Electrophysiologic tests are likewise normal or virtually so; a few show diminished sural nerve potentials and minor changes of motor amplitudes. When the causes listed in the table have been excluded, a substantial group of patients is left and are in need of symptomatic relief. Some have been helped by gabapentin or by antidepressants and analgesic cream applied nightly to the soles and toes. A few of the more severe cases have apparently responded to gamma globulin infusions, but these observations require corroboration (Gorson and Ropper, 1995). In a number of cases of burning feet, the intradermal sensory nerves in skin biopsy specimens are depleted, but the meaning of this finding is not certain (Periquet et al) and the clinical diagnosis of a small-fiber neuropathy in affected older patients can be inferred without this procedure.
Identifiable causes for painful sensory neuropathy in the elderly include mainly diabetes, alcoholic–nutritional deficiency states, connective tissue disease, amyloidosis, and vasculitis. Presumably, in the idiopathic cases, there is a similar small-fiber neuropathy, but the common clinical situation is that an etiology cannot be found. An alternative cause in these neuropathies that are characterized mainly by painful burning is that there is an abnormality of the sodium channel that renders the sensory neurons or fibers hyperexcitable. In the experience of the group from Maastricht, 8 of 28 patients in whom no etiologic diagnosis for small-fiber neuropathy could be found, there were mutations in the gene (SCN9A) encoding voltage-gated sodium channel Nav1.7. The mutation caused a gain of function in this gene and allowed dorsal root ganglion neurons to become hyperexcitable (Faber at al). Yet another rare cause of this syndrome has been the finding of antibodies to peripherin, which is a dominantly inherited trait (Stogbauer et al).
A polyneuropathy that advances slowly over 10 years or more is almost invariably genetic in origin. The neuropathic disease may be remarkably restricted, as in familial analgesia with foot ulcers, or extensive, as in familial peroneal muscular atrophy. The time of onset of these very chronic neuropathies is usually in early life but often cannot be dated with certainty by the patient or family. In infants, the condition may be mistaken for muscular dystrophy or infantile muscular atrophy until sensory testing becomes possible. In the developing child, whose musculature naturally increases in power and volume with age, it may be difficult to decide whether the disease is progressive but typically, there is trouble running or walking making it difficult to keep up with other children, repeated ankle injuries, toe catching, labeled as “clumsiness,” or falls. Strongly indicative of one of these conditions at any age are pes cavus, hammertoes, and, in extreme forms, talipes equinus. One of these deformities is commonly detected in most cases of inherited polyneuropathy. In later life, some of the inherited neuropathies are manifest as trophic changes of skin and bone in distal parts of the limbs indicate involvement of small (pain) fibers and the presence of deformed and degenerated joints (Charcot joint). The mutilating effects are the result of repeated injury to analgesic parts and to a lack of autonomic vascular reflexes. Atrophy of muscle and trophic changes in the skin are generally more marked than in the acquired forms of polyneuropathy.