Autoimmune complications and clinical outcomes of herpes simplex encephalitis in children: A case series

Objective:To report the neurologic prognosis and autoimmune complications of 16 cases of childhood herpes simplex virus encephalitis.Methods:The study was conducted atŞanlıurfa Training and Research Hospital,Turkey from June 2017 to August 2019.The study included 16 pediatric patients aged between 6 months and 17 years(median age 77.7 months)who were diagnosed with herpes simplex virus type 1 encephalitis by pediatric infectious disease and pediatric neurology clinics.Patients were followed using patient records,and interviews at the pediatric neurology clinic or via the telephone.Clinical and demographic data,received therapies,neurologic prognosis and complications were evaluated.Results:Patients with and without autoimmune encephalitis were compared in terms of age,sex,symptom duration before treatment,initial cerebrospinal fluid protein,glucose,red blood count and white blood count but no significant difference was found.Autoimmune complications were seen in four patients.N-methyl-D-aspartate encephalitis was observed in three patients and choreoathetosis was seen in one patient.The average follow-up period was 48.3 months.Twenty-five percent of the patients were receiving multiple antiepileptic drug(AED)treatment,43.8%were receiving single AED treatment and 31.3%were not receiving AED treatment at the end of the follow-up.Motor disability was observed in 12.5%and drug-resistant epilepsy was observed in 6.3%who had autoimmune complications.Conclusions:Seizures and movement disorders were controlled with immunotherapy and autoantibodies should be studied routinely.Treatment should be started early upon recognition of autoimmune complications through follow-up by measuring autoantibody levels and clinical examination results.Effective prevention and curative treatment modalities are needed to avoid herpes simplex virus encephalitis complications.

Expression of Cytokines IL-2, IL-10 and TNF-α in Mice with Herpes Simplex Viral Encephalitis

The expression of the cytokines IL-2, IL-10, TNF-α and their roles in mice with herpes simplex viral encephalitis （HSE） were studied. By using semiquantitative reverse transcription polymerase chain reaction （RT-PCR）, the expressions of IL-2, IL-10 and TNF-α mRNA in control group, HSE group and acyclovir （ACV）-treated group were detected and the pathological changes of brain were observed. It was found that after HSV1 infection, the cerebral lesions of haemorrhage and necrosis in mice were observed under the microscopy, and the levels of IL-2, IL-10 and TNF-α were increased remarkably. After treatment with ACV after HSV1 infection, the cerebral lesions in mice were improved, the level of IL-2 maintained stable, IL-10 was increased consistently, and TNF-α was decreased significantly as compared with those in HSE group. In acute HSE, many cytokines are upregulated, including IL-2, IL-10 and TNF-α to eliminate virus and TH1 type response is dominant. In convalescence, there is a shift in the cytokine expression profile from TH1 profile to TH2 profile and the shift can inhibit the overexpression of immune response in animals. ACV has remarkable effects in the treatment of HSE.

Decompressive craniectomy in herpes simplex encephalitis

Intracranial hypertension is a common cause of morbidity in herpes simplex encephalitis(HSE).HSE is the most common form of acute viral encephalitis.Hereby we report a case of HSE in which decompressive craniectomy was performed to treat refractory intracranial hypertension.A 32-year-old male presented with headache,vomiting,fever,and focal seizures involving the right upper limb.Cerebrospinal fluid-meningoencephalitic profile was positive for herpes simplex.Magnetic resonance image of the brain showed swollen and edematous right temporal lobe with increased signal in gray matter and subcortical white matter with loss of gray,white differentiation in T2-weighted sequences.Decompressive craniectomy was performed in view of refractory intracranial hypertension.Decompressive surgery for HSE with refractory hypertension can positively affect patient survival,with good outcomes in terms of cognitive functions.

Continuous video electroencephalogram for herpes simplex encephalitis:a case report and literature review

Background:Electroencephalogram(EEG)is an important tool for the diagnosis of herpes simplex virus encephalitis(HSE).However,the diagnosis of non-convulsive status epilepticus(NCSE)in HSE is challenging without the help of continuous video EEG(CVEEG),and whether EEG is a predictor of outcome remains controversial.Case presentation:A 63-year-old woman presented with a 5 day history of fever,coma and seizures.Results of EEG,magnetic resonance imaging and polymerase chain reaction(PCR)in cerebrospinal fluid(CSF)were suggestive of herpes simplex encephalitis-1(HSE-1).Preliminary EEG showed periodic discharges at the prefrontal and temporal lobes,which were particularly synchronized with intermittent lip smacking movements,and the discharges were terminated by diazepam.After 2-week treatment with acyclovir,high-dose hormone pulse therapy and high-dose immunoglobulin therapy,the CSF was improved,but the patient’s consciousness became worsen,consistent with the diffuse slow waves in the delta range and low voltage of EEG activity.In the following 1 month,the patient had non-responsiveness to pain and sound as shown by CVEEG with diffuse slow waves.Sometimes paroxysmal very slow waves(0.5–1 Hz)were synchronized with intermittent paroxysmal eye movements,pupil abnormality,and sweating in the frontal area.After 2 months of treatment,the EEG abnormalities improved to have alpha rhythm.Conclusion:The CVEEG not only helps identify NCSE but can also be used to monitor HSE progression.

Persistent inflammation and neuronal loss in the mouse brain induced by a modified form of attenuated herpes simplex virus type I

Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LMR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.