The Lewis family revisited: no evidence for autosomal dominant multiple system atrophy.

In 1964, Lewis reported a familial ataxia-dysautonomia syndrome reminiscent of Shy-Drager syndrome subsequently known as multiple system atrophy (MSA). Here we review this report and propose that the Lewis family may represent an unusual form of autosomal dominant cerebellar ataxia type I, which might be categorized either as SCA3 (Machado-Joseph disease) or a new SCA subtype. There remains no conclusive evidence to support the notion of hereditary MSA.

[Syndromes of autonomic insufficiency associated with orthostatic intolerance: classification, diagnostic and therapeutic approach]. / Syndrome der autonomen Dysfunktion mit orthostatischer Intoleranz: Klassifikation, Diagnostik und Therapie.

Stimulated by the widespread use of tilt table testing, disorders of autonomic function with orthostatic hypotension have recently gained attention by clinical cardiologists. At the same time, improved characterization of the underlying circulatory responses have led to a reclassification of these syndromes. In particular, three subgroups of chronic primary dysautonomia have been defined such as Pure Autonomic Dysfunction, Multiple System Atrophy, and the Postural Orthostatic Tachycardia Syndrome. On the other hand, acute dysautonomias represent a rare yet clinically sometimes dramatic form of autonomic disorders. Several diseases as well as enzymatic disorders, and pharmacological drugs may cause secondary dysautonomia. The clinical correlate of all these forms of dysautonomia is orthostatic hypotension and syncope. Thus, a careful history forms the basis of a successful diagnostic workup of the underlying cause of syncope. This review summarizes the current knowledge of autonomic disorders, their classification and diagnostic and therapy strategies.

Classification of autonomic disorders.

Recent advances in our understanding of the pathophysiology of cardiovascular regulation and the metabolism of catecholamines have enabled us to develop an improved system of classification of autonomic disorders. Patients with autonomic impairment, clinically unassociated with other neurological abnormalities, are considered to have the Bradbury-Eggleston syndrome (idiopathic orthostatic hypotension, pure autonomic failure). Individuals whose autonomic failure is accompanied by degeneration in other neurological systems are classified as having the Shy-Drager syndrome (multiple system atrophy with autonomic failure). Patients in whom a deficiency of the enzyme dopamine-beta-hydroxylase is present from birth have many features suggestive of the Bradbury-Eggleston syndrome but manifest normal sweating and biochemically have an elevated plasma and urinary dopamine level. Recognition of these individuals is of particular importance because they are uniquely responsive to treatment with oral dihydroxyphenylserine (L-DOPS). A fourth disorder is baroreflex failure; this disorder is usually due to surgery, trauma, radiation or other injury to the ninth or tenth cranial nerves or the medullary nuclei which their fibers innervate. Patients with baroreflex failure have oscillations between hypertension and hypotension, but these alterations are poorly correlated with posture. Very high levels of plasma norepinephrine are found during the hypertensive phase of baroreflex failure. Baroreflex failure is generally responsive to treatment with clonidine. In conclusion, the diagnosis and therapy of autonomic disorders has improved due to the more precise taxonomy now current.