Short report 1Division of Infection and Immunity, Centre for Virology (UCL Campus), Windeyer Institute of Medical Sciences, University College Medical School, London, UK 2Health Protection Agency, Centre for Infections, London, UK 3Child Studies Department, King’s College, London, UK 4Child Development Centre, Addenbrooke’s Hospital, Cambridge, UK Correspondence to Dr Katherine N Ward, Division of Infection and Immunity, Centre for Virology (UCL Campus), Windeyer Institute of Medical Sciences, University College Medical School, 46 Cleveland Street, London W1T 4JF, UK; k.n.ward@ucl.ac.uk Accepted 18 May 2011 Published Online First 17 June 2011 162 Herpes simplex serious neurological disease in young children: incidence and long-term outcome Katherine N Ward,1 Anu Ohrling,2 Naomi J Bryant,1 Jennifer S Bowley,1 Euan M Ross,3 Christopher M Verity4 ABSTRACT Objective To determine the contribution of herpes simplex virus (HSV) to serious neurological disease. Setting and patients A 3-year prospective survey of children aged 2–23 months in Britain and Ireland. Results 19 children had HSV central nervous system (CNS) infection; 13 aged 2–11 months had focal neuroimaging abnormalities and 11 long-term neurological sequelae. Of six aged 12–35 months, one had abnormal neuroimaging and three long- term neurological sequelae. 17 of the 19 had serious neurological disease. HSV CNS infection accounted for 23% of serious neurological disease in children aged 2–11 months and 4.5% in older children. Conclusions The incidence of HSV-induced serious neurological disease in the UK was estimated at 1 in 64 000/year in younger children and 1 in 230 000 in older children. HSV CNS infection has clinical effects ranging from frank encephalitis to severe illness with fever and convulsions to milder disease lacking encephalopathy. INTRODUCTION Herpes simplex encephalitis (HSE) is the most common cause of sporadic encephalitis and with- out treatment 70% of patients die. Our knowledge of HSE relies on two clinical trials of antiviral drugs from the 1980s. Since then substantial changes in diagnostic methods, including PCR to test cerebrospinal ﬂuid (CSF) for herpes sim- plex virus (HSV) DNA together with the use of aciclovir, have improved survival. However, the spectrum of clinical manifestations and long- term outcome need to be better deﬁned so as to improve management and thereby decrease the still considerable morbidity and mortality associ- ated with this devastating condition. A prospective survey of children aged 2–23 months in Britain and Ireland with serious neurological disease showed for the ﬁrst time that human herpesvirus-6 and -7 contributed sig- niﬁcantly to this illness.1 Data collected included information on other pathogens, including HSV, and thus its contribution to the burden of disease could be assessed. The present paper reports the results obtained. METHODS Patients Case ascertainment Between October 1998 and September 2001 paedi- atricians were requested by the British Paediatric Surveillance Unit to report the cases of all children 2–35 months old with serious neurological dis- ease.1 Neonates were excluded from the survey to avoid inclusion of inherited and mechanical neurological damage which often presents before 2 months of age. Details of each child’s neurologi- cal illness were collected using a short standard questionnaire. A further brief questionnaire was sent after at least a year to check long-term out- come, that is, whether the child had recovered or suffered developmental delay, persisting neu- rological deﬁcit or convulsions. An additional questionnaire was sent to the referring hospital’s microbiology laboratory to conﬁrm the microbi- ological results at the time of the child’s illness. Each questionnaire was scrutinised by a physi- cian (KNW) to determine whether the details ﬁtted the case deﬁnition (see below). Difﬁcult cases were referred to one or more paediatricians (AO, CMV, EMR) for a ﬁnal decision. The data- base of all reported disease episodes, regardless of whether or not they met the case deﬁnition, was re-examined by KNW for individuals with HSV central nervous system (CNS) infection. Deﬁnitions Fever Fever was deﬁned as a temperature ≥37.5°C. Serious neurological disease 1. Severe illness with fever and convulsions i. with a total duration of >30 min ii. followed by encephalopathy for 2–23 h iii. followed by paralysis or other neuro- logical signs not previously present for ≥24 h. 2. Encephalitis i. Encephalopathy for ≥24 h and two or more of the following: a. fever b. convulsions c. focal neurological ﬁndings (≥24 h) d. pleocytosis (>5 leucocytes/μl CSF) e. characteristic abnormal CT or MRI results. 3. Exclude i. viral (aseptic) meningitis without encephalopathy ii. the following conﬁrmed causes: hypoxic/ ischaemic, vascular, toxic, metabolic, neo- plastic, traumatic and pyogenic infections iii. uncomplicated convulsions or a series of convulsions lasting <30 min iv. immunocompromised children. Arch Dis Child 2012;97:162–165. doi:10.1136/adc.2010.204677