Synucleinopathies

Abstract

Purpose of review: This article reviews the α-synucleinopathies pure autonomic failure, multiple system atrophy, dementia with Lewy bodies, and Parkinson disease with respect to autonomic failure.

Recent findings: The pattern and severity of autonomic involvement in the synucleinopathies is related to differences in cellular deposition and neuronal populations affected by α-synuclein aggregation, which influences the degree and manifestation of autonomic failure. Clinical and laboratory autonomic features distinguish the different synucleinopathies based on pattern and severity. These features also determine which patients are at risk for evolution from pure autonomic failure to the synucleinopathies with prominent motor involvement, such as multiple system atrophy, dementia with Lewy bodies, or Parkinson disease.

Summary: Autonomic failure is a key feature of the synucleinopathies, with varying type and degree of dysfunction from predominantly peripheral involvement in the Lewy body disorders to central involvement in multiple system atrophy.

FIGURE 5-1

Pure autonomic failure. Autonomic testing demonstrates reduced heart rate responses (red) to deep breathing and Valsalva maneuver, indicative of severe cardiovagal failure. Beat-to-beat blood pressure responses to Valsalva maneuver show adrenergic failure with absent late phase II and phase IV with prolonged blood pressure time, whereas tilt shows immediate and sustained orthostatic hypotension. The thermoregulatory sweat test demonstrates anhidrosis over the abdomen and lower extremities, and the quantitative sudomotor axon reflex test (QSART) shows reduction in sweat volumes over the lower extremity sites, indicative of postganglionic sudomotor failure.

FIGURE 5-2

Multiple system atrophy with predominant parkinsonism. Autonomic testing demonstrates severe cardiovagal failure with reduced heart rate responses (red) to deep breathing and Valsalva maneuver. Severe adrenergic failure is shown on beat-to-beat blood pressure responses to Valsalva maneuver, with absent late phase II and phase IV with prolonged blood pressure time. Orthostatic hypotension is immediate and progressive on tilt. Thermoregulatory sweat test demonstrates global anhidrosis with acral hypohidrosis. In conjunction with the quantitative sudomotor axon reflex test (QSART) showing intact postganglionic sudomotor function, this pattern is indicative of a central autonomic disorder.

FIGURE 5-3

MRI findings in multiple system atrophy. Axial MRIs show characteristic changes in multiple system atrophy with predominant parkinsonism of abnormal T2 hyperintensity adjacent to the putamen with putaminal atrophy (A, arrow) and low signal on gradient recalled echo (GRE) sequence (B, arrow). Patients with multiple system atrophy with prominent cerebellar ataxia may demonstrate abnormal T2 hyperintensity in a cruciform pattern in the central pons (the hot cross bun sign) as shown on axial T2-weighted imaging (C, circle), as well as marked cerebellar and pontine atrophy as shown on a sagittal T1-weighted image (D, arrows).

FIGURE 5-4

Neuropathologic features of multiple system atrophy. Immunostaining for α-synuclein reveals a characteristic glial cytoplasmic inclusion (arrow).

FIGURE 5-5

Neuropathologic features of dementia with Lewy bodies and Parkinson disease. Immunostaining for α-synuclein reveals a characteristic Lewy body (arrow).