Encephalitis syndrome: Look for autoimmune causes

Abstract

Background: Encephalitis with lymphocytic-normal glucose CSF profile usually is caused by viral infections. Search for viruses is, however, successful in only half of the cases. It has been increasingly recognized that encephalitis can also be due to autoimmune causes. We attempted to identify patients presenting with immune encephalitis syndrome. We also tried to determine whether there were specific clinical patterns that might help identify such patients. Methods: Patients with encephalitis admitted between January 2011 and January 2012 were examined for evidence of viral infections [CSF-PCR for herpesviruses 1-6, Japanese encephalitis (JEV) and dengue viruses and enteroviruses; serology for dengue and JEV]. Autoimmune panel consisted of NMDA, AMPA, GABA, CASPR-2 and LGI-1 and 14 paraneoplastic antibodies. They were determined by indirect immunofluorescence (IIF) assay in sera. Results: There were 84 patients with an encephalitis presentation. Thirty-four patients (40.5%) had no etiologies identified. Twenty-six (31%) were associated with infections. These were 8 with herpes simplex virus, 4 varicella-zoster virus, 3 JEV, 3 Epstein-Barr virus, 3 fungal infection, 2 Mycobacterium tuberculosis, 1 dengue, 1 rabies and 1 with dual infection with herpes simplex and dengue. Initially misdiagnosed subjects were 8 patients (9.5%) with fever who had cerebral venous thrombosis (1), subarachnoid hemorrhage (1), metabolic encephalopathy (2), and cerebral infarction (4). There were 16 febrile encephalitis patients with immune disorders (19%). These were Neurobehcet's disease (1), neuropsychiatric-lupus erythematosus (2), multiple sclerosis (1) and neuromyelitis optica (1), anti- ANNA-2 (4), anti-NMDA (3), anti-AMPA2 (1), anti-GABA (1), anti-VGKC (1) and anti-NMDA coexisting with ANNA-2 (1). Ages ranged in the immune group were between 3 and 90 (2 <15 years old). Presenting symptoms were fever, altered consciousness, behavioral changes or psychosis and seizures. Facial dyskinesia was evident in one anti-NMDA receptor encephalitis patient. Conclusion: Immune encephalitis is not rare and can occur in all age groups. Diagnosis in most such cases cannot be made based on clinical grounds alone. In cases where there is no definitive diagnosis, antibody assays should be ordered to identify possible autoimmune diseases that require specific treatment.