The clinical state of idiopathic orthostatic hypotension is now known to be caused by at least two conditions. One is a degenerative disease of middle and late adult life, first described by Bradbury and Eggleston in 1925 and designated by them as idiopathic orthostatic hypotension and by subsequent authors, “primary autonomic failure.” In this disorder, the lesions involve mainly the postganglionic sympathetic neurons (Petito and Black); the parasympathetic system is relatively spared and the CNS is uninvolved. In the second more common disorder that is now classified as a multiple system atrophy, described initially by Shy and Drager, the preganglionic lateral horn neurons of the thoracic spinal segments degenerate; these changes are responsible for the orthostatic hypotension. Later, signs of basal ganglionic or cerebellar disease or both are added as discussed later and in Chaps. 17 and 38 but a few cases remain as a pure autonomic failure. In both types of orthostatic hypotension, anhidrosis, erectile dysfunction and atonicity of the bladder may be conjoined, but orthostatic fainting is the main problem.
The clinical differentiation of these two types of orthostatic hypotension depends largely on the appearance, with time, of associated CNS signs as described later. The distinction between the sympathetic postganglionic and the central preganglionic types of disease is also based on pharmacologic and neurophysiologic evidence, but it must be emphasized that the results of these tests do not always conform to clinical expectations from the examination. Nonetheless, Cohen and associates, who studied the postganglionic sudomotor and vasomotor functions of 62 patients with IOH, found that the signs of postganglionic denervation were uncommon in patients classified as having the central type.
In the postganglionic type of autonomic failure, plasma levels of NE are subnormal while the patient is recumbent because of failure of the damaged nerve terminals to synthesize or release catecholamines. When the patient stands, the NE levels do not rise, as they do in a normal person. Also, in this type, there is denervation hypersensitivity to infused NE. In the central preganglionic (Shy-Drager) type, the resting NE levels in the plasma are normal but again, on standing, there is no rise, and the response to exogenously administered NE is normal. In both types, the plasma levels of dopamine b-hydroxylase, the enzyme that converts dopamine to NE, are subnormal (Ziegler et al). The use of these neurochemical tests in clinical practice is difficult and the data in the literature are inconsistent. Low’s monograph should be consulted for procedural details.
Pathologic studies have disclosed the central type of autonomic failure to be somewhat heterogeneous. Oppenheimer, who collected all the reported central cases with complete autopsies, found that they fell into two groups: (1) that which was designated by Adams as striatonigral degeneration or, later, Shy-Drager syndrome, where autonomic failure was associated with a parkinsonian syndrome and often with the presence of cytoplasmic inclusions in sympathetic neurons, and (2) another with involvement of the striatum, cerebellum, pons, and medulla but without inclusions, formerly designated olivopontocerebellar degeneration (there are now reported to be glial and neuronal cytoplasmic inclusions in all these cases). Both conditions are now referred to as multiple system atrophy, the term introduced by Oppenheimer, the first type, MSA-P to denote the parkinsonism and the second type, MSA-C reflecting cerebellar degeneration as discussed in Chap. 38. If the process remains purely an autonomic failure, MSA-A is used.