Neuropathies Associated with Systemic & Metabolic Disorders

Key Features

• Weakness, sensory disturbances, or both in the extremities

• Pain sometimes common

Clinical Findings

• Diabetes mellitus

  • Peripheral nervous system involvement may lead to

    • Symmetric sensory or mixed sensorimotor polyneuropathy

    • Asymmetric motor radiculoneuropathy or plexopathy (diabetic amyotrophy)

    • Thoracoabdominal radiculopathy

    • Autonomic neuropathy

    • Isolated lesions of individual nerves (mononeuritis multiplex)

• Uremia

  • May lead to a symmetric sensorimotor polyneuropathy that tends to affect the lower limbs more than the upper limbs

  • More marked distally than proximally

• Alcoholism and nutritional deficiency

  • Many patients with alcoholism have an axonal distal sensorimotor polyneuropathy

    • Frequently accompanied by painful cramps, muscle tenderness, and painful paresthesias

    • Often more marked in the legs than in the arms

  • Symptoms of autonomic dysfunction may also be conspicuous

  • A similar distal sensorimotor polyneuropathy is a well-recognized feature of beriberi (thiamine deficiency)

  • In vitamin B₁₂ deficiency, distal sensory polyneuropathy may develop but is usually overshadowed by central nervous system manifestations (eg, myelopathy, optic neuropathy, or cognitive impairment and dementia)

• Paraproteinemias

  • A symmetric sensorimotor polyneuropathy may occur in patients with plasma cell myeloma

    • Onset is gradual

    • Course is progressive

    • Often accompanied by pain and dysesthesias in the limbs

  • In classic lytic myeloma, neuropathy is axonal

  • In sclerotic myeloma, segmental demyelination (primary or secondary) and axonal loss may occur and lead to predominantly motor clinical manifestations

  • Both demyelinating and axonal neuropathies are also observed in patients with paraproteinemias without myeloma

  • Polyneuropathy may also occur in association with macroglobulinemia and cryoglobulinemia

  • With polyneuropathy due to amyloidosis, sensory and autonomic symptoms are especially conspicuous, whereas distal wasting and weakness occur later

Diagnosis

• Diabetes mellitus

  • Motor and sensory nerve conduction velocities are significantly slower, and the ratio of motor nerve conduction velocity to F-wave conduction velocity ratio (M/F ratio) is significantly lower, than those of normal subjects

• Uremia

  • Motor and sensory conduction velocity is moderately reduced

• Alcoholism and nutritional deficiency

  • Motor and sensory conduction velocity may be slightly reduced, even in subclinical cases

  • Gross slowing of conduction is uncommon

• Paraproteinemias

  • Electrophysiologic studies show distal demyelinating changes, correlating with predominantly sensory losses

Treatment

• Diabetes mellitus

  • Control of hyperglycemia to reduce hemoglobin A_1c to < 6.5%

    • Diet, exercise, weight reduction

    • Hypoglycemic medications, insulin, metformin

• Uremia

  • Kidney transplantation

  • Long-term dialysis

• Alcoholism and nutritional deficiency

  • Abstinence from alcohol

  • Vitamin repletion

• Paraproteinemias

  • Neuropathy of classic plasma cell myeloma: poorly responsive to therapy

  • Polyneuropathy of benign monoclonal gammopathy: may respond to immunosuppressant drugs and plasmapheresis

  • Polyneuropathy associated with macroglobulinemia and cryoglobulinemia: plasmapheresis

  • Polyneuropathy due to amyloidosis: no specific treatment