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Abstract Encephalitis is defined as the presence of an inflammatory process of the brain in association with clinical evidence of neurologic dysfunction. The most common cause is viral infection. (Tunkel, et al; 2011).Herpes simplex virus causes encephalitis in 2–4 per million population per year .(Rozenberg , et al ;2011) Early diagnosis of herpes simplex encephalitis (HSE) is very important since it is treatable with the antiviral drug acyclovir , and treatment delay is associated with significantly poor outcome. (Solomon , et al ;2012 ). The characteristic symptoms of HSE are abnormal behavior/psychosis (66 %), confusion/disorientation (81 %) and speech disturbance (66 %), which are justifiable due to the preferential involvement of the frontal and temporal lobes. Other symptoms of HSE include fever (76–90 %), headache (70–90 %) and seizure (50–55 %) .However, these symptoms are not unique as they can be present in encephalitis caused by other viruses. Moreover, these symptoms can also be found in immune-mediated encephalitis, in particular the anti-NMDA receptor encephalitis, which can mimic or occur as a relapse encephalitis after the first episode of HSE. Hence, diagnosis of HSE requires an integration of clinical presentations, neuroimaging, and laboratory tests, especially molecular diagnostic techniques. |