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In adults a subtle encephalopathy characterized primarily by memory impairment, irritability and somnolence may occur months to years after classic manifestations of Lyme disease. However, only limited information is available about whether there is an equivalent disorder in children.Case series of five children seen in a Lyme disease clinic in a university referral center for evaluation of neurocognitive symptoms that developed near the onset of infection or months after classic manifestations of Lyme disease. The diagnosis was based on clinical symptoms, serologic reactivity to Borrelia burgdorferi and intrathecal antibody production to the spirochete. Evaluation included detailed neuropsychologic testing. After evaluation the children were treated with intravenous ceftriaxone for 2 or 4 weeks. Follow-up was done in the clinic and a final assessment was made by telephone 2 to 7 years after treatment.Along with or months after erythema migrans, cranial neuropathy or Lyme arthritis, the five children developed behavioral changes, forgetfulness, declining school performance, headache or fatigue and in two cases a partial complex seizure disorder. All five patients had IgG antibody responses to B. burgdorferi in serum as well as intrathecal IgG antibody production to the spirochete. Two patients had CSF pleocytoses and three did not. Despite normal intellectual functioning the five children had mild to moderate deficits in auditory or visual sequential processing. After ceftriaxone therapy, the four children in whom follow-up information was available experienced gradual improvement in symptoms.Children may develop neurocognitive symptoms along with or after classic manifestations of Lyme disease. This may represent an infectious or postinfectious encephalopathy related to B. burgdorferi infection.