In all forms of multiple system atrophy, the autonomic failure is attributable to degeneration of lateral horn cells of the thoracic cord. There is also a degeneration of nerve cells in the vagal nuclei as well as nuclei of the tractus solitarius, locus ceruleus, and sacral autonomic nuclei, accounting for laryngeal abductor weakness (laryngeal paralysis and stridor are features in some cases), incontinence, and erectile dysfunction. NE and dopamine are depleted in the hypothalamus (Spokes et al). The sympathetic ganglia have usually been normal. In Parkinson disease, where fainting is sometimes a problem, Lewy bodies are found in degenerating sympathetic ganglion cells but the medications used for treatment also exaggerate hypotension.
Treatment of orthostatic hypotension consists of adequate hydration (at least 1.5 L of fluids per day) with high salt intake, up 8 g of sodium per day, small and frequent meals (to reduce postprandial hypotension) and compression stockings or corset. Fainting can sometimes be avoided by the countermaneuvers of having the patient tightly cross his legs upon standing. Medical treatment can be initiated if nonmedical approaches fail. The peripherally acting alpha agonist, midodrine can be started at 2.5 mg q4h, slowly raising the dose to 5 mg q4h, taking the last dose before about 7 p.m. to void supine hypertension while asleep. The mineralocorticoid fludrocortisone acetate (Florinef) alleviates orthostatic hypotension by volume expansion due to the sodium retention by kidneys. Florinef can be started at dose 0.1 mg daily which may be slowly (over weeks) titrated up 0.9 mg daily. Fludrocortisone may cause hypokalemia and should be used cautiously in patients with severe supine hypertension; its effect may take up to 2 weeks to be manifest so rapid elevation of the dose is not advised. Pyridostigmine stimulates sympathetic ganglia and at doses 30 to 60 mg twice to thrice a day was also reported to be effective in treatment of orthostatic hypotension. Compared to florinef and midodrin, pyridostigmine is less potent pressor but it is much less likely causing supine hypertension. Pyridostigmine also may help to reduce constipation. A newer addition is droxidopa that is a prodrug to the neurotransmitter norepinephrine, acting both centrally and peripherally. Northera is usually started at the dose 100 mg three times a day which can be titrated up to 600 mg three times a day. Northera also increases risk of supine hypertension.
Impairment of autonomic function, of which orthostatic hypotension is the most serious feature, occurs as part of many acute and chronic peripheral neuropathies (e.g., diabetic, alcoholic–nutritional, amyloid, Guillain-Barré, heavy metal, toxic, and porphyric). Disease of the peripheral nervous system may affect the circulation in two ways: the nerves from baroreceptors may be affected, interrupting normal afferent homeostatic reflexes, or postganglionic efferent sympathetic fibers may be involved in their course in the spinal nerves. The severity of the autonomic failure need not parallel the degree of motor weakness. An additional feature of the acute dysautonomias is a tendency to develop hyponatremia, presumably as a result of dysfunction of afferent fibers from venous, right atrial, and aortic arch volume receptors; this elicits a release of antidiuretic hormone arginine vasopressin (AVP). These same stretch baroreceptors are implicated in the intermittent hypertension that sometimes complicates these acute neuropathies.