A 12-year-old girl presented with an atypical, recurrent, increasingly treatment-resistant case of obsessive-compulsive disorder and chronic tic disorder associated with profound separation anxiety, learning difficulty, and intermittent upper respiratory symptoms. In addition to detailed reviews of history and findings from many clinical caretakers from the prior 7 years, current pediatric, psychiatric, neuropsychological, neuroimaging, and clinical laboratory data were also available. Treatment options were considered from multiple perspectives: psychoanalytically oriented psychotherapy, conventional pharmacotherapy, family interventions, cognitive-behavioral therapy, and learning-supportive strategies. Psychological, neuropsychiatric, and neuroimmunological formulations of etiology were considered. Subsequent treatments included supportive psychotherapy, neuroleptic augmentation of selective serotonin reuptake inhibitors, prophylactic penicillin, and a course of six sessions of plasmapheresis over a 2-week period. The case raises questions for ongoing consideration that juxtapose dynamic, neuropsychiatric, and neuroimmunological perspectives.