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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 (formerly multiple 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 A1c 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

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