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Lyme disease, the multi-system infection caused by the tick-borne spirochaete Borrelia burgdorferi, can involve the nervous system, most commonly causing, alone or in combination, lymphocytic meningitis or abnormalities of cranial or peripheral nerves, the latter most typically presenting as a painful radicular syndrome. Diagnosis is based on appropriately used, standard serological tests; in instances where the central nervous system is involved, cerebrospinal fluid assessment for organism-specific antibodies can be useful. Treatment with any of several standard regimens of oral or parenteral antimicrobials is highly effective. Prolonged treatment beyond four weeks is rarely if ever warranted, and carries significant risk.