- Physicians are faced daily with the challenges of accurately diagnosing patients by employing the current diagnostic criteria, recommended structural neuroimaging techniques, and/or guidelines put forth by ad hoc committees, consensus groups, and data from large, multicenter, placebo-controlled studies. A comprehensive understanding of the approach to PACNS from the etiology to optimal treatment is currently not clearly defined. This is a rare disorder that represents a unique diagnostic challenge for the neurologist given the lack of uniformity with respect to the clinical presentation, radiological and histopathological findings, and the varying natural history of the disease. This condition is restricted to the CNS with no signs of systemic involvement and biopsy of the brain parenchyma and leptomeninges is paramount in the diagnosis. A delay in the diagnosis and proper treatment of the disorder may cause increased morbidity and death. Current treatment strategies should be initiated aggressively, but only after confirmation of the diagnosis has been made. The diagnosis should not be made based on any single study. Instead, historical, clinical, serological, radiological, and histopathological correlation is needed for an accurate diagnosis. It is only by this approach that appropriate treatment interventions can be instituted in a timely manner to increase the likelihood of a better outcome. Future studies may focus on the genetic predilection for this condition which may provide insight into its pathogenesis and varied clinical course as well as treatment response.