Lab mat 2
Orpha Number: 102
Synonym(s):
cerebellar type, MSA, MSA - urinary dysfunction, MSA-c, MSA-p, Multiple system atrophy - urinary dysfunction, Multisystem atrophy, parkinsonian type, SDS, Sporadic olivopontocerebellar atrophy type 1, Sporadic OPCA type 1

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure (cardiovascular and/or urinary), parkinsonism, cerebellar impairment and corticospinal signs with a median survival of 6-9 years.Prevalence ranges from 1-2.5/50,000. MSA-parkinsonian type (MSA-p) predominates in Western Hemisphere and MSA-cerebellar type (MSA-c) (see these terms) predominates in Eastern Hemisphere. Genders are equally distributed.MSA is an adult-onset disorder (>30 years, mean age 55-60 years). Clinical manifestations include autonomic failure (orthostatic hypotension, syncope, respiratory disturbances (sleep apnea, stridor and inspiratory sighs), constipation, bladder dysfunction (early urinary incontinence), erectile dysfunction in males and Raynaud syndrome). In some cases, pyramidal signs (generalized hyperreflexia and positive Babinski sign) are observed. MSA-p, a form of MSA with predominant parkinsonian features, comprises bradykinesia, rigidity, irregular jerky postural tremor and abnormal postures (camptocormia (see this term), Pisa syndrome and disproportionate antecollis). Patients with MSA-p may develop levodopa-induced orofacial and craniocervical dystonia. Classic pill-rolling rest tremor is uncommon. MSA-c is a form of MSA with predominant cerebellar features such as gait and limb ataxia, oculomotor dysfunction and dysarthria. The predominant motor feature can change with time and patients with cerebellar ataxia can develop increasingly severe parkinsonian features which dominate the clinical presentation. Neuropsychiatric features, oculomotor dysfunction and sleep disturbances are also observed in MSA and include apathy, anxiety, depression, rapid eye movement sleep behavior disorder and periodic limb movements in sleep.Etiology of MSA is unknown but presence of cytoplasmic aggregates of α-synuclein, primarily in oligodendroglia, in combination with neurodegeneration in striatonigral and olivopontocerebellar structures are pathological hallmark features. Mutations in COQ2 (encoding an enzyme involved in biosynthesis of coenzyme Q10) have been shown in multiplex families with MSA, while some variants were associated with increased risk for sporadic MSA.Diagnosis of ''probable'' MSA requires presence of parkinsonism with poor levodopa response or cerebellar signs together with severe autonomic failure (otherwise unexplained urinary incontinence or an orthostatic decrease of blood pressure within 3 min of standing by at least 30 mm Hg systolic or 15 mm Hg diastolic). MRI findings include atrophy of putamen and middle cerebellar peduncles, as well as putaminal and cerebellar hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography. ''Definite'' MSA requires post-mortem demonstration of α-synuclein positive glial cytoplasmic inclusions with neurodegeneration of striatonigral and olivopontocerebellar structures.Differential diagnosis of MSA-p includes Parkinson's disease and other atypical parkinsonian disorders (progressive supranuclear palsy, corticobasal syndrome). Differential diagnosis of MSA-c includes dominantly inherited spinocerebellar ataxias (SCAs 1, 2, 3, 6, and 7), fragile X-associated tremor/ataxia syndrome (FXTAS) and mitochondriopathies (POLG1 gene mutations).MSA occurs sporadically. However, some familial cases have been described.Therapy mainly targets parkinsonism and autonomic failure. Levodopa may transiently improve parkinsonism (20-30% of patients). No effective neuroprotective therapy is available.MSA is rapidly progressive and is associated with wheelchair dependence, unintelligible speech, intermittent urinary catheterization, disabling orthostatic hypotension, cognitive impairment (executive dysfunction). Disease progression is assessed using the Unified MSA rating scale (UMSARS), which rates activities of daily life, autonomic and motor impairment, as well as overall disability. Prognosis is poor with a median survival of 6-9 years.
source: Orphanet

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, postural instability).MSA-p is observed predominantly in patients from the Western Hemisphere. 68% of MSA cases are MSA-p. Genders are equally distributed.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 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 early develop levodopa-induced orofacial and craniocervical dystonia.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 pathological hallmark features of MSA-p. The gene COQ2 (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.MSA-p occurs sporadically. However, some familial cases of MSA have been described.
source: Orphanet
Orpha number: 98933

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).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.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 sleep (REM) sleep behavior disorder (RBD) and periodic limb movements in sleep (PLMS) are frequently observed.The exact etiology of MSC-c is unknown while the presence of cytoplasmic aggregates of α-synuclein, primarily in oligodendroglia, in combination with predominant neurodegeneration of the olivopontocerebellar structures are pathological hallmark features of MSA-c. Mutations in the gene COQ2 (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.MSA-c occurs sporadically. However, some familial cases of MSA have been described.
source: Orphanet
Orpha number: 227510

Shy-Drager syndrome. Disease description under development.
source: Orphanet
Orpha number: 98932