Multiple System Atrophy, Parkinsonian Type

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Retrieved

2021-01-23

Source

Orphanet

Trials

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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, parkinsonian type (MSA-p) is a form of multiple system atrophy (MSA; see this term) with predominant parkinsonian features (bradykinesia, rigidity, irregular jerky postural tremor, and postural instability).

Epidemiology

MSA-p is observed predominantly in patients from the Western Hemisphere. 68% of MSA cases are MSA-p. Genders are equally distributed.

Clinical description

The mean age of disease onset is 55 to 60 years. MSA-p is characterized by parkinsonism (bradykinesia, rigidity, irregular jerky tremor and postural instability) and autonomic failure in the form of bladder dysfunction (including early urinary incontinence) and/or orthostatic hypotension. The presence of autonomic failure is mandatory for the diagnosis of MSA-p. Additional features include dysphonia, dysphagia and other autonomic features (respiratory disturbances such as sleep apnea, stridor and inspiratory sighs, as well as constipation and sexual dysfunction). In the course of the disease, all patients with MSA-p display at least some cerebellar signs (gait and limb ataxia, oculomotor dysfunction, dysarthria). Abnormal postures (camptocormia (see this term), Pisa syndrome and disproportionate antecollis) are frequently observed. Neuropsychiatric features and sleep disturbances may be observed and include: rapid eye movement (REM) sleep behavior disorder (RBD), periodic limb movements in sleep (PLMS), depression, apathy and anxiety. In some cases, pyramidal signs (generalized hyper-reflexia with a positive Babinski sign) may also be observed. Patients with MSA-p may develop early-onset levodopa-induced orofacial and craniocervical dystonia.

Etiology

The exact etiology of MSA-p is still unknown but the presence of cytoplasmic aggregates of α-synuclein, primarily in oligodendroglia, in combination with predominant neurodegeneration of the striatonigral pathway are the pathological hallmark features of MSA-p. 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 risk for sporadic MSA.

Genetic counseling

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