Table 2. Multiple system atrophy.

Areas	Findings/recommendations
Neuropathology	Aggregates of α -synuclein in cytoplasm of oligodendrocytes (glial cytoplasmic inclusions) and neurons in a typical distribution (cerebellum, pons, and basal ganglia)
Clinical syndrome	Dysautonomia: urinary incontinence, erectile dysfunction, orthostatic hypotension At least one of Parkinsonian syndrome (MSA-P, about 60% of the following syndromes: cases, PPV about 90%): bradykinesia with rigidity, tremor, or postural instability Cerebellar syndrome (MSA-C, about 40% of cases, PPV about 90%): gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
MRI results	Atrophy of putamen, middle cerebellar peduncle, pons, or cerebellum Cross shaped hyperintensity in the pons (T2 axial) Hypointense putamen with hyperintense rim (T2 axial)
Basic diagnostic evaluation	Levodopa test: poor response to levodopa Schellong test: orthostatic drop in blood pressure after 3 minutes’ standing up from supine position (≥ 20 mm Hg systolic or (≥ 10 mm Hg diastolic) Urological examination: exclusion of other causes of erectile dysfunction and urinary incontinence
Extended diagnostic evaluation	123I-FP-CIT-SPECT/18F-Dopa-PET: symmetric striatal dopaminergic denervation 99 Tc-HMPAO-SPECT/ 18 FDG-PET: hypometabolism in putamen, brainstem, or cerebellum 123 I-IBZM-SPECT/ 18 F-DMFP-PET: symmetric postsynaptic, striatal degeneration 123 I-MIBG-SPECT: intact cardiac noradrenergic innervation (DD PD with dysautonomia) Oculomotor function: cerebellar pattern (saccadic pursuit movement, gaze-evoked or downbeat nystagmus) Sleep laboratory: rapid eye movement (REM) sleep behavior disorder
Symptomatic treatment	Levodopa (3–4 × 100–200 mg): mild to moderate improvement of akinetic-rigid symptoms (evidence level 2–, recommendation grade B) Amantadine (3 × 100–200 mg): mild positive effect on akinetic-rigid symptoms (evidence level 1–, recommendation grade 0) Botulinum toxin A: positive effect on focal dystonia (evidence level 3, recommendation grade 0) Droxydopa (2x 200–600 mg) (not approved in Germany for this indication): positive effect on orthostatic hypotension (evidence level 1, recommendation grade A) Ephedrine (3 × 15–45 mg): positive effect on orthostatic hypotension (evidence level 3, recommendation grade 0) Midodrine (3 × 5–10 mg): positive effect on orthostatic hypotension (evidence level 1+, recommendation grade A) Fludrucortisone (1–3 × 0,1 mg): positive effect on orthostatic hypotension (evidence level 3, recommendation grade 0) Octreotide (25–50 mg s. c. 30 minutes before meals): positive effect on postprandial hypotension (evidence level 2–, recommendation grade 0) Desmopressin (10–40 μg spray, 100–400 µg tablets): positive effect on nocturnal polyuria (evidence level 3, recommendation grade 0) Oxybutinin (2–3 × 2.5–5 mg): for urge incontinence (evidence level 4, recommendation grade 0)

Evidence level 1 = randomized controlled study (studies); 2 = case-control study (studies); 3 = non-analytic case study (studies); 4 = expert opinion;

recommendation grade A = strong recommendation [should]; B = recommendation; 0 = open recommendation [can]

MSA, multiple system atrophy; MRI, magnetic resonance imaging; PPV, positive predictive value; DD, differential diagnosis; PD, Parkinson’s disease; s. c., subcutaneous; SPECT, single photon emission computed tomography; PET, positron emission tomography