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Neonatal infection with herpes simplex virus (HSV) is associated with significant morbidity, high mortality, and long-term neurological sequelae. We report the clinical case of an infant with HSV encephalitis, where the initial diagnosis was established based on cranial ultrasound (CUS) findings. These findings revealed localized, asymmetrically distributed hyperechoic areas in the parenchyma and signs of brain swelling. CUS dynamics on days 7 and 14 after the onset of clinical symptoms demonstrated multiple subcortical and perivascular zones of encephalomalacia in the right hemisphere, accompanied by ex vacuo ventricular dilatation. The cerebellum, left basal ganglia, and left hemisphere appeared to be less affected by the pathological process., (© 2024 Wiley Periodicals LLC.)

Background: Herpes simplex virus encephalitis (HSE) frequently triggers secondary anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), but markers predicting the occurrence of this entity (HSE-NMDARE) are lacking., Methods: We conducted a retrospective description of patients with HSE-NMDARE diagnosed between July 2014 and August 2022 and compared them to both patients with regular forms of HSE and NMDARE., Results: Among the 375 patients with NMDARE, 13 HSE-NMDARE were included. The median age was 19 years (0.5-73), 4/13 (31%) were children < 4 years old, and 7/13 (54%) were male. The median time between HSE and NMDARE onset was 30 days (21-46). During NMDARE, symptoms differed from HSE, including increased behavioral changes (92% vs 23%, p = 0.008), movements disorders (62% vs 0%, p = 0.013), and dysautonomia (54% vs 0%, p = 0.041). Compared to 21 patients with regular HSE, patients with HSE-NMDARE more often achieved severity-associated criteria on initial MRIs, with extensive lesions (11/11, 100% vs 10/21, 48%, p = 0.005) and bilateral diffusion-weighted imaging sequence abnormalities (9/10, 90% vs 6/21, 29%, p = 0.002). Compared to 198 patients with regular NMDARE, patients with HSE-NMDARE were more frequently males (7/13, 54% vs 43/198, 22%; p = 0.015) and children < 4 (4/13, 31% vs 14/198, 7%; p = 0.016), with a worse 12-month mRS (2[1-6] vs 1[0-6], p = 0.023)., Conclusions: Herein, patients with HSE-NMDARE have a poorer long-term prognosis than patients with regular NMDARE. We report a greater rate of severity-associated criteria on initial MRIs for HSE-NMDARE compared to regular HSE, which may help identify patients with higher risk of HSE-NMDARE., (© 2024. The Author(s).)

Herpes simplex virus (HSV) infections necessitate careful management of urinary dysfunction and retention, which are underestimated conditions. Here, we present a rare case of HSV encephalomyeloradiculitis in a 76-year-old man, whose initial symptoms included urinary dysfunction and retention that alone lasted for approximately 1 week. Unlike in meningoencephalitis, high fever and headache were absent; however, the patient subsequently developed cauda equina syndrome and consciousness disturbance. Gadolinium-enhanced spinal MRI suggested enhanced cauda equina at the L2/3 level. Upon admission, he was treated for meningoencephalitis with acyclovir and steroid pulse therapy. Subsequent cerebrospinal fluid analysis result was positive for HSV DNA. A ‍brain MRI conducted 1 week after admission displayed high-intensity lesions in the white matter of the right temporal lobe, confirming HSV encephalomyeloradiculitis. These treatments were highly effective and gradually improved the patient's condition. He was discharged 1 month after hospitalization, and the urinary catheter was removed 2 weeks later. HSV infections can cause life-threatening encephalomyeloradiculitis. Therefore, both neurologists and urologists must pay attention to their occurrence and characteristics in clinical settings.

Sinus arrest and inappropriate sinus bradycardia are sinus node dysfunction (SND), which cause loss of consciousness. Cardiac pacing is recommended in patients with symptoms, such as syncope or dizziness. Several conditions can induce these arrhythmias; however, whether or not intracranial infectious diseases, such as herpes simplex encephalitis (HSE), can cause secondary SND is unclear. We encountered a patient with sinus arrest and transient sinus bradycardia associated with HSE. Since cardiac pause was never monitored and the bradycardia improved after HSE treatment, HSE was suspected to be the cause of SND. Although the underlying mechanisms have not yet been completely elucidated, HSE may cause secondary SND.

Background: Nonspecific clinical manifestations and unclear radiological features may delay treatment initiation in pediatric patients with Herpes simplex encephalitis (HSE). The aim of this study is to analyze the clinical and radiological features of the disease., Methods: Clinical, laboratory, and magnetic resonance imaging (MRI) data were obtained retrospectively from a group of 37 hospitalized pediatric patients older than two months and with a polymerase chain reaction-confirmed HSE diagnosis. Clinical severity (i.e., mechanical ventilatory support) and outcome at discharge (i.e., pediatric modified Rankin Scale [ped-mRS]) were also assessed., Results: Median age was 14 months (interquartile range: 10-36). All patients survived, 15 (41%) had complete recovery (i.e., ped-mRS = 0), and 10 (27%) had significant residual disability at discharge (i.e., ped-mRS ≥3). Brain MRI was obtained in 31 patients. T2-hyperintense lesions were usually bilateral (28, 90%) and multifocal (30, 97%). Hemorrhage and mass effect were observed in 13 (42%) and 15 (48%) patients, respectively. Parenchymal lesions involved the temporal lobes (94%), insula (90%), parietal lobes (84%), and frontal lobes (61%). Occipital lesions were rare. In multivariable binary logistic regression models the presence of altered consciousness was associated with mechanical ventilation (odds ratio [OR] = 8.2, Nagelkerke R 2  = 0.22), whereas the involvement of the occipital lobes (OR = 7.8) and the administration of vasopressors (OR = 12.1) were independent predictors of poor outcome (Nagelkerke R 2  = 0.41)., Conclusions: Brain MRI is useful for diagnosis and outcome assessment in pediatric HSE. Radiological patterns with common frontotemporal involvement overlap adults, but multifocal and parietal lobe abnormalities are observed as well., Competing Interests: Declaration of competing interest Thai Son Pham, Federico Montini, Hoang Nhat Pham, Minh-Thu Nguyen Tran, and Tien Huy Nguyen report no disclosures. Laura Cacciaguerra received speaker and consultant honoraria from ACCMED, Biomedia, Roche, BMS Celgene, and Sanofi and travel support for conferences by Merck Serono. Massimo Filippi is Editor-in-Chief of the Journal of Neurology, is Associate Editor of Human Brain Mapping, Neurological Sciences, and is Associate Editor of Radiology. He received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, and Sanofi; for speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; for participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, and Takeda; and for scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, and Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To describe the clinical and radiological characteristics of anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis., Methods: We reviewed the clinical data of five patients with anti-mGluR5 encephalitis, and performed a literature review., Results: The five cases included a 52-year-old man who developed a biphasic course of anti-mGluR5 encephalitis after herpes simplex encephalitis, a 22-year-old woman who showed bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI), and a 36-year-old man with mixed aphasia and generalized tonic-clonic seizures, a 51-year-old man presented with personality changes, hallucinations, delusions, sleeping disorders and a 58-year-old man with short-term memory deficits and absence seizures.. There are 16 reported cases of anti-mGluR5 encephalitis worldwide. Of all 21 patients, with a median onset age of 35 years old, the main neurological symptoms were cognitive impairment (85.7%, 18/21), psychiatric or behavior problems (76.2%, 16/21), seizures (57.1%, 12/21), sleeping disorders (52.4%, 11/21), different degrees of decreased consciousness (42.9%, 9/21), and movement disorders (23.8%, 5/21). Brain MRI was normal in 11 of 21 patients. Lesions of the limbic lobes were presented in 5 patients, while involvement of other extralimbic regions was also reported. Seven of 21 (33.3%) cases were combined with tumors. Elevated white blood cell counts or specific oligoclonal IgG bands in the cerebrospinal fluid were found in 18 of 21 patients, with marked improvements observed after immunotherapy., Discussion: Patients with anti-mGluR5 encephalitis typically present with diffuse, rather than purely limbic, encephalitis. Anti-mGluR5 encephalitis can be triggered by herpes simplex encephalitis. The risk of a combined tumor may be reduced in anti-mGluR5 encephalitis patients., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: To determine whether diffusion-weighted imaging (DWI) can help to distinguish early stage autoimmune (AI) and herpes simplex virus (HSV) encephalitides., Methods: This case-control study included patients from a multi-center cohort of AI encephalitides whose initial MRI including DWI was performed within ten days after symptoms onset. They were compared with patients with HSV encephalitis enrolled prospectively in a single-center from June, 2020 to December, 2020. The final diagnosis of AI encephalitis required a positive autoantibody assay, and that of HSV encephalitis required a positive HSV polymerase chain reaction based on cerebrospinal fluid. Brain MRI were evaluated for restricted diffusion, fluid-inversion recovery (FLAIR) abnormalities, lesion topography, hemorrhagic changes, and contrast enhancement., Results: Forty-nine patients were included of which, 19 (38.8%) had AI encephalitis. Twenty-seven patients (55.1%) were males and the median age was 46.0 years (interquartile range (IQR):[22.0; 65.0]). Brain MRI were performed after a median of 4 days (IQR:[2.0; 7.0]) of symptom onset and time between symptom onset and MRI was not significantly different (p = 0.60). Twenty-six patients had restricted diffusion lesions in the medial temporal lobe, including 25/30 in the HSV encephalitis group (p < 0.001). FLAIR abnormalities were observed in 36 patients, including 29/30 in the HSV encephalitis group (p < 0.001). Lesion topography, hemorrhagic changes, and contrast enhancement did not differ significantly between the two groups., Conclusion: Our results suggest that restricted diffusion lesions in the medial temporal lobe are a hallmark of HSV encephalitis and may help distinguish it from early-stage AI encephalitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Herpes simplex encephalitis (HSE) is associated with severe mortality and morbidity. Its incidence is estimated at 1:250 000, and the typical symptomatology of acute disease including headaches, mental state disturbances, confusion, sleepiness, and seizures. The chronic phase of the disease is occasionally characterized by epilepsy and neurological deficits., Study Rationale: The present retrospective single-center study aims to identify risk factors for predicting the development of epilepsy (epileptogenesis) following HSE., Methods: Medical records were screened for patients older than 18 years, hospitalized between January 2005 and September 2019 with a diagnosis of "encephalitis" and "herpes simplex virus, HSV" infection. HSE diagnosis was based on an analysis of the cerebrospinal fluid with positive HSV testing results., Results: Twenty-three patients fit our inclusion criteria: fever and behavioral changes, followed by seizures, were reported in 58.3 % of patients. On follow-up (59.7 ± 38.8 months), eight patients (34.8 %) developed epilepsy. Pathological imaging and EEG were correlated with acute symptomatic seizures (ASS). ASS was associated with an 8-fold risk increase to develop post-encephalitis epilepsy (PE). PE was associated with younger age but not with CSF results, imaging, or EEG., Conclusion: Our retrospective single-center study on PE, following HSE, shows that younger age and ASS were associated with PE. Brain imaging, CSF analysis, and EEG were not associated with the development of epilepsy following HSE., Competing Interests: Conflicts of Interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of this research was to analyze the MRI changes and the expression of neuron-specific enolase (NSE) and monocyte chemoattractant protein-1 (MCP-1) in cerebrospinal fluid (CSF) of patients with severe herpes simplex encephalitis. For this purpose, 68 patients with severe herpes simplex virus encephalitis diagnosed and treated in our hospital from April 2020 to April 2021 were selected as the study objects of the study group. In addition, 68 healthy people who underwent normal physical examinations in our hospital were selected as the control group at the same time. They were examined by magnetic resonance imaging (MRI) within one week after the study group was enrolled. CSF samples were collected one week after the onset of the disease in the study group and 2-4 days after the first spinal anesthesia in the control group, Enzyme linked immunosorbent assay (ELIEA) was used to detect the expression of NSE and MCP-1 in cerebrospinal fluid of the two groups, and the linear correlation between NSE and MCP-1 were analyzed. Results showed that compared with the control group, the expression of NSE and MCP-1 in the cerebrospinal fluid of the study group increased significantly (P<0.05). The expression of NSE and MCP-1 in patients with severe herpes simplex encephalitis in a coma was significantly higher than that in patients without severe herpes simplex encephalitis in a coma (P<0.05). NSE and MCP-1 were positively correlated (r=0.597, P=0.001). NSE and MCP-1 were risk factors for severe herpes simplex encephalitis, and the difference was statistically significant (P<0.05). In conclusion, magnetic resonance imaging of patients with severe herpes simplex encephalitis is characterized by multiple lesions in the temporal lobe, insula, and frontal lobe base (especially the marginal system involved) with unilateral or bilateral asymmetric distribution, and abnormal high expression of NSE and MCP-1 in the cerebrospinal fluid of such patients, which has important value in the early diagnosis of this disease.

Purpose: Hyperglycemia can present as many neurological problems, one of them is seizure. Different brain MRI features can be seen in focal seizures associated with nonketotic hyperglycemia that subcortical T2 hypointensity is the only characteristic one. Finding this MRI feature is highly valuable in early diagnosis and treatment., Methods: Our patient was a 60-year-old female, a case of type 2 diabetes mellitus. She was brought to Emergency Room (ER) with focal colonic status epilepticus of right face and arm associated with confusion and drowsiness progressed over 2 weeks prior to admission. At first, acyclovir was started alongside anti-seizure medication with doubt of herpes encephalitis but antiviral was discontinued after normal LP result and characteristic MRI features., Results: Subcortical T2 hypointensity in left temporal and insular lobe was seen on first MRI that was resolved on follow up MRI after she was treated., Conclusion: Epilepsia partialis continua in the setting of non ketotic hyperglycemia should be differentiated from that in herpes encephalitis in a diabetic patient presenting with subacute confusional state and focal status epilepticus considering characteristic MRI finding of subcortical T2 hypointensity.

Introduction: We aim to assess the imaging manifestations of brain involvement in paediatric immunocompromised patients with haematological malignancies on chemotherapy presenting with encephalitis and positive HSV CSF PCR. We also aim to determine whether our findings are similar or different to those described in literature for paediatric patients in general., Methods: A retrospective study was performed in paediatric ALL/lymphoma patients on chemotherapy, and cases with positive CSF HSV-PCR with at least one head MRI scan were included. On imaging, location(typical/atypical), post-contrast enhancement and haemorrhage/diffusivity/gliosis were evaluated., Result: A total of 28 scans were included in study from 16 patients fulfilling inclusion criteria, 12 (75%) HSV-1 and 4 (25%) HSV-2. Of the 16 initial scans (CT n = 10, MRI n = 6), 11 were normal (CT = 7, MRI = 4). Fourteen patients had follow-up MRI, of which two had normal scans. On the abnormal initial scan (5/16), only 20% had typical medial temporal/inferomedial frontal/cingulate involvement. Most had frontal (80%), parietal (60%) and non-medial temporal (40%) lesions. Abnormal diffusivity/haemorrhage was absent in all, and postcontrast enhancement was seen in 20%. On follow-up, more patients (33%) had typical medial temporal/inferomedial frontal/cingulate involvement. Widespread atypical site involvement of frontoparietal (75%), thalamus (58%), non-medial temporal (50%), occipital/basal ganglia (33%) and cerebellum (8%) was noted. Most lesions were cortical (91%)/subcortical (75%) with few periventricular lesions (58%). Few showed abnormal diffusivity (16%), post-contrast parenchymal enhancement/haemorrhage (8%), post-contrast meningeal enhancement (25%) and gliosis (16%)., Conclusion: Immunocompromised paediatric patients with haematological malignancies have widespread atypical brain involvement in herpes simplex encephalitis with lack of diffusion restriction and post-contrast enhancement, likely due to haematogenous spread of HSV across the blood-brain barrier, lack of cellular immunity and limited inflammatory cytokine response., (© 2021 The Royal Australian and New Zealand College of Radiologists.)

Background: Prognosis of herpetic encephalitis remains severe, with a high proportion of deaths and sequelae. Its treatment is based on acyclovir, but the precise and most effective modalities of this treatment are not established. The objective of this study was to determine them., Methods: For this, we carried out a descriptive, retrospective, monocentric study, using the current coding database at Marseille University Hospitals. Cohort was intended to be exhaustive for the disease, from January 2000 to June 2019, including patients hospitalized in intensive care and conventional hospitalization sector. Patients (n = 76) included were at least 16 years of age and had a clinical presentation, cerebral Magnetic Resonance Imaging, and/or electroencephalogram abnormalities consistent with herpetic encephalitis confirmed by a positive HSV-PCR in the CSF. Clinical data and treatment, including the doses actually administered to the patient, were compared according to patient's outcome., Results: The mortality rate was 12%, whereas 49% had complete recovery and 39% sequelae impeding independence. Poor outcome was statistically associated with persistence of confusion, aphasia, and impaired consciousness lasting more than 5 days, superinfection, status epilepticus, and length of stay in intensive care unit. A statistical decision tree, constructed using the Classification And Regression Tree model, to prioritize treatment management, showed two main factors that influence the outcome: the patient's weight, and the average daily acyclovir dose actually administered., Conclusion: These results suggest to modify acyclovir management in herpetic encephalitis, for low-weight patients (< 79 kg) with a minimum dosage of 2550 mg/day (850 mg/ 8 h), when possible., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

BACKGROUND Neurosyphilis is a central nervous system infection caused by Treponema pallidum, that can develop at any time after the initial infection. The clinical signs of neurosyphilis are very variable, as well as its radiological features, and it is a diagnostic challenge. Knowledge of clinical symptoms and correct laboratory diagnostics, combined with routine radiological examination and additional diagnostic tools, such as high-resolution, three-dimensional FLAIR sequence, T2-weighted, and T1-weighted contrast-enhanced magnetic resonance imaging (MRI) are key to making an accurate diagnosis of neurosyphilis. CASE REPORT We present the clinical case of a patient who presented a 1-year history of vague clinical symptoms and was misdiagnosed with herpes simplex virus (HSV) encephalitis. Initial head MRI revealed extensive cerebral white matter lesions with cortical contrast enhancement, mainly of anterior and medial parts of the left temporal lobe, as typically seen in HSV encephalitis. Empirical therapy with acyclovir was started until a diagnosis of syphilis was confirmed with laboratory findings. Later, the therapy was changed to penicillin G. The patient's condition improved after receiving targeted treatment. A control MRI scan was performed, and previously detected changes in the brain had decreased significantly. CONCLUSIONS MRI is the imaging of choice to support the diagnosis of neurosyphilis. Our findings suggest that neuroimaging can play an important role in indicating suspicion of syphilitic encephalitis. Enhancement of the anterior and medial parts of the temporal lobe is an atypical imaging finding, and it can simulate an infection with HSV. Early treatment is critical to a positive outcome.

Background: Granulomatous herpetic encephalitis is a rare inflammatory complication of acute herpes simplex encephalitis., Methods: We describe 3 cases of granulomatous herpetic encephalitis in children arising between 1 to 10 years after the initial presentation with acute herpes simplex encephalitis. We focus on the clinical course and neuroimaging phenotype with a discussion of possible mechanisms underpinning this entity., Results: The clinical course was highly variable. However, the dominant neuroimaging phenotype in each of our cases was that of confluent gyriform cortical enhancement with predominantly solid foci of enhancement in the subjacent white matter +/- deep gray nuclei. Cerebrospinal fluid was negative for herpes simplex virus DNA in all cases. All 3 cases required brain biopsy to help establish the diagnosis., Conclusions: Increased recognition of granulomatous herpetic encephalitis in children will facilitate earlier diagnosis and treatment. Although the exact role played by the host immune response, genetics, and environment in determining the different outcomes of herpes simplex encephalitis remains to be determined, we postulate a role for inflammasome dysregulation in this entity.

Introduction: The typical herpes simplex viral encephalitis (HSVE) course is an acute illness, less commonly it may present as a chronic course, mainly in children, and rarely may it be subacute. Subacute HSVE is rarely described in the literature being reported 4 times only., Case Report: We here report 2 cases of subacute HSV1 encephalitis diagnosed based on cerebrospinal fluid polymerase chain reaction and magnetic resonance imaging findings and review the literature trying to find any specific clinical, laboratory, radiologic diagnostic or prognostic criteria regarding this subacute form of HSVE., Conclusion: There is subacute form of HSVE and should be suspected with any subacute febrile illness with nonspecific cognitive impairment even in the absence of focal neurological symptoms and in cases with rapidly progressive dementia. This form has similar radiologic finding and good response to acyclovir but carry even better prognosis than that the acute HSVE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The pathophysiology of the memory impairment following Herpes Simplex virus encephalitis is not yet established and understood. This study attempts to elucidate the role of white matter injury and its impact on neuropsychological outcome in patients with history of Herpes Simplex virus encephalitis. This is a single-institution prospective study assessing 9 patients and 15 matched controls utilizing a combination of MRI with diffusion tensor imaging and neuropsychological testing. Tract-based spatial statistics analysis was performed and correlated with neuropsychological outcomes. Significantly decreased fractional anisotropy (FA) values were noted in corpus callosum, corona radiata, left posterior thalamic radiation, cingulum, superior longitudinal fasciculus, fornix, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinated fasciculus. Impaired facial recognition significantly correlated with reduction in FA of right uncinate fasciculus, right inferior longitudinal fasciculus, and splenium genu of corpus callosum. FA value of left cingulum significantly correlated with logical memory, auditory verbal learning. FA value of fornix correlated with visual recognition; FA value of left uncinate fasciculus with auditory verbal learning and delayed recall. In conclusion, this study demonstrates microstructural abnormalities involving several white matter tracts corresponding to neuropsychological deficits., (© 2021. Journal of NeuroVirology, Inc.)

Competing Interests: None

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting., Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission., Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020., Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission., Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale., Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions)., Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Background: Infectious encephalitis represents a rare but potentially severe clinical condition. However, limited international data are available in pediatric age., Methods: We conducted a retrospective study to review (a) the clinical presentation; (b) laboratory, radiology, and neurophysiology findings; (c) the correlations between these exams and outcome; and (d) the therapy performed., Results: Fifty-six patients were enrolled [22 female (39.6%), mean age 4.7 years, IQR 0.7-8.7 years], 19.6% presented neurologic sequelae. HSV was the single most frequently isolated pathogen (19.6%), although in most cases, the etiology remained undefined. 41.1% children presented prodromal before the development of neurologic signs. Fever was the most frequent constitutional symptom (83.9% of cases). Cerebrospinal fluid was normal in 48.5% of cases and electroencephalograpy in 24.5% cases. Brain computed tomography scans was normal in 33 (91.7%) cases, while cerebral magnetic resonance imaging (MRI) showed pathologic findings in 62.5% of cases. MRI was the only parameter associated with neurologic sequalae [P = 0.01; OR, 8.1 (95% CI: 1.52-42.84)]., Conclusions: Pediatric encephalitis is a heterogeneous entity with nonspecific clinical and laboratory findings, with undefined etiologies in most times. MRI can play a primary role, both on a diagnostic and prognostic point-of-view, and its role should be implemented and made more accessible. Further studies are needed to define the exact role and timing of steroids., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Herpes simplex virus encephalitis (HSE) is the most common sporadic fatal encephalitis. Although timely administered acyclovir treatment decreases mortality, neuropsychiatric sequelae is still common among survivors. Magnetic resonance imaging is frequently utilized for the diagnosis of HSE, which typically involves temporal lobe(s) and can be mixed with brain tumors involving the same area. Here, we report a case of HSE, who received acyclovir with a delay of 90 days because of presumptive tumor diagnosis and survived with minimal sequelae.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (AE) is a common cause of nonviral infectious encephalitis, which can be triggered by herpes simplex virus infection. Previous studies have shown that approximately 27% of herpes simplex encephalitis (HSE) patients produce anti-NMDAR antibodies within 3 months. Immunotherapy is recommended in this situation, but some symptoms usually remain in the 1-year follow-up., Case Presentation: A previously healthy 23-year-old Chinese young woman developed epileptic attack followed by psychiatric symptoms of confusion and irritation as well as cognitive deficits. Brain MRI showed hyperintense lesions of the right temporal lobe on DWI and T2 without contrast enhancement effects. Twenty-one days of acyclovir was administered based on the primary diagnosis of HSE. The anti-NMDAR antibody (IgG) was detected positively on day 11 after disease onset. She had improved cognitive function but suffered another grand mal epilepsy after the first course of intravenous immunoglobulin (IVIG) therapy combined with 1000 mg intravenous methylprednisolone. After discussion, another course of IVIG was started for 5 days. Her symptoms were well controlled with only mild cognitive deficits at the 1-year follow-up (mRS = 1)., Conclusions: Our case indicated that anti-NMDAR antibodies could develop earlier after HSE compared with previous data from adults. We suggested detecting AE antibodies simultaneously with each CSF analysis. Meanwhile, the second course of IVIG therapy was reasonable when symptoms were not controlled after the first course of IVIG combined with IV steroid treatment.

Objective: Herpes 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., Methods: We 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., Results: Of 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., Conclusion: Cerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Current guidelines for severe herpes simplex virus infection recommend 21 days of intravenous therapy. The thrice-daily administration of intravenous acyclovir makes it challenging to deliver as outpatient therapy. We describe 2 cases with confirmed or presumed neonatal herpes simplex virus encephalitis treated with acyclovir administered as a continuous-infusion at home and review the pharmacologic and clinical evidence for continuous infusions of acyclovir.

Case Report: We describe the case of a 73-year-old woman who was diagnosed with herpes simplex virus-1 encephalitis during the COVID-19 pandemic. The diagnosis was somehow delayed because relatives were initially cautious in bringing the patient to the hospital and, here, the work-up focus was on coronavirusrelated aspects as the patient was initially reputed to be infected with COVID-19., Conclusions: During the current viral outbreak, physicians should not neglect the possibility of other diseases that represent neurological emergencies and require immediate recognition and treatment.

A 71-year-old man presented with sudden onset, generalized tonic-clonic seizures and altered mental status. Initial brain magnetic resonance imaging was normal but a brain FDG-PET scan showed hypermetabolism in the left ventral striatum and septal area. Initial cerebrospinal fluid (CSF) examination showed mildly elevated protein but herpes simplex virus (HSV) polymerase chain reaction (PCR) was negative. A repeat CSF examination performed 9 days later showed a positive HSV PCR. Histopathological and immunohistochemical examination of autopsy specimen confirmed the presence of CD45+ lymphocytes and HSV antigen, suggesting the presence of both inflammation and viral infection corresponding to PET abnormality.

Background and Purpose: Early diagnosis and treatment of herpes simplex encephalitis are crucial to reduce morbidity and mortality. Our aim was to investigate the role of 3D pseudocontinuous arterial spin-labeling in herpes simplex encephalitis., Materials and Methods: From 2014 to 2019, seventeen consecutive patients with herpes simplex encephalitis and 15 healthy volunteers were recruited in the study. Conventional MR imaging and 3D pseudocontinuous arterial spin-labeling were performed in all subjects. According to the disease duration, the lesions were classified into 3 groups, including acute, subacute, and chronic stages, respectively. Clinical, neuroradiologic, and follow-up features were studied. The normalized lesion/normal tissue CBF values of lesions at different stages were measured and compared with those in the control group, respectively., Results: Compared with the control group, herpes simplex encephalitis demonstrated hyperperfusion in 11 acute cases and 6 subacute cases and hypoperfusion in 6 chronic cases. The mean normalized lesion/normal tissue CBF values of the lesions were 2.68 ± 0.54 in the acute stage, 2.42 ± 0.52 in the subacute stage, and 0.87 ± 0.30 in the chronic stage, respectively. The mean normalized lesion/normal tissue CBF values of acute and subacute lesions were significantly higher than those of the control group (1.33 ± 0.08; P < .001, respectively), while the mean normalized lesion/normal tissue CBF values of chronic lesions were lower than those of the control group ( P < .05). Gradual perfusion reduction on serial 3D pseudocontinuous arterial spin-labeling was observed in herpes simplex encephalitis after effective therapy., Conclusions: Conventional MR imaging remains most helpful in the diagnosis of herpes simplex encephalitis, while 3D pseudocontinuous arterial spin-labeling could be an adjunctive technique by providing dynamic CBF features at different stages in herpes simplex encephalitis., (© 2019 by American Journal of Neuroradiology.)

Background: The inflammatory or non-inflammatory changes caused by the virus entering the nervous system and related tissues are central nervous system virus infections. Viral infection is a common infectious disease of the central nervous system, of which herpes simplex virus encephalitis is the most common. However, conventional laboratory techniques to detect an infectious agent are difficult to achieve etiological diagnosis., Case Presentation: Here we present a patient with severe and progressive encephalitis, requiring diagnosis of the specific pathogen to guide clinical treatments., Conclusions: Application of next-generation sequencing provided a quick and definite diagnosis of the etiology of encephalitis and enabled our patient to be treated appropriately.

Purpose: Herpes simplex virus (HSV) encephalitis continues to be the most common form of sporadic lethal encephalitis worldwide. The wide spectrum of clinical presentations and laboratory findings often poses a diagnostic challenge for physicians which might delay administration of life-saving therapy with acyclovir. Atypical presentations of HSV encephalitis have become increasingly prevalent with better diagnostic techniques and have not been well studied., Methods: We retrospectively evaluated all consecutive PCR-proven HSV encephalitis cases treated at the Hospital of the Ludwig-Maximilians-University in Munich, Germany from January 1, 2013 to February 28, 2018., Results: We included 18 patients with PCR-proven HSV encephalitis. The most common clinical features were altered mental status (77.8%), focal neurologic deficits (72.2%) and fever (72.2%). Remarkably, four of these patients (22.2%) had a normocellular cerebrospinal fluid (CSF) on admission. Electroencephalography and magnetic resonance imaging abnormalities were highly sensitive for HSV encephalitis independent of CSF cell count. Striking atypical findings on MRI were extensive global brain swelling and severe brainstem involvement in single patients. Of note, initial CT scans were normal in 11 out of 16 patients (68.8%). All patients were treated with acyclovir. Three patients still developed a clinical deterioration under therapy with acyclovir with one patient requiring decompressive craniotomy due to bilateral space-occupying temporal lobe hemorrhage. 94.4% of the patients survived but only 38.9% were discharged with a good clinical outcome (Glasgow Outcome Score = 5)., Conclusion: Atypical presentations of HSV encephalitis seem to be more common than previously thought and physicians should apply a high level of clinical suspicion and a low threshold to initiate life-saving acyclovir therapy in suspected cases.

The case is a 64-year-old male who had a past history of herpes simplex virus encephalitis (HSE) two years prior to his admission. He was admitted to our hospital due to severe pneumonia and sepsis. Several days later, he developed HSE again. It has been known that immunosuppressive state called immune paralysis occurs in the patient with sepsis due to the amplification of anti-inflammatory responses after the initial hyper-inflammatory phase, which increases the susceptibility to various latent viruses including herpes simplex virus. In the present case, we consider that the severe infection may trigger the recurrence of HSE through the viral reactivation due to immune paralysis. When we see a patient suffering from severe infection who had a past history of HSE, we should keep in mind that such a patient may have a risk of the recurrence of HSE.

Isotretinoin can have significant adverse reactions on multiple systems. We report a unique case of pseudotumour cerebri and herpes encephalitis resulting due to isotretinoin. A 19-year-old female patient was admitted to our clinic, presenting with headache, nausea, vomiting and fever since three days. She had used isotretinoin for the last two months. The patient's neurological examination revealed the presence of neck stiffnes and a body temperature of 39,0◦C. MRI showed high signal localized to the temporal lobe and insula on the right and widened cerebrospinal fluid signal intensity on either side of the optic nerve. Electroencephalogram sharp and wave paroxysms on the right temporo-parietal region. Lumbar puncture showed an opening pressure of 320 mm H2O. The cerebrospinal fluid displayed the presence of 4-5 lymphocytes. On these grounds, the diagnosis of pseudotumour cerebri and herpes encephalitis was made. It is thus suggested that the physicians must keep in mind that pseudotumour cerebri and herpes encephalitis are possible adverse effects of isotretinoin.

Purpose of Review: This article discusses meningitis and encephalitis infections caused by viruses, excluding herpes family and human immunodeficiency virus (HIV)., Recent Findings: The viral infections of the nervous system detailed in this article have no specific treatment other than supportive care. However, many of the viruses discussed are highly preventable by vaccination, proper skin protection against transmitting vectors, and postexposure prophylaxis., Summary: While meningitis and encephalitis caused by viruses may have some clinical overlap, the management and outcomes can be highly disparate, making distinction between the two imperative. Furthermore, despite their relative rarity in terms of clinical disease, many of the viral infections discussed herein are highly preventable. Given the morbidity and mortality attached to such infections, provider and patient education are the best approach available to prevent these potentially devastating illnesses.

Background: Herpes simplex encephalitis can trigger autoimmune encephalitis that leads to neurological worsening. We aimed to assess the frequency, symptoms, risk factors, and outcomes of this complication., Methods: We did a prospective observational study and retrospective analysis. In the prospective observational part of this study, we included patients with herpes simplex encephalitis diagnosed by neurologists, paediatricians, or infectious disease specialists in 19 secondary and tertiary Spanish centres (Cohort A). Outpatient follow-up was at 2, 6, and 12 months from onset of herpes simplex encephalitis. We studied another group of patients retrospectively, when they developed autoimmune encephalitis after herpes simplex encephalitis (Cohort B). We compared demographics and clinical features of patients who developed autoimmune encephalitis with those who did not, and in patients who developed autoimmune encephalitis we compared these features by age group (patients ≤4 years compared with patients >4 years). We also used multivariable binary logistic regression models to assess risk factors for autoimmune encephalitis after herpes simplex encephalitis., Findings: Between Jan 1, 2014, and Oct 31, 2017, 54 patients with herpes simplex encephalitis were recruited to Cohort A, and 51 were included in the analysis (median age 50 years [IQR 5-68]). At onset of herpes simplex encephalitis, none of the 51 patients had antibodies to neuronal antigens; during follow-up, 14 (27%) patients developed autoimmune encephalitis and all 14 (100%) had neuronal antibodies (nine [64%] had NMDA receptor [NMDAR] antibodies and five [36%] had other antibodies) at or before onset of symptoms. The other 37 patients did not develop autoimmune encephalitis, although 11 (30%) developed antibodies (n=3 to NMDAR, n=8 to unknown antigens; p<0·001). Antibody detection within 3 weeks of herpes simplex encephalitis was a risk factor for autoimmune encephalitis (odds ratio [OR] 11·5, 95% CI 2·7-48·8; p<0·001). Between Oct 7, 2011, and Oct 31, 2017, there were 48 patients in Cohort B with new-onset or worsening neurological symptoms not caused by herpes simplex virus reactivation (median age 8·8 years [IQR 1·1-44·2]; n=27 male); 44 (92%) patients had antibody-confirmed autoimmune encephalitis (34 had NMDAR antibodies and ten had other antibodies). In both cohorts (n=58 patients with antibody-confirmed autoimmune encephalitis), patients older than 4 years frequently presented with psychosis (18 [58%] of 31; younger children not assessable). Compared with patients older than 4 years, patients aged 4 years or younger (n=27) were more likely to have shorter intervals between onset of herpes simplex encephalitis and onset of autoimmune encephalitis (median 26 days [IQR 24-32] vs 43 days [25-54]; p=0·0073), choreoathetosis (27 [100%] of 27 vs 0 of 31; p<0·001), decreased level of consciousness (26 [96%] of 27 vs seven [23%] of 31; p<0·001), NMDAR antibodies (24 [89%] of 27 vs 19 [61%] of 31; p=0·033), and worse outcome at 1 year (median modified Rankin Scale 4 [IQR 4-4] vs 2 [2-3]; p<0·0010; seizures 12 [63%] of 19 vs three [13%] of 23; p=0·001)., Interpretation: The results of our prospective study show that autoimmune encephalitis occurred in 27% of patients with herpes simplex encephalitis. It was associated with development of neuronal antibodies and usually presented within 2 months after treatment of herpes simplex encephalitis; the symptoms were age-dependent, and the neurological outcome was worse in young children. Prompt diagnosis is important because patients, primarily those older than 4 years, can respond to immunotherapy., Funding: Mutua Madrileña Foundation, Fondation de l'Université de Lausanne et Centre Hospitalier Universitaire Vaudois, Instituto Carlos III, CIBERER, National Institutes of Health, Generalitat de Catalunya, Fundació CELLEX., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that usually arises in the context of severe immunosuppression but has incompletely understood etiology, limiting effective treatments., Case Description: We present the case of an 81-year-old immunocompetent man who developed a PCNSL in the right temporal lobe, at the site of a remote episode of herpes simplex virus (HSV) encephalitis 8 years prior. There are numerous viruses with known oncogenic associations; however, to our knowledge, this is the first reported case of PCNSL with an antecedent HSV infection., Conclusions: We discuss this case in the context of our current understandings of the pathogenesis of HSV encephalitis and PCNSL and postulate mechanisms through which the 2 could be associated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune disease. This is the first report of a case of autoimmune GFAP astrocytopathy after herpes simplex viral encephalitis (HSVE). A 35-year-old female patient presented with a combination of headache, fever, seizure and psychiatric/behavioral abnormalities. She had GFAP-IgG in both serum and cerebrospinal fluid (CSF). Magnetic resonance imaging (MRI) with gadolinium-enhancement revealed linear enhancement oriented radially to the ventricles. After treatment with corticosteroids, her symptoms were alleviated, the lesions enhancement reduced, and the immunoreactive intensity of GFAP-IgG decreased. This case shows an observational link between HSVE and autoimmune GFAP astrocytopathy, suggesting that autoimmune GFAP astrocytopathy may provide a new differential diagnosis for relapsing HSVE., (Copyright © 2018 Elsevier B.V. All rights reserved.)