Unmasking bipolarity in recurrent depressive disorder following herpes simplex virus triggered n-methyl-D-aspartate encephalitis.

OBJECTIVE: Herpes simplex virus (HSV) infection triggered n-methyl-D-aspartate (NMDA) encephalitis can lead to varied neuropsychiatric manifestations, including movement disorders and manic symptoms. HSV is known to affect the same brain regions as in secondary mania. METHOD: We present a 35-year-old female diagnosed with recurrent depressive disorder (RDD) who developed NMDA encephalitis triggered by HSV infection. RESULT: HSV-triggered NMDA encephalitis led to a manic switch in a woman with RDD on antidepressants, along with the new onset of dyskinetic movements. CONCLUSION: A neurological insult predisposed our patient to the variable effects of antidepressant drugs.

Clinical features of COVID-19-related encephalitis: comparison with the features of herpes virus encephalitis and autoimmune encephalitis.

INTRODUCTION: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types. METHODS: Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8). RESULTS: The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis. DISCUSSION: COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.

State of the Art: Acute Encephalitis.

Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.

Metagenomic search of viral coinfections in herpes simplex encephalitis patients.

Little is known about concomitant central nervous system (CNS) infections by more than one virus. Current diagnostics are based on molecular tests for particular pathogens making it difficult to identify multi-viral infections. In the present study, we applied DNA- and RNA-based next-generation sequencing metagenomics (mNGS) to detect viruses in cerebrospinal fluids from 20 patients with herpes simplex encephalitis. Coinfection was detected in one patient: sequences in cerebrospinal fluids matched enterovirus A (2.660 reads; 4% of recovered genome) and enterovirus B (1.571 reads; 13% of recovered genome). Subsequent PCR combined with serotyping allowed to identify human echovirus 6, a representative of enterovirus B. Several other mNGS hits (human pegivirus, Merkel cell polyomavirus, human papillomavirus type 5) were not considered to represent a genuine signal as they could not be confirmed by specific RT-PCR/PCR. HSV DNA, while being detectable by PCR in every patient, was detected by mNGS in only one. In conclusion, contaminations and false signals may complicate mNGS interpretation; however, the method can be useful in diagnostics of viral coinfections in CNS, particularly in the case of rare pathogens.

Outcomes of HSV-1 encephalitis infection in glioblastoma: An integrated systematic analysis.

INTRODUCTION: Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma (GBM) due to similar radiographic imaging and clinical presentation. Limited data exist on the co-occurrence of GBM and HSV-1. To better describe the pathophysiology of HSV-1 superinfections in GBM, we performed a comprehensive review of GBM cases with superimposed HSV-1. METHODS: A comprehensive literature search of six electronic databases with apriori search criteria was performed to identify eligible cases of GBM with HSV-1. Relevant clinic-radiographic data were collected, Kaplan-Meier estimates, Fisher's exact test, and logistic regression analyses were used. RESULTS: We identified 20 cases of HSE in GBM with an overall survival (OS) of 8.0 months. The median age of presentation was 63 years (range: 24-78 years) and the median interval between GBM or HSE diagnosis was 2 months (range: 0.05-25 months). HSE diagnosis before GBM diagnosis was a predictor for improved survival (HR: 0.06; 95% CI: [0.01-0.54]; p < 0.01). There is a significant reduction in OS in patients with concomitant HSE and GBM compared to the cancer genome atlas (TCGA) cohort (median OS: 8 months vs. 14.2 months; p < 0.05). Finally, HSV does not directly infect GBM cells but indirectly activates a local immune response in the tumor microenvironment. CONCLUSIONS: Superimposed HSE in GBM may contribute to a significant reduction in OS compared to uninfected controls, potentially activating proto-oncogenes during active infection and latency. Preoperative HSE may induce an antiviral immune response, which may serve as a positive prognostic factor. Prompt antiviral treatment upon co-occurrence is necessary.

A case of herpes simplex virus induced peripheral neuropathy and encephalitis with positive GM3 and CASPR2 antibody.

BACKGROUND: We reported on a case involving an older patient with HSV-1 encephalitis who simultaneously experienced the onset of peripheral nerve symptoms associated with the presence of anti-GM3 immunoglobulin G (IgG). CASE PRESENTATION: A 77-year-old male was admitted to hospital with high fever, weakness of both lower limbs, and an unstable gait. A CSF test revealed a strikingly increased protein level (1,002 mg/L, normative values: 150-450 mg/L) and MRI revealed hyper-signal lesions in the right temporal lobe, right hippocampus, right insula, and right cingulate gyrus. The CSF was positive for HSV PCR (HSV-1,17870). In addition, the serum samples were positive for CASPR2 antibodies (antibody titer: 1/10) and anti-GM3 immunoglobulin G (IgG) (+). The patient was diagnosed with HSV-1-induced peripheral nerve symptoms that were associated with encephalitis and the presence of anti-GM3 IgG and anti-CASPR2 antibodies. The patient had received included intravenous immunoglobulin, intravenous acyclovir, and corticosteroids therapy. At the one-year follow-up examination, he had regained the necessary skills associated with daily life. CONCLUSIONS: Herpes simplex virus infection often induces encephalitis, and reaction to the virus may trigger an autoimmune response. Early diagnosis and treatment can avoid the progression of the disease to include autoimmune encephalitis.

Autoimmune Encephalitis with Autoantibodies to NMDAR1 following Herpes Encephalitis in Children and Adolescents.

Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy. Here, we report 15 patients (age range 3 months to 15 years) who suffered from autoimmune encephalitis with autoantibodies to NMDAR1 following Herpes encephalitis, presenting with movement abnormalities (young children) or neuropsychiatric symptoms (older children) as major complaints, respectively. The diagnosis was based on positive cerebrospinal fluid (CSF) and/or serum anti-NMDAR-antibodies with two children showing only positive CSF antibody findings. The time lag between first symptoms and diagnosis of autoimmune encephalitis was significantly longer than between first symptoms and diagnosis of HSVE (p <0.01). All patients improved during immunosuppressive treatment, during which plasmapheresis or rituximab treatments were applied in 11 patients, irrespective of their age. Despite immunotherapy, no patients relapsed with HSVE. Early diagnosis and treatment of autoimmune encephalitis after HSVE may be associated with a better outcome so that high clinical awareness and routine testing for anti-NMDAR-antibodies after HSVE seems advisable. If autoimmune encephalitis is suspected, antibody testing should also be performed on CSF if negative in serum.

Life-Threatening Enterovirus 71 Encephalitis in Unrelated Children with Autosomal Dominant TLR3 Deficiency.

PURPOSE: Enterovirus A71 (EV71) causes a broad spectrum of childhood diseases, ranging from asymptomatic infection or self-limited hand-foot-and-mouth disease (HFMD) to life-threatening encephalitis. The molecular mechanisms underlying these different clinical presentations remain unknown. We hypothesized that EV71 encephalitis in children might reflect an intrinsic host single-gene defect of antiviral immunity. We searched for mutations in the toll-like receptor 3 (TLR3) gene. Such mutations have already been identified in children with herpes simplex virus encephalitis (HSE). METHODS: We sequenced TLR3 and assessed the impact of the mutations identified. We tested dermal fibroblasts from a patient with EV71 encephalitis and a TLR3 mutation and other patients with known genetic defects of TLR3 or related genes, assessing the response of these cells to TLR3 agonist poly(I:C) stimulation and EV71 infection. RESULTS: Three children with EV71 encephalitis were heterozygous for rare mutations-TLR3 W769X, E211K, and R867Q-all of which were shown to affect TLR3 function. Furthermore, fibroblasts from the patient heterozygous for the W769X mutation displayed an impaired, but not abolished, response to poly(I:C). We found that TLR3-deficient and TLR3-heterozygous W769X fibroblasts were highly susceptible to EV71 infection. CONCLUSIONS: Autosomal dominant TLR3 deficiency may underlie severe EV71 infection with encephalitis. Human TLR3 immunity is essential to protect the central nervous system against HSV-1 and EV71. Children with severe EV71 infections, such as encephalitis in particular, should be tested for inborn errors of TLR3 immunity.

Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact.

OBJECTIVES: To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. DESIGN: Retrospective multicenter study from 2007 to 2017. SETTING: Forty-seven French ICUs. PATIENTS: Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). CONCLUSIONS: In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

SARS-CoV-2-associated haemorrhagic encephalitis mimicking Herpes encephalitis.

Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today's pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis.

Herpes simplex encephalitis following ChAdOx1 nCoV-19 vaccination: a case report and review of the literature.

BACKGROUND: Ever since the administration of early doses of COVID-19 vaccines, instances of adverse effects have been reported. Viral infections, specifically herpes simplex reinfection and coinfections, have been reported following administration of different types of vaccines. To our knowledge, there have not been any reports of herpes simplex encephalitis following administration of any type of COVID-19 vaccine to date. CASE PRESENTATION: In this article intends to report a case of herpes simplex encephalitis in a 27-year-old male patient who was vaccinated with the ChAdOx1 nCoV-19 vaccine. CONCLUSIONS: Our study suggests a possible but very rare side effect of ChAdOx1 nCoV-19 vaccine, which requires immediate medical attention and can lead to devastating consequences if left undiagnosed and untreated.

Human viral encephalitis associated with suid herpesvirus 1.

BACKGROUND: Suid herpesvirus type 1 (SHV1) is a type of neurotropic virus able to infect various species. However, the clinical cases of human SHV1 encephalitis are still rarely reported, and the clinical characteristics, treatment, and prognosis of human SHV1 encephalitis are still unclear. METHODS: In this study, we reported 2 cases of human encephalitis associated with SHV1 infection and reviewed the other 18 cases from the literatures. A total of 20 cases with human SHV1 encephalitis were summarized and re-analyzed. RESULTS: Nineteen of 20 patients had a history of swine-related occupational exposure before illness onset. All patients initially presented with influenza-like symptoms and then developed seizures, disturbed consciousness, and endophthalmitis. All patients with clinical outcome of modified Rankin Scale of 5 or 6 suffered from rapid progressive respiratory failure. The results of cerebrospinal fluid (CSF) indicated aseptic or viral infection. MRI findings of SHV1 encephalitis were prone to distribute in temporal-frontal and insular cortex, which was similar to the pattern of herpes simplex virus encephalitis, while some cases with involvements of gray matter nuclei had a high rate of mortality. Metagenomic next-generation sequencing (mNGS) revealed that all patients had unique SHV1 sequences with variable reads in the CSF. CONCLUSIONS: The variant SHV1 can cause a new type of human viral encephalitis, characterized by acute, fulminating, and catastrophic central nervous system infection. Rapid progressive respiratory failure and extensive lesions of deep gray matter nuclei might be indicators to poor prognosis. No approved treatments for the encephalitis are available, but it is possible to diagnose encephalitis quickly by mNGS.

Intensive care management of patients with viral encephalitis.

Viral encephalitis is a severe syndrome that can lead to encephalopathy, seizures, focal deficits, and neurological sequelae and death. It is mainly caused by neurotropic herpes viruses (i.e., HSV and VZV), although other pathogens may be observed in specific geographic regions or conditions. Recent advances in neuroimaging and molecular biology (PCR, metagenomics) allow for faster and more accurate etiological diagnoses, although their benefits need to be confirmed to provide guidelines for their use and interpretation. Despite intravenous acyclovir therapy and supportive care, outcomes remain poor in about two-thirds of herpes encephalitis patients requiring ICU admission. Randomized clinical trials focusing on symptomatic measures (i.e. early ICU admission, fever control, and treatment of seizures/status epilepticus) or adjunctive immunomodulatory therapies (i.e. steroids, intravenous immunoglobulins) to improve neurologic outcomes have not been conducted in the ICU setting. Large prospective multicenter studies combining clinical, electrophysiological, and neuroimaging data are needed to improve current knowledge on care pathways, long-term outcomes, and prognostication.

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis.

Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

[Treatment with Intravenous Acyclovir Desensitization for Severe Acyclovir Allergy: A Case of Herpes Encephalitis]. / Ciddi Asiklovir Alerjisinde Intravenöz Asiklovir Desensitizasyon Tedavisi: Herpes Ensefaliti Olgusu.

Herpes simplex virus (HSV) is a sporadic viral encephalitis agent that causes high mortality and morbidity, accompanied by neurological dysfunction findings. Acyclovir is the only antiviral treatment option that should be initiated in all patients with suspected encephalitis as soon as possible. Acyclovir is rarely possible to cause allergic reactions. It may occur in a wide range from generalized cutaneous rash to Stevens-Johnson syndrome. A case of HSV-1 encephalitis who had no treatment option other than intravenous acyclovir and was successfully treated with intravenous desensitization was presented in this report. A 59-year-old male patient was admitted to the emergency department with complaints of high fever and altered consciousness. Diagnostic lumbar puncture was performed and intravenous acyclovir treatment was initiated empirically with the preliminary diagnosis of encephalitis. On the third day of the treatment, HSV type 1 polymerase chain reaction (PCR) was detected as positive. Acyclovir treatment was discontinued due to the development of a severe allergic reaction on the fifth day of acyclovir treatment. Allergic symptoms of the patient regressed with discontinuation of acyclovir treatment and application of concomitant methylprednisolone treatment. The intravenous acyclovir desensitization protocol was applied to the patient, and the patient was successfully treated. In this case, it has been shown that intravenous acyclovir desensitization can be applied in the treatment of life-threatening infections with no treatment options other than intravenous acyclovir. Our case is the first adult case in the literature to be treated with intravenous acyclovir desensitization.

Association of G84A and C276T polymorphism in neuronal nitric oxide synthase (nNOS) gene with herpes simplex encephalitis in eastern Indian population.

In this study, a hypothesis that genetic variations in neuronal nitric oxide synthase (nNOS) could influence the susceptibility and outcome of herpes simplex encephalitis was investigated. Polymorphic loci of nNOS gene, G84A and C276T were genotyped in 132 HSE cases (Age 8.2 ± 1.3yr) and 143 in healthy individuals (Age-9.2 ± 1.6yr) of the same ethnic background from Odisha. A significantly increased risk for HSVE was associated with the AG genotype (OR = 1.73, 95%CI = 1.03-2.9, P = 0.03) and AA genotype (OR = 2.96, 95%CI = 1.04-8.4, P = 0.04) of nNOS 84G →A locus. In case of nNOS 276C→T variation, HSVE risk was linked to CT genotype (OR = 1.79, 95%CI = 1.07-3.0, P = 0.03) and TT genotype (OR = 3.6, 95%CI = 1.2-10.8, P = 0.02). Patients with poor outcome either had homo or heterozygous genotype for both SNPs, but separate genotype analysis could not show significance. But combined genotype analysis of both SNPs confirmed that GG + CC was a risk factor for development of poor outcome. (OR = 6.3, CI-1.9-20.7, P = 0.0033). Haplotype analysis of both SNP did show that "at" haplotype was significantly higher and associated with HSVE cases (OR = 2.322,CI: 1.43-3.77, P = 0.00070). The result observed in this study suggested that variation at these loci of nNOS may have decreased its expression and caused low production of NO, which have resulted in risk of HSVE but provided good outcome in these patients.

Herpes simplex virus type 1 related acute retinal necrosis following an encephalitis illness: a case report.

BACKGROUND: Virus encephalitis is found to be a risk factor for acute retinal necrosis (ARN). CASE PRESENTATION: We herein presented a case of a 20-year-old teenage boy who suffered from encephalitis of unknown etiology with early negative pathologic results, and was primarily treated with systemic administration of high-dose steroids without antiviral therapy. He later had sudden vision loss in his right eye. Intravitreal and intravenous antiviral treatments were immediately started due to suspected ARN. Herpes simplex virus (HSV)-1 was identified later in the vitreous humor of the patient. After the surgery of retinal detachment (RD), obvious improvements in vision were observed. However, the patient had recurrent RD and vision declination 5 weeks later. CONCLUSIONS: The case with suspected viral encephalitis should be treated with antiviral therapy regardless of early virologic results in order to avoid complications of a missed viral encephalitis diagnosis, especially if systemic steroid treatment is being considered.

A rare case of adult herpes simplex encephalitis complicated with rhabdomyolysis.

BACKGROUND: Compelling evidence indicates that status epilepticus is a prevalent cause of rhabdomyolysis. However, cases of rhabdomyolysis induced by a single seizure accompanied by viral encephalitis are rarely reported. Herein, we present a case of adult Herpes Simplex Encephalitis complicated with rhabdomyolysis. CASE PRESENTATION: A 32-year-old male was patient presented with fever accompanied by episodes of convulsions, myalgia, and oliguria, which exacerbated the delirium. Routine blood examination showed impaired kidney function and elevated myoglobin (Mb) and creatine phosphokinase (CK) levels. MRI scanning revealed a damaged frontotemporal lobe and limbic system. In addition, herpes simplex virus (HSV) pathogen was identified in the cerebrospinal fluid thus indicating HSV infection. Therefore, a diagnosis of rhabdomyolysis triggered by HSV infection accompanied by epilepsy was made. Notably, the patient recovered well after early intervention and treatment. CONCLUSION: The case presented here calls for careful analysis of rhabdomyolysis cases with unknown causes, minor seizures, and without status epilepticus. This case also indicates that HSV virus infection might contribute to the rhabdomyolysis.

Intraventricular hemorrhage as clinical presentation of herpes simplex virus encephalitis. A case report and review of the literature.

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) represents the most common cause of sporadic encephalitis in humans. The development of intracerebral hematomas is rare and late during the course of HSVE. To report a case of a patient with HSVE who initially presented a diffuse intracranial hemorrhage with predominant intraventricular bleeding. CASE REPORT: A 66-year-old man was admitted to the Emergency Department with acute headache. Antecedents: alcohol consumption and ethylic hepatopathy. The brain computed tomography showed acute tetraventricular hemorrhage and hydrocephalus. The blood analysis showed pancytopenia and alteration of all hepatic parameters. After external drainage of cerebrospinal fluid the patient presented a worsening of headache, disorientation, mild left hemiparesis, neck stiffness and temperature of 37.6 °C. The cerebrospinal fluid was hemorrhagic, with 3 lymphocytes/mm3, 60 mg/dL of proteins and PCR positive for Herpes simplex virus type 1. The patient improved with intravenous acyclovir, however he experienced several medical complications which caused his dead. DISCUSSION: The patient presented an atypical cerebral bleeding related to HSVE because the development of hematoma was early and the topography of hemorrhage was basically intraventricular. Probably, both atypical characteristics were related to thrombocytopenia and severe coagulation disorder. This case expands the spectrum of cerebrovascular disorders associated with HSVE.

Next-generation sequencing technology as a powerful detection and semi-quantitative method for herpes simplex virus type 1 in pediatric encephalitis.

This case report presents a 1-year-old boy from China, with sudden onset of fever, convulsion, and sleepiness, screened for viral DNA in blood and cerebrospinal fluid (CSF) sample using next-generation sequencing (NGS) to diagnose herpes simplex virus type 1 (HSV-1) encephalitis, further validated by PCR. After acyclovir treatment, the patient's symptom disappeared and HSV-1 DNA unique reads decreased from 4290 to zero in CSF, and from 23 to zero in blood detected by NGS. The clinical presentation and outcome were consistent with the pathogenic diagnostic results of NGS. NGS of CSF samples can be used as a diagnostic assay for HSV-1 encephalitis and also might be a semi-quantitative method for evaluation of treatment effect.