Parkinson's Plus

A cut off of 4 or more on the ROC curve resulted in a sensitivity of 87.1% and specificity of 70.5%.

A better predictive model occurred if the following features up to death were included:

The resulting ROC curve based on individual scores showed a best cut off score of at least 11 of 17 (sensitivity 90.3%, specificity 92.6%).

CONCLUSIONS: Predictive models may help differentiate MSA and PD premortem.

Hitherto poorly recognised features, suggestive of MSA, included preserved cognitive function and absence of psychiatric effects from antiparkinsonian medication.

Diagnostic accuracy was higher in those models taking into account all clinical features occurring up to death. Further studies need to be based on new incident cohorts of parkinsonian patients with subsequent neuropathological evaluation.

J Neurol Neurosurg Psychiatry 2000 Apr;68(4):434-440
Wenning GK, Ben-Shlomo Y, Hughes A,
Daniel SE, Lees A, Quinn NP
Department of Neurology, University Hospital, Innsbruck, Austria.

PMID: 10727478

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10727478&dopt=Abstract

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Society for Progressive Supranuclear Palsy, Inc
in Baltimore Maryland
Suite 515, Woodholme Medical Building
1838 Greene Tree Rd. Baltimore, MD 21208
Toll free in USA 1 800 457 4777
Fax 410-486-4283
email: spsp@erols.com
web http://www.psp.org

England (for europe too)
the PSP Association
fax 44(0)1327 860923
email: 10072.30@compuserve.com

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National Parkinson's Foundation, Inc.

VOLUME XIX - ISSUE 2 / Spring 1998

http://www.parkinson.org/atrophy.htm

Multiple System Atrophy

By members of the National Parkinson Foundation Center of Excellence at Vanderbilt University, including David A. Robertson, Director, Nathan S. Blaser Shy-Drager Research Laboratories; Thomas L. Davis, Director, Movement Disorder Clinic; and Ariel Y. Deutch, Director, NPF Center of Excellence

Although the cause of idiopathic Parkinsonís disease is unknown, Parkinsonís disease is probably the best characterized of the neurodegenerative disorders. The loss of dopamine in the striatum is the major contributor to the disorder. However, there are several other neurodegenerative disorders involving several different systems in the brain, in which striatal dopamine loss is also found.

Among these other neurodegenerative disorders is multiple system atrophy (MSA), in which degeneration in diverse brain regions leads to problems in the control of movement, balance, blood pressure, and sexual and urinary tract function. MSA is often accompanied by some striatal dopamine loss and in certain patients typical parkinsonian symptoms are either the first noted or the most prominent.

Between 25,000 and 100,000 American have multiple system atrophy. However, many will not receive the correct diagnosis during their lifetime. This is due to the difficulty in differentiating MSA from other disorders (including relatively common degenerative disorders such as Parkinsonís disease and more rare ones such as pure autonomic failure). MSA usually occurs after age 50, with a slightly higher incidence in males. Patients usually have autonomic nervous system dysfunction first. Genitourinary dysfunction (difficulty with urination) is the most frequent initial complain in women, while impotence is the most frequent initial complaint in men. Orthostatic hypotension (a large drop in blood pressure upon standing) is common and may cause dizziness, dimming of vision, head or neck pain, yawning, temporary confusion, slurred speech, and if the hypotension is severe, the patient may "faint" upon arising from a recumbent position. In spite of low blood pressure while standing, it is common for MSA patients to have high blood pressure when lying down. A fall in blood pressure following meals or in hot weather or following infection is quite common.

When MSA begins with non-autonomic features, imbalance is the most common feature. This difficulty in maintaining balance may be due to either cerebellar or Parkinsonian abnormalities. Some patients complain of stiffness, clumsiness, or a change in handwriting at the onset of MSA. The concurrent involvement in MSA of multiple brain systems subserving movement, including the striatum, cerebellum, and cortex, leads to the movement disorder as often being the most profound disability. Hoarseness or even vocal paralysis are relatively common, as are sleep disturbances, including snoring and sleep apnea. The ability to swallow foods and liquids may be impaired.

The characteristic involvement of multiple brain systems is a defining feature of MSA, and one that on autopsy confirms the diagnosis. Recently, several groups have reported the presence of unusual inclusions in certain types of brain cells. These glial cytoplasmic inclusions are, as the name indicates, typically found in glial cells, which are the structural and metabolic support elements of the brain but are not neurons (nerve cells). Glial cells are central to maintaining the correct balance of ions in the brain, without which neurons cannot survive. Moreover, glial cells express certain proteins that accumulate and thereby limit extracellular excitatory amino acids that can be toxic to neurons. These functions of glial cells, coupled with the presence of glial cytoplasmic inclusions in MSA but not Parkinsonís disease, have sparked considerable research interest. It is noteworthy that a different type of intracellular inclusion in nerve cells, the Lewy body, is present in Parkinsonís disease but not MSA.

In MSA, there is loss of function in the two divisions of the peripheral nervous system: the sympathetic and parasympathetic nervous systems. Although the autonomic nerves themselves are largely intact, the brain loses its capacity to properly engage them to control the autonomic function. Consistent with the involvement of many brain regions in MSA, the concentrations of many neurotransmitters in the brain are reduced in MSA.

As with Parkinsonís disease, the cause of MSA remains unknown. Antibodies in the spinal fluid of patients with MSA have been shown to react with a specific area in an experimental animal brain, raising the possibility that MSA may be related to an abnormality of the immune system. It is also possible that MSA is due to abnormal folding of some unknown protein. At this time, however, these observations require independent confirmation in large groups of patients, and the relationship of such changes to specific symptoms in MSA remains unclear. What is clear is that there is a compelling need for research into the causes, and hence treatment and cure, of MSA and Parkinsonís disease.

MSA is a rare and sporadic disorder and available evidence does not support a hereditary component to the disorder. Among more than 400 patients evaluated at Vanderbilt University Medical Centerís Autonomic Dysfunction Center during the past 20 years, not one had a family member with MSA, although a number of them had family members with Parkinsonís or Alzheimerís disease. While it is possible that a few of these family members diagnosed with Parkinsonís or Alzheimerís disease might have actually had MSA, available data strongly suggests that MSA is not inherited. In Parkinsonís disease there is a similar but not identical situation, with hereditary forms of the disease representing only a small minority of the patients; even in these patients, the disease process differs somewhat from idiopathic Parkinsonís disease. There is no evidence that MSA is contagious; we have never observed people in the same house who developed the disease.

Given the relative rareness of MSA and the frequent misdiagnosis of the disorder, it is not surprising that there is a paucity of careful epidemiological investigations of MSA that allow one to identify predisposing environmental factors. Although one report raised the possibility of a small effect of exposure to environmental toxins and another report suggested a slight correlation with prior head injury, these claims have not yet been supported by other studies. In particular, MSA does not appear to be related to or caused by prior alcohol or drug abuse, poor nutrition, or other disease process earlier in life.

In summary, MSA is a severe neurodegenerative disorder of unknown cause. There is currently no cure for MSA, nor is there any therapy available that stops or slows the progression of the disease. At this time, treatment is aimed at treating problems as they arise, and thus requires careful monitoring of the patient by a skilled and experienced clinician with expertise in MSA.

The lack of specific treatments to cure or slow the progression of MSA is disheartening to patients and their loved ones and caregivers. However, exensive research efforts aimed at advancing our understanding of MSA, Parkinsonís disease and other neurodegenerative disorders are in place, and we have enjoyed a period of very rapid advances in understanding of the pathophysiology of neurodegenerative disorders. We can expect such advances to culminate in a better understanding and treatment for MSA and Parkinsonís disease over the next decade.

Multiple System Atrophy

Symptoms of MSA

Treatment of MSA

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Lewy Body
http://easyweb.easynet.co.uk/vob/alzheimers/information/lewbody.htm

Lewy Body Dementia
http://www.psychejam.com/lewy_body_dementia.htm

Lewy Body Parkinson's Disease
http://www.adrc.wustl.edu/adrc/lewy_pd.html

LewyNet
http://www.ccc.nottingham.ac.uk/~mpzjlowe/lewy/lewyhome.html

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Item # Date Time Recs Subject
------ ---- ---- ---- -------
039455 98/03/26 16:02 250 Dr. Lieberman's testimony before Congress: 3/26/98
048519 98/09/17 01:24 31 low blood pressure / stability / medication
056430 99/02/10 13:29 11 Check out LEWY BODY DEMENTIA
057343 99/03/13 07:19 85 Differences between Parkinsons and other dementia

To order a copy of these postings, send the following command:
GETPOST PARKINSN 39455 48519 57343 to:

LISTSERV@LISTSERV.UTORONTO.CA

Here are some "snippets of context" from the above messages:

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Item #39455 (26 Mar 1998 16:02) - Dr. Lieberman's testimony before Congress:

Thirty percent of Parkinson's disease patients develop a dementia which has many similarities to Alzheimer's disease. A smaller portion of PD patients develop a dementia, at an earlier age, called Lewy-body dementia. Whether the dementia of Parkinson's disease and Alzheimer's disease are different, or the same is now under intense investigation. Approximately 50% of Parkinson's

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Item #48519 (17 Sep 1998 01:24) - low blood pressure / stability / medication
background: my father has been diagnosed with parkinsonism and lewy body dementia. pd symptoms are not extensive at this point. (has the masked face, shuffled gait, quiet voice, rigidity on right side, etc. no sign of tremor as

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Item #57343 (13 Mar 1999 07:19) - Differences between Parkinsons and other dementia
Subject: Differences between Parkinsons and other dementia a relatively recently described disorder in which there is Parkinson's disease as well as a particular type of dementia. in the substantia nigra have abnormal accumulations of material called "Lewy bodies," which is a characteristic finding under the microscope. In Lewy body dementia, these same abnormalities are seen in cells in the grey matter of the brain.

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GO TO http://groups.yahoo.com/ AND TYPE IN "cbgd" (no quotes) in the search textbox. A mailing list created for anyone effected by CBGD (Corticobasal Ganglionic Degeneration) a rare progressive degenerative brain disease.