Multiple System Atrophy

This term abbreviated MSA defines a specific syndrome within the larger less well defined category of multiple system degenerations. The features of the MSA include: parkinsonism, cerebellar or corticospinal signs, orthostatic hypotension, impotence, and urinary incontinence or retention, usually preceding or within two years after the onset of the motor symptoms. The previous division into Shy Drager Syndrome (SDS), Striato Nigral Degeneration (SND), and Olivopontocerebellar Atrophy (OPCA) has been dropped. Immunohistochemistry demonstrates that these three disorders share a common pathology. The latest diagnostic criteria are shown in the table below.

Wenning et. al. determined that the combination of autonomic insufficiency, speech or bulbar dysfunction, absence of dementia, postural instability with falls, poor response to levodopa, and absence of levodopa-induced confusion gave a diagnostic sensitivity and specificity greater than 90%.

Median age of onset of MSA is about age 55 years (range of 33 to 76). It affects men slightly more than women. Nearly half of patients are disabled or wheelchair bound within 5 years of the onset of motor symptoms. Mean survival is 6 to 7 years. 80% of MSA patients develop predominant parkinsonism (MSA-P) and 20% develop predominant cerebellar signs (MSA-C). The latter statistics are likely skewed by referral patterns to movement disorder centers. There is considerable overlap. Cerebellar features are present in over 40% of patients with SND type, and parkinsonism is detectable in 50% of OPCA type patients.

30% and 65% of MSA patients had a good levodopa response at some stage. Between 13% and 30% maintained some response through the course of the illness. 25% to 50% of those treated with levodopa had dyskinesias (particularly orofacial) and dystonia, even if they did not experience improvement in motor state.

Autonomic symptoms were the initial feature in 41% of patients, but ultimately 97% of patients developed some degree of autonomic dysfunction. The most frequent autonomic symptom in men was impotence and in women urinary incontinence. Orthostatic hypotension occurred in 68%.

A mild restriction of downgaze may develop in about 10% of MSA cases.. Anterior horn cell loss may occur but is uncommon. Anal sphincter EMG (90% have an abnormality) is a sensitive and specific diagnostic test for MSA. Even less frequently seen is a mild sensory neuropathy. Classic rest tremor is uncommon (29%) Cerebellar signs occurred in 54% of patients and upper motor neuron signs in 49% of the cases. SND type generally demonstrates more tremor, pyramidal signs, and myoclonus than OPCA type. Severe dementia is uncommon

Respiratory stridor (which ultimately occurs in 1/3 of cases) in combination with parkinsonism is highly suggests MSA until proved otherwise; although stridor can also occur in PD, it is exceptionally rare.

Multiple System Atrophy: Clinical Diagnostic Criteria

Striato Nigral Degeneration Type

(predominant parkinsonism)

Sporadic adult-onset (age 30 years or above)

Possible

Non/poorly levodopa responsive parkinsonism*

Probable

Above**, plus severe symptomatic autonomic failure*** or cerebellar signs or pyramidal signs or pathological sphincter EMG  

 

 

Definite

Post mortem confirmed

 

OLIVOPONTOCEREBELLAR Type

(predominantly cerebellar)

Sporadic adult-onset (age 30 years or above)

Possible

Cerebellar syndrome with parkinsonism

 

Probable

Sporadic adult-onset cerebellar syndrome*

(with or without parkinsonism or pyramidal signs) plus severe symptomatic autonomic failure*** or pathological sphincter EMG

Definite

Post mortem confirmed

 

* Without DSM III dementia, generalised tendon areflexia, downgaze PSNP or other identifiable cause.

** Moderate or good, but often waning, response to levodopa may occur, in which case multiple atypical features need to be present.

*** Postural syncope or presyncope and/or urinary incontinence or retention not due to other causes.

Sporadic: one other case of typical clinical IPD among 1st or 2nd degree relatives allowable.

Frequency of individual clinical features in 203 cases of MSA

From Wenning, et al, MSA: A Review of 203 Pathologically proven Cases Movement Disorders Vol 12 No 2 1997 133-147

Autonomic symptoms

Urinary incontinence      55%     

Postural faintness            51%

Impotence                     47%

Recurrent syncope        18%

Fecal incontince             12%

 

Parkinsonism

    Akinesia                     83%

    Tremor                       67%

     Rigidity                      63%

     Best L-Dopa response      

               Poor               72% 

               Good              28%

     Last  L-Dopa response 

                Poor              95% 

                Good              5%

 Dyskinesias

                Orofacial        15%

                Limbs             10%

Fluctuations                  24%

Cerebellar Signs

    Gait ataxia                      49%

    Limb ataxia                     47%

    Intention Tremor            24%

    Nystagmus                     23%

 

Pyramidal signs

    Hyperreflexia                  46%

    Babinski                         41%

    Spasticity                        10%

 

Other features

    Intellectual deterioration

        Mild                           22%

        Moderate                   2%

       Severe                        0.5%

    Stridor                           13%

    Dystonia                        12%

    Anisocoria                      8%

    Contractures                  7%

General References On Clinical Features of Parkinsonisms
 

*Handbook of Clinical Neurology Vol 49 Extrapyramidal disorders: Vinken, Bruyn, Klawans eds. 

Elsevier Science publishers 1996

Movement Disorders a Comprehensive Survey;: Weiner, Lang A. eds. Futura publishing company 1989

Neurodegenerative Diseases, Calne, D., eds. W.B. Saunders Company 1994

Parkinson's Disease and Movement Disorders, Jankovic, Tolosa ,eds. Urban & Scharzenberg 1988

Clinics of North America Volume 83  Number 2  March 1999

MSA

Wenning, et al, MSA: A Review of 203 Pathologically Proven Cases. Movement Disorders Vol 12 No 2 March 1997 133-147

Quinn, N; Lecture notes in AAN syllabus on Multiple System Atrophy  AAN 1999 Toronto

Margery H. Mark  Lumping and splitting the parkinson plus syndromes Neurologic Clinics Volume 19  Number 3  August 2001