Definition

While there are numerous historical clues in a variety of organ systems to suggest the presence or absence of autonomic dysfunction, bedside evaluation of the autonomic system is confined for the most part to careful study of the cardiovascular system. The most common and most prominent clinical feature of autonomic dysfunction is orthostatic hypotension. When severe, the fall in blood pressure with assumption of the upright posture is usually accompanied by dramatic symptoms of syncope or near syncope. Early in its course, however, the symptoms associated with orthostatic hypotension may be so vague as to be misleading. In these instances the postural hypotension associated with autonomic dysfunction would be overlooked unless the measurement of blood pressure in the supine and standing positions was recorded routinely in the course of the physical examination.

Normally, assumption of the upright posture is accompanied by a slight decrease in systolic pressure, usually 10 mm Hg or less, and a slight increase in diastolic blood pressure, usually less than 5 mm Hg. These changes in blood pressure may be accompanied by a physiologic increase in heart rate of 10 beats per minute or less. Under certain circumstances, normal blood pressure response to standing may include a decrease in the systolic blood pressure of up to 25 mm Hg and an increase in diastolic pressure of as much as 10 mm Hg. Although there is no uniform consensus, most authors define orthostatic hypotension as a sustained decrease in systolic pressure of 30 mm Hg or more and a decrease in diastolic pressure of 15 mm Hg or more upon standing. Orthostatic hypotension is not synonymous with autonomic dysfunction, but the association of symptomatic decrease in blood pressure of the above magnitude without an accompanying increase in heart rate must suggest a disordered autonomic response.

Technique

Bedside evaluation of the autonomic nervous system consists primarily of observations of: (1) cardiovascular reflexes, (2) pupillary changes, and (3) casual sweating patterns.

Basic Science

Postural hypotension in autonomic dysfunction represents failure of autoregulation of peripheral vascular resistance that normally occurs upon standing. This problem is compounded by sympathetic denervation of the heart, which prevents a compensatory increase in heart rate. This interplay of perfusion pressure and heart rate is demonstrated by the physiology of the Valsalva maneuver in normal individuals. The declining mean arterial blood pressure during forced expiration is accompanied by an appropriate tachycardia during phases 2 and 3 of the maneuver. But in spite of diminishing venous return, blood pressure levels off due to intense peripheral vasoconstriction as a consequence of sympathetic outflow. The "overshoot" blood pressure observed during recovery, or stage 4, is a consequence of increased cardiac output associated with increased venous return pumped into a still vasoconstricted vascular bed. The overshoot hypertension results in reflex bradycardia and return of normal blood pressure, normal cardiac output, and reduced peripheral vascular resistance.

The compensatory vascular reflexes required for normal adaptation to restricted venous return associated with standing require the integrity of afferent, central, and efferent components of the autonomic reflex arc that may be disrupted at one or more loci in syndromes of autonomic dysfunction. Characterization of the nature of the lesion responsible for autonomic dysfunction is frequently helpful in narrowing the focus of etiologic possibilities. Diseases resulting in autonomic dysfunction are commonly categorized as preganglionic (presynaptic) or postganglionic (postsynaptic). Examples of the former include the central forms of autonomic dysfunction associated with movement disorders (Shy–Drager) or parkinsonian symptoms. In these syndromes, postganglionic neurons are intact, but the preganglionic neurons of the interomediolateral cells columns of the spinal cord undergo degeneration. The most common example of postganglionic autonomic dysfunction is the autonomic neuropathy associated with diabetes mellitus, which results from degeneration of peripheral autonomic fibers. Characteristically, the vasculature in syndromes of autonomic dysfunction associated with peripheral denervation is hyperresponsive to infused alpha-receptor stimulants. This feature is sometimes helpful in distinguishing preganglionic from postganglionic causes of autonomic dysfunction. Such tests are fraught with potentially serious complications and should be performed only by experienced individuals and under the most carefully monitored circumstances.

Preservation of a positive pressor response to ice water immersion of an extremity or to mental stress maneuvers implies an intact efferent autonomic pathway. Absence of a pressor response to these two tests, especially if associated with absent sweating, suggests an abnormality in the efferent limb of the reflex arc, but does not rule out abnormalities in other components of the autonomic system.

Clinical Significance

Autonomic insufficiency may result from any disease that affects the central or peripheral components of the autonomic nervous system. The diseases may involve primary (idiopathic) degeneration of autonomic postganglionic fibers without other neurologic abnormalities, as occurs in the syndrome of primary autonomic dysfunction. Alternatively, diseases may involve a central degenerative process in which orthostatic hypotension is associated with diffuse autonomic dysfunction and motor and cerebellar abnormalities, as described in the Shy–Drager syndrome. A related central degenerative process involving preganglionic neuronal degeneration and presenting with orthostatic hypotension and typical parkinsonian symptoms has been described.

More commonly, autonomic dysfunction occurs as a consequence of some other identifiable disease. The most frequently associated disease entity is diabetes meliitus and is usually accompanied by obvious peripheral polyneuropathy. Other nutritional or toxic/metabolic disorders that may result in autonomic dysfunction include porphyria, vitamin B₁₂ deficiency, Wernicke's encephalopathy, and alcoholism. Orthostatic hypotension due to autonomic dysfunction is a frequent presenting feature of the neuropathy of amyloidosis and may also occur in tabes dorsalis, usually in combination with other typical tabetic symptoms. The autonomic reflex arc may also be interrupted by a variety of central factors including tumors of the posterior fossa, cerebral vascular accidents, central hemorrhages, and syringomyelia. One must be cautious to distinguish poor postural adjustment of blood pressure in the elderly from autonomic dysfunction. The former generally occurs upon standing after prolonged recumbency and is accompanied by appropriate acceleration of heart rate. Orthostatic hypotension associated with episodes of hypertension must lead one to the consideration of pheochromocytoma.

The significance of autonomic dysfunction secondary to other diseases is related to the severity of orthostatic symptoms and its response to therapy and especially to the prognosis of the primary disease process. The primary forms of autonomic dysfunction, both peripheral and central, have a generally poor prognosis, especially those associated with movement disorders or parkinsonian symptoms. The mean age of onset of these primary syndromes is in the sixth decade, and survival 5 years after onset of neurologic symptoms is less than 50%.

References

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