Multiple System Atrophy, Cerebellar Type

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Retrieved

2021-01-23

Source

Orphanet

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Genes

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Drugs

1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d] pyrimidin-4-one, 5,7-dichloro-2-((ethylamino)methyl)-8-hydroxy-3-methylquinazolin-4(3H)-one mesilate, Droxidopa ( NORTHERA )

1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d] pyrimidin-4-one, 5,7-dichloro-2-((ethylamino)methyl)-8-hydroxy-3-methylquinazolin-4(3H)-one mesilate, Droxidopa ( NORTHERA ), Ile-Ser-Ile-Thr-Glu-Ile-Lys-Gly-Val-Ile-Val-His-Arg-Ile-Glu-Thr-Ile-Leu-Phe-Lys-Lys-Lys-Lys-Glu-Met-Pro-Ser-Glu-Glu-Gly-Tyr-Gln-Asp, L-threo-3,4-dihydroxyphenylserine, Midodrine hydrochloride ( AMATINE )

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Multiple system atrophy, cerebellar type (MSA-c) is a form of multiple system atrophy (MSA; see this term) with predominant cerebellar features (gait and limb ataxia, oculomotor dysfunction, and dysarthria).

Epidemiology

MSA-c is observed predominantly in patients from Asia. A Japanese study reported a high percentage of patients (83.8%) exhibiting MSA-c features with only 16.2% of patients being categorized as MSA-parkinsonian type (MSA-p; see this term). In the Western Hemisphere, one third of all MSA patients have MSA-c. Genders are equally distributed.

Clinical description

The mean age of disease onset is 55 to 60 years. Gait ataxia is the most typical early symptom of MSA-c. Autonomic dysfunction (bladder dysfunction including early urinary incontinence, orthostatic hypotension, constipation, Raynaud syndrome) occurs early and is mandatory for the diagnosis of MSA-c. Additional features of MSA-c include dysphonia, dysphagia and other cerebellar features including limb ataxia and occulomotor dysfunction (sustained gaze-evoked nystagmus, positional down-beat nystagmus). All patients develop at least some parkinsonian signs (bradykinesia, rigidity, irregular jerky postural tremor) in the course of the disease. Pyramidal signs (generalized hyper-reflexia and, in some cases, positive Babinski sign) may be observed. Respiratory disturbances (sleep apnea, stridor and inspiratory sighs) and night time sleep disturbances, including rapid eye movement (REM) sleep behavior disorder (RBD) and periodic limb movements in sleep (PLMS), are frequently observed.

Etiology

The exact etiology of MSC-c is unknown while the presence of cytoplasmic aggregates of α-synuclein, primarily in the oligodendroglia, in combination with predominant neurodegeneration of the olivopontocerebellar structures are pathological hallmark features of MSA-c. Mutations in the COQ2 gene (4q21.23 ) (encoding an enzyme involved in the biosynthesis of coenzyme Q10) have been shown in multiplex families with MSA, while some variants were associated with an increased for sporadic MSA.

Genetic counseling

MSA-c occurs sporadically. However, some familial cases of MSA have been described.