DESCRIPTION

Peripheral neuropathy is a disorder of a peripheral nerve that causes abnormal sensory, motor, or autonomic function.

Sensory Complaints

• Paresthesia (tingling, prickling, burning, or stinging) often starts in the fingers and toes and progresses proximally in a symmetrical fashion.
• Symptoms may start unilaterally but eventually become symmetrical in a "stocking-glove" distribution.
• Lower extremity involvement usually precedes involvement of the upper extremities.

Motor Complaints

• Weakness often progresses from distal to proximal in a symmetrical fashion.
• Lower extremities are often affected more than the upper extremities.
• Decreased deep tendon reflexes occasionally progress to diffuse areflexia.

PATHOPHYSIOLOGY

• Peripheral neuropathy can be divided into three general categories based on the part of the nerve affected:
  • Neuronopathy occurs when the cell body of the anterior horn (motor), dorsal root ganglion (sensory), or autonomic nervous system is affected.
  • Axonopathy, the most common form of drug-induced peripheral neuropathy, occurs when the axon is affected.
  • Myelinopathy is demyelination that involves large-diameter axons more than small axons; proprioception, vibration, and light touch are involved to a greater extent than smaller fibers that mediate pain and temperature.
• Mononeuropathy occurs when there is involvement of just one isolated peripheral nerve.
• Polyneuropathy
  • Polyneuropathy is the involvement of multiple areas of the peripheral nervous system.
  • Most toxic peripheral neuropathies are diffuse, symmetric, and involve many different nerves and nerve roots.

Section Outline:

• DESCRIPTION
  • Sensory Complaints
  • Motor Complaints
• PATHOPHYSIOLOGY

DIFFERENTIAL DIAGNOSIS

Further information on each poison is available in SECTION IV, CHEMICAL AND BIOLOGICAL AGENTS.

Toxicologic Causes of Predominantly Sensory Neuropathy

• Axonopathy. Colchicine, ethambutol, ethionamide, glutethimide, nitrous oxide, nucleosides (dideoxyinosine), cisplatin, and taxol
• Neuronopathy. Pyridoxine
• Unknown Lesion Location. Dimethylamino propionitrile, thalidomide, nalidixic acid, colistin, thiamphenicol, chloramphenicol, sulthiame, phenelzine, ergotamine, and methysergide

Toxicologic Causes of Combined Sensory and Motor Neuropathy

• Axonopathy. Acrylamide, ethanol, allyl chloride, arsenic, disulfiram, carbon disulfide, gold, ethylene oxide, hydralazine, isoniazid, methylbromide, metronidazole, misonidazole, nitrofurantoin, organophosphates, polychlorinated biphenyls, phenytoin, podophyllin, thallium, vincristine, hexacarbons (n-hexane and methyl n-butyl ketone are both metabolized to 2,5-hexanedione), and triorthocresyl phosphate
• Myelinopathy. Ethanol, amiodarone, diphtheria, gold, lead, trichloroethylene, and arsenic
• Unknown Lesion Location. Aurothioglucose, perhexilene, allopurinol, streptomycin, amitriptyline, penicillamine, indomethacin, phenylbutazone, clofibrate, disopyramide, chlorambucil, chlorpropamide, and tolbutamide

Toxicologic Causes of Predominantly Motor Neuropathy

• Axonopathy. Dapsone, mercury, and vacor
• Neuronopathy. Doxorubicin
• Myelinopathy. Buckthorn and lead
• Unknown Lesion Location. Benzene, bismuth, chloramphenicol, chlorphenoxy herbicides, chloroquine, organochlorines, dinitrophenols, emetine, paralytic shellfish poisoning, styrene, amphotericin B, sulfonamide, and cimetidine

Nontoxicologic Causes of Peripheral Neuropathy

• Common Causes. Diabetes mellitus, direct nerve trauma, compression or entrapment, Guillain-Barré syndrome, uremia, vitamin B₁₂ deficiency, thiamine deficiency, carcinoma, carpal tunnel syndrome, mononeuropathy multiplex, small vessel disease vasculitis, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, multiple sclerosis, frostbite, herpes zoster neuritis, leprous neuritis, and Bell's palsy
• Uncommon Causes. Porphyria, primary biliary cirrhosis, amyloidosis, hypothyroidism, acromegaly, polycythemia vera, lymphoma, multiple myeloma, celiac disease, mononucleosis, macroglobulinemia, diphtheria, Friedreich's ataxia, neurofibroma, leprosy, immune-mediated acquired demyelinating neuropathy (acute hemorrhagic leukoencephalitis and smallpox or measles infection), genetically determined demyelinating neuropathy, progressive multifocal leukoencephalopathy, peripheral nerve tumors (usually either schwannoma or neurofibroma), collagen vascular disease, hysteria, malingering, and psychogenic numbness

Neuromuscular Problems Misdiagnosed as Peripheral Neuropathy

Botulism, myasthenia gravis, drug-induced muscular weakness (polymyxin, propranolol, procainamide, phenytoin, chlorpromazine, aminoglycosides, d-penicillamine), Eaton-Lambert syndrome, tick paralysis, Lyme disease, hypokalemia, strychnine, tetanus, and coral snake envenomation

SIGNS AND SYMPTOMS

Associated physical signs may help reveal the poison involved when they occur in a patient with peripheral neuropathy.

Vital Signs

Orthostatic hypotension is common in autonomic neuropathy.

HEENT

• Cranial nerve palsies following a sore throat suggest diphtheria, but this is unlikely if immunization status is up to date.
• Optic neuropathy during tuberculosis (TB) treatment suggests ethambutol poisoning.
• Stomatitis and gingivitis suggest elemental mercury vapor poisoning.

Dermatologic

• Alopecia suggests arsenic or thallium poisoning.
• Hyperhidrosis and cool cyanotic limbs suggest acrylamide toxicity.
• Allergic dermatitis, stomatitis, alopecia, and hypersensitivity pneumonitis suggest exposure to gold salts or gold drugs.

Pulmonary

Pulmonary fibrosis suggests amiodarone poisoning.

Hepatic

• Elevated hepatic transaminase during TB treatment suggests isoniazid poisoning.
• Increased liver function tests and glomerulonephritis suggest exposure to allyl chloride.

Renal

Renal insufficiency with predominant loss of vibration and proprioception suggests cisplatin toxicity.

Hematologic

• Hypochromic microcytic anemia suggests chronic lead toxicity.
• Aplastic anemia developing during chelation therapy suggests penicillamine or arsenic poisoning.

Musculoskeletal

• Bilateral foot and wrist drop suggests exposure to lead.
• Muscle weakness during treatment of gout suggests colchicine poisoning.
• Muscle atrophy suggests that neuropathy is chronic.

Neurologic

• Recurrent exacerbations of focal or multifocal neurologic dysfunction suggest multiple sclerosis.
• Onset of neuropathy one to several days following exposure suggests acrylamide poisoning.
• Paresthesia in hands preceding that in feet suggests vincristine poisoning.
• Predominantly vision and hearing deficits suggest trichlorethylene exposure.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Complete neurologic examination includes mental status; cranial nerves; sensory including pain, temperature, light touch, vibration, and position sense; muscle strength; cerebellar function; and deep tendon reflexes.

Recommended Tests

• Complete blood count is used to check for hypochromic microcytic anemia and basophilic stippling (lead), or pancytopenia (arsenic, thallium, or colchicine).
• Serum electrolytes, BUN, and creatinine are measured to check for hypokalemia, a common cause of muscle weakness.
• Urinalysis is used to detect concurrent renal injury.
• Lumbar puncture
  • Elevated protein without an increased number of cells suggests Guillain-Barré syndrome.
  • Increased immunoglobin gamma G with relatively normal protein and oligoclonal bands on protein electrophoresis suggest multiple sclerosis.
• Blood lead level is usually elevated in lead neuropathy.
• 24-hour urine collection for mercury, arsenic, or thallium should be ordered as indicated by history of exposure.
• Electrodiagnostic studies are used to differentiate demyelinating disorders from axonal disorders.
• Spirometry, which checks for decreases in negative inspiratory flow, may be the earliest finding of respiratory muscle weakness and should be used on patients with muscle weakness.
• Chest radiograph detects amiodarone-induced pulmonary fibrosis.
• Magnetic resonance imaging is used for screening the brain and spinal cord for metastatic disease and detecting multiple sclerosis.

Not Recommended Tests

Nerve biopsy is usually of limited value in confirming a toxic neuropathy.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes of Predominantly Sensory Neuropathy
  • Toxicologic Causes of Combined Sensory and Motor Neuropathy
  • Toxicologic Causes of Predominantly Motor Neuropathy
  • Nontoxicologic Causes of Peripheral Neuropathy
  • Neuromuscular Problems Misdiagnosed as Peripheral Neuropathy
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Pulmonary
  • Hepatic
  • Renal
  • Hematologic
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• peripheral neuropathy may have potential toxic cause.
• coingestant, drug interaction, or underlying disease present unusual problems.

DECONTAMINATION

Owing to the time required for a neuropathy to develop, decontamination is not usually helpful.

ANTIDOTES

There are no specific antidotes for peripheral neuropathy.

ADJUNCTIVE TREATMENT

Symptomatic therapy should be provided to treat pain.

Section Outline:

• DIRECTING PATIENT COURSE
• DECONTAMINATION
• ANTIDOTES
• ADJUNCTIVE TREATMENT

EXPECTED COURSE AND PROGNOSIS

• Neurologic deficits may continue to worsen for days to weeks after therapy is initiated before either stabilizing or improving.
• Although motor or sensory function may not return to baseline, the peripheral neuropathy will usually improve.
• It is difficult to predict which patients will have full recovery.

DISCHARGE CRITERIA/INSTRUCTIONS

Most patients can be discharged following evaluation and if concurrent toxic effects of poison are not present.

Section Outline:

• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Failure to remove a patient from potential sources of exposure may lead to irreversible neurologic dysfunction.
• Following removal from a source of exposure, the neurologic deficits may continue to worsen for days to a few weeks before either stabilizing or improving.

Poisoning by drugs primarily affecting the autonomic nervous system.

RECOMMENDED READING

POISINDEX Editorial Staff. Peripheral neuropathy. In: Rumack BH, Sayre NK, Gelman CR, eds. POISINDEX System. Englewood, CO: MICROMEDEX, Inc.

Author: Edwin K. Kuffner

Reviewer: Richard C. Dart