A Diagnostically Challenging Case of Recurrent Encephalitis With Impending Herniation.

Encephalitis is characterized by inflammation of the brain parenchyma with typical presenting symptoms of altered mental status and seizures. However, diagnostic workup is complex given the multitude of possible etiologies for encephalitis. Further, recurrence of encephalitis is rare, and understanding its risk factors, mechanisms, prognosis, and optimal treatment remains incomplete. Here, we present the case of a 69-year-old woman admitted to our hospital with altered mental status who was diagnosed with encephalitis based on clinical and imaging findings. This case highlights the diagnostic approaches required to obtain the final diagnosis and the treatment plan that resulted in the patient's eventual return to baseline and functional independence.

The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.

Herpes simplex virus encephalitis (HSE) is the leading cause of non-epidemic encephalitis in the developed world and, despite antiviral therapy, mortality and morbidity is high. The emergence of post-HSE autoimmune encephalitis reveals a new immunological paradigm in autoantibody-mediated disease. A reductionist evaluation of the immunobiological mechanisms in HSE is crucial to dissect the origins of post-viral autoimmunity and supply rational approaches to the selection of immunotherapeutics. Herein, we review the latest evidence behind the phenotypic progression and underlying immunobiology of HSE including the cytokine/chemokine environment, the role of pathogen-recognition receptors, T- and B-cell immunity and relevant inborn errors of immunity. Second, we provide a contemporary review of published patients with post-HSE autoimmune encephalitis from a combined cohort of 110 patients. Third, we integrate novel mechanisms of autoimmunization in deep cervical lymph nodes to explore hypotheses around post-HSE autoimmune encephalitis and challenge these against mechanisms of molecular mimicry and others. Finally, we explore translational concepts where neuroglial surface autoantibodies have been observed with other neuroinfectious diseases and those that generate brain damage including traumatic brain injury, ischaemic stroke and neurodegenerative disease. Overall, the clinical and immunological landscape of HSE is an important and evolving field, from which precision immunotherapeutics could soon emerge.

Autoimmune encephalitis with double positive anti-NMDAR and anti-GABABR secondary to herpes simplex virus encephalitis:A case report and literature review / 吉林大学学报(医学版)

Objective:To analyze the clinical presentations and diagnostic and treatment process of one patient with autoimmune encephalitis(AE)with double positive anti-N-methyl-D-aspartate receptor(NMDAR)and anti-γ-aminobutyric acid B receptor(GABABR)secondary to herpes simplex virus encephalitis(HSVE),and to improve the clinicians'awareness of this disease.Methods:The clinical data of one AE patient with double positive anti-NMDAR and anti-GABABR secondary to HSVE were collected,the diagnostic and therapeutic processes were summarized,and the relevant literatures were reviewed.Results:The patient,a 36-year-old male,developed a headache followed by limb convulsions,and progressed to disturbed consciousness.After admission,the routine biochemistry of the cerebrospinal fluid(CSF)was abnormal,and the herpes simplex virus-1(HSV-1)IgG antibody showed positive in the CSF;both CSF and serum tests for NMDAR antibodies were positive;the head magnetic resonance imaging(MRI)results showed abnormal signals in the right occipital white matter,leading to the diagnosis of HSVE secondary to anti-NMDAR encephalitis.Several months later,the patient experienced psychiatric behavior abnormalities,cognitive dysfunction,and sleep disorders,and both the serum NMDAR and GABABR antibodies showed positive results,prompting the diagnosis of HSVE secondary anti-NMDAR encephalitis and anti-GABABR encephalitis.After treatment with steroid pulse therapy and intravenous immunoglobulin(IVIG),the patient's condition was improved and the patient was discharged.At one-year follow-up,the patient's psychiatric symptoms had completely resolved,leaving mild cognitive impairment.Conclusion:If the clinical symptoms of the patients recovering from antiviral treatment for HSVE is worsened,secondary AE should be highly suspected;it is important to complete autoimmunity antibody testing as soon as possible for the early diagnosis and treatment to improve the prognosis of the patient.

Changing Clinical Profile and Predictors of Mortality in Patients of Acute Febrile Encephalopathy from North India.

Introduction: Acute encephalitis syndrome (AES) or acute febrile encephalopathy is a clinical condition characterized by altered mental status occurring after or along with a short febrile illness. In developing countries, infections are the predominant cause of AES. Prominent infections known to cause AES include viruses (such as herpes simplex virus [HSV], Japanese Encephalitis [JE] virus, dengue, enteroviruses [EVs]), bacteria, fungus, and parasites. In the present study, we aim to analyze the etiology, clinical features, and predictors of mortality in patients presenting with acute febrile encephalopathy or acute encephalitic syndrome. The present study was a prospective observational study conducted at Post Graduate Institute of Medical Education and Research a tertiary care center in Chandigarh, India. Methods: A total of 105 patients with ≥18 years of age with fever (body temperature >101° F for duration ≤14 days) and altered sensorium (Glasgow coma scale [GCS] score ≤10) lasting for more than 24 h, either accompanying the fever or following it were enrolled. Demographic and clinical details were recorded on pro forma. Cerebrospinal fluid (CSF) analysis was performed for all the enrolled patients at admission for cytology, CSF glucose to blood glucose ratio, protein levels, gram stain and culture sensitivity, adenosine deaminase levels, polymerase chain reaction for HSV/EV/mycobacterium tuberculosis (TB) and immunoglobulin M Enzyme-linked immune assay for JE. Computed tomography of the brain was done in all patients while magnetic resonance imaging (MRI) of the brain was carried out in 75 patients. Results: Among the 105 patients, tubercular meningitis was seen in 27 (25.7%) patients followed by acute pyogenic meningitis in 18 (17.1%) patients. Probable viral encephalitis was present in 12 (11.4%) cases. Septic encephalopathy (n = 10) and scrub typhus encephalitis (n = 8), HSV encephalitis (n = 6), dengue encephalitis (n = 4), leptospirosis (n = 3) were the other infections causing acute febrile encephalitis in our study. In addition to fever and altered sensorium common symptoms observed were headache (52.4%), vomiting (35.2%), and seizures (29.5%). The factors predicting increased mortality were female gender, fever of more than 38°C at admission, GCS <7, MRI showing disease-related findings like altered signal intensity bilateral medial temporal and insular area in herpes simplex encephalitis, etc., changes, and the group of patients where a definite diagnosis could not be established during the hospital stay. Conclusions: Tubercular meningitis/central nervous system TB is the predominant cause of acute febrile encephalopathy in developing countries. Scrub and dengue encephalitis are emerging as an important cause of acute febrile encephalopathy and occur predominantly in postmonsoon seasons. Acute febrile encephalopathy remains an important cause of mortality in patients presenting to Emergency Department (ER). The strongest predictors of mortality are low GCS and undiagnosed cases of AES.

Understanding Herpes Simplex Virus Type 1 Versus Herpes Simplex Virus Type 2 Encephalitis After Neurosurgery: A Case Series and Literature Review.

Abstract Background: Herpes simplex virus encephalitis (HSVE) is a rare post-operative infection that can be fatal if treatment is delayed. Herpes simplex virus type 1 (HSV-1) is a more common cause of encephalitis than herpes simplex virus type 2 (HSV-2), however, a significant overlap exists. The goal of this project was to understand the frequency and trend of HSVE after neurosurgery through a case series at our institution and in the literature with a focus on comparing HSV-1 versus HSV-2. Patients and Methods: A literature review of all published cases and case series of HSVE after neurosurgery was performed. Descriptive statistics comparing HSV-1 and HSV-2 encephalitis were computed. Data on demographics, symptoms, surgery, treatment, immunosuppression, imaging findings, steroids, and mortality were collected. Results: We identified 55 total cases of HSVE post-neurosurgery. These included 28 cases of HSV-1, 10 cases of HSV-2, and 17 cases of HSV-unspecified encephalitis. There were no differences in age, gender, symptoms, surgery, or latency between surgery and symptom onset between HSV-1 and HSV-2. Mortality was higher with HSV-1 versus HSV-2 although not statistically significant. The primary surgical indication varied substantially between HSV-1 and HSV-2. Conclusions: Herpes simplex virus encephalitis is often overlooked in the setting of encephalitis after surgery. A high index of suspicion is needed to prevent a delay in treatment.

Herpes Simplex Virus Encephalitis.

Herpes simplex virus (HSV) encephalitis (HSVE), which is caused by HSV-1 or HSV-2, is a rare neurologic disorder associated with focal or global cerebral dysfunction. HSVE is a syndrome of altered mental status, fever, and se.

Temporal lobe hemorrhage as a complication of HSV encephalitis: a case report.

Key Clinical Message: This case underlined the importance of having high suspicion for lobar hemorrhage as a rare but deadly complication of herpes simplex virus encephalitis and shone light upon the added complexity it poses on management on an already deadly disease. Abstract: Herpes simplex virus (HSV) encephalitis is the most common type of sporadic encephalitis that inflicts high rates of morbidity and mortality. Differentiating a progressing encephalitis syndrome from a lobar hemorrhage as a complication presents a challenge and requires great vigilance and insight on part of the treating physician.

Case report: Tongdu Xingshen acupuncture for a patient with persistent vegetative state after herpes simplex virus encephalitis.

Introduction: A persistent vegetative state (PVS) can be caused by traumatic or non-traumatic brain injury. PVS is a complex clinical condition with numerous complications. Nursing care, medical treatment, and comprehensive rehabilitation are necessary to improve the outcomes of PVS. However, the prognosis remains unsatisfactory. Acupuncture therapy has been used as a rehabilitation strategy to treat patients with PVS in China, showing better results in the recovery of consciousness, intellectual capability, and motor function. Case description: We present the case of a 4-month-long PVS after herpes simplex virus encephalitis (HSVE) in a 3.5-year-old boy who underwent Tongdu Xingshen acupuncture integrated with Western medicine and rehabilitation. The patient regained consciousness post-treatment. His intelligence and motor function gradually recovered after seven treatment sessions. Conclusion: Tongdu Xingshen acupuncture is a potential complementary therapy to optimize clinical outcomes in PVS.

Herpes Simplex Virus 1 Induces Microglia Gasdermin D-Dependent Pyroptosis Through Activating the NLR Family Pyrin Domain Containing 3 Inflammasome.

Herpes simplex virus type 1 (HSV-1) is a highly prevalent virus in humans and causes severe forms of inflammation, such as herpes simplex encephalitis (HSE). Pyroptosis is a new inflammatory cell death triggered by inflammasome and cysteine-requiring aspartate protease-1 (caspase-1) activation. Nonetheless, HSV-1 induces encephalitis, and cell death mechanisms are not understood. In this study, we confirmed for the first time that the DNA virus HSV-1 triggers Gasdermin D-dependent pyroptosis by activating NLR family pyrin domain containing 3 (NLRP3) inflammasomes in mouse microglia, leading to mature IL-1ß production and active caspase-1 (p10) release. Inhibition of microglial NLRP3 inflammasome activation suppressed HSV-1-induced Gasdermin D-dependent pyroptosis. In addition, NLRP3 and IL-1ß expression levels were significantly increased in the mouse model of herpes simplex encephalitis compared with normal mice without viral infection. Collectively, our data revealed that the activation of inflammasomes and GSDMD-dependent pyroptosis is the mechanism of HSV-1 inducing inflammation and provides treatment targets for viral inflammation.

Analysing triggers for anti-NMDA-receptor encephalitis including herpes simplex virus encephalitis and ovarian teratoma: results from the Queensland Autoimmune Encephalitis cohort.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (anti-NMDA-R) encephalitis is a complex autoimmune neuropsychiatric syndrome. Although initially associated with ovarian teratoma, subsequent studies have demonstrated that anti-NMDA-R encephalitis may occur without an identifiable cause or be triggered by viral infection of the central nervous system such as herpes simplex virus encephalitis (HSVE). AIM: To present details from a Queensland cohort analysing triggering events in patients with anti-NMDA-R encephalitis in an Australian context. METHODOLOGY: The authors identified patients with anti-NMDA-R encephalitis diagnosed and managed through public hospitals in Queensland, Australia, between 2010 and the end of 2019. Data collected included demographics, clinical presentation, investigation results, management and outcome measurements. RESULTS: Thirty-one cases of anti-NMDA-R encephalitis were included in the study. Three cases of anti-NMDA-R encephalitis were triggered by prior HSVE, five cases were associated with ovarian teratoma and 23 cases had no identifiable trigger. There were an additional three cases in which anti-NMDA receptor antibodies were present in the context of other disease states but where the patient did not develop anti-NMDA-R encephalitis. Cases triggered by HSVE or associated with ovarian teratoma experienced a more severe disease course compared to cases with no identifiable trigger. All groups responded to immunosuppressive or immunomodulatory therapy. Analysis of clinical characteristics revealed a complex heterogeneous syndrome with some variability between groups. CONCLUSION: In this cohort, the number of cases of anti-NMDA-R encephalitis triggered by HSVE is comparable to those triggered by ovarian teratoma. However, the majority of cases of anti-NMDA-R encephalitis had no identifiable trigger or associated disease process.

Non-convulsive status epilepticus as an initial manifestation of herpes simplex virus encephalitis.

Herpes simplex encephalitis (HSVE), manifesting with non-convulsive status epilepticus (NCSE), normocellular CSF findings and CT features of acute ischemic stroke, is a rare finding that can be hard to diagnose accurately. We present a case of HSVE and compare our results to those of previously published cases with the same pathology, in order to provide information to support more rapid and effective diagnosis and treatment. A Pubmed search of reported cases was conducted and five cases of HSVE manifesting with NCSE were found. Each of the cases, including ours, was compared in terms of clinical manifestations and CSF, CT and EEG findings. The clinical manifestations in our patient correlated with those of the other cases. EEG showing sharp fronto-temporo-centro-parietal waves was only observed in our patient. Similar CT manifestations were found in one other patient, normocellular CSF was registered in three other cases and positive PCR for HSV in four patients. Information about the possible clinical manifestations and CT, EEG and CSF findings in patients with HSVE manifesting with NCSE is crucial for a fast diagnosis and successful treatment, leading to higher survival rates and fewer complications and neurological deficits.

Herpes Simplex Virus-2 Encephalitis Complicated with Multiple Cranial Neuritis and Dysautonomia.

Introduction: Herpes simplex encephalitis (HSE) is mainly caused by herpes simplex virus-1 infection (HSV-1). Herpes simplex virus-2 (HSV-2) infection is rare except in neonates or the immune-compromised. Cranial neuritis is rarely reported in association with HSE. This case study in an eleven-month-old followed by a literature review on cranial neuritis in HSE in children is presented due to the rarity of both situations. Case Report: An eleven-month old otherwise healthy infant presented with encephalitis due to HSV-2 infection which was complicated with dysautonomia manifesting as blood pressure fluctuations and tachycardia, and cranial neuritis manifesting as unilateral ptosis and palatal palsy. The clinical presentation of brain stem encephalitis was confirmed by the Magnetic Resonance Imaging findings of hyperintense foci and contrast enhancement in the medulla oblongata. Following treatment with acyclovir, he made a complete recovery. He did not have any clinical or laboratorial evidence suggestive of immune deficiency. Conclusion: HSV-2 infection can occur beyond the neonatal age group even in the absence of immune compromise. The brainstem encephalitis manifesting as cranial neuritis and autonomic dysfunction made a complete recovery.

Opsoclonus-myoclonus syndrome associated with herpes simplex virus infection: a case report.

Purpose: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease that can be associated with autoimmunity, paraneoplastic tumour, infection or unknown aetiology.Methods: We describe a 54-year-old woman who developed severe OMS, with the clinical onset occurring 2 months and 15 days after she experienced dizziness, vomiting and fever related to a herpes simplex virus infection. The patient was treated with hormones and clonazepam, and the symptoms of myoclonus and ataxia disappeared.Results: The patient was followed up for 1 year with no recurrence of symptoms.Conclusions: The case suggests that herpes simplex virus infection is a possible cause of OMS.

An Early Microglial Response Is Needed To Efficiently Control Herpes Simplex Virus Encephalitis.

The role of a signaling pathway through macrophage colony-stimulating factor (MCSF) and its receptor, macrophage colony-stimulating factor 1 receptor (CSF1R), during experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE) was studied by two different approaches. First, we evaluated the effect of stimulation of the MCSF/CSF1R axis before infection. Exogenous MCSF (40 µg/kg of body weight intraperitoneally [i.p.]) was administered once daily to BALB/c mice on days 4 and 2 before intranasal infection with 2,500 PFU of HSV-1. MCSF treatment significantly increased mouse survival compared to saline (50% versus 10%; P = 0.0169). On day 6 postinfection (p.i.), brain viral titers were significantly decreased, whereas beta interferon (IFN-ß) was significantly increased in mice treated with MCSF compared to mice treated with saline. The number of CD68+ (a phagocytosis marker) microglial cells was significantly increased in MCSF-treated mice compared to the saline-treated group. Secondly, we conditionally depleted CSF1R on microglial cells of CSF1R-loxP-CX3CR1-cre/ERT2 mice (in a C57BL/6 background) through induction with tamoxifen. The mice were then infected intranasally with 600,000 PFU of HSV-1. The survival rate of mice depleted of CSF1R (knockout [KO] mice) was significantly lower than that of wild-type (WT) mice (0% versus 67%). Brain viral titers and cytokine/chemokine levels were significantly higher in KO than in WT animals on day 6 p.i. Furthermore, increased infiltration of monocytes into the brains of WT mice was seen on day 6 p.i., but not in KO mice. Our results suggest that microglial cells are essential to control HSE at early stages of the disease and that the MCSF/CSF1R axis could be a therapeutic target to regulate their response to infection.IMPORTANCE Microglia appear to be one of the principal regulators of neuroinflammation in the central nervous system (CNS). An increasing number of studies have demonstrated that the activation of microglia could result in either beneficial or detrimental effects in different CNS disorders. Hence, the role of microglia during herpes simplex virus encephalitis (HSE) has not been fully characterized. Using experimental mouse models, we showed that an early activation of the MCSF/CSF1R axis improved the outcome of the disease, possibly by inducing a proliferation of microglia. In contrast, depletion of microglia before HSV-1 infection worsened the prognosis of HSE. Thus, an early microglial response followed by sustained infiltration of monocytes and T cells into the brain seem to be key components for a better clinical outcome. These data suggest that microglia could be a potential target for immunomodulatory strategies combined with antiviral therapy to better control the outcome of this devastating disease.

Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000-2016.

BACKGROUND: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated. PATIENTS AND METHODS: We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830). RESULTS: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (-0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference -19.8%; 95% CI: -34.7% to -4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: -0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4). CONCLUSION: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.

Acute hemorrhagic leukoencephalitis of Weston Hurst secondary to herpes encephalitis presenting as status epilepticus: A case report and review of literature.

Acute hemorrhagic leukoencephalitis (AHL) is a rare and mostly fatal fulminant demyelinating disease. This case describes a 63-year old male in status epilepticus associated with an intracerebral hemorrhage following a one week viral prodrome with rapid decline to coma. He exhibited peripheral leukocytosis, neutrophilic pleocytosis with normal glucose and high protein in cerebrospinal fluid (CSF). Additionally, CSF was positive for herpes simplex virus (HSV) polymerase chain reaction (PCR). Medical decompression, low-dose dexamethasone, antibiotics and acyclovir were initially given. Magnetic resonance imaging (MRI) was suggestive of AHL, thus he was treated with methylprednisolone 1 g/day for 5 days. The patient improved and was discharged with significant neurologic morbidity. This is the first reported case of AHL in the Philippines presenting as a diagnostic dilemma with a protracted clinical course who responded to high dose intravenous steroids.

Cerebrovascular manifestations of herpes simplex virus infection of the central nervous system: a systematic review.

BACKGROUND: Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). AIM OF THE STUDY: To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. METHODS: Systematic literature review from January 2000 to July 2018. RESULTS: We identified 38 patients (median age 45 years, range 1-73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. CONCLUSION: We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.

Both IRF3 and especially IRF7 play a key role to orchestrate an effective cerebral inflammatory response in a mouse model of herpes simplex virus encephalitis.

The impact of a deficiency in interferon regulatory factor (IRF)3 and IRF7 was evaluated in an herpes simplex virus encephalitis (HSE) model. Compared to wild type (WT), the mortality rates of infected IRF3-/- and IRF7-/- mice were higher and associated with increased brain viral titers. At a critical time post-infection, IRF7-/- mice exhibited a deficit in IFN-ß production. At a later time point, levels of type I IFNs and cytokines were increased in brains of both deficient mice compared to WT. Our results suggest that IRF3, and especially IRF7, are important for an effective control of inflammatory responses during HSE.

Insular cortex lesion and autonomic instability in a herpes simplex virus encephalitis patient.

The cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex, anterior cingulate gyrus, and amygdala. Because the insular cortex often tends to be damaged in patients with herpes simplex virus (HSV) encephalitis, the autonomic instability observed in these patients was suggested to be moderated by an insular cortex lesion. Here, we report the case of a 51-year-old Japanese male who was hospitalized following a collapse 5 days earlier; he was diagnosed as herpes encephalitis. Diffusion-weighted MRI revealed asymmetric right greater hyperintensity throughout his insular cortex and anterior cingulate gyrus. At 1 week after admission, transthoracic echo showed diffuse hypokinesis in the left ventricle (LV). Cardiac 123I-meta-iodobenzylguanidine uptake (123I-MIBG) scintigraphy revealed reduced uptake in the inferior and posterior wall. Electrocardiograhy at rest showed that the coefficient variation of RR intervals (CVR-R) was reduced, and the corrected QT (QTc) interval length was prolonged. In this HSV encephalitis patient, signs of a right insular cortex lesion and autonomic instability were observed: LV hypokinesis, regional reduced 123I-MIBG uptake, decreased CVR-R, and QTc interval prolongation. Our patient's autonomic instability may thus be derived from disrupted autonomic balance due to the right insular cortex lesion.

Burden of herpes simplex virus encephalitis in the United States.

Herpes simplex virus encephalitis (HSVE) is a disease of public health concern, but its burden on the healthcare of United States has not been adequately assessed recently. We aimed to define the incidence, complications and outcomes of HSVE in the recent decade by analyzing data from a nationally representative database. Healthcare Cost and Utilization Project databases were utilized to identify patients with primary discharge diagnosis of HSVE. Annual hospitalization rate was estimated and several preselected inpatient complications were identified. Regression analyses were used to identify mortality predictors. Key epidemiological factors were compared with those from other countries. Total 4871 patients of HSVE were included in our study. The annual hospitalization rate was 10.3 ± 2.2 cases/million in neonates, 2.4 ± 0.3 cases/million in children and 6.4 ± 0.4 cases/million in adults. Median age was 57 years and male:female incidence ratio was 1:1. Rates of some central nervous system complications were seizures (38.4%), status epilepticus (5.5%), acute respiratory failure (20.1%), ischemic stroke (5.6%) and intracranial hemorrhage (2.7%), all of which were significantly associated with mortality. In-hospital mortality in neonates, children and adults were 6.9, 1.2 and 7.7%, respectively. HSVE still remains a potentially lethal infectious disease with high morbidity and mortality. Most recent epidemiological data in this study may help understanding this public health disease, and the patient outcome data may have prognostic significance.