Consensus statement on the diagnosis of multiple system atrophy

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Abstract

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). 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 MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Introduction

Multiple system atrophy (MSA), a progressive neurodegenerative disease of undetermined etiology, occurs sporadically and causes parkinsonism and cerebellar, autonomic, urinary, and pyramidal dysfunction in many combinations 1, 3, 7, 21. The disease affects both sexes, usually beginning in middle age and progressing over intervals of 1–18 years, with a median survival of 9.3 years from the first symptom 9, 26. The parkinsonian features include bradykinesia with rigidity, postural instability, hypokinetic speech, and often tremor, usually with a poor or unsustained response to chronic levodopa therapy. The cerebellar dysfunction consists of ataxia of gait, limb movements and speech, and disorders of extraocular movements [6]. Autonomic insufficiency results in orthostatic hypotension, often with an inadequate heart rate response to standing, male erectile dysfunction (MED), constipation, and decreased sweating 18, 22. Urinary symptoms include urgency, frequency, nocturia, incomplete bladder emptying, and incontinence [2]. The diagnosis of MSA requires primarily clinical assessment, however, a number of laboratory tests may help to support the diagnosis.

The neuropathological changes consist of a high density of glial cytoplasmic inclusions (GCIs) in association with degenerative changes in some or all of the following structures: putamen, caudate nucleus, globus pallidus, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, autonomic nuclei of the brainstem, and the intermediolateral cell columns and Onufs nucleus in the spinal cord 4, 12. GCIs are ubiquitin-, tau- and a-synuclein-positive oligodendroglial inclusions [12].

Some efforts have been made to establish diagnostic criteria [3], but no consistent detailed guidelines have been developed. Accordingly, a consensus conference was convened on April 23 and 24, 1998 in Minneapolis, Minnesota, cosponsored by the American Autonomic Society and the American Academy of Neurology. The goal of the conference was to develop guidelines for the diagnosis of MSA. We achieved consensus on the items listed below and shown in Table 1, Table 2, Table 3. These guidelines have not yet been validated, and will almost certainly require further modification in the light of future experience.

Section snippets

Autonomic and urinary dysfunction

Orthostatic hypotension (OH) may indicate autonomic failure and can be asymptomatic or symptomatic. When symptomatic, it typically occurs after the onset of MED and urinary symptoms. Symptoms of OH result from cerebral hypoperfusion, and syncope may occur. The consensus conference determined that the clinical diagnosis of probable MSA requires a reduction of systolic blood pressure by at least 30 mmHg or of diastolic blood pressure by at least 15 mmHg within 3 min of standing from the recumbent

Response to levodopa

Levodopa responsiveness should be tested by administering escalating doses (with a peripheral decarboxylase inhibitor) over a 3-month period up to at least 1 g/day (if necessary and if tolerated). A positive response is defined as clinically significant improvement. This should be demonstrated by objective evidence such as an improvement of 30% or more on part III (motor examination) of the Unified Parkinson's Disease Rating Scale [5].

Laboratory investigations

Autonomic function tests, sphincter electromyography (EMG), and neuroimaging may be used to support the diagnosis, and neuroimaging is helpful in excluding other conditions. The abnormalities described below have been defined principally in clinically well-established cases rather than in the early stages of the disease. In the early stages, the tests may give equivocal results. We consider it premature to incorporate laboratory results into the entirely clinical guidelines that we established,

Diagnostic categories

We established three diagnostic categories reflecting differing levels of certainty: definite, probable and possible. The diagnosis of definite MSA can only be made after neuropathological examination of the central nervous system revealing the characteristic density and distribution of GCIs and degenerative changes outlined above. The diagnosis of probable or possible MSA can be made utilizing different combinations of clinical domains, criteria and features, as indicated in Table 1, Table 2.

Terminology

MSA is a distinct clinicopathological entity. The term should not be used to describe other neurodegenerative diseases affecting multiple systems. The use of confusing terms such as `multisystem degeneration' for MSA is inappropriate and now should be discouraged. We recommend designating patients as having MSA-P if parkinsonian features predominate or MSA-C if cerebellar features predominate 16, 24. These terms are intended to replace the striatonigral degeneration (SND) and sporadic

Acknowledgements

This conference was supported in part by the Office of Rare Diseases and the National Institute of Neurological Disorders and Stroke, National Institutes of Health; Glaxo Wellcome, Inc.; Hoechst Marion Roussell; and Roberts Pharmaceutical Corporation.

References (26)

  • RO Beck et al.

    Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases

    J Urol

    (1994)
  • PA Low

    The composite autonomic scoring scale for the laboratory quantitation of generalized autonomic failure

    Mayo Clin Proc

    (1993)
  • A Albanese et al.

    Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria

    J Neurol Neurosurg Psychiatry

    (1995)
  • Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the...
  • Daniel SE. The neuropathology and neurochemistry of multiple system atrophy. In: Bannister R, Mathias CJ, editors....
  • Fahn S, Elton R. Unified Parkinson's disease rating scale committee: unified Parkinson's disease rating scale. In: Fahn...
  • Gilman S. Multiple system atrophy. In: Jankovic J, Tolosa E, editors. Parkinson's disease and movement disorders, 3rd...
  • JG Graham et al.

    Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy

    J Neurol Neurosurg Psychiatry

    (1969)
  • AJ Hughes et al.

    The dopaminergic response in multiple system atrophy

    J Neurol Neurosurg Psychiatry

    (1992)
  • T Klockgether et al.

    The natural history of degenerative ataxia: a retrospective study in 466 patients

    Brain

    (1998)
  • KJ Kluin et al.

    Characteristics of the dysarthria of multiple system atrophy

    Arch Neurol

    (1996)
  • AE Lang et al.

    Striatonigral degeneration: iron deposition in putamen correlates with the slit-like void signal of magnetic resonance imaging

    Can J Neurol Sci

    (1994)
  • PL Lantos

    Multiple system atrophy

    Brain Pathol

    (1997)
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