Often symmetrical, with bradykinesia, rigidity and postural instability.

30%–50% have transient benefit with L-dopa, lasting up to 3.5 years, however, are more susceptible to orthostatic hypotension side effects.23 35

L-dopa-induced dyskinesias are often dystonic, affecting the cranio-cervical region, rather than limbs.36

Manifests as gait ataxia, limb ataxia, cerebellar dysarthria and oculomotor signs (eg, ocular dysmetria, saccadic pursuit, sustained gaze-evoked nystagmus, positional downbeat nystagmus).

Patients often have a mixed tremor profile with >1 type of tremor

Only 8%–12% have a typical Parkinson’s disease (PD) ‘pill-rolling’ tremor, while around half have a ‘jerky postural tremor’ with polyminimyoclonus.37

Up to 35% have a resting tremor, which is often atypical (fast, irregular, myoclonic and remains present on action).37 Cerebellar patients can have an intention tremor.

Mixed dysarthria with hypokinetic, spastic and ataxic components.38

Dysphagia is usually symptomatic within 5 years of motor onset, but silent aspiration probably precedes this.39

MSA-P patients often have more severe dysphagia requiring earlier dietary modification, but time to tube feeding is no different.40

Sialorrhoea is extremely common, and likely related to oral hypokinesia or pharyngeal dystonia.39

Up to 61% of MSA patients show pyramidal signs, for example, upgoing Babinski and hyperreflexia26

Abnormal dystonic posturing can occur with Pisa syndrome, disproportionate antecollis and hand/foot contractures. Although uncommon, specificity of these findings is high for MSA vs PD (96.6%–99.2%)41

Recurrent falls within 3 years of motor onset are a potential red flag for MSA compared with PD, with a specificity of >97%.41

Decreased standing BP by at least 20/10 mm Hg after 3 min, unrelated to cardiogenic causes or hypovolaemia.

Manifests as syncope, light headedness or coat-hanger pain (suboccipital and paracervical pain).42

Worse in the early morning and hot environments.

BP drop postmeal (particularly if carbohydrate rich) due to splanchnic vasodilation.

Manifests as postural symptoms or generalised fatigue usually within 30–60 min postmeal, but up to 2 hours.43

Urinary symptoms can begin years before motor symptoms.44

In men, erectile dysfunction often precedes urinary symptoms.45

Often, storage symptoms (frequency/urgency±urge incontinence) precede voiding symptoms (reduced stream/flow, dribbling).46 47

8% require catheterisation within 3 years, and 16% over their lifetimes.24

Typically, MSA patients present with constipation and delayed gastric emptying, similar to PD, which precedes motor symptoms.

Heat intolerance or flushing due to progressive hypohidrosis, which is more severe in MSA than in Parkinson’s disease.48

Impaired peripheral vasomotor function/ circulation leading to ‘reddish-blue’ discolouration of the extremities, often associated with the ‘cold hand’ or ‘cold foot’ sign.49

Defined as a strained, high-pitched, harsh inspiratory sound, due to vocal cord paralysis or dystonia in MSA).

Typically begins at night. Patients are often not aware themselves, but caregivers will often report a ‘peculiar snore’. It can be useful to ask for a video/audio recording of this, but otherwise video polysomnography can differentiate it from oropharyngeal snoring Laryngospasm.51

Sudden, prolonged, forceful apposition of the vocal cords causing sudden suffocation or stridor and is a medical emergency if persistent.

Central respiratory insufficiency.52

MSA patients may have impaired ventilatory drive with minimal to no chemosensitivity to hypoxia, abnormal respiratory rhythm during sleep and central hypoventilation, some of which may explain sudden death in MSA (despite tracheostomy).

The most common sleep-related disorder in MSA; can precede motor symptoms by years.53 It is characterised by sleep-related vocalisations and often violent complex motor behaviour during REM sleep.

The gold standard diagnosis is polysomnography showing loss of atonia during REM sleep; Where polysomnography is unavailable, standardised questionnaires for example, Innsbruck REM sleep behaviour disorder inventory may help54 Periodic limb movements—in 44%–60% of MSA patients.55

Defined as repetitive movements of the limbs during sleep, of which patients are typically unaware, but sleep quality is affected.

This is a sensorimotor disorder characterised by an urge to move the limbs, often with paraesthesia or pain. Symptoms are more noticeable in the evenings or when inactive.

Associated with low serum iron concentrations.

Up to 49% of MSA patients have some executive dysfunction on in-depth testing.57

Like progressive supranuclear palsy, MSA patients can report emotional lability with pathological laughter or crying, although their symptoms are less severe, and without memory difficulties.58–60

Unlike PD, well-formed visual hallucinations and fluctuating cognition are infrequent in MSA.61

Anosmia is not typical of MSA, and might instead indicate PD.45

Intermittent diplopia can occur due to midbrain dysfunction.62