A Study on Herpes Simplex Encephalitis in 18 Children, Including 3 Relapses

Mustafa A. M. Salih1, *, Heba Y. El Khashab1, Hamdy H. Hassan2, Amal Y. Kentab1, Sara S. Al Subaei3, Radwan M. Zeidan4, Mohammed N. Al-Nasser1, Saleh A. Othman5
1 Division of Pediatric Neurology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Department of Radiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 Division of Infectious Diseases, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
4 Division of Neurology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
5 Nuclear Medicine Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia

© 2009 Salih et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Pediatrics, Division of Pediatric Neurology, College of Medicine, P.O. Box 2925, King Saud University, Riyadh 11461, Saudi Arabia; E-mail:



Herpes Simplex Virus (HSV) is the most common cause of acute sporadic focal encephalitis. Early Diagnosis is, therefore, crucial for predicting outcome. Improved laboratory technology and improved neuroimaging accessibility have enhanced our ability to diagnose this condition.


To assess the reliability of different investigative tools in diagnosing and subsequent management of herpes simplex encephalitis (HSE); as well as the impact of infection and its relapse on the outcome of a cohort of 18 children evaluated during a period of 13 years.


This combined prospective and retrospective study describes the clinical, laboratory, electroencephalographic and diagnostic imaging studies; and outcome in a cohort of 18 children with HSE over a period of 13 years. It also details the clinical and diagnostic features of 3 patients who relapsed.


The commonest initial presenting symptoms and signs were fever (100%), seizures (72%) irritability (50%) and weakness/hemiparesis (39%). Cerebrospinal fluid (CSF) pleocytosis was found in 62%, red blood cells (RBCs) >10x106/L in 81% and raised proteins (>0.59g/L) in 52%. Examination for herpes simplex virus (HSV) by polymerase chain reaction (PCR) was positive in 50% (6/12). Electroencephalographic changes were universally abnormal (17/17; 100%) and periodic lateralization discharges (PLEDS) were seen in 35% (6/17). During the acute stage (days 1-8 from symptom onset), magnetic resonance imaging (MRI) revealed abnormalities in 91% (10/11), cranial computed tomography (CT) in 50% (5/10) and single photon emission computed tomography (SPECT), within < 7 days, in 75% (6/8). All patients were treated with intravenous acyclovir. There were no deaths but 3 patients relapsed after periods ranging between 18 days and 66 months. Eleven (61%) patients had no or minor sequelae (good outcome) and 7 (39%) had moderate or severe sequelae (poor outcome). Delayed initiation of therapy (> 3days from onset of symptoms) had significant association with poor outcome (P = 0.002). Initial negative PCR results may become positive on subsequent CSF specimen.


Diagnosis of HSE requires combined clinical, laboratory, electroencephalographic and neuroimaging studies. Negative results of PCR do not exclude the infection and should not interrupt the treatment. Early diagnosis and initiation of treatment minimize the devastating effect of HSE. Full course treatment with acyclovir for 21 days is also crucial for prognosis and prevention of subsequent relapse.

Keywords: Herpes simplex virus, encephalitis, children, relapse, outcome, PCR, EEG, CT, MRI, SPECT brain scan.