Neuropathies Secondary to Systemic Disorders

Chronic Renal Failure

The neuropathy of chronic renal failure is typically an axonal degenerative type, which in most children is asymptomatic. Nerve conduction studies in long-term hemodialysis-dependent children generally show normal or only mildly impaired values. The evaluation of the “H” reflex has been reported as a useful indicator of clinically asymptomatic uremic polyneuropathy, identifying this complication in almost 60% of one series of children with chronic renal failure.

This neuropathy usually remains stable or improves with treatment; if not, increasing the frequency and duration of dialysis may result in improvement. Rapid improvement usually follows successful renal transplantation, even in patients with long-standing neuropathy.

Diabetes Mellitus

Diabetic neuropathy may manifest as a polyneuropathy, focal neuropathy, or autonomic neuropathy. The latter is the most common and has the most serious side effects, related to unawareness of hypoglycemia and cardiovascular dysfunction. Children with a length-dependent polyneuropathy suffer distal sensory loss (numbness) and paraesthesiae; they may also have pain manifesting as burning, aching, and electric-sharp sensations. Weakness, clumsiness, loss of balance, and falls may be associated with distal anhidrosis, postprandial bloating, constipation, diarrhea, and lack of awareness of hypoglycemia. Glove and stocking sensory loss, loss of deep tendon reflexes, distal weakness, and even foot ulcers may occur.

Between 10% and 68% of children with diabetes suffer from neuropathies. In one large cohort of 146 children (under 18 years of age) with diabetes, 27.4% had peripheral neuropathy. Of this affected group, 62.5% had subclinical disease, a minority being clinically affected.

Although patients with diabetic neuropathy may not complain of it, their physical examination may reveal variable degrees of sensory loss. In one study, 30.8% of subjects had numbness and about 7% to 10% showed large myelinated nerve fiber dysfunction, while only 1.4% had impairment in pain or temperature sensation. Nerve conduction studies most often show abnormalities of the peroneal and sural nerves.

Large studies have suggested that neuropathy can develop in young children with short illness duration and despite good glycemic control. As such, the concept of the duration of illness as a key disease-inducing factor has not been established; it has been suggested that the nerve damage can occur acutely and rapidly at the onset of the diabetes, subsequent to which the neuropathy develops more slowly or may even plateau. The best way to prevent this complication is still strict blood glucose control.

Since the neuropathy can progress and ultimately affect quality of life, but is often initially subclinical, regular nerve conduction studies are recommended in order to monitor for development of this serious disease complication.

Multiple Endocrine Neoplasia Type 2B

Multiple endocrine neoplasia (MEN) type 2B is a rare, dominantly inherited syndrome accounting for 5% of all cases of MEN 2, characterized by medullary thyroid carcinoma, pheochromocytoma, ganglioneuromatosis, and a variety of skeletal and connective tissue abnormalities. MEN 2B cases usually carry either an M918T or A883T mutation of the RET (REarranged during Transfection) oncogene. Affected patients have an arresting appearance because of a diffuse, thick, fleshy enlargement of the everted lips, apparent eversion of the eyelids, and a marfanoid habitus. Other oral manifestations include a high arched palate and small, whitish-yellow, firm, protruding neuromatous nodules on the tongue. Fibular atrophy, pes cavus, scoliosis, and proximal or distal muscle atrophy are common.

A polyneuropathy, with mild weakness of ankle dorsiflexion or occasionally of the intrinsic hand muscles, may be the presenting manifestation of this disorder. Nerve conduction studies demonstrate mild abnormalities of motor and sensory nerve conduction. Chronic denervation is apparent on needle EMG.

Sural nerve biopsy reveals moderate loss of small- and large-diameter myelinated fibers. At autopsy, unusual plaques of hyperplastic interlacing bands of Schwann cells and myelinated fibers overlie the posterior columns of the spinal cord. Autonomic nerves are also involved and are responsible for the severe constipation or diarrhea frequently seen in these patients.

Early diagnosis is extremely important because of the high risk of malignancy. Medullary thyroid carcinoma is almost always present at the time of diagnosis.