Shy-Drager/MSA Support Group

February 1, 2001

Table of Contents
1. Iron Metabolism and MSA
2. Oxidative Stress and MSA
3. Dr. Sid Gilman to Speak at National Ataxia Foundation Annual Conference
4. Research Articles by Dr. Sid Gilman
5. Curing Parkinson's Disease in Our Lifetime

-------------

1. Iron Metabolism and MSA

-------------

2. Oxidative Stress and MSA

-------------

3. Dr Sid Gilman to speak at National Ataxia Foundation Annual Conference

Dr. Gilman who specializes in Multiple System Atrophy and sporadic cerebellar degeneration (ataxia) will speak at the conference to be held in Prior Lake, Minnesota from April 5 - 8, 2001.

If you decide to attend please email me (pbower@accesscable.net) and I can help ensure you meet up with others. At registration they will give you a name badge with a sticker that says MSA if you request it. This will identify your interest in MSA at their "Birds of a Feather" events.

-------------

4. Research Articles by Dr. Sid Gilman

Neurology 2000 Aug 22;55(4):527-32
Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy.
Gilman S, Little R, Johanns J, Heumann M, Kluin KJ, Junck L, Koeppe RA, An H
Department of Neurology, University of Michigan, Ann Arbor, 48109-0316,USA.

OBJECTIVE: To determine the percentage of sporadic olivopontocerebellar atrophy (sOPCA) patients who later develop multiple system atrophy (MSA).

METHODS: Observations of the course of 51 sOPCA patients 20 years of age or older initially evaluated in an ataxia clinic over 14 years and followed at 3- to 6-month intervals for 3 months to 10 years (median 2.5 years, interquartile range 5 months to 4 years). RESULTS: Seventeen patients evolved to develop MSA, whereas the remaining 34 manifested only progressively worsening cerebellar ataxia. The features of the MSA cases included autonomic failure and parkinsonism in 10 patients, autonomic failure without parkinsonism in six, and parkinsonism without autonomic failure in one. Using survival analysis methods, the authors estimated that 24% of subjects in this population will evolve to MSA within 5 years of the onset of sOPCA symptoms (95% CI 10% to 36%). An older age at onset of symptoms and a shorter time from onset of symptoms to first presentation in a neurology specialty clinic were both highly predictive of evolution to MSA. Six of the 17 patients who evolved to MSA died 4 months to 5 years after they had met diagnostic criteria for MSA. The estimated median survival time from time of transition was 3.5 years. In contrast, death occurred in only one of the 34 patients with sOPCA who did not evolve to MSA. Autopsy examination of all six patients with MSA who died confirmed the diagnosis. CONCLUSIONS: Approximately one-fourth of sporadic olivopontocerebellar atrophy patients will evolve to multiple system atrophy within 5 years, and this transition carries a poor prognosis for survival. Older age at onset of ataxia and earlier presentation in a neurologic specialty clinic predicted transition to MSA.

PMID: 10953186, UI: 20411665

-------------

Neurologia 1999 Nov;14(9):425-8
[Consensus on the diagnosis of multi-system atrophy].
Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Klockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G
Department of Neurology, University of Michigan Medical Center, Ann Arbor, USA.

We report the results of a consensus conference on the diagnosis of multiple system atrophy. We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible multiple system atrophy requires one criterion plus two features from separate domains. The diagnosis of probable multiple system atrophy requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite multiple system atrophy requires pathological confirmation.

PMID: 10613015, UI: 20079839

-------------

Am J Pathol 1999 Oct;155(4):1241-51
Widespread alterations of alpha-synuclein in multiple system atrophy.
Dickson DW, Liu W, Hardy J, Farrer M, Mehta N, Uitti R, Mark M, Zimmerman T, Golbe L, Sage J, Sima A, D'Amato C, Albin R, Gilman S, Yen SH
Department of Pathology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA. dickson.dennis@mayo.edu

Glial cytoplasmic inclusions (GCI) are the hallmark of multiple system atrophy (MSA), a rare movement disorder frequently associated with autonomic dysfunction. In this study of 21 cases of MSA, GCI were consistently immunoreactive for alpha-synuclein and double-immunostained for ubiquitin and oligodendroglial markers, but not glial fibrillary acidic protein. No statistically significant difference was found in the density of GCI in various brain regions in the two forms of MSA, striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA). Postmortem brain samples from 9 cases of MSA were fractionated according to solubility in buffer, Triton-X 100, sodium dodecyl sulfate (SDS), and formic acid, and alpha-synuclein immunoreactivity was measured in Western blots. Total alpha-synuclein immunoreactivity was increased in MSA compared to controls, with no statistically significant difference between SND and OPCA. Most of the increase was due to alpha-synuclein in SDS fractions. In controls this fraction had little or no immunoreactivity. In 7 cases and 4 controls correlations were investigated between quantitative neuropathology and biochemical properties of alpha-synuclein. Surprisingly, the amount of SDS-soluble alpha-synuclein correlated poorly with the number of GCI in adjacent sections. Furthermore, areas with few or no GCI unexpectedly had abundant SDS-soluble alpha-synuclein. These findings provide evidence that modifications of alpha-synuclein in MSA may be more widespread than obvious histopathology. Moreover, these alterations may constitute a biochemical signature for the synucleinopathies.

PMID: 10514406, UI: 99445341

-------------