Striatonigral degeneration. Clinical picture resembles Parkinson’s disease but without tremor. These patients do not respond to antiparkinsonian medications and often develop adverse reactions to these agents.

Shy–Drager syndrome. Clinical picture consists of Parkinson’s disease combined with severe autonomic neuropathy (particularly postural hypotension). Other important clinical features are impotence and bladder disturbances.

Olivopontocerebellar atrophy. Combination of extrapyramidal manifestations and cerebellar ataxia. Patients may also have autonomic neuropathy and anterior horn cell degeneration.

Parkinsonism and motor neuron disease. Rare.

• The more common typical radiological findings in multisystem atrophy include atrophy of the cerebellum, most prominently in the vermis, middle cerebellar peduncles, pons and lower brainstem (Neuroimag Clin North Am 2010;20: Issue 1; on imaging of movement disorders).

• In addition to putaminal atrophy, a characteristic hypointense signal in T₂ with hyperintense rim, corresponding to reactive gliosis and astrogliosis, can be observed in the external putamen and is termed the ‘slit-like void sign’ (Fig. 95.1B). This combination of hypointense and hyperintense putaminal signal change is specific for multisystem atrophy and its finding can be used to differentiate multisystem atrophy from progressive supranuclear palsy and Parkinson’s disease.

• The ‘hot-cross bun’ sign is characterized by cruciform signal hyperintensity on T₂-weighted images in mid pons (Fig. 95.1A). This finding is said to correspond to the loss of pontine neurons and myelinated transverse cerebellar fibres with preservation of the corticospinal tracts. However, this sign is not specific to multisystem atrophy and has been reported in other conditions such as spinocerebellar ataxia.

• Hypointensity alone without hyperintense rim is a sensitive radiological feature but non-specific for multisystem atrophy.

• autonomic failure involving urinary incontinence (with erectile dysfunction in males) or

• orthostatic decrease of BP within 3 min of standing by at least 30 mmHg systolic or 15 mmHg diastolic and either

• poorly levodopa-responsive parkinsonism (bradykinesia with rigidity, tremor, or postural instability) or

• a cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia or cerebellar oculomotor dysfunction).

• parkinsonism (bradykinesia with rigidity, tremor, or postural instability) or

• a cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia or cerebellar oculomotor dysfunction) and

• at least one feature suggesting autonomic dysfunction (otherwise unexplained urinary urgency, frequency or incomplete bladder emptying, erectile dysfunction in males, or significant orthostatic BP decline that does not meet the level required in probable MSA) and

• at least one of the additional features:

• rapidly progressive parkinsonism

• poor response to levodopa

• postural instability within 3 years of motor onset

• gait ataxia, cerebellar dysarthria, limb ataxia or cerebellar oculomotor dysfunction

• dysphagia within 5 years of motor onset

• atrophy on MRI of putamen, middle cerebellar peduncle, pons or cerebellum

• hypometabolism on fludeoxyglucose PET (FDG-PET) in putamen, brainstem or cerebellum.

• parkinsonism (bradykinesia and rigidity)

• atrophy on MRI of putamen, middle cerebellar peduncle or pons

• hypometabolism on FDG-PET in putamen

• presynaptic nigrostriatal dopaminergic denervation on single photon emission CT (SPECT) or PET.

• Orofacial dystonia

• Disproportionate antecollis

• Camptocormia (severe anterior flexion of the spine) with or without Pisa syndrome (severe lateral flexion of the spine)

• Contractures of hands or feet

• Inspiratory sighs

• Severe dysphonia

• Severe dysarthria

• New or increased snoring

• Cold hands and feet

• Pathological laughter or crying

• Jerky, myoclonic postural or action tremor.

• Classic pill-rolling rest tremor

• Clinically significant neuropathy

• Onset after age 75 years

• Family history of ataxia or parkinsonism

• Dementia (on Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV))

• White matter lesions that suggest multiple sclerosis

• Hallucinations not induced by drugs.

• Inclusions could trigger microglial activation, which causes chronic oxidative stress and ultimately leads to neuronal cell death

• Inclusions could exacerbate susceptibility to exogenous oxidative stress and lead to neuronal cell death in striatonigral and olivopontocerebellar systems

• Inclusions could lead to secondary axonal α-synuclein aggregation or oligodendroglial mitochondrial dysfunction, which eventually lead to neuronal cell death.