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

Abstract

Background: 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. Aims: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.Methods: 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. Results: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) >10x10 6 /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. Conclusion: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.

Approach to recurrent Herpes Simplex Encephalitis in children

“…Periodic lateralization epileptiform discharge is characteristic for HSE. Worsening bilateral abnormality with slow wave activity and recurrent periodic complexes are seen in recurrent HSE [3,41,42].…”

“…Although it is rare, the management of such condition is challenging in the sense of treatment dose and duration where the recent Infectious Diseases Society of America guideline has demonstrated that relapses were not documented in increased dose and prolonged period of treatment with acyclovir up to 20 mg/kg every 8 h for 21 days (IDSA guideline). Even though this treatment modality has been used, still there are reported cases of relapses long time up to 5 years after initial treatment had stopped provided negative PCR on follow-up in one of the reported cases [3]. Other treatment modalities were also used and are discussed in the treatment section.…”

Auto-immune anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: three case reports

“…9 Case 3 had an abnormal MRI compatible with the findings in herpes simplex encephalitis although her CSF PCR for HSV was negative. 10 HSV has recently been recognised as a trigger of anti-NMDAR encephalitis and several cases were reported in association with HSV, whereas other reported cases manifested as clinical relapses of HSV owing to anti-NMDARencephalitis. 11 Two infants aged 8 months and 6 months with severe hyperkinetic movements owing to anti-NMDAR encephalitis associated with HSV have been reported.…”

Clinical and Laboratory Characteristics of Herpes Simplex Encephalitis in Children in Qena Governorate, Egypt

“…In Al-Shekhlee et al's study [31], periodic lateralized epileptiform discharges and/or focal temporal slowing were present in 90% of the PCR-positive patients at symptom onset compared with only 30% of the PCR-negative group. By others [32], EEG abnormalities were detected in 94% of children with HSE. These consisted of non-specific diffuse slow waves in four (24%) patients and focal slow waves in 13 (76%) patients.…”