Herpes Simplex Encephalitis Research Articles

Epilepsy P-EP001. Status epilepticus and intractable seizure in herpes simplex encephalitis patient: Case series

Introduction . Herpes Simplex Encephalitis (HSE) is a rare disorder caused by infection of the CNS by HSV that could have a potentially fatal outcome particularly with delayed treatment. The early presentation is relatively nonspecific consisting of fever, headaches, seizures and unconsciousness. Seizures have been associated with death in HSE. This case report aims to publish case series of status epilepticus and intractable seizure in HSE patient at Sardjito Hospital Yogyakarta. Results . CASE 1: A 26year-old male was admitted to the ER Sardjito Hospital in 2018 presented with GTCS and behavior changes. GCS of this patient was E4V4M6 and there were no signs of meningeal irritation, no weakness found in extremity but increase of physiological reflex indicating UMN sign. After being transferred to the ward, patient developed to status epilepticus, then patient was referred to ICU; midazolam & propofol were administered to reduce seizures. Laboratory, CSF analysis and MRI were consistent with HSE. After aggressive treatments with anti-edema, antiviral and multiple antiepileptic drug (AED), there was a reduction in seizure but sometimes patient still developed GTCS. He was discharged after 25 days treatments with full consciousness, reduction of seizure frequency but the focal aware seizures were still remained. CASE 2: A 29-year-old female was admitted to the ER Sardjito in 2019 presented with focal to bilateral tonic-clonic seizure and status epilepticus. The complaints begin with acute progressive headache, fever, visual hallucinations and weakness of the left limbs. GCS of this patient was E2VTM2 (on midazolam) and there were no signs of meningeal irritation. Laboratory and CSF analysis were consistent with HSE. CT scan showed cerebral edema. After treatments with anti-edema, antiviral and AED, the patient regained full consciousness and there was a reduction of seizure frequency but focal aware seizures were still remained. Conclusion . Seizures in HSE are reported to be intractable seizures and more likely to develop status epilepticus. The seizures are typically refractory to AED, often requiring combination and aggressive treatments.

WS1.11. EEG in the ICU: Status Epilepticus and the Ictal-Interictal Continuum

Epileptic seizures and nonconvulsive status (NCSE) are common in the critically ill, but non- epileptic movements and posturing are even more common. EEG can provide clarification when seizures are suspected. Different EEG patterns form a continuum of non-seizure to seizure activity, and over- interpretation of these patterns may lead to inappropriate advice and treatment. Recurrent seizures are easiest to recognise, with rhythmic discharges having spatiotemporal evolution in frequency (>4Hz), morphology and distribution. Periodic patterns are the most difficult. Generalised periodic discharges (GPDs) may or may not be ictal, and the specific EEG findings combined with the clinical context determines the approach. Severe myoclonic encephalopathy may occur after cardiac arrest, and the EEG may show burst suppression, unreactive GPDs separated by isoelectric intervals, ± electrographic seizures. The prognosis is extremely poor irrespective of treatment. Lateralised periodic discharges (i.e. PLEDs) may be an interictal finding in epilepsy and after any acute cerebral insult such as stroke or herpes encephalitis, and usually indicates a predisposition to seizures rather than ongoing seizure activity. Generalised triphasic waves are mainly seen with metabolic and toxic encephalopathies and are usually not an ictal finding. Whilst they can be sharply contoured, they are recognised by their other characteristics including morphology, state-dependent reactivity, and lag in phase and/or morphology changes from front to back. Triphasic waves (and almost all periodic patterns) are suppressed by benzodiazepines, along with consciousness and respiration. Such EEG suppression, in the absence of clinical improvement, does not diagnose NCSE. Ambiguous patterns can also be seen, with stimulus-induced rhythmic, periodic or evolving discharges. Whilst non-convulsive seizures and NCSE may be detected in comatose patients, prognosis is largely determined by the underlying aetiology and its complications. Unresolved questions include what particular EEG patterns should consistently prompt aggressive treatment. It is not always possible to be certain that an EEG pattern is ictal or non- ictal, and in the correct clinical context (especially patients presenting with seizures or with a history of epilepsy) a treatment trial may be indicated to see if temporally associated clinical improvement occurs. EEG interpretation needs to be made within the clinical context by an expert reporter.

US Hospitalizations and 60-Day Readmission Rates Associated With Herpes Simplex Virus Encephalitis: Analysis of All Cause Readmissions and Encephalopathy Associated Readmissions.

Herpes simplex encephalitis (HSE) is the most common cause of encephalitis hospitalizations. We sought to describe and analyze features associated with all cause readmissions and encephalopathy associated readmissions amongst HSE cases. HSE hospitalizations and 60-day rehospitalizations were assessed in a retrospective cohort using linked hospitalizations from the Healthcare Utilization Project (HCUP) National Readmission Database (NRD) from 2010 through 2017. Risk factors for all-cause readmissions and encephalopathy associated readmissions were assessed with a weighted logistic regression model. There were 10 272 HSE cases in the US between 2010 and 2017, resulting in a national rate of 4.95 per 100 000 hospitalizations. A total of 23.7% were readmitted at least once within 60-days. Patients that were readmitted were older (mean age 62.4 vs 57.9, P < .001), had a greater number of procedures at the index hospitalization (adjusted odds ratio [aOR] 1.03, P < .001) and have a higher Charlson comorbidity score (aOR 1.11, P < .001). Among those readmitted, 465 (16.5%) had an encephalopathy related diagnosis. Over 8 years, the rate of encephalopathy associated readmissions increased from 0.12 to 0.20. Encephalopathy specific readmissions were found to be associated with greater age (mean age 65.9 vs 61.7, P = .004) and findings of cerebral edema at index hospitalization (aOR 2.16, P < .001). HSE readmissions are relatively common, particularly among older and sicker individuals. However, early signs and symptoms of neurological disease at index were correlated with encephalopathic specific readmissions.

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management.

Antibody-mediated disorders of the central nervous system (CNS) are increasingly recognized as neurologic disorders that can be severe and even life-threatening but with the potential for reversibility with appropriate treatment. The expanding spectrum of newly identified autoantibodies targeting glial or neuronal (neural) antigens and associated clinical syndromes (ranging from autoimmune encephalitis to CNS demyelination) has increased diagnostic precision, and allowed critical reinterpretation of non-specific neurological syndromes historically associated with systemic disorders (e.g., Hashimoto encephalopathy). The intracellular vs. cell-surface or synaptic location of the different neural autoantibody targets often helps to predict the clinical characteristics, potential cancer association, and treatment response of the associated syndromes. In particular, autoantibodies targeting intracellular antigens (traditionally termed onconeural autoantibodies) are often associated with cancers, rarely respond well to immunosuppression and have a poor outcome, although exceptions exist. Detection of neural autoantibodies with accurate laboratory assays in patients with compatible clinical-MRI phenotypes allows a definite diagnosis of antibody-mediated CNS disorders, with important therapeutic and prognostic implications. Antibody-mediated CNS disorders are rare, and reliable autoantibody identification is highly dependent on the technique used for detection and pre-test probability. As a consequence, indiscriminate neural autoantibody testing among patients with more common neurologic disorders (e.g., epilepsy, dementia) will necessarily increase the risk of false positivity, so that recognition of high-risk clinical-MRI phenotypes is crucial. A number of emerging clinical settings have recently been recognized to favor development of CNS autoimmunity. These include antibody-mediated CNS disorders following herpes simplex virus encephalitis or occurring in a post-transplant setting, and neurological autoimmunity triggered by TNFα inhibitors or immune checkpoint inhibitors for cancer treatment. Awareness of the range of clinical and radiological manifestations associated with different neural autoantibodies, and the specific settings where autoimmune CNS disorders may occur is crucial to allow rapid diagnosis and early initiation of treatment.

Neurodegenerative proteinopathies associated with neuroinfections.

Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer’s disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aβ and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis (n = 13) and neurosyphilis (n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24–65 years) and survival was 9 days–6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36–86 years) and 1–5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aβ-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00702-021-02371-7.

Management and outcome predictors during Herpes simplex virus encephalitis

Background: Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic acute viral encephalitis in adults associated with a high incidence of severe and permanent neurologic sequelae. We aimed to identify the epidemiological, clinical, evolutionary features and to study the outcome predictors of HSE.

Sydenham’s Chorea with Silent Cardiac Lesions, Mimicking Encephalitis in a 13 Year Old Girl

Sydenham’s chorea is an uncommon neurological manifestation of rheumatic fever and has many and varied differential diagnosis. It may mimic encephalitis when presents as an isolated feature even when silent cardiac lesions are present. Early diagnosis, treatment and penicillin prophylaxis prevents recurrence and progression of cardiac lesions. Prompt symptomatic relief and alleviation of distress is obtained with therapeutic intervention. A case of rheumatic chorea with silent cardiac valve lesions which mimicked herpes simplex encephalitis with choreoathetosis, in a 13 year old girl is presented along with review of literature.

Bortezomib-Thalidomide-Dexamethasone (VTD) As Salvage Treatment in Patients with Multiple Myeloma Candidates for Transplantation in the Real World

BackgroundTreatment for Multiple Myeloma (MM) has evolved greatly, ranging from corticosteroids to monoclonal antibodies. In low-resource countries, however, the first-choice treatment is still based on cyclophosphamide-thalidomide-dexamethasone (CTD) regimen, either in patients who are candidates or non-candidates for stem cell transplantation (SCT). In Peru, a few years ago, bortezomib has been introduced as salvage treatment. Bortezomib as salvage treatment has reported 6.22 months of time to progression and combined complete and partial response rates of 38% in pivotal study. 1ObjectivesTo determine the response to treatment to VTD in patients with multiple myeloma candidates to transplant. To determine progression-free survival (PFS) to VTD. To determine the percentage of transplant patients.MethodsWe retrospectively assessed the clinical efficacy and toxicity of VTD (bortezomib 1.3mg/m2 subcutaneously on days 1, 4, 8 and 11; thalidomide 100mg orally on days 1 through 21; dexamethasone 40mg orally on days 1, 2, 4, 5, 8, 9, 11, 12 for three-week cycles), as salvage treatment in patients with relapsed/refractory MM candidate to autologous stem cell transplantation treated at Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, between January 2014 and December 2016. Patients received only one prior treatment and at least 2 cycles of VTD. SPSS program was used for data analysis. Survival outcomes were estimated by Kaplan-Meier Method.ResultsSixteen patients were found to fulfill the selection criteria. The median age was 52 (39-62), fifty-six percent (n=9) were male. International Staging System III disease was present in 75%. ECOG 1-2 was present in 94%. Ig G and IgA MM were 62.5% and 12.5% respectively; lambda light chain was present in 56.3%. 37.5% of patient had renal impairment. B2µg was >3.5mg/dL in 57% of patients. CTD was the first-line in 94%, with overall response rate (ORR) of 62.5% (complete response (CR) 6.3%, very good partial response (VGPR) 12.5%, and partial response (PR) 43.8%). For VTD regimen the median number of treatment cycles delivered was three (range 2-5), totally 59 cycles. After a median of 14 months follow-up for VTD (range 4-34), the overall response rate was 75%, stringent complete response (SCR) was 18.8% (n= 3), complete response 37.5%, very good partial response 6.3%, and partial response 12.5%. Six out of 16 patients (37.5%) with VTD treatment who were candidates for transplantation finally were transplanted. Among the causes for not undergoing transplantation, infections was 40% (20% (two) of cases were pulmonary tuberculosis, one case (10%) was herpes simplex encephalitis, one case (10%) was probable pulmonary aspergillosis), relapsed disease 40%, renal failure 10%, failure of stem cell collection 10%. Median PFS was 14 months (4-33m). 2-years PFS was 37.5%. 5-years overall survival (OS) was 55%, the median was not reached (18-110m). The most common adverse events for all patients were grade 2 peripheral neuropathy and infections (four infections described above), both in 25%, deep venous thrombosis was not reported. Three deaths was reported (18.75%) all for progression disease.ConclusionVTD is an effective treatment in transplant candidates with multiple myeloma who have relapsed after one previous therapy including thalidomide. PFS is superior to Bortezomib pivotal study in relapsed disease. Infectious diseases represent 40% of cause for not undergoing transplantation.

Focused Workshops

The initial trigger leading to the immune tolerance breakdown is still unknown in most autoimmune encephalitites associated with antibodies targeting neuronal surface antigens. Nevertheless, prodromal symptoms compatible with mild infections are not infrequent, suggesting that some common and benign microbiological agents could act as triggers of the autoimmune reaction. Conversely, herpes simplex virus (HSV) encephalitis is now a well-characterized trigger of autoimmune encephalitis, and is particularly related to the development of anti- NMDAR antibodies, though other specificities have also been reported. Serological studies as well as an animal model further support the association between HSV and anti-NMDAR encephalitis, but the underlying pathogenesis is still obscure. However, a genetic predisposition involving the Toll-like receptor 3-pathway might exist at least in a subset of patients. In addition to HSV, anti-NMDAR and other autoimmune encephalitis have also been associated with other infections, chiefly Japanese encephalitis and HIV, but new epidemic and pandemic diseases such as COVID-19 are raising concern as potential triggers of autoimmune encephalitis. On the contrary, despite the recent description of anti-neural antibodies against different targets in some patients, solid evidence regarding the autoimmune pathogenesis is still lacking for several historically reported post-infectious neurological diseases, such as Sydenham chorea and von Economo's encephalitis lethargica. Interestingly, type 1 narcolepsy constitutes a good example of neurological autoimmunity triggered by infection in genetic susceptible subjects that might provide some clues for future research in autoimmune encephalitis.

Prevalence and clinical manifestations of herpes simplex virus infection among suspected patients of herpes simplex encephalitis in Shiraz, Iran.

Encephalitis has infectious and noninfectious etiology. Among infectious agents, viruses are the main causes of encephalitis; Herpes simplex virus (HSV) is known as the most common causative agent of viral encephalitis. In this current cross-sectional investigation, we aimed to assess the prevalence of HSV in the cerebrospinal fluid (CSF) specimens of Herpes Simplex Encephalitis (HSE) suspected patients and also determining the clinical symptoms and laboratory findings of this viral complication. Two hundred consecutive HSE suspected patients with clinical diagnosis of encephalitis were included in the study and then the presence of HSV DNA in their CSF was applied by Polymerase Chain Reaction (PCR) assay. Molecular detection of two hundred (117 males with mean age: 43years, 83 females with mean age: 39years) CSF samples showed that 22 (11.11%) cases were positive for HSV infection. 15(68.18%) of the positive samples were more than 50years old, however, there was no significant correlation between age distribution, gender and HSE clinical manifestations. Fever (91%), headache (72.7%), seizer (59%), and weakness (59%) were the most common symptoms in positive patients and also mortality rate was (18.18%). CSF laboratory abnormalities of HSE cases were as follows; lymphocytic pleocytosis 19 (86.3%), leukocytosis 19 (86.3%), elevated protein level 16 (72.7%), and hypoglycorrhachia 3(13.6%). Screening of HSE suspected patients is crucial in the treatment of patients and reduce the mobility and morbidity of patients. Qualitative PCR as an available method in most developing countries could be a reliable method to monitor consecutive HSE suspected patients.

A computational approach for detecting physiological homogeneity in the midst of genetic heterogeneity

The human genetic dissection of clinical phenotypes is complicated by genetic heterogeneity. Gene burden approaches that detect genetic signals in case-control studies are underpowered in genetically heterogeneous cohorts. We therefore developed a genome-wide computational method, network-based heterogeneity clustering (NHC), to detect physiological homogeneity in the midst of genetic heterogeneity. Simulation studies showed our method to be capable of systematically converging genes in biological proximity on the background biological interaction network, and capturing gene clusters harboring presumably deleterious variants, in an efficient and unbiased manner. We applied NHC to whole-exome sequencing data from a cohort of 122 individuals with herpes simplex encephalitis (HSE), including 13 individuals with previously published monogenic inborn errors of TLR3-dependent IFN-α/β immunity. The top gene cluster identified by our approach successfully detected and prioritized all causal variants of five TLR3 pathway genes in the 13 previously reported individuals. This approach also suggested candidate variants of three reported genes and four candidate genes from the same pathway in another ten previously unstudied individuals. TLR3 responsiveness was impaired in dermal fibroblasts from four of the five individuals tested, suggesting that the variants detected were causal for HSE. NHC is, therefore, an effective and unbiased approach for unraveling genetic heterogeneity by detecting physiological homogeneity.

Decompressive craniectomy as a rescue treatment in Herpes simplex encephalitis-related cerebral edema: a case report and literature review

We present a case of herpes simplex encephalitis requiring decompressive craniectomy for high intracranial pressure, and a review of decompressive craniectomy in herpes simplex encephalitis. Case description and review: a 32-year-old man was brought to emergency department for headache and fever. The cerebral spinal fluid examination found lymphocytic meningitis; treatment by acyclovir was initiated 4 days after admission. At day 5, patient developed clinical signs of high intracranial pressure and CT-scan showed cerebral herniation. After medical management fail, a decompressive craniectomy was performed on the same day. The procedure resulted in a good clinical recovery with minor neurological sequelae. A literature review, presented here, found few cases of decompressive craniectomy in herpes simplex encephalitis. Due to a lack of robust clinical data, no guideline are yet available. In summary, a surgical approach, such as a decompressive craniectomy, in herpes simplex encephalitis with high intracranial pressure should be discussed early, in association with the medical treatment. Prospective data are needed to better define timing of surgery and decision-making criteria.

Living with global amnesia: self-established compensation strategies of a patient with severe memory impairment – a narrative report

ABSTRACT We report the case of C.H., a 48-year-old patient with global amnesia caused by herpes simplex encephalitis at the age of 20 and subsequent extensive bilateral temporal lobe lesions. Neuropsychological examinations performed at various intervals found persistent dense explicit memory impairment and limited vocabulary, yet intact procedural memory. Despite these limitations, C.H. self-developed and acquired a variety of effective strategies. As a result, C.H. achieved a high level of autonomy in everyday life. Her remarkable case is an encouraging and helpful example for successful implementation of creative methods and procedures to compensate and alleviate cognitive limitation, even if extensive.

Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

Pediatric N-Methyl-d-Aspartate (NMDA) Receptor Encephalitis, With and Without Herpes Encephalitis.

To compare clinical, diagnostic, management, and outcome factors in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and a history of herpes simplex encephalitis (HSE) to children with NMDAR encephalitis without a history of HSE. All patients with anti-NMDAR antibodies in cerebrospinal fluid treated at our institution between 2012 and 2019 were identified and divided into those with a history of HSE (HSE+NMDAR group) and those without a history of HSE (NMDAR-only group). Demographic data, clinical characteristics, immunotherapy, and outcome data were collected on all patients and compared between the 2 groups. Seventeen patients were identified with anti-NMDAR antibodies in cerebrospinal fluid, 6 of whom had a history of HSE. Mean age in the HSE+NMDAR cohort was significantly younger in the HSE+NMDAR cohort, as 5 of the 6 patients were infants. Of HSE+NMDAR patients, 50% had behavioral symptoms, 67% had movement disorders, and 100% had seizures at disease nadir. In the NMDAR-only group, 100% had behavioral symptoms, 73% had movement disorders, and 73% had seizures at nadir. HSE+NMDAR patients received a median of 1 immunotherapy, compared to a median of 4.5 immunotherapies in the NMDAR-only group. Behavioral symptoms were more common in NMDAR-only patients, whereas seizures were more common in HSE+NMDAR patients. Both groups had significant disability at disease nadir, with more improvement in disability over time in the NMDAR-only group. HSE+NMDAR patients received fewer immunotherapies than NMDAR-only patients. Outcomes of infants with HSE appear to primarily reflect sequelae from HSE.

Hemispheric encephalitis secondary to HAV

A 2-year male child, presented to National Institute of Child Health (NICH), with acute onset high grade fever and focal left sided seizures for 1 day, followed by left hemiparesis and encephalopathy. Developmental and family history was unremarkable. On physical examination, patient’s body temperature rose up to 38.7 °C. Though he had pallor along with hepatomegaly, there were no signs of jaundice or ascites. Central nervous system examination showed encephalopathy as well as positive neck stiffness. Motor system examination revealed generalized decrease in bulk of upper and lower limbs, but rest of the findings were localized to left side of the body, showing hypertonia, decreased power, brisk muscle stretch reflex, and positive ankle clonus and left Babinski sign.&#x0D; Blood investigations showed anemia (hemoglobin 9.1g/dl), leukocytosis (white blood cells 22.1 cells/μL) and raised aspartate aminotransferase (AST) levels (826 IU/L). Total bilirubin and direct bilirubin levels were normal (0.3 mg/dL and 0.1 mg/dL, respectively). Serum ammonia (64 μg/dL) and lactic acid (1.6 μg/dL) levels were also within normal ranges. The cerebrospinal fluid (CSF) was also clear, with 0 leukocytes/μL, protein levels of 25 mg/dL, and normal glucose levels (82 mg/dL), no organism was seen on gram stain. Hepatitis A Ig M antibody came out to be reactive.&#x0D; Brain computed tomography showed large hypo density along with effacement of sylvian fissure, sulci, gyri on right side involving frontal, parietal, and temporal and occipital lobe on ipsilateral side. On post contrast, there was remarkable meningeal enhancement on right side. MRI brain revealed cortical and subcortical large area of abnormal signal intensity seen in fronto-parietal and occipital cortex on the right side along with laminar necrosis.&#x0D; Seizures were controlled by given intravenous injection phenytoin and leviteracetam in bolus and then maintenance doses. Intravenous acyclovir was started&#x0D; due to clinical suspicion of herpes encephalitis but was stopped after observing clinical improvement and identification of Ig M antibody of HAV. Patient conscious level improved after 2 weeks. AST levels also decreased to 20 IU/L and he was discharged with advice to follow up after 14 days

US Hospitalizations and 60-Day Readmission Rates Associated With Herpes Simplex Virus Encephalitis: Analysis of All Cause Readmissions and Encephalopathy Associated Readmissions

Background: Herpes Simplex encephalitis (HSE) is the most common cause of encephalitis hospitalizations. We sought to describe and analyze features associated with all cause readmissions and encephalopathy associated readmissions amongst HSE cases. Methods: HSE hospitalizations and 60-day rehospitalizations were assessed in a retrospective cohort using linked hospitalizations from the Healthcare Utilization Project (HCUP) National Readmission Database (NRD) from 2010 through 2017. Risk factors for all-cause readmissions and encephalopathy associated readmissions were assessed with a weighted logistic regression model. Findings: There were 10,272 HSE cases in the US between 2010 and 2017, resulting in a national rate of 4·95 per 100,000 hospitalizations. A total of 23·7% were readmitted at least once within 60-days. Patients that were readmitted were older (mean age 62·4 vs. 57·9, p<0·0001), had a greater number of procedures at the index hospitalization (aOR 1·03, p<0·0001) and have a higher Charlson comorbidity score (aOR 1·11, p<0·0001). Amongst those readmitted, 465 (16·5%) had an encephalopathy related diagnosis. Over eight years, the prevalence of encephalopathy associated readmissions increased from 0·12 to 0·20. Encephalopathy specific readmissions were found to be associated with greater age (mean age 6·9 vs. 61·7, p = 0·004) and findings of cerebral edema at index hospitalization (aOR 2·16, p <0·0001). Interpretations: HSE readmissions are relatively common, particularly among older and sicker individuals. However, early signs and symptoms of neurological disease at index were correlated with encephalopathic specific readmissions. Funding Statement: This research was supported by the Health Resources and Services Administration, an agency of the US Department of Health and Human Services, grant number T32 HP10031 (Michael A. Hansen’s postdoctoral funding). The funding source/study sponsor had no role in the writing of this manuscript, or decision to submit the manuscript for publication. Declaration of Interests: RH has received research support and fees from Biofire®. All other authors have no conflicts of interest. Ethics Approval Statement: The project was submitted and deemed exempt from Baylor College of Medicine’s Institutional Review Board.

P0634 / #1809: LATE ONSET HSV ENCEPHALITIS

Aims & Objectives: CASE REPORT Introduction: 22day old baby girl presented to ED with left sided jerky movment and 1 day H/O low grade fever other wise normal, later developed HSV1 encephalitis followed by left side upper limb weakness. Methods: 22day old girl presented to Emergency Room with H/O fever and associated with jerky movements of left upper limb lasted for about 5osec. and continued about every 2 to 3hrly.Her physical exam and vital signs at ER were with in normal range.including CNS exam.Labs were normal except CSF, which showed WCC 98 and RCC 0 with no bacterial growth, Baby was started on cefotaxime and Acyclovir and transfered to paediatric ward. No significant maternal risk factors, normal pregnancy and delivery no perinatal or post natal abnormalities. Results: Her CSF PCR showed HSV1. MRI showed Infarction in the right internal capsuel extending to the vertex. EEG showed asymetry in the frontocentral location.. she was treated with Acyclovir IV for 21days followed by Acyclovir PO for 6months. She was followed in the paediatric clinic and by physiotherapy, she continued to have left sided hemiparesis on the left upper limb which was improved gradually with minimal weakness in the latest clinic review. Conclusions: Even though baby was presented with casual presentation and resulted with Herpes encaphalopathy and left sided hemiparesis. So new born babies with HSV may not present with typical signs. Babies with low grade fever and jerky movements could result in encephalopaththy. HSV shoud be in the differentials and should be investigated and treated.

Neurosyphilis presenting as herpes simplex virus encephalitis

AbstractA 63‐year‐old woman was admitted to our hospital complaining of sudden slow response and irrelevant answer for three days. The brain magnetic resonance imaging revealed a left‐sided hyperintense lesion and moderate expansiveness involving the hippocampus, insular cortex, and temporal lobe, which mimicking herpes simplex virus encephalitis. Her cerebrospinal fluid examination disclosed the Treponema pallidum particle agglutination assay and rapid plasma regain test were both positive. A diagnosis of neurosyphilis was made, and the patient was benefited from penicillin therapy.

ASC-dependent inflammasomes contribute to immunopathology and mortality in herpes simplex encephalitis.

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis, and despite targeted antiviral therapy, outcomes remain poor. Although the innate immune system is critical for restricting herpes simplex virus type I (HSV-1) in the brain, there is evidence that prolonged neuroinflammation contributes to HSE pathogenesis. In this study, we investigated the contribution of inflammasomes to disease pathogenesis in a murine model of HSE. Inflammasomes are signaling platforms that activate the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. We found that mice deficient in the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), had significantly improved survival and lower levels of IL-1β and IL-18 in the brain. Importantly, this difference in survival was independent of viral replication in the central nervous system (CNS). We found that microglia, the resident macrophages of the CNS, are the primary mediators of the ASC-dependent inflammasome response during infection. Using in vitro glial infections and a murine HSE model, we demonstrate that inflammasome activation contributes to the expression of chemokine (C-C motif) ligand 6 (CCL6), a leukocyte chemoattractant. The lower concentration of CCL6 in the brains of ASC-/- mice correlated with lower numbers of infiltrating macrophages during infection. Together, these data suggest that inflammasomes contribute to pathogenic inflammation in HSE and provide a mechanistic link between glial inflammasome activation and leukocyte infiltration. The contribution of inflammasomes to survival was independent of viral replication in our study, suggesting a promising new target in combating harmful inflammation in HSE.