Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2000 Apr;68(4):434–440. doi: 10.1136/jnnp.68.4.434

What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease?

G Wenning 1, Y Ben-Shlomo 1, A Hughes 1, S Daniel 1, A Lees 1, N Quinn 1
PMCID: PMC1736862  PMID: 10727478

Abstract

OBJECTIVES—Few studies have attempted to identify what premortem features best differentiate multiple system atrophy (MSA) from Parkinson`s disease (PD). These studies are limited by small sample size, clinical heterogeneity, or lack of postmortem validation. We evaluated the sensitivity and specificity of different clinical features in distinguishing pathologically established MSA from PD.
METHODS—One hundred consecutive cases of pathologically confirmed PD and 38 cases of pathologically confirmed MSA in one Parkinson's disease brain bank were included. All cases had their clinical notes reviewed by one observer (AH). Clinical features were divided into two groups: those occurring up to 5 years after onset of disease and those occurring up to death. Statistical analysis comprised multivariate logistic regression analysis to choose and weight key variables for the optimum predictive model.
RESULTS—The selected early features and their weightings were: autonomic features (2), poor initial levodopa response (2), early motor fluctuations (2), and initial rigidity (2). 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: poor response to levodopa (2), autonomic features (2), speech or bulbar dysfunction (3), absence of dementia (2), absence of levodopa induced confusion (4), and falls (4). 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.



Full Text

The Full Text of this article is available as a PDF (161.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADAMS R., VAN BOGAERT L., VAN DER EECKEN H. [Nigro-striate and cerebello-nigro-striate degeneration. (Clinical uniqueness and pathological variability of presenile degeneration of the extrapyramidal rigidity type]. Psychiatr Neurol (Basel) 1961;142:219–259. [PubMed] [Google Scholar]
  2. Albanese A., Colosimo C., Bentivoglio A. R., Fenici R., Melillo G., Colosimo C., Tonali P. Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria. J Neurol Neurosurg Psychiatry. 1995 Aug;59(2):144–151. doi: 10.1136/jnnp.59.2.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ben-Shlomo Y., Wenning G. K., Tison F., Quinn N. P. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology. 1997 Feb;48(2):384–393. doi: 10.1212/wnl.48.2.384. [DOI] [PubMed] [Google Scholar]
  4. Colosimo C., Albanese A., Hughes A. J., de Bruin V. M., Lees A. J. Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease. Arch Neurol. 1995 Mar;52(3):294–298. doi: 10.1001/archneur.1995.00540270090024. [DOI] [PubMed] [Google Scholar]
  5. Fearnley J. M., Lees A. J. Striatonigral degeneration. A clinicopathological study. Brain. 1990 Dec;113(Pt 6):1823–1842. doi: 10.1093/brain/113.6.1823. [DOI] [PubMed] [Google Scholar]
  6. Graham J. G., Oppenheimer D. R. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1969 Feb;32(1):28–34. doi: 10.1136/jnnp.32.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gray F., Vincent D., Hauw J. J. Quantitative study of lateral horn cells in 15 cases of multiple system atrophy. Acta Neuropathol. 1988;75(5):513–518. doi: 10.1007/BF00687140. [DOI] [PubMed] [Google Scholar]
  8. Hughes A. J., Ben-Shlomo Y., Daniel S. E., Lees A. J. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. Neurology. 1992 Jun;42(6):1142–1146. doi: 10.1212/wnl.42.6.1142. [DOI] [PubMed] [Google Scholar]
  9. Hughes A. J., Colosimo C., Kleedorfer B., Daniel S. E., Lees A. J. The dopaminergic response in multiple system atrophy. J Neurol Neurosurg Psychiatry. 1992 Nov;55(11):1009–1013. doi: 10.1136/jnnp.55.11.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hughes A. J., Daniel S. E., Blankson S., Lees A. J. A clinicopathologic study of 100 cases of Parkinson's disease. Arch Neurol. 1993 Feb;50(2):140–148. doi: 10.1001/archneur.1993.00540020018011. [DOI] [PubMed] [Google Scholar]
  11. Hughes A. J., Daniel S. E., Kilford L., Lees A. J. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181–184. doi: 10.1136/jnnp.55.3.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kluin K. J., Gilman S., Lohman M., Junck L. Characteristics of the dysarthria of multiple system atrophy. Arch Neurol. 1996 Jun;53(6):545–548. doi: 10.1001/archneur.1996.00550060089021. [DOI] [PubMed] [Google Scholar]
  13. Litvan I., Goetz C. G., Jankovic J., Wenning G. K., Booth V., Bartko J. J., McKee A., Jellinger K., Lai E. C., Brandel J. P. What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study. Arch Neurol. 1997 Aug;54(8):937–944. doi: 10.1001/archneur.1997.00550200007003. [DOI] [PubMed] [Google Scholar]
  14. Litvan I., Mangone C. A., McKee A., Verny M., Parsa A., Jellinger K., D'Olhaberriague L., Chaudhuri K. R., Pearce R. K. Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):615–620. doi: 10.1136/jnnp.60.6.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Magalhães M., Wenning G. K., Daniel S. E., Quinn N. P. Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson's disease--a retrospective comparison. Acta Neurol Scand. 1995 Feb;91(2):98–102. doi: 10.1111/j.1600-0404.1995.tb00414.x. [DOI] [PubMed] [Google Scholar]
  16. Mark M. H., Sage J. I., Dickson D. W., Schwarz K. O., Duvoisin R. C. Levodopa-nonresponsive Lewy body parkinsonism: clinicopathologic study of two cases. Neurology. 1992 Jul;42(7):1323–1327. doi: 10.1212/wnl.42.7.1323. [DOI] [PubMed] [Google Scholar]
  17. Mayeux R., Denaro J., Hemenegildo N., Marder K., Tang M. X., Cote L. J., Stern Y. A population-based investigation of Parkinson's disease with and without dementia. Relationship to age and gender. Arch Neurol. 1992 May;49(5):492–497. doi: 10.1001/archneur.1992.00530290076015. [DOI] [PubMed] [Google Scholar]
  18. McKeith I. G., Galasko D., Kosaka K., Perry E. K., Dickson D. W., Hansen L. A., Salmon D. P., Lowe J., Mirra S. S., Byrne E. J. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov;47(5):1113–1124. doi: 10.1212/wnl.47.5.1113. [DOI] [PubMed] [Google Scholar]
  19. Oppenheimer D. R. Lateral horn cells in progressive autonomic failure. J Neurol Sci. 1980 Jun;46(3):393–404. doi: 10.1016/0022-510x(80)90064-7. [DOI] [PubMed] [Google Scholar]
  20. Papp M. I., Kahn J. E., Lantos P. L. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989 Dec;94(1-3):79–100. doi: 10.1016/0022-510x(89)90219-0. [DOI] [PubMed] [Google Scholar]
  21. Papp M. I., Lantos P. L. Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci. 1992 Feb;107(2):172–182. doi: 10.1016/0022-510x(92)90286-t. [DOI] [PubMed] [Google Scholar]
  22. Papp M. I., Lantos P. L. The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain. 1994 Apr;117(Pt 2):235–243. doi: 10.1093/brain/117.2.235. [DOI] [PubMed] [Google Scholar]
  23. Polinsky R. J. Multiple system atrophy. Clinical aspects, pathophysiology, and treatment. Neurol Clin. 1984 Aug;2(3):487–498. [PubMed] [Google Scholar]
  24. Quinn N. P., Marsden C. D. The motor disorder of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1993 Dec;56(12):1239–1242. doi: 10.1136/jnnp.56.12.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Quinn N. Multiple system atrophy--the nature of the beast. J Neurol Neurosurg Psychiatry. 1989 Jun;Suppl:78–89. doi: 10.1136/jnnp.52.suppl.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Quinn N. Parkinsonism--recognition and differential diagnosis. BMJ. 1995 Feb 18;310(6977):447–452. doi: 10.1136/bmj.310.6977.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. SHY G. M., DRAGER G. A. A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study. Arch Neurol. 1960 May;2:511–527. doi: 10.1001/archneur.1960.03840110025004. [DOI] [PubMed] [Google Scholar]
  28. STEELE J. C., RICHARDSON J. C., OLSZEWSKI J. PROGRESSIVE SUPRANUCLEAR PALSY. A HETEROGENEOUS DEGENERATION INVOLVING THE BRAIN STEM, BASAL GANGLIA AND CEREBELLUM WITH VERTICAL GAZE AND PSEUDOBULBAR PALSY, NUCHAL DYSTONIA AND DEMENTIA. Arch Neurol. 1964 Apr;10:333–359. doi: 10.1001/archneur.1964.00460160003001. [DOI] [PubMed] [Google Scholar]
  29. Spokes E. G., Bannister R., Oppenheimer D. R. Multiple system atrophy with autonomic failure: clinical, histological and neurochemical observations on four cases. J Neurol Sci. 1979 Sep;43(1):59–82. doi: 10.1016/0022-510x(79)90073-x. [DOI] [PubMed] [Google Scholar]
  30. Wagner M. L., Fedak M. N., Sage J. I., Mark M. H. Complications of disease and therapy: a comparison of younger and older patients with Parkinson's disease. Ann Clin Lab Sci. 1996 Sep-Oct;26(5):389–395. [PubMed] [Google Scholar]
  31. Wenning G. K., Ben Shlomo Y., Magalhães M., Daniel S. E., Quinn N. P. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain. 1994 Aug;117(Pt 4):835–845. doi: 10.1093/brain/117.4.835. [DOI] [PubMed] [Google Scholar]
  32. Wenning G. K., Ben-Shlomo Y., Magalhães M., Daniel S. E., Quinn N. P. Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1995 Feb;58(2):160–166. doi: 10.1136/jnnp.58.2.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wenning G. K., Quinn N., Magalhăes M., Mathias C., Daniel S. E. "Minimal change" multiple system atrophy. Mov Disord. 1994 Mar;9(2):161–166. doi: 10.1002/mds.870090206. [DOI] [PubMed] [Google Scholar]
  34. Wenning G. K., Tison F., Ben Shlomo Y., Daniel S. E., Quinn N. P. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord. 1997 Mar;12(2):133–147. doi: 10.1002/mds.870120203. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES