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A 40-year-old female presents with bilateral numbness, weakness, and loss of sensation in all fingers above the proximal interphalangeal joints sparing the thumbs. The pain has been constant for approximately a month and worsening; there are no other neurologic system complaints or any positive findings on physical examination. What are the differential diagnoses for peripheral neuropathy?

Stephanie Cullinane, PA-C

from Blaine Carmichael, PA-C, 09/07/00
The most common categories of peripheral neuropathy are either acquired or inherited. Two sets of questions must be addressed initially: Is the neuropathy a polyneuropathy or mononeuropathy? Second, is the process acute, subacute, or chronic?

The causes of acute ascending motor paralysis with minimal sensory disturbance comprise Guillain-Barré syndrome and diphtheritic polyneuropathy; subacute causes may include nutritional deficiency, alcoholism (beriberi), pellagra, and vitamin B12 deficiency. Another category of subacute causes of polyneuropathy includes poisoning with heavy metals and solvents, such as arsenic, lead, mercury, thallium, methyl-n-butylketone, n-hexane, methyl bromide, organophosphates, and acrylamide. Additional causes may include drug intoxication (isoniazid, ethionamide, hydralazine, nitrofurantoin, disulfiram, vincristine, chloramphenicol, phenytoin, dapsone), uremic neuropathy, mononeuropathy multiplex typically seen in diabetes mellitus, sarcoidosis, and polyarteritis nodosa.

Causes of chronic polyneuropathy may include a benign form seen in elderly patients, connective tissue diseases, uremia, beriberi carcinoma (paraneoplastic syndrome), paraproteinemias, hypothyroidism, amyloidosis, diabetes mellitus, and leprosy.[1]

In terms of this patient's symptoms, particularly the tingling sensation in all of her fingers, all of these causes of peripheral neuropathy should be considered. A number of the polyneuropathies have obvious and well-defined causes such as diabetes, uremia, or nutritional deficiencies. Other entities to consider include mechanical pressure (eg, compression or entrapment [carpal tunnel syndrome]), direct trauma, penetrating injuries, contusions, fracture or dislocated bones; pressure involving the superficial nerves (ulna, radial, or peroneal) which can result from prolonged use of crutches or staying in 1 position for too long. Among the collagen vascular disorders, systemic lupus erythematosus, scleroderma, sarcoidosis, rheumatoid arthritis, and polyarteritis nodosa may be included in the differential diagnosis.

Common causes of peripheral mononeuropathies include repetitive activities such as typing or working on an assembly line.[2] In this case, the neuropathy may be isolated to the upper extremities, such as with carpal tunnel syndrome (CTS); although sparing of the thumbs is unusual, it does not exclude this diagnosis. Other entities to consider include medications and chemical exposures. Medications causing peripheral neuropathy include several AIDS drugs (HIVID (zalcitabine) [formerly called 2',3'-dideoxycytidine (ddC)], and VIDEX® (didanosine) [formerly called dideoxyinosine (ddI)]), the antibiotics metronidazole and isoniazid, gold compounds, and antineoplastic agents such as vincristine.

The initial evaluation should include a fasting serum glucose, glycosylated hemoglobin, blood urea nitrogen, creatinine, complete blood cell count, erythrocyte sedimentation rate, urinalysis, vitamin B12 and thyrotropin stimulating hormone levels. Electromyelogram and nerve conduction studies are often the most useful initial laboratory studies in the evaluation of a patient with peripheral neuropathy.[3] A neurology referral is indicated if the initial evaluation does not result in a diagnosis.

Treatment includes removal of the offending agents in toxic neuropathies. For example, in alcoholic neuropathy alcohol cessation is advised, while In Lyme disease pathogens are removed with antibiotic treatment. In deficiency state syndromes as beriberi, scurvy, or pernicious anemia, appropriate vitamin replacement is indicated, and in relapsing demyelinating polyneuritis, steroids and plasma exchanges may be needed. Neuropathic pain in polyneuropathies is treated with a bedtime dose of amitriptyline. Neuralgic pain (stabbing, shooting) is treated with anticonvulsant doses of phenytoin or carbamazepine. Capsaicin cream is useful for neuropathic pain. For compression mononeuropathies (such as carpal tunnel syndrome), first treat with splints, nonsteroidal antiinflammatory drugs, or local steroid injections. If these primary care approaches fail, a referral for surgical release is indicated.

References
Dyck P, Thomas P, eds. Peripheral Neuropathy, vol. 2, 3rd ed. Philadelphia, Pa: W.B. Saunders Co.; 1992.
Hallett M, Tandon D, Berardelli A. Treatment of peripheral neuropathies. J Neurol Neurosurg Psychiatry. 1985;48;1193-1207.
Dyck PJ, Thomas PK, eds. Diabetic Neuropathy, 2nd ed. Philadelphia, Pa: W.B. Saunders Co.; 1999.
Suggested Reading
Bracker MD, Ralph LP. The numb arm and hand. Am Fam Physician. 1995;51:103-116.

McLeod JG. Investigation of peripheral neuropathy. J Neurol Neurosurg Psychiatry. 1995;58:274-283.

Poncelet AN. An algorithm for the evaluation of peripheral neuropathy. Am Fam Physician. 1998;57:755-764.