimer’s Disease Research Center, the National Institute on Aging, and the Alzheimer’s Association, and the VA Rehabilitation Career Development Award.

Study coauthors include BIDMC investigators Edward Marcantonio and Sharon Inouye; Hebrew Senior Life investigators Richard Jones, Peilin Shi, James Rudolph, Frances Yang and Douglas Kiely; and Liang Yap of Massachusetts General Hospital.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.