Introduction

The autonomic nervous system (ANS) mediates neuroendocrine, visceral, and behavioral responses to environmental and inner challenges in order to ensure body homeostasis. The insular cortex, together with the medial prefrontal cortex and the extended amygdala, exerts high-order autonomic control on multiple parallel interconnections of the ANS subcortical integrative network constituted from hypothalamus, periaqueductal grey matter, parabrachial pontine complex, and ventro-lateral medullary nuclei (Benarroch 1993). Main output of the central ANS runs through pre-ganglionic sympathetic and parasympathetic cholinergic neurons, the former located in the intermediolateral columns of the thoraco-lumbar spinal cord, the latter in the brainstem and sacral spinal metameria. Parasympathetic cholinergic post-ganglionic fibers arise from ganglia which are generally located close to or within the target organ. Regional activation of parasympathetic fibers induces myosis, promotes salivation, intestinal peristalsis, vesical detrusor contraction, penis (clitoral) engorgement, and decreased heart rate. Noradrenergic sympathetic post-ganglionic neurons originate from the paravertebral ganglia and mediate midriasis, blood vessel constriction, and inotropic and cronotropic cardiac effects, among others. Further, a subgroup of cholinergic sympathetic fibers runs stimulation to cutaneous sweat glands (Goldstein 2006).

Disorders of the ANS are described as primary, if displaying a neurodegenerative origin, or secondary, if developing after brain injury of any cause or metabolic diseases like diabetes. The first report of degenerative dysautonomia dates back to 1925 when Bradbury and Egglestone described a case of orthostatic hypotension (OH) with impotence and anhidrosis of idiopathic origin (Bradbury et al. 1925). In the 1960s Shy and Drager further reported the case of two men who developed multi-domain autonomic failure along with cerebellar, parkinsonian, and pyramidal signs (Shy et al. 1960). Since then, dysautonomia (see Table 24.1) has been recognized as a major non-motor feature of multiple system atrophy (MSA), Parkinson’s disease (PD), as well as other movement disorders with prominent diagnostic, therapeutic, and prognostic implications.

Historical review

The term multiple system atrophy (MSA) was introduced by Graham and Oppenheimer in 1969 to denote a neurodegenerative disease characterized clinically by various combinations of autonomic, parkinsonian, cerebellar or pyramidal symptoms and signs and pathologically by cell loss and gliosis in some or all of the following structures: putamen, caudate nucleus, globus pallidus, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, intermediolateral cell columns and Onuf's nucleus of the spinal cord.

Previously, cases of MSA were reported under the rubrics of olivopontocerebellar atrophy (OPCA), idiopathic orthostatic hypotension (IOH) or progressive autonomic failure (PAF), Shy–Drager syndrome (SDS) and striatonigral degeneration (SND). Although Dejerine and Thomas were the first to introduce the term OPCA in 1900 reporting two sporadic cases of late-onset ataxia, the case of Stauffenberg in 1918, diagnosed in life as OPCA, was the first to associate cerebellar, parkinsonian and autonomic features with identified pathological lesions not only of olives, pons and cerebellum, but also of basal ganglia pigmentation and atrophy of putamen, with additional cell loss in caudate and globus pallidus (Quinn, 1994).

The term SND was introduced in 1960 by van der Eecken, Adams and van Bogaert (van der Eecken et al., 1960; Adams et al., 1961, 1964) who noted pronounced shrinkage and brownish discoloration of the putamen and pallidum as well as depigmentation of the substantia nigra in three patients with progressive and severe parkinsonism associated with cerebellar, pyramidal and autonomic features.