Table 1 Characteristics of the included studies

Schleede L, 2012

Germany

0.934

Cross-sectional

Inclusion criterion: Proven herpes simplex virus encephalitis as shown by a positive polymerase chain reaction in cerebrospinal fluid or serologic evidence such as a significant rise in serum IgG-anti herpes simplex virus antibodies combined with a positive antibody-specific index

Exclusion criteria:?

32

7.5

(5 months–16 years)

9/23

Liquor PCR,

31 (97%)

Fever, 20 (63%)

Headache, 14 (44%)

Fatigue, 11 (34%)

Vomiting, 10 (31%)

Dizziness, 4 (13%)

Diarrhea, 2 (6%)

Abdominal pain, 1 (3%)

Neurological symptoms, 12 (38%)

 Seizures,7 (58%)

 Meningism, 3 (25%)

 Disorientation, 3 (25%)

Acyclovir (100%)

Dose: 40 mg/kg/d (20–60 mg/kg/d)

Duration (10–36)

Discharge from hospital

18 (56.2%)

Elbers JM, 2007

Canada

0.896

Cross-sectional

Inclusion criteria: Encephalopathy, defined as depressed or altered level of consciousness persisting for > 24 h, plus ≥ 2 of the following: fever (> 38 °C), seizure, focal central nervous system (CNS) findings, CSF pleocytosis (> 5 × 106 cells per L), EEG abnormalities, or diagnostic imaging abnormalities (in brain computed tomography [CT]/MRI scans)

Exclusion criteria: Patients who had an underlying neurologic disease or were known to have immunosuppression

16

5.5

(2 months–14 years)

8/8

Liquor PCR,

12 (75%)

Fever, 16 (100%)

Focal seizure, 11 (69%)

Hemiparesis, 5 (31%)

Dysphasia, 2 (13%)

Acyclovir (100%)

Dose?

Duration (7–21)

Minimum: 3 months after discharge

Mean: 4 years

10 (62.5%)

Yoshinori I, 1998

Japan

0.849

Case–Control

Inclusion criteria: Patients aged 3 months to 16 years in whom HSE was diagnosed between September 1982 and January 1995. The diagnosis of HSE was confirmed by the detection of HSV DNA in CSF by the PCR assay. They also studied patients aged 1 month to 15 years with other infections of the central nervous system. In all control subjects the CSF in the acute phase was negative for HSV DNA by PCR

Exclusion criteria: Neonates with HSV

24

5

(3 months–16 years)

8/16

Liquor PCR,

24 (100%)

Fever, 24 (100%)

Seizures, 22 (92%)

Initial neurological symptoms

 Seizures (9/20): 45%

 Altered consciousness (7/20): 35%

 Dysarthria (3/20): 15%

Glasgow on admission:

 ≥ 11 (2/23) 9%

7–10 (8/23) 35%

 ≤ 6 (13/23) 56%

Acyclovir (100%)

Dose 30 mg/kg/day

Duration (10–14)

6 months

17 (70.8%)

Chen T, 2018

China

0.758

Cross-sectional

Inclusion criteria: Patients who had a clinical diagnosis of acute CNS infection. Patients with meningitis and/or encephalitis was defined as those with (1) an acute onset of illness; (2) at least one abnormality of the cerebrospinal fluid (CSF): WBC count > 15 cells/mm³ or protein level > 400 g/L; (3) temperature > 38 °C; and (4) decreased consciousness, seizures, altered mental status or focal neurological signs

Exclusion criteria: (1) aged ≤ 28 days or aged ≥ 16 years; (2) tuberculous meningitis; (3) proven or probable noninfectious etiology of CNS disease

15

1.9

(4 months–7.7 years)

?

Viral antibody IgM and/or DNA/RNA in CSF

?

Acyclovir (100%)

Dose 30 mg/kg/d

Duration (14–24)

3.8–4.7 years after discharge

10 (66.6%)

Kumar R, 2018

India

0.647

Cross-sectional

Inclusion criteria: Patients from 1 mo to 16 y with acute encephalitis syndrome were included in the study. The classification of AES was based on the World Health Organization (WHO)

Exclusion criteria: Patients with non-viral etiology (acute bacterial meningitis, tubercular meningitis, cerebral malaria, and electrolyte imbalance)

23

4.2

1:1.9

Serology, culture and/or PCR (liquor)

Fever, 23 (100%)

Change in mental status, 23 (100%)

?

Discharge from hospital

7 (30.4%)

Zhang R, 2016

China

0.746

Cross-sectional

Inclusion criteria: Patients were diagnosed as having encephalitis and also had positive PCR for HSV from cerebrospinal fluid, and/or positive immunoglobulin M (IgM), from July 1996 to June 2007 in the Pediatric Department of Qingdao Municipal Hospital

Exclusion criteria:?

36

6.43

(9 months–15 years)

15/21

Liquor PCR and/or HSV-IgM

Fever, 28 (78%)

Seizures, 17 (47%)

Somnolence, 15 (42%)

Coma, 12 (33%)

Vomiting, 12 (33%)

Behavioral change, 5 (14%)

Headache, 3 (8%)

Acyclovir (72%)

Dose?

Duration?

?

13 (36%)

Lahat E, 1999

Israel

0.859

Cross-sectional

Inclusion criteria: Patients aged between 9 months and 16 years with a diagnosis of HSV, who were treated in the pediatric department of the two university affiliated medical centers near Tel Aviv, Israel, from January 1984 until June 1995

Exclusion criteria?

28

7.16

(9 months–16 years)

6/22

Antibody anti-HSV (liquor)

HSV IgM and IgG (ELISA)

PCR (liquor)

Fever, 22 (79%)

Altered consciousness, 19 (68%)

Personality changes, 12 (43%)

Headache, 14 (50%)

Vomiting, 16 (57%)

Seizures, 19 (68%)

Acyclovir (100%)

Dose: 30 mg/kg/d

Duration (8–10)

First years of follow-up to 5 years after HSV

10 (35.7%)

Woźniakowska-Gesicka T, 1996

Poland

0.753

Cross-sectional

Inclusion criteria: Children treated at the Department of Observation and Isolation and at the Department of Child Neurology at the Medical University of Warsaw in the years 1992–1994 with HSV. The diagnosis of HSV neuroinfection was made on the basis of changes in the cerebrospinal fluid in the form of lymphocytic inflammation and flies serological conditions

Exclusion criteria:?

24

?

(4 years–15 years)

9/15

HSV IgM antibody in CSF, 2

IgM anti-HSV antibody in the blood, 9

Increase IgG titers, 15

Fever, 16 (66%)

Headache, 16 (66%)

Neurological symptoms, 6 (25%)

Vomiting, 5 (20,8%)

Acyclovir (100%)

Dose 30 mg/kg/d

Duration (mean 10)

6 months

8 (33.3%)

Ward KN, 2011

Britain and Ireland

0.906

Cross-sectional

Inclusion criteria: Children 2–35 months old with serious neurological disease between October 1998 and September 2001 according to the British Paediatric Surveillance Unit

Exclusion criteria:?

19

0.97

(3 months–35 months)

13/6

HSV DNA detected in CSF or an HSV-specific intrathecal antibody response OR

Seroconversion to IgG or IgM, within 2 weeks of onset of serious neurological disease

Fever, 18 (94%)

Seizures, 19 (100%)—partial 12 (63%)

?

10 months–4 years

(mean 2.3 years)

14 (73.6%)