Table 2

Details of 51 children treated for possible viral encephalitis with aciclovir

Patient number (age in days (D), months (M) or years (Y))	Most likely diagnosis considered by admitting clinician	Laboratory investigations (PCR results in next column) (CSF WCC (differential as percentage (%) or count); RCC (×10⁶/l); CSF protein (P) (g/l), CSF glucose (G) (mmol/l), glucose ratio (GR); other investigations (if performed))	PCR results (results from CSF unless stated otherwise)	Neuroimaging	Final diagnosis
Met case definition of suspected viral encephalitis on admission
(1) 9 D	Staphylococcal sepsis	WCC 47 (L 66%, N 21%, M 13%); RCC 0; P 0.8, G ND; scalp vesicle fl uid HSV type 2 pos (tissue culture and direct detection)	HSV PCR ND	CT and MRI – temporal lobe abnormalities consistent with HSV VE	HSV type 2 VE
(2) 13 Y	URTI	WCC 542 (M 96%, N 4%); RCC 0; P 0.46, G 2.7, GR NR	HSV PCR pos type 1	CT and MRI – changes in left temporal lobe suggestive of HSV VE	HSV type 1 VE
(3) 14 Y	BM or VE	WCC 23 (M 17, N 4, DC 2); RCC 0; P 0.71, G 3.4, GR 0.6	HSV PCR neg	CT and MRI – N	Clinically diagnosed VE
(4) 2 Y	Herpes stomatitis	WCC 10 (M 9, N 1); RCC 0; P 0.3, G 2.9, GR 0.42	HSV PCR neg	CT – non-specific changes in the frontal and temporal lobes; MRI – high signal in basal ganglia, thalami, external capsule and insular white matter	Clinically diagnosed VE
(5) 22 D	Neonatal sepsis	WCC 2; RCC 10; P 1.63, G NS	HSV PCR neg, Pneumo and Meningo neg	CT – Normal	Neonatal sepsis – no cause found
(6) 4 M	Intussusception or BM	WCC 55 (M 90%, N 10%); RCC 0; P 1.2, G 2.5, GR 0.46; BC Pneumo pos	HSV PCR neg, Pneumo pos	CT – frontal subdural collection	Pneumococcal BM
(7) 11 M	BM	WCC 946 (N 62%, M 30%, DC 8 %); RCC 5; P 0.98, G 2.3, GR NR	HSV PCR ND, Pneumo PCR pos; serum PCR Pneumo pos	ND	Pneumococcal BM
(8) 2.5 Y	BM or VE	WCC 2080 (DC 91%, M 7%, N 2%); RCC 0; P 0.72, G 2.3, GR 0.42; BC Pneumo pos	HSV PCR ND, Pneumo PCR neg; serum PCR Pneumo pos	CT – Normal	Pneumococcal BM
(9) 6 M	BM or VE	LP ND; BC Pneumo pos	LP ND	CT – signal abnormality in basal ganglia and internal capsule Pneumococcal BM
(10) 4.5 Y	BM or VE	WCC 4500 (N 80%, M 10%, DC 10%); RCC 0; P 2.61, G 3.5, GR NR	HSV PCR neg, group B Meningo PCR pos	CT – Normal	Meningococcal (group B) BM
(11) 11 M	BM	WCC 5; RCC 224; P 0.26, G 2.6, GR NR; CSF culture TB pos	HSV PCR neg	CT – communicating hydrocephalus and signs of raised intracranial pressure	TB meningitis
(12) 11 M	BM or VE	WCC 12 (M 10, DC 2); RCC 2; P 1.05, G 0.5, GR 0.16; CSF culture TB pos	HSV PCR neg	CT – obstructive hydrocephalus	TB meningitis
(13) 8 Y	VE	WCC 13 (M 8, L 5); RCC 220; P 0.21, G 2.8, GR 0.68	HSV PCR neg	CT and MRI – N	Panyayiopoulous syndrome
(14) 4 Y	BM or VE	WCC 22 (N 64%, M 36%); P 0.37, G 2.4, GR 0.36	HSV PCR neg	CT – Normal; MRI – abnormalities in basal ganglia and white matter	ADEM
(15) 1.5 Y	BM or VE	WCC 26 (L 18, N 8); RCC 0; P 0.41, G 2.3, GR 0.88	HSV PCR neg	MRI – diffuse abnormalities in white matter	ADEM
(16) 9 M	Neurodegenerative disorder	WCC 0; RCC 2; P 0.5, G 3.6, GR ND	HSV PCR ND	MRI – abnormal signal in the basal ganglia	Undiagnosed Met Enceph
(17) 2.8 Y	Afebrile SE. Child with EP	WCC 0; RCC 1; P 0.11, G 5.9, GR ND	HSV PCR ND	ND	SE in child with EP
(18) 15 M	Partially treated BM. Child with CP and EP	LP ND	LP ND	ND	Pneumonia in child with CP and EP
(19) 3 Y	BM or VE	WCC 2; RCC 0; P 0.23, G 4.2, GR ND	PCR HSV ND	CT – Normal	Atypical FC with pneumonia
(20) 5.5 Y	Sepsis or BM	LP ND	LP ND	CT and MRI – area of gliosis in frontal lobe	EP
(21) 2 Y	Sepsis or BM	WCC 1; RCC 138; P 0.17, G 4, GR 0.81	PCR HSV neg	CT – Normal	Atypical FC
(22) 5 Y	Deterioration in child with Leigh syndrome or VE	WCC 1; RCC 0; P 0.56, G 3.8, GR 0.61	HSV PCR neg	MRI – abnormalities in thalamus, pons and cerebellar peduncles	Leigh syndrome (exacerbation)
(23) 7 Y	Met Enceph or VE	WCC 1; RBC 397; P 0.44, G 4; GR 0.57	HSV PCR neg	CT and MRI – diffuse white matter encephalopathy	Leukodystrophy (exacerbation)
(24) 17 M	BM or VE	CSF microscopy ND (bloodstained); P ND, G 3.5, GR ND	HSV PCR neg	CT – Normal	Atypical FC
(25) 28 D	Neonatal sepsis	WCC 0; RCC 0; P 0.31, G 2.8, GR 0.52	HSV PCR ND	CT – Normal	Neonatal sepsis – cause unknown
(26) 5 Y	BM or VE in child with leukaemia	WCC 13; RCC 1; P ND, G ND, GR ND	HSV PCR ND	CT – Normal	Seizures with Todd’s paresis
(27) 6 M	BM or VE	WCC 0; RCC 388; P 0.19, G 4.4, GR 0.6	PCR HSV neg	CT – Normal	Atypical FC
(28) 4 Y	BM or VE	LP ND	LP ND; serum Pneumo and Meningo PCR neg	CT – Normal	Atypical FC
(29) 3 M	VE or atypical FC in child with CP	WCC 0; RCC 18 000; P 0.86, G 3.3, GR 0.57	PCR HSV neg	MRI – bilateral cystic encephalomalacia	EP in child with CP
(30) 2.5 Y	VE	WCC 0; RCC 0; P 0.18, G 3.3, GR 0.71	HSV PCR neg	CT – Normal	Atypical FC
(31) 2 Y	VE	LP ND	LP ND	CT – Normal	Atypical FC
(32) 2 M	BM or VE	WCC 0; RCC 160; P 0.24, G 3.6, GR ND	HSV PCR ND; CSF Meningo, Pneumo and Entero PCR neg	ND	Viral illness
(33) 4 Y	Blocked VP shunt or VE	WCC 40 (DC 100%); RCC 4160; P 0.11, G ND	HSV PCR neg	CT – shunt in situ, N sized ventricles	Focal seizures. Infected VP shunt
(34) 11 Y	BM or VE	WCC 0; RCC 401; P 0.21, G 4.1, GR 0.59	HSV PCR neg	CT and MRI – abnormalities in white matter consistent with ADEM	ADEM
(35) 12 M	BM or VE	WCC 2, RCC 3680; P 0.28, G 4.1, GR 0.68	HSV PCR neg	CT and MRI – N	Atypical FC
(36) 14 Y	BM or VE	LP ND	LP ND	CT – Normal	Atypical FC
(37) 3.5 Y	Ophthalmic shingles and LRTI	WCC 0; RCC 0; P 0.14, G 3.3, GR 0.69	HSV PCR neg	ND	Ophthalmic shingles. LRTI
Did not meet case defi nition of suspected viral encephalitis on admission/No evidence base for starting aciclovir
(38) 2 Y	Afebrile seizure	LP ND	LP ND	CT – Normal	First seizure
(39) 2 M	Sepsis	WCC 5; RCC 3; P 0.58, G 2.6, GR 0.49	HSV PCR neg	CT – Normal	Sepsis, cause not found
(40) 2 M	Sepsis	LP ND	LP ND; serum PCR for CMV pos	ND	Cardiomyopathy; CMV pos
(41) 2 Y	Afebrile seizures. Diarrhoea	WCC 0; RCC 0; P 0.16, G 2.6, GR 0.92; stool – rotavirus detected	HSV PCR neg	CT – Normal	Rotavirus encephalopathy
(42) 10 D	Neonatal sepsis	WCC 2; RCC 1810; P 0.71, G 3.9, GR 0.54	HSV PCR ND	ND	Chest infection
(43) 2.5 Y	VP shunt infection	WCC 17 (N 12, DC 5); RCC 2790; P 0.6, G ND	HSV PCR neg	CT and MRI no new changes	VP shunt infection
(44) 2 D	Sepsis. Joint contractures and hypotonia	WCC 0; RCC 540; P 1.5, G 2.7, GR 0.77	HSV PCR ND	MRI – Normal	Congenital myopathy
(45) 5 Y	Focal seizures after head injury	LP ND	LP ND	CT – Normal	Head injury
(46) 8 M	Afebrile SE in child with Met Enceph and EP	WCC 0; RCC 810; P 0.25, G 4.2, GR 0.68	HSV PCR neg	MRI – bilateral high signal densities in globus pallidus. Abnormalities seen previously	Met Enceph and EP
(47) 2 M	Afebrile seizures	WCC 2; RCC 294; P 0.5, G 2.6, GR 0.71	HSV PCR ND	CT and MRI – Normal	New onset EP
(48) 9 Y	Afebrile SE in child with Met Enceph and EP	LP ND	LP ND	MRI – no acute changes	Afebrile SE in child with Met Enceph and EP
(49) 3 Y	Afebrile focal seizures	Smear ++++ pus cells (surgical specimen); P NR, G NR; CSF culture Pneumo pos	HSV PCR ND	CT – right temporal lobe abscess	Pneumococcal abscess
(50) 5 Y	Acute cerebellitis	WCC 0; RCC 0; P 0.28, G 3.1, GR ND	HSV PCR neg	CT – Normal	Acute cerebellitis
(51) 14 Y	Drug overdose	LP ND	LP ND	CT – Normal	Deliberate drug overdose

Those with “suspected VE“ (see Methods section) listed first.
ADEM, acute disseminated encephalomyelitis; BC, blood culture; BM, bacterial meningitis; CP, cerebral palsy; CSF, cerebrospinal fl uid; CMV, cytomegalovirus; DC, degenerated cells; Entero, Enterovirus; EP, epilepsy; FC, febrile convulsion; G, glucose; GR, glucose ratio; HSV, herpes simplex virus; L, lymphocytes; LP, lumbar puncture; LRTI, lower respiratory tract infection; M, monocytes; Meningo, Meningococcal; Met Enceph, metabolic encephalopathy; N, neutrophils; ND, not done; neg, negative; NR, not recorded; P, protein; Pneumo, Pneumococal; pos, positive; RCC, red cell count; SE, status epilepticus; TB, tuberculous; VE, viral encephalitis; VP, ventriculo-peritoneal; WCC, white cell count.