Laboratory Diagnosis in Neurology, 1 Ed.

Multiple System Atrophy

M. Otto

Definition of Multiple System Atrophy

Multiple system atrophy (MSA) is a neurodegenerative disease involving the central motor, corticocerebellar, pontomedullary, and preganglionic autonomic portions of the nervous system in very different ways (Gilman et al., 1999). The various syndromes were initially described as distinct entities under the names striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome. Because patients share many signs and symptoms, it has been recommended that this old nomenclature be replaced by the designations “MSA-P” (with predominantly parkinsonian features) and “MSA-C” (with prominently cerebellar dysfunction).

Epidemiology

The mean age at which the disease develops is 53 years.

Clinical Features

Although dementia may occur with striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome, it is neither the typical nor the first symptom. Early signs include symmetric extrapyramidal motor symptoms or autonomic disturbances. Common symptoms are impotence in men and urinary incontinence in women. Extrapyramidal, cerebellar, or other autonomic dysfunctions occur only later in the course of the disease.

Diagnosis

Neuroimaging and other diagnostic tests. Determination of residual urine or a neurovegetative examination (e. g., Schellong test) may be helpful to assess any involvement of the autonomic nervous system. Electromyography of the external sphincter muscle is regarded as highly sensitive, since distinct signs of denervation are detectable. In some studies, T2-weighted MRI showed atrophy of the compact part of the substantia nigra and hypointensity of the putamen. In addition, a hyperintense margin was detected at the boundary between putamen and external capsule (Schulz et al., 1994). In the MSA-C type, the T2-weighted image showed instead hyperintense areas in the pontocerebellar region and atrophy of the cerebellum and pons.

CSF analysis. The CSF of patients with MSA is described as normal. However, elevated levels of tau protein are occasionally found. Thus far, it has not been established how far determination of tau protein and Aβ peptide1–42 is helpful in distinguishing MSA from Alzheimer's disease.

Neuropathology. Neuropathological examination reveals selective neuronal multisystem degeneration with deposition of glial cytoplasmic inclusions. Like Lewy bodies, these inclusions react with antibodies against α-synuclein.

Differential Diagnosis

Parkinson's disease. MSA-P may be difficult to distinguish from Parkinson's disease; the hyperintense margin of the putamen in the MRI of MSA patients may be helpful. In addition, tremor occurs much less often in MSA than in Parkinson's disease, and MSA-P shows an involvement of the pyramidal tract that is absent in Parkinson's. Cerebellar signs are not a typical clinical feature of Parkinson's disease either.

MSA exclusion criteria. Onset before the age of 30, a positive family history, secondary causes, and spontaneous hallucinosis exclude a diagnosis of MSA. Focal disturbances such as aphasia, alien hand sign, and parietal dysfunction are not characteristic of MSA. A slow-down in vertical gaze saccades or vertical supranuclear gaze paresis also argues against MSA. In such a case, progressive supranuclear gaze paresis (Steele-Richardson-Olszewski syndrome) should be considered instead. This syndrome is associated with marked development of dementia, recurrent falls, and (usually vertical) gaze paresis.

References

Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163:94–98

Schulz JB, Klockgether T, Petersen, D, et al. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry 1994;57:1047–1056

Further Reading

Hüll H, Bauer J. Demenzen. In: Berlit P, ed. Klinische Neurologie. Heidelberg: Springer; 1999:829–856

Kretzschmar HA, Neumann M. Neuropathological diagnosis of neurodegenerative and dementia diseases. Pathologe 2000;21:364–374