Of particular importance is the autonomic disorder that accompanies diabetic neuropathy. It presents as erectile dysfunction, constipation, or diarrhea (especially at night), hypotonia of the bladder, gastroparesis, and orthostatic hypotension, in some combination. Invariably, there are signs of a sensory polyneuropathy, consisting of a distal loss of vibratory and thermal-pain sensation and reduced or lost ankle reflexes; but again, the severity of affection of the two systems of nerve fibers may not be parallel. The pupils are often small and the amplitude of constriction to light is reduced (similar to Argyll Robertson pupils); this has been attributed to damage of cells in the ciliary ganglia. A curious syndrome or “insulin neuritis” has been described, in which, autonomic failure and painful sensory neuropathy arise at the time of rapid glycemic control (see Gibbons and Freeman, 2010).
Gastroparesis can be disabling, painful, and difficult to treat, for example, in diabetic autonomic neuropathy. Camilleri has reviewed the subject and outlined the defect in gastric emptying that interrelates with glucose metabolism and an unexplained association with psychiatric symptoms. Management is by altering nutritional intake and with metoclopramide for mild cases and additional domperidone, prochlorperazine, and erythromycin in severe ones.
Another polyneuropathy with unusually prominent dysautonomia is that caused by amyloidosis. Extensive loss of pain and thermal sensation is usually present; other forms of sensation may also be reduced to a lesser degree. Motor function is much less altered. Sympathetic function is more affected than parasympathetic. Iridoplegia (pupillary paralysis) and disturbances of other smooth muscle and glandular functions are variable. Diabetic and amyloid polyneuropathy are further described in Chap. 46.
Both the primary and secondary types of orthostatic hypotension are also discussed in connection with syncope in Chap. 17.
Familial Autonomic Neuropathy in Infants and Children (Riley-Day Syndrome) and Other Inherited Dysautonomias (See Also Chap. 43)
Riley-Day syndrome is a disease of children, inherited as an autosomal recessive trait. The main symptoms are postural hypotension and lability of blood pressure, faulty regulation of temperature, diminished hearing, hyperhidrosis, blotchiness of the skin, insensitivity to pain, emotional lability, and cyclic vomiting. The tendon reflexes are hypoactive, and mild slowing of motor nerve conduction velocities is common. There is denervation sensitivity of the pupils and other structures. The main pathologic feature is a deficiency of neurons in the superior cervical ganglia and in the lateral horns of the spinal cord. Also, according to Aguayo and to Dyck and their colleagues, the number of unmyelinated nerve fibers in the sural nerve is greatly decreased. It is likely that this disease represents a failure of embryologic migration or formation of the firstand second-order sympathetic neurons. It is now known that this defect is the result of a mutation in the gene (IKBKAP) that codes for a protein (IKAP) that is currently considered to be associated with transcription regulation (Anderson et al). This results in a decrease in the amount of functional protein in autonomic neurons.
Autonomic symptoms are also a prominent feature of the small-fiber neuropathy of Fabry disease (alpha-galactosidase deficiency) as a result of the accumulation of ceramide in hypothalamic and intermediolateral column neurons (see “Fabry Disease” in Chap. 43).