Herpes Simplex Encephalitis Research Articles

Herpes Simplex Virus Infection in Infants: 13 Year Evaluation (2005-2017) of Laboratory Confirmed Cases in Queensland, Australia.

National neonatal surveillance for herpes simplex virus (HSV) disease suggests that the incidence of HSV disease may be higher in Queensland (QLD) than in other Australian States. We sought to investigate the incidence via a retrospective 13-year evaluation of statewide laboratory data, autopsy data and linked clinical records of infants with laboratory confirmed infection. All positive polymerase chain reaction HSV 1 and 2 results were obtained for infants 0-3 months of age from January 1, 2005 to December 31, 2017. Clinical data were obtained from patient records and parent questionnaires were used to evaluate long-term sequelae. One hundred seventy-two infants with HSV positive polymerase chain reaction results: 121 (70.3%) with HSV 1. Of 104 (60.5%) infants with signs of HSV disease, 76 (73.1%) were neonates (≤28 days of age) [incidence 9.6 (95% confidence interval, 7.0-11.5) per 100,000 live births] and 28 (26.9%) were young infants (29-90 days of age) [3.6 (95% confidence interval, 2.4-5.4) per 100,000 live births]. The annual incidence of neonatal HSV disease increased significantly in Queensland over the study period (P < 0.01). Of the 76 neonates with HSV disease, 58 (76.3%) presented with the skin, eye, mouth (SEM) disease, 17 (22.4%) with HSV encephalitis and 11 (14.5%) had disseminated disease. Young infants presented with HSV skin, eye, mouth disease (21, 75.0%) or HSV encephalitis (6, 21.4%). Death occurred in 12/104 (11.5%) infants (all neonates) with 10 attributable to HSV disease. The incidence of neonatal HSV disease in QLD is almost 3 times the national reported incidence. Further research is being undertaken to explore reasons for this change and implications for practice.

Nadir Bir Olgu: Herpes Simpleks Ensefaliti

Herpes Simplex Encephalitis (HSE) is one of the most common causes of sporadic encephalitis and has the most mortal progression. A 22-year-old female patient applied to the emergency department with nausea and vomiting that lasted three days. The patient Cerebrospinal Fluid (CSF) was clear, the glucose ratio was low, and the protein ratio was high in the Lumbar Puncture (LP). HSV-DNA tests were requested with CSF culture and Polymerase Chain Reaction (PCR). Based on the LP results, and considering viral encephalitis, acyclovir treatment was started. The patient died on the 5th day while her treatment was continuing. HSV-DNA with PCR in BOS is the gold standard for the diagnosis of HSE. The most effective agent in treatment is acyclovir. The prognosis of the disease is poor.

Practical progression in the clinical management of neuroinfections and related diseases in Japan

AbstractNeuroinfections and related diseases are a life‐threatening disease. The practical progression of the clinical management in these diseases in Japan was reviewed. The guidelines for the clinical management of bacterial meningitis in Japan were published in 2014 which were established based on the current knowledge of microbiological evidence in Japan. The guidelines for the clinical management of herpes simplex virus encephalitis (HSVE) in Japan were also published in 2017. Aciclovir should be initiated in all patients with suspected encephalitis. Polymerase chain reaction (PCR) for HSVE has high sensitivity and specificity and is the gold standard diagnostic tool. However, when the negative result of PCR is obtained at the acute stage with the highly suspicious patients with HSVE, our clinical guidelines recommend to continuing aciclovir and repeating PCR. The viral resistance to aciclovir has been reported. In the case of aciclovir‐nonresponding and treatment‐resistant patients, an alternative treatment with foscarnet is recommended. Autoimmune encephalitis (AIE) is considered one of the most common causes of noninfectious acute encephalitis. As a series of anti‐neuronal surface antibodies (NSAs) were found, the diagnostic approach to AIE has undergone a paradigm shift. Different techniques are currently available to detect NSAs: tissue‐based assays (TBAs) with rodent brain sections, cell‐based assays (CBAs), and assays for primary cultured neurons of rodent. The diagnosis of AIE in Japan could previously be delayed owing to limited access to specialized laboratory; the assay system used by TBAs and CBAs for AIE was established and started to use in Japan since 2019.

Cerebrovascular complications and vasculopathy in patients with herpes simplex virus central nervous system infection

ObjectiveHerpes simplex viruses (HSV) are neurotropic and known to cause central nervous system (CNS) infections. We aimed to describe the clinical and imaging features of cerebrovascular complications in patients with HSV CNS infections. MethodsWe reviewed records of patients with HSV infections by querying acyclovir use in a clinical registry of parenteral anti-infective therapy at a tertiary medical center from January 2010 until September 2018. One patient who met the inclusion criteria is subsequently added. Diagnostic criteria for HSV CNS infection were intrathecal presence of viral DNA with clinical signs of CNS involvement. ResultsOf 36 patients who met the criteria for HSV CNS infections, cerebrovascular complications occurred in 6 patients (17%). Two patients with HSV-1 encephalitis had cerebrovascular complications (1 ischemic stroke, 1 intraparenchymal hemorrhage). Four patients had HSV-2 infection without encephalitis had cerebrovascular complications (3 ischemic strokes, 1 cerebral vein thrombosis). All 3 patients with ischemic strokes without encephalitis had pattern of vasculitis on vessel imaging on MRI with segmental narrowing and vessel wall irregularities of large intracranial arteries with circumferential wall enhancement. ConclusionCerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis.

Generalized Epilepsy with Right Hemiparesis Secondary to Herpes Encephalitis

Herpes simplex encephalitis (HSE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis.&#x0D; A 7-year-old Malay girl with known case of right hemiplegia secondary to herpes encephalitis presented to the neuropediatric ward, in General Hospital with refractory seizure. She had a moderate learning disability and diagnosed as right hemiparesis secondary to herpes encephalitis complicated with epilepsy. She was planned for the positron emission tomography (PET) scan and to undergo operation if PET scan was feasible (Hemispherectomy). However, the patient refused for operation.&#x0D; Prompt clinical recognition is important in the HSE to prevent progressive brain tissue damage, haemorrhagic changes, and worsening of the encephalitis. Diagnosis is usually confirmed through an extensive evaluation, including a thorough clinical examination with attention to findings on mental status changes, cerebrospinal fluid (CSF) analysis, electroencephalogram (EEG) testing and findings on neuroimaging.&#x0D; Once HSE is suspected, high-dose acyclovir should be started immediately before lumbar puncture (LP), and only stopped once a definitive alternate diagnosis has been established.&#x0D; This case is reported because the patient has generalized epilepsy with right hemiparesis secondary to herpes encephalitis. Herpes encephalitis with right hemiparesis cases are quite rare.

Herpes simplex virus and central nervous system infections: encephalitis, meningitis, myelitis

Central nervous system (CNS) infections caused by herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) greatly vary in frequency and severity. HSV-1 causes mostly herpes simplex encephalitis (HSE) which represents 5% to 15% of infectious encephalitis in children and adults. Despite available molecular diagnosis tools and antiviral drugs, the prognosis of HSE remains unacceptably low. In addition to mortality and immediate sequelae, auto-immune encephalitis (AIE) may occur, associated with the development of anti-neuronal antibodies in 1/4 of cases. Replicative relapses have been associated in few cases with genetic defects altering the innate immune response of neuronal cells. Herpetic meningitis is frequent, mostly associated with HSV-2 and genital herpes, sometimes recurrent and, mostly benign, except in immunocompromised individuals. Finally, exceptional cases of myelitis have been reported, due to ascending propagation of HSV-2 in the CNS. This review does not include neonatal infections.

Next-generation sequencing in the diagnosis of viral encephalitis: sensitivity and clinical limitations

Identification of pathogens causing viral encephalitis remains challenging, and in over 50% of cases the etiologic factor remains undetermined. Next-generation sequencing (NGS) based metagenomics has been successfully used to detect novel and rare infections, but its value for routine diagnosis of encephalitis remains unclear. The aim of the present study was to determine the sensitivity of shotgun metagenomic sequencing protocols, which include preamplification, and testing it against cerebrospinal fluid (CSF) samples from encephalitis patients. For sensitivity testing HIV and HBV positive sera were serially diluted in CSF from an uninfected patient. NGS repeatedly detected HIV and HBV sequences present at concentrations from 105 to 102 and from 105 to 10 viral copies/reaction, respectively. However, when the same protocols were applied to RT-PCR/PCR positive CSF samples from 6 patients with enteroviral encephalitis (median viral load 47 copies/ml) and 15 patients with HSV, CMV or VZV encephalitis (median viral load 148 copies/ml), only 7 (28.6%) were identified as positive. In conclusions, while NGS has the advantage of being able to identify a wide range of potential pathogens it seems to be less sensitive compared to the standard amplification-based assays in the diagnosis of encephalitis, where low viral loads are common.

HSV encephalitis with normal initial CT scan - a case report with a review of the literature

Introduction. HSV-1 is the most common cause of viral encephalitis with a high mortality rate if left untreated and causes frequent diagnostic difficulties. It commonly involves the temporal, inferior frontal lobes and the limbic system. HSV can be differentiated by a combination of symptoms, laboratory tests and neuroimaging findings.Case report. A 29-year old female with HSV encephalitis, who, despite prevailing symptoms of altered mental status, had no abnormalities on initial CT head scan. Three MRI follow-up examinations revealed imaging findings with characteristic evolution. Despite CSF results being negative for HSV antibodies, the combination of symptoms, CSF analysis, and characteristic MRI findings were highly suggestive to diagnosing HSV encephalitis and to implement proper treatment.Discussion. In case of radiological changes in temporal lobe, the involvement of the Herpes simplex encephalitis (HSE) should always be considered. Although the laboratory tests happen to be inconclusive or even falsely negative, neuroimaging often helps to determine the diagnosis. Despite HSE being a severe neurological disorder, initial CT scans can be normal. MRI has become superior, especially at the early phase of the disease and is capable of determining the extensiveness of lesions.

Epilepsy after brain infection in adults: A register-based population-wide study.

To describe risk and risk factors of epilepsy after hospitalization for brain infection in adults in Sweden. This was a matched retrospective cohort study based on the comprehensive National Patient and Cause of Death Registers. All individuals age >18 without prior epilepsy who received inpatient care in 2000-2010 for a brain infection were included, with 3 age- and sex-matched unexposed controls per exposed individual (n = 12,101 exposed and 36,228 controls). Kaplan-Meier risks of epilepsy after different brain infections were calculated and risk factors identified by Cox regression. Patients were followed until the end of 2017. The 10-year risk of epilepsy was 5.9% (95% confidence interval [CI] 5.5-6.3) in cases and 1.2% (95% CI 1.0-1.4) in controls: 1.7% (95% CI 0.7-2.7) after tick-borne encephalitis, 4.1% (95% CI 3.3-4.9) after bacterial meningitis, 26.0% (95% CI 21.5-30.5) after herpes simplex virus encephalitis, and 30.2% (95% CI 27.1-33.3) after brain abscess. In Cox regression, seizure during the index admission and mechanical ventilation were epilepsy risk factors. Epilepsy is common after several types of brain infections in adults. The type of infection, its severity, and propensity to cause seizures in the acute phase influence the risk of subsequent epilepsy. This study provides Class II evidence that in adults, brain infection is associated with an increased risk of subsequent epilepsy.

Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis

ObjectivesThe aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE). MethodsA total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months. ResultsImpaired cognitive performance significantly correlated with NFL levels (rho = –0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = –0.6249, p = 0.024) and age (z-score beta = –0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006). DiscussionOur findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.

The association of herpes simplex type 1 encephalitis and anti –N methyl D aspartate receptor antibody encephalitis in a case

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a type of autoimmune encephalitis characterized by seizures, psychiatric symptoms, and movement disorder, which may present with an acute or subacute course. It has been reported that the production of anti-NDMA receptor antibodies can be triggered in the course of herpes simplex encephalitis and anti-NMDA receptor encephalitis may occur clinically. It has been reported that 25% of patients with HSV encephalitis have anti-NDMA receptor antibodies and are associated with impaired improvement in cognitive performance. In this article, we present a case of anti-NMDA receptor encephalitis associated with HSV-type 1 encephalitis in a 30-year-old woman and review the literature. After the patient's treatment for HSV encephalitis ended, her psychiatric symptoms such as anxiety, agitation, hallucinations and euphoria persisted and he was diagnosed with anti NMDA receptor antibodies detected in CSF. The patient was transferred to the neurology clinic and intravenous immunoglobulin treatment was started.

New-onset super-refractory status epilepticus: A case series of 26 patients.

To better understand the heterogeneous population of patients with new-onset refractory status epilepticus (NORSE), we studied the most severe cases in patients who presented with new-onset super-refractory status epilepticus (NOSRSE). We report a retrospective case series of 26 adults admitted to the Columbia University Irving Medical Center neurologic intensive care unit (NICU) from February 2009 to February 2016 with NOSRSE. We evaluated demographics, diagnostic studies, and treatment course. Outcomes were modified Rankin Scale score (mRS) at hospital discharge and most recent follow-up visit (minimum of 2 months post discharge), NICU and hospital length of stay, and long-term antiepileptic drug use. Of the 252 patients with refractory status epilepticus, 27/252 had NORSE and 26/27 of those had NOSRSE. Age was bimodally distributed with peaks at 27 and 63 years. The majority (96%) had an infectious or psychiatric prodrome. Etiology was cryptogenic in 73%, autoimmune in 19%, and infectious in 8%. Seven patients (27%) underwent brain biopsy, autopsy, or both; 3 (12%) were diagnostic (herpes simplex encephalitis, candida encephalitis, and acute demyelinating encephalomyelitis). On discharge, 6 patients (23%) had good or fair outcome (mRS 0-3). Of the patients with long-term follow-up data (median 9 months, interquartile range 2-22 months), 12 patients (71%) had mRS 0-3. Among our cohort, nearly all patients with NORSE had NOSRSE. The majority were cryptogenic with few antibody-positive cases identified. Neuropathology was diagnostic in 12% of cases. Although only 23% of patients had good or fair outcome on discharge, 71% met these criteria at follow-up.

Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis

Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.

Herpes simplex virus encephalitis after temporal lobe resection: an infrequent but treatable complication of epilepsy surgery

Herpes simplex virus encephalitis after temporal lobe resection: an infrequent but treatable complication of epilepsy surgery

Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis

Herpes simplex virus (HSV)-1 encephalitis has significant morbidity partly because of an over-exuberant immune response characterized by leukocyte infiltration into the brain and increased blood-brain barrier (BBB) permeability. Determining the role of specific leukocyte subsets and the factors that mediate their recruitment into the brain is critical to developing targeted immune therapies. In a murine model, we find that the chemokines CXCL1 and CCL2 are induced in the brain following HSV-1 infection. Ccr2 (CCL2 receptor)-deficient mice have reduced monocyte recruitment, uncontrolled viral replication, and increased morbidity. Contrastingly, Cxcr2 (CXCL1 receptor)-deficient mice exhibit markedly reduced neutrophil recruitment, BBB permeability, and morbidity, without influencing viral load. CXCL1 is produced by astrocytes in response to HSV-1 and by astrocytes and neurons in response to IL-1α, and it is the critical ligand required for neutrophil transendothelial migration, which correlates with BBB breakdown. Thus, the CXCL1-CXCR2 axis represents an attractive therapeutic target to limit neutrophil-mediated morbidity in HSV-1 encephalitis.

The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus.

Infections of the brain with herpes simplex virus type 1 (HSV-1) cause life-threatening Herpes simplex encephalitis (HSE) characterized by viral replication in neurons and neuro-inflammation including an infiltration of peripheral immune cells. HSV-1 reprograms host cells to foster its own replication and for immune evasion, but eventually the immune responses clear the infection in most patients. However, many survivors suffer from long-term neuronal damage and cannot regenerate all brain functions. HSV-1 influences the physiology of neurons, astrocytes, oligodendrocytes and microglia, and significantly changes their protein expression and secretion pattern. To characterize temporal changes upon HSV-1 infection in detail, we inoculated mixed primary cultures of the murine brain cortex, and performed quantitative mass spectrometry analyses of the cell-associated proteome and the secretome. We identified 28 differentially regulated host proteins influencing inflammasome formation and intracellular vesicle trafficking during endocytosis and secretion. The NIMA-related kinase 7 (NEK7), a critical component of the inflammasome, and ArfGap1, a regulator of endocytosis, were significantly up-regulated upon HSV-1 infection. In the secretome, we identified 71 proteins including guidance cues regulating axonal regeneration, such as semaphorin6D, which were enriched in the conditioned media of HSV-1 infected cells. Modulation of inflammasome activity and intracellular membrane traffic are critical for HSV-1 cell entry, virus assembly, and intracellular spread. Our proteome analysis provides first clues on host factors that might dampen the inflammasome response and modulate intracellular vesicle transport to promote HSV infection of the brain. Furthermore, our secretome analysis revealed a set of proteins involved in neuroregeneration that might foster neuronal repair processes to restore brain functions after clearance of an HSV-1 infection.

Management and results of epilepsy surgery associated with acyclovir prophylaxis in four pediatric patients with drug-resistant epilepsy due to herpetic encephalitis and review of the literature.

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis in children and is responsible for epilepsy in approximately half of patients. In addition to medical treatment, epilepsy surgery may be offered to drug-resistant patients but carries a high risk of relapse of herpetic encephalitis. We are reporting our series of patients operated on between 2000 and 2019 with the systematic administration of acyclovir (ACV). Four pediatric patients aged 4.5-12.8 years with drug-resistant epilepsy post-HSE underwent a tailored focal resection following invasive recordings (three patients) and a complete callosotomy (one patient). The total number of the surgical procedures for the four patients was eight, and a systematic administration of ACV as a prophylactic treatment of herpetic encephalitis relapse was done at each step. No patients had a relapse and the ACV was well-tolerated in all the cases. Following surgery two patients are seizure free, the patient who underwent callosotomy is Engel 3 and the fourth patient, in whom a large epileptic zone has contraindicated a second surgery, is Engel 4. Our series demonstrated the dramatic efficacy of systematic ACV prophylaxis during all cranial surgeries. Moreover, our results on epilepsy, together with those of the literature, encourage more consideration regarding epilepsy surgery in this specific etiology. All types of surgical procedures (curative or palliative) can be offered to the patients, but in the case of focal surgery, due to the poor anatomical limits, invasive recordings are highly recommended.

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

BackgroundElectroencephalogram (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 presentationA 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.ConclusionThe CVEEG not only helps identify NCSE but can also be used to monitor HSE progression.

Herpes zoster in HIV-1 infection: The role of CSF pleocytosis in secondary CSF escape and discordance.

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed longitudinally. We suggest that HZ provides a ‘model’ of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology provoked local HIV-1 production by enhanced trafficking or activation of HIV-1-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determined the plasma HIV-1 RNA concentrations, in this setting the CSF WBC counts established the relation of the CSF HIV-1 RNA levels to this plasma set-point.

Anti-NMDA receptor encephalitis presenting as new onset refractory status epilepticus in COVID-19

• Autoimmune encephalitis and status epilepticus in COVID-19 can be challenging. • Immunotherapy could be useful for anti-NMDAr encephalitis and SARS-Cov-2 infection. • Cytokines storm could play a role for NORSE presentation in NDMA-R encephalitis.