The epidemiological, clinical, laboratory, and imaging findings of patients with M. pneumoniae encephalitis referred to the California Encephalitis Project are reported from the California Department of Health Services, Viral and Rickettsial Disease Laboratory, Richmond, CA, and the Centers for Disease Control and Prevention, Atlanta, GA. Of 1988 patients referred, 111 (5.6%) had M. pneumoniae infection, of which 84 (76%) were children <18 years old. Eighty percent were positive by serology alone, whereas only 2% showed a positive CSF polymerase chain reaction for M. pneumoniae. The median age was 11 years (range, 6 mo-18y); and the interval from CNS onset to hospitalization was 2 (0-92) days. Length of hospital stay was a median of 8 (1-72) days; 46 were admitted to ICU. General symptoms were fever (70%), gastrointestinal (45%) respiratory (44%), and rash (14%). Neurological symptoms were lethargy (68%), altered consciousness (58%), seizures (40%), focal neurologic signs (37%), nuchal rigidity (24%), hallucinations (18%), and coma (14%). Laboratory findings showed CSF mild-moderate pleocytosis, predominantly mononuclear cells; a median protein of 45 mg/dL, and normal glucose. CT was normal in 82% of 56, whereas MRI was abnormal in 49% (diffuse in 24%, white matter abnormalities in 16%). EEG was abnormal in 79% (diffuse slowing in > half (51%), and focal in 19%). Diagnosis was confirmed by M pneumoniae IgM in acute and/or convalescent serum. Patients with M pneumoniae-associated encephalitis had fewer seizures and a less severe hospital course compared to those with other bacterial or viral agents (eg HSV-1). Their clinical presentation and course resembled enterovirus infection encephalitis. 
COMMENT. The majority of patients referred to the California Encephalitis Project are positive for M pneumoniae, and these are predominantly pediatric. M pneumoniae is more than twice as frequent as enterovirus and more than 7 times that of HSV-1 encephalitis. Respiratory symptoms are less common in patients with cerebral involvement. In this series, children presented with gastrointestinal symptoms as frequently as respiratory. The course resembled that of enterovirus encephalitis rather than HSV-1. The value of antibiotics in treatment and the mechanism of encephalitic disease with M pneumoniae require further study. The literature includes references to cases with direct invasion of the CNS, and others with immune-mediated “para-infectious” disease. The authors cite recommendation of azithromycin, ciprofloxacin, doxycycline, or chloramphenicol, but penetration of the blood-brain barrier is limited. IV immunoglobulin and steroids have been used in patients with M pneumoniae-associated white matter involvement and acute disseminated encephalomyelitis. Full recovery followed treatment with steroids and antibiotics in 3 patients treated at Great Ormond Street Hospital, London, UK (Ped Neur Briefs August 2004; 18:62). 
Role of viruses in Rasmussen's encephalitis. Several viruses have been implicated in Rasmussen's encephalitis, including enterovirus, Epstein-Barr, cytomegalovirus, and herpes simplex virus, but none has shown a specific link. Astrocytic degeneration or apoptosis and loss caused by cytotoxic T lymphocytes are demonstrated by immunohistochemical studies at Medical University of Vienna, Austria; and University of Bonn, Germany.