Radiological Features of Herpetic Encephalitis in Children.

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 R2 = 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 R2 = 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.

The importance of MRI in the acute phase of herpes encephalitis mimicking an acute ischemic stroke.

The diagnosis of herpes simplex encephalitis (HSE) can present challenges for neurologists and neuroradiologists due to its variable clinical presentation and atypical radiological features. Brain magnetic resonance imaging (MRI) plays a crucial role by identifying some mimicking conditions, including ischemic strokes, through the accurate interpretation of specific sequences. This report highlights a case of misdiagnosed HSE, aiming to discuss the management of similar cases and underscore the relevance of MRI in the emergency setting.

Anti-metabotropic glutamate receptor 5 encephalitis: Five case reports and literature review.

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.

Epilepsy following herpes simplex encephalitis - A case series.

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.

Contribution of diffusion-weighted imaging to distinguish herpetic encephalitis from auto-immune encephalitis at an early stage.

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.

Neurosyphilis Mimicking Herpes Simplex Encephalitis on Magnetic Resonance Imaging: A Case Report.

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.

Granulomatous Herpetic Encephalitis A Possible Role for Inflammasomes.

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.

Herpetic encephalitis: which treatment for which body weight?

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.

MRI changes and expressions of neuron-specific enolase and monocyte chemoattractant protein-1 in cerebrospinal fluid in patients with severe herpes simplex virus encephalitis.

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.

Temporal subcortical T2 hypointensity on MRI in epilepsia partialis continua, a non ketotic hyperglycemia rather than herpes encephalitis.

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.

Atypical imaging presentation of herpes simplex virus encephalitis in paediatric immunocompromised oncology patients.

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.

Subacute Herpes Simplex Type 1 Encephalitis: Case Report With Literature Review.

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.

Long-term sequelae of herpes simplex virus encephalitis-related white matter injury: correlation of neuropsychological outcome and diffusion tensor imaging.

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.

Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis.

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.

Diagnosis and Therapy of Infectious Encephalitis in Children: A Ten-Years Retrospective Study.

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.