Encephalitis Patients Research Articles

Hippocampal dysfunction after autoimmune encephalitis depending on the antibody type.

Comprehensive neurocognitive function analyses of autoimmune encephalitis (AE) patients, especially long-term ones, are rare. This study aims to measure cognitive function in patients diagnosed with AE. This case-control study included AE patients (n = 11) with antibodies against NMDA receptor (NMDAR) (n = 4), VGKC (n = 3), GAD (3), and one antibody-negative patient. The control group contained 12 pneumococcal meningo-encephalitis patients (PC). Subgroup analyses compared AE patients with and without NMDAR antibodies. Neurocognitive tests were performed to evaluate verbal and visual memory, face recognition, attentional capacity, incidental learning capacity, and overall cognitive function (Montreal cognitive assessment, MoCA). Limbic structural involvement was assessed through magnetic resonance imaging (MRI). Statistical analyses investigated correlations between antibody status, results of neurocognitive tests, and MRI findings. Follow-up (AE vs. PC) was 33 (11-95) vs. 96 (26-132) months after diagnosis. Neurocognitive functions were normal in both AE and PC groups in all tests except face recognition, which was pathological in both groups. The overall/recognition/long-delay visual memory (p = 0.009/0.008/0.005) and incidental learning (p = 0.017) scores were significantly higher in NMDAR patients compared to non-NMDAR patients. Non-NMDAR patients with right-sided limbic MRI pathologies had significantly lower overall/recognition/long-delay visual memory (p = 0.006/0.044/0.024) and incidental learning (p = 0.009) scores compared to NMDAR patients. We observed mainly normal neurocognitive functions after autoimmune and bacterial encephalitis. However, compared to NMDAR patients, patients with non-NMDAR autoimmune encephalitis showed a significant and material-specific association between a right-sided hippocampal lesion and limitations in figural-mnestic and incidental learning capacities. Neurocognitive functions in AE patients should be further evaluated prospectively and in more detail.

P-913. Etiologies, Clinical Characteristics and Prognostic impact of Increased Intracranial Pressure in Adults with Encephalitis

Abstract Background Encephalitis involves symptoms like reduced consciousness and seizures, diagnosed via lumbar puncture and brain imaging. Increased intracranial pressure (ICP) and its effect is well described in meningitis/ventriculitis and serve as poor prognostic factors. Data on ICP in encephalitis is limited, highlighting the need for further research.Table 1.Demographic, Clinical Characteristics, and Initial Presentations of 647 Adults with Encephalitis by Opening Pressure Measurement Status and DegreeAbbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; GCS, Glasgow Coma Scale; MAP, Mean Arterial Pressure; qSOFA, Quick Sequential Organ Failure Assessment. Methods Retrospective study at University of Texas and Johns Hopkins, 2002-2023, on 647 patients over 17 years old with encephalitis. Data analyzed via SPSS software.Table 2.Laboratory Findings, Etiology, and Imaging Results in Encephalitis Patients by Opening Pressure Measurement Status and DegreeAbbreviations: CSF, cerebral spinal fluid; CT, computed tomography; EEG, electroencephalogram; HSV, herpes simplex virus; MRI, magnetic resonance imaging; PMN, polymorphonuclear leukocyte; RBC, red blood cell; VZV, varicella zoster virus; WBC, white blood cell. Results Our study had 647 patients, with ICP measured in 298 (46%). Patients were categorized by ICP levels: < 30mmHg (242) and ≥30mmHg (56). Demographics such as gender, race, and age showed no variance across ICP. Comorbidity profiles were similar, though immunocompromised patients more frequently had ICP measurement (p=0.010). Symptoms like photophobia were uniformly distributed, but seizures and fever were more common in those measured for ICP (p=0.007 & p=0.013). Nuchal rigidity was higher in those with ICP ≥30mmHg (31% vs. 15%, p=0.031). Blood and cerebrospinal fluid analyses did not differ across groups. The leading etiologies identified were viral (32.9%) and autoimmune (18.1%), with no cause specifically linked to elevated ICP. Neuroimaging was more likely to be abnormal in patients with ICP measured (65% vs. 53%, p=0.004). Those with abnormal EEGs were more likely to have ICP measured (82% vs. 74%, p=0.050), but abnormal EEGs were less common in patients with ICP >30mmHg (p=0.008). No differences were found in given treatments like vancomycin, acyclovir, or steroids between ICP groups. ICU admission, vasopressor support, and ventilation needs were comparable, though patients with higher ICP had longer median hospital stays (12 days vs. 10 days, p=0.012) and mechanical ventilation (1.5 days vs. 0 days, p=0.005). Mortality and readmission rates showed no differences, but patients with higher ICP had worse Glasgow Outcome Scale (GOS) scores (61% vs. 46%, p=0.045).Table 3.Management Approaches and Outcomes in Encephalitis Patients Categorized by Opening Pressure LevelsAbbreviations: ICU, intensive care unit; GOS, Glasgow outcome scale. Conclusion This retrospective study on ICP in encephalitis across two centers emphasizes presentation variability and the need for standardized diagnostic and management protocols. Noted differences include ventilation duration, hospital stays, and GOS in patients with higher ICP.Figure 1.Breakdown of 647 cases of encephalitis, categorized by their determined etiologies and ICP measurements. The chart illustrates the distribution across three groups: OP not measured, OP <30mmHg, and OP ≥30mmHg, detailing the total number of cases alongside the percentages for each etiological category, including viral, bacterial, autoimmune, and unknown origins.CMV; Cytomegalovirus, EBV; Epstein-Barr Virus, HSV; Herpes Simplex Virus, JCV; JC Virus, MTB; Mycobacterium tuberculosis NMDA; N-Methyl-D-Aspartate, T. pallidum; Treponema pallidum, VGKC; Voltage-Gated Potassium Channel, WNV; West Nile Virus. Disclosures John Probasco, MD, Genentech: Study site investigator for multicenter study Rodrigo Hasbun, MD MPH FIDSA, Biomeriaux: Grant/Research Support|Biomeriaux: Honoraria

P-918. Rabies encephalitis: Spectrum of MRI findings and predicted probability of abnormality detection based on symptom duration

Abstract Background Rabies is a highly lethal infectious disease and is equivalent to a death sentence for the patient. With currently available tests, the ante-mortem diagnostic sensitivity is only ∼40%. Currently, there are only isolated case reports or small case series exploring the MRI features in rabies encephalitis. T2 TSE showing hyperintensities in bilateral basal ganglia (caudate nucleus, putamen and globus pallidus) and thalamus and corresponding DWI and ADC images showing true diffusion restriction Methods A prospective observational study was designed to explore the patterns of MRI abnormalities in rabies patients. A total of 31 patients were enrolled in the study, out of which 21 underwent Contrast-Enhanced Magnetic Resonance Imaging of Brain and spinal cord. FLAIR/T2 images showing hyperintensities in dorsal brainstem, cervical spinal cord Results Overall, MRI was normal in 10(47.6%) patients, whereas 11(52.4%) patients showed abnormalities. Abnormalities were detected in various brain regions with brainstem, spinal cord and basal ganglia being the most commonly affected regions. Other regions such as the cortex, sub-cortical white matter, limbic system, internal capsule, corona radiata, thalamus, and sub-thalamic region were also involved to varying degrees. Diffusion-weighted-imaging showed typical pattern of diffusion restriction in 6 cases (28.5%). No gadolinium contrast enhancement was observed in any patient. Overall, no significant difference in neuroimaging findings were observed between encephalitic and paralytic forms of rabies. In addition, univariate logistic regression analysis revealed that the likelihood of detecting abnormalities on MRI increases with the duration from the symptom onset. T2 hyperintensity in conus medullaris with contrast enhancing cauda equina nerve roots Conclusion Till date this is the largest prospective study (21 cases) exploring the MRI findings in the patients of rabies encephalitis. The study demonstrated certain patterns of brain imaging in rabies which in the appropriate clinical context could significantly aid in establishing the ante-mortem diagnosis of rabies encephalitis. At the same time, the study also highlights the fact that a normal MRI brain does not rule out the diagnosis and that the probability of finding specific abnormalities on MRI increases as the disease progresses. Univariable logistic regression to estimate predicted probability of appearance of MRI abnormality after appearance of 1st cardinal symptom Disclosures All Authors: No reported disclosures

Comparison of mNGS with conventional methods for diagnosis of cryptococcal meningitis: a retrospective study

The application of metagenomic next-generation sequencing (mNGS) in the diagnosis of cryptococcal meningitis is relatively under characterized. Here, we retrospectively evaluated data from cryptococcal meningitis patients who were tested using mNGS and/or routine testing, including fungal culture, India ink staining, and cryptococcal antigen (CrAg) testing. The performance of mNGS was then assessed. Initial cerebrospinal fluid (CSF) samples were collected from 65 patients with suspected central nervous system (CNS) infection and tested using conventional tests and/or mNGS. mNGS offers a culture-independent approach, facilitating a rapid and unbiased detection of a broad spectrum of pathogens. Patients with bacterial tuberculous or viral meningitis were used as mNGS-positive controls and one autoimmune encephalitis patient was used as an mNGS-negative control. In the 45 patients diagnosed with cryptococcal meningitis, the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of mNGS were 92%, 100%, 100%, 90.9%, and 95.6%, respectively. Compared to conventional methods, the sensitivity of mNGS was slightly lower than CrAg tests (96.7%) but higher than India ink (79.5%) and culturing (63.4%). Of the two negative mNGS cases (2/25, 8.0%), one was positive by India ink staining, culture, and CrAg testing, while the other was positive only by CrAg testing. A combination of mNGS and conventional methods enhanced the detection rate to 100%. Our study demonstrates that both CrAg and mNGS offer excellent diagnostic accuracy for cryptococcal meningitis, and utilizing both tests can enhance clinical assessment and patient management.

The weight of multiple hits: how TBI and infectious encephalitis co-modulate adverse outcomes

ABSTRACT Background Chronic neurologic deficits from traumatic brain injury (TBI) and subsequent infectious encephalitis are poorly characterized. Methods Using TriNetX database we queried patients 18 years or older with a confirmed diagnosis of encephalitis between 2016 and 2024. Patient cohorts included those with a diagnosis of TBI at least one month before encephalitis (N = 1,038), those with a diagnosis of a TBI anytime before encephalitis (N = 1,886), and those with encephalitis but no TBI, (N = 45,210; N = 45,215). A murine model of controlled cortical impact (CCI) injury and Venezuelan equine encephalitis virus (VEEV) infection was used to reflect the clinical model, followed by extracting hippocampal tissue for bulk RNA sequencing and analysis. Results Patients with a TBI history at least one month before infectious encephalitis have an increased risk of mortality, epilepsy, and dementia or delirium. Bulk RNA sequencing of the hippocampus from mice subjected to CCI injury and VEEV infection demonstrated that key pathways, specifically those involved in granzyme mediated cell death, were enriched compared to VEEV infection alone. Conclusion Our findings reveal that infectious encephalitis in patients with TBI history portends worse neurologic outcomes, and the hippocampus may be vulnerable to granzyme mediated cell death under these conditions.

Clinical and radiological characteristics and 1-year self-reported outcomes from patients with encephalitis and coronavirus disease 2019

IntroductionSevere acute respiratory syndrome coronavirus infection is responsible for multisystemic disease and has high transmissibility. It culminated in a pandemic, challenging scientific knowledge and care capacity. Neurological symptoms are highly prevalent, and cases of encephalitis have been described, in both peri- and postinfectious periods. However, pathogenesis and prognosis are unclear. Thus, we aim to describe the clinical findings in cases of encephalitis in patients infected with severe acute respiratory syndrome coronavirus, together with a 1-year follow-up of self-perception of recovery and remaining neuropsychiatric symptoms.MethodsThis is a retrospective observational study in which patients with cerebrospinal fluid collection and a recent diagnosis of severe acute respiratory syndrome coronavirus infection were screened for encephalitis through analysis of medical records. We describe their clinical and paraclinical findings using descriptive statistics, together with their long-term outcome, through a self-assessment questionnaire.ResultsAmong the 135 patients screened, 11 patients were included. Most of them were admitted for neurological symptoms (73%), and in 63% of cases, those symptoms occurred within the first 7 days of systemic symptoms. Most patients had minor pulmonary involvement assessed on chest computed tomography. On cerebrospinal fluid analysis, the most relevant finding was hyperproteinorrachia. Three patients (27%) had positive changes on magnetic resonance studies. In the outcome analysis, most patients (77%) reported gait difficulties and 66% reported memory and concentration problems.ConclusionEncephalitis associated with severe acute respiratory syndrome coronavirus 2 infection is rare but responsible for chronic sequelae in cognitive and motor aspects. The pathophysiology seems to be associated with both the immune-mediated and inflammatory processes, and the low frequency of paraclinical findings demands a high clinical suspicion.

Anti-Tick-Bourne Encephalitis IgM Intrathecal Synthesis as a Prediction Marker in Tick-Borne Encephalitis Patients.

The aim of this study was to evaluate the usefulness of IgM anti-Tick-Borne Encephalitis (anti-TBE) intrathecal synthesis in the diagnosis and prediction of the clinical course of the disease. Thirty-six patients were included in the study (patients reported symptoms such as fever, headache, fatigue, and nausea/vomiting). CRP, White Blood Cells (WBC), pleocytosis, Cerebrospinal Fluid (CSF) protein concentration, CSF albumin concentration, serum IgM, serum IgG, CSF IgM, CSF IgG, IgM Index, IgG Index, and IgG Index/IgM Index ratio were the parameters which were examined in the individuals. An analysis of correlation presented statistical significance between IgM Index and pleocytosis and protein concentration in CSF in the whole group of individuals. IgM Index and IgG Index/IgM Index ratio may be used in the prediction of severity of TBE. The most probable link between the IgM intrathecal production and severity of TBE may be a result of delayed seroconversion to IgG, and therefore not an adequate response to the virus presence.

Clinical features and factors associated with outcomes of antibody-negative autoimmune encephalitis in patients requiring intensive care

Background and objectivesAntibody-negative autoimmune encephalitis (AE) is a form of encephalitis characterized by the absence of detectable autoimmune antibodies, despite immunological evidence. However, data on management of patients with antibody-negative AE in the intensive care unit (ICU) are limited. This study aimed to explore the characteristics and subtypes of antibody-negative AE, assess the effects of immunotherapy, and identify factors independently associated with poor functional outcomes in patients requiring intensive care.MethodsThis retrospective, single-center study analyzed consecutive adult patients diagnosed with antibody-negative AE and admitted to the ICU of a large tertiary hospital between 2019 and 2023. Multivariate regression analysis was used to identify factors linked to poor functional outcomes six months after ICU admission, as defined by a modified Rankin Scale score of 3–6. Generalized linear mixed models were applied to evaluate the effect of immunotherapy on longitudinal changes in the Clinical Assessment Scale in Autoimmune Encephalitis and modified Rankin Scale scores.ResultsOf the 1220 patients with severe encephalitis admitted to the ICU, 107 were diagnosed with antibody-negative AE and included in the analysis. Six months after ICU admission, 67 patients (62.6%) had poor functional outcomes, including 28 deaths (26.2%). Factors independently associated with poor outcomes were high-dose corticosteroid therapy (odds ratio [OR] 8.734, 95% confidence interval [CI] 2.483–30.717), older age at onset (OR 1.063, 95% CI 1.028–1.099), acute respiratory failure at ICU admission (OR 10.931, 95% CI 2.062–57.751), and dyskinesia/dystonia (OR 14.109, 95% CI 1.336–148.957). The generalized linear mixed model also indicated that high-dose corticosteroid therapy was associated with poorer longitudinal outcomes.ConclusionsWhile high-dose corticosteroids are frequently used to treat AE, their risks may outweigh their benefits in severe antibody-negative AE cases. Older patients and those with dyskinesia/dystonia or respiratory failure, may require more careful monitoring and timely intervention for improved outcomes. However, prospective validation of these findings is necessary to confirm their applicability and guide future treatment strategies.

EVALUATION OF GRA6 AS GENETIC MARKER FOR DETERMINING TOXOPLASMA GONDII GENOTYPE IN THE CEREBROSPINAL FLUID OF HIV/AIDS PATIENTS WITH TOXOPLASMIC ENCEPHALITIS.

Toxoplasmic encephalitis is a severe manifestation of Toxoplasma gondii infection, with potentially fatal outcomes, particularly among immunocompromised patients. Clinical manifestation of this infection is associated with a specific genotype of T. gondii, requiring the use of genetic marker for genotype determination. This study critically evaluated the application of GRA6 gene as genetic marker for genotyping T. gondii in cerebrospinal fluid (CSF) samples from HIV/AIDS patients diagnosed with Toxoplasmic encephalitis. The study analyzed 69 CSF samples from HIV/AIDS patients with Toxoplasmic encephalitis. These samples tested positive for Toxoplasma IgG serology and SAG2 PCR, while GRA6 genotyping was conducted using PCR-sequencing methods. The results showed that GRA6 had potential for genotyping in positive control settings from culture cells. However, there was limited effectiveness in CSF samples from Toxoplasmic encephalitis patients. GRA6 had been proven effective as a genetic marker for the identification of T. gondii genotype among HIV/AIDS patients with Toxoplasmic encephalitis. However, the evaluation of GRA6 showed more effectiveness in cultured cells compared to direct clinical samples, such as cerebrospinal fluid obtained from HIV/AIDS patients with Toxoplasmic encephalitis.

Presentation, Management, and Outcome of Tick-Borne Encephalitis in Patients Referred to Infectious Diseases or Neurology

Background: In Slovenia, patients with suspected tick-borne encephalitis (TBE) were historically referred to infectious diseases (ID), but during the COVID-19 pandemic, there were increased referrals to neurology. This study compared the clinical management of TBE patients between ID specialists and neurologists and assessed patients’ outcomes. Methods: We retrospectively reviewed the clinical, laboratory, and imaging data of 318 adult patients with TBE managed by ID (n = 256; 80.5%) and neurology (n = 62; 19.5%) at a tertiary centre in Slovenia between March 2020 and September 2022 to explore variations in diagnostic and therapeutic approaches by specialty and to assess the severity and outcome of acute illness. Results: Patients referred to ID or neurology did not differ regarding their basic demographic and epidemiologic characteristics or basic laboratory parameters. However, patients referred to neurology more often presented with severe illness, including impaired consciousness and/or focal neurological signs (72.6% vs. 55.5%; p < 0.001). ID specialists used head imaging before lumbar puncture (6.6% vs. 64.5%; p < 0.001), performed microbiological tests other than for TBE (16.0% vs. 51.6%; p < 0.001), and empirically prescribed antimicrobials less often than neurology (5.1% vs. 22.6%; p < 0.001). When adjusting for age, sex, comorbidities, vaccination status, and the severity of acute illness, clinical outcomes were similar between the two groups of patients, but those with more severe acute illness had higher odds for incomplete recovery. Conclusions: Differences in clinical presentation between ID and neurology referrals could only partially explain the narrower diagnostic and therapeutic approach used by ID, which, given the study design, was not associated with adverse outcomes. Additionally, in patients with clinical characteristics suggestive of TBE in endemic areas, tremor in the absence of other focal neurological signs or impaired consciousness may not necessitate head imaging before lumbar puncture. Future prospective studies could help to optimise the management of this clinical syndrome.

Metagenomic next-generation sequencing of cerebrospinal fluid: a diagnostic approach for varicella zoster virus-related encephalitis.

Varicella zoster virus-related encephalitis (VZV-RE) is a rare and often misdiagnosed condition caused by an infection with the VZV. It leads to meningitis or encephalitis, with patients frequently experiencing poor prognosis. In this study, we used metagenomic next-generation sequencing (mNGS) to rapidly and accurately detect and identify the VZV pathogen directly from cerebrospinal fluid (CSF) samples, aiming to achieve a definitive diagnosis for encephalitis patients. In this retrospective study, we analyzed the clinical characteristics and laboratory evaluations of 28 patients at the Harrison International Peace Hospital in Hebei, China, between 2018 and 2024. These patients were diagnosed with neurological disorders using mNGS techniques applied to CSF. In this cohort of 28 patients, 11 were females and 17 males, with a median age of 65 (IQR: 42.3-70). VZV-RE presented with a range of clinical manifestations, the most common being headaches (81.2%), fever>38°C (42.9%), and vomiting (42.9%). Less frequent symptoms include personality changes (10.7%), speech impairments (21.4%), cranial nerve involvement (21.4%), altered consciousness (17.9%) and convulsions (3.6%). Herpes zoster rash was observed in 35.7% of the cases. Neurological examination revealed nuchal rigidity in only 5 patients. CSF analysis indicated mild pressure and protein levels increase, with all patients having negative bacterial cultures. Abnormal electroencephalogram (EEG) findings were noted in 10.7% (N=3), and encephalorrhagia on Magnetic Resonance Imaging (MRI) was observed in 3.6%. VZV-RE was confirmed through mNGS analysis of CSF within three days of admission. All patients received empiric treatment with acyclovir or valacyclovir, with 21.4% receiving hormonotherapy, and 7.14% receiving immunoglobulin therapy. At the three-month follow-up, 10.7% of the patients had persistent neurologic sequelae, and the mortality rate was 3.6%. Performing mNGS on CSF offers a rapidly and precisely diagnostic method for identifying causative pathogens in patients with VZV central nervous system (CNS) infections, especially when traditional CNS examination results are negative. Furthermore, the cases reported highlight the positive therapeutic effect of ganciclovir in treating VZV infections.

Short Communication: Coinfection of Japanese Encephalitis and Scrub Typhus in Acute Encephalitis Patients in North India.

Background: Acute encephalitis syndrome (AES) is a significant public health issue in India, attributed to various etiologies. In eastern Uttar Pradesh, Japanese encephalitis (JE) was the leading cause of AES (10-14% of total AES) until scrub typhus (ST), caused by Orientia tsutsugamushi, was identified in cerebrospinal fluid and blood samples of AES patients contributing more than 60% of AES cases. This study investigates the prevalence of JE-ST coinfection and compares clinical outcomes among JE mono-infection, ST mono-infection, and JE-ST coinfection. Materials and Methods: AES cases admitted to BRD Medical College, Gorakhpur, Uttar Pradesh, India, from January 1, 2017, to December 31, 2017, were included. JE and ST diagnosis was confirmed by serological (IgM) and molecular (PCR) tests. Statistical analysis was done to correlate clinical outcomes and infection group. Results: Total 1180 cases were tested positive for JE and/or ST. The prevalence of JE-ST coinfection was 8.9% among AES cases. JE mono-infection showed a mortality rate of 34.5%, ST mono-infection 13.4%, and JE-ST coinfection 9.5%. JE-ST co-infected cases experienced less severe clinical outcomes compared to mono-infected cases. Conclusion: JE-ST coinfection in AES cases is relatively common, with better clinical outcomes and lower mortality rates compared to JE or ST mono-infections.

Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria.

We describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis. Medical records of neural-IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006-December 31, 2022) were reviewed. Ninety-eight patients (57 male) were included. Median age of symptom onset was 51 years (range, 8 months-85 years). Frequent presenting features were ≥1: diplopia (80%), ataxia (78%), dysarthria (68%), vestibulocochlear symptoms (67%), dysphagia (61%), nausea/vomiting (42%), and facial weakness (32%). Altered mental status (11%) was uncommon. Neural antibodies detected were as follows: KLHL-11 (26 patients), GAD65 (high titer, 12), ANNA-1 (anti-Hu, 8), ANNA-2 (anti-Ri, 8), Ma2 (7), IgLON-5 (6), AQP4 (6), MOG (4), glycine receptor (4), GQ1B (4), PCA-1 (anti-Yo, 4), DPPX (2), neurochondrin (2), neurofilament (2), NMDA-R (2), AGNA-1 (SOX-1, 1), ANNA-3 (DACH1, 1), amphiphysin (1), CRMP-5 (1), ITPR-1 (1), PCA-Tr (DNER, 1), and PDE10A (1). Cancer was identified in 55 patients: germ cell (23 patients; 3 extra-testicular), ductal breast adenocarcinoma (8), small cell carcinoma (6, lung 4), adenocarcinomas (6), neuroendocrine carcinoma (3), hematologic (2), squamous cell (2), and other (7). Median modified Ranking score (mRS) at last follow-up was 3 (range, 0-6). Factors associated with poor outcome included abnormal brain MRI, bulbar symptoms, and elevated CSF IgG index. Kaplan-Meier analysis revealed faster progression to wheelchair in patients who were immunotherapy refractory and with elevated CSF IgG index. Diagnostic criteria for autoimmune brainstem encephalitis (definite and probable) are proposed. Autoimmune brainstem encephalitis is a distinct clinical subphenotype of autoimmune encephalitis. Abnormal brain MRI, bulbar symptoms, and elevated CSF-IgG index associate with poor outcome.

To analyze the efficacy and safety of plasma exchange in the treatment of anti-NMDA receptor encephalitis.

To investigate the clinical efficacy and safety of plasma exchange (PE) in the treatment of glucocorticoid-insensitive patients with serum anti-N-methyl-d-aspartate (anti-NMDA) receptor antibody-negative and serum anti-NMDA receptor antibody-positive encephalitis. The clinical data of 20 patients with anti-NMDA receptor antibody encephalitis treated between January 2015 and December 2022 were collected. The general information, clinical symptoms, auxiliary examination, treatment (hormone, PE, etc.), adverse reactions, clinical efficacy, and other related data were retrospectively compared and analyzed. A total of 8 cases had adverse reactions (9.76%, 8/82), including 4 cases (4.88%, 4/82) of allergy and 2 cases (2.44%,2/82) of thrombocytopenia. In patients with anti-NMDA receptor antibody encephalitis who were not sensitive to glucocorticoids, the effective rate of PE was 80.0% (p = 0.0005). PE combined with glucocorticoid is more effective than glucocorticoid alone in the treatment of anti-NMDA receptor antibody encephalitis patients with positive or negative anti-NMDA receptor antibodies. Most adverse reactions were mild and easy to manage. It does not cause obvious blood cell loss. PE is a safe and acceptable treatment. However, our study has limitations, and due to the small number of people and the fact that plasmapheresis was performed after glucocorticoid therapy, further prospective clinical studies are warranted.

Recent advances in autoimmune encephalitis.

Since the description of autoimmune encephalitis (AE) associated with N-methyl-D-aspartate receptor antibodies (anti-NMDARE) in 2007, more than 12 other clinical syndromes and antibodies have been reported. In this article, we review recent advances in pathophysiology, genetics, diagnosis pitfalls, and clinical phenotypes of AE associated with cell surface antibodies and anti-GAD associated neurological syndromes. Genetic studies reported human leukocyte antigen (HLA) associations for anti-LGI1, anti-Caspr2, anti-IgLON5, and anti-GAD. Follow-up studies characterized cognitive dysfunction, psychiatric symptoms, sleep disorders, and adaptative behavior dysfunction, mainly for anti-NMDARE. Late-onset anti-NMDARE and anti- GABA-B receptor (GABA-BR) encephalitis patients were described to have worse prognoses and different tumor associations. Additionally, the clinical spectrum of anti-LGI1, anti-AMPAR, anti-CASPR2, and anti-IgLON5 was expanded, comprising new differential diagnoses. The diagnostic criteria for AE were adapted to the pediatric population, and a diagnostic algorithm was proposed, considering potential mimics and misdiagnosis. We also review the limitations of commercial assays for AE and treatment recommendations, as well as clinical scales for short and long-term assessment of AE patients, along with cognitive evaluation.

Establishment of an Early Prediction Model for Severe Fever With Thrombocytopenia Syndrome-Associated Encephalitis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease primarily transmitted by ticks. The development of encephalitis in SFTS patients significantly increases the risk of adverse outcomes. However, the understanding of SFTS-associated encephalitis (SFTSAE) is still limited. This study aimed to identify the clinical characteristics of SFTSAE and develop a predictive model for early detection. We retrospectively collected data from 220 SFTS patients admitted to Nanjing Drum Tower Hospital between May 2019 and January 2024. The patients were first randomly divided into a training set (154 people, 70%) and a validation set (66 people, 30%). The patients in the training set were divided into SFTSAE and non-SFTSAE groups according to the presence of encephalitis. A prediction model was constructed using the training set: important clinical parameters were selected using univariate logistic regression, and then multivariate logistic regression was performed to determine the independent risk factors for SFTSAE. A prediction model was constructed using these independent risk factors. Finally, the validation set was used to verify the predictive ability of the model. Age, C-reactive protein, d-dimer, and viral load were independent risk factors for SFTSAE (p < 0.05). A nomogram containing these four indicators was constructed, and the predictive performance of the nomogram was evaluated using the ROC curve. The AUC of the model was 0.846 (95% confidence interval [CI]: 0.770-0.921), which had good predictive ability for SFTSAE. Conclusion: The overall mortality rate of SFTS patients was 17.53%, and the mortality rate of encephalitis patients was 50%. Old age, high C-reactive protein, elevated d-dimer, and high viral load were independent risk factors for SFTSAE. The nomogram constructed based on these four indicators had good predictive ability and could be used as an evaluation tool for clinical treatment.

Efficacy of ofatumumab combined with corticosteroids in the treatment of autoimmune encephalitis: a 6-month cohort study.

This study investigated the efficacy of ofatumumab (OFA) combined with corticosteroids in autoimmune encephalitis (AE) patients refractory to conventional treatment. Eighteen AE patients admitted to Ruijin Hospital between June 2022 and September 2023 received four subcutaneous 20-mg OFA injections at 0, 1, 6, and 12 weeks combined with standard corticosteroid therapy. Clinical symptoms, modified Rankin scale (mRS) scores, Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, serum immunoglobulin (Ig) levels (IgG and IgM), and peripheral blood CD20 + B cell levels were documented before OFA administration and at 1, 2, 6, 12, and 24 weeks post-treatment. OFA treatment significantly improved psychiatric symptoms (P = 0.025), cognitive dysfunction (P = 0.008), and seizure frequency (P = 0.014). The mRS and CASE scores improved after two injections in patients with anti-NMDAR encephalitis (P = 0.041), but not in patients with anti-LGI1 encephalitis (P > 0.05). The mRS scores significantly improved at 12 weeks post-treatment in antibody-negative encephalitis. Blood CD20 + B cell levels dropped to zero after an average of 2.5 injections. No significant changes could be observed in serum IgG and IgM levels (P > 0.05). Seven patients had mild fever or pulmonary infections post-treatment. This study suggests that OFA is a safe and effective treatment for a subset of AE patients, particularly in cases of anti-NMDAR encephalitis, though further research is needed on long-term outcomes and recurrence.

Comparative analysis of European subtype tick-borne encephalitis virus strains isolated from patients from Eastern Siberia and Eastern and Northern Europe

Background. Isolation of strains from tick-borne encephalitis (TBE) patients proved that the European subtype tick-borne encephalitis virus (TBEV-Eur) in Siberia is involved in regional human infectious pathology and causes a clinical picture similar to Western TBE. However, a comparative analysis of the genomes of TBEV-Eur strains isolated from TBE patients in Eastern Siberia and Europe has not been carried out.The aim. Genome comparative analysis and search for virulence determinants in TBEV-Eur strains isolated from patients in Eastern Siberia and Northern and Eastern Europe.Materials and methods. In current work, TBEV-Eur strain 1G-98 from the collection of Scientific Сentre for Family Health and Human Reproduction Problems (GenBank Acc. No. KY069119) was used. The analysis also included all complete genome sequences of TBEV-Eur strains from patients submitted in GenBank database at the time the study began. Complete genome sequencing of strain 1G-98 was performed using the Sanger method. The virulence of the strain was assessed by intracerebral and subcutaneous infection of laboratory mice.Results. It has been shown that, according to the coding region of the genomes, the level of differences between TBEV-Eur strains from Siberia does not exceed the previously established maximum for this subtype of 3.1 %. The strain 1G-98, isolated from the blood of TBE patient from the Irkutsk region demonstrated high cerebral and peripheral activity. In this strain, D67G mutation in E protein DII domain was revealed, which could potentially be associated with virulence, and a long deletion in the variable part of the 3’-noncoding genome region, comparable in length to the highly virulent strain Hypr from Europe was found.Conclusions. For the first time, a comparative analysis of the genomes of TBEV-Eur strains from TBE patients from the Asian part of Russia and Europe was carried out showing their genetic similarity, and potential virulence determinants were identified. Key words: tick-borne encephalitis virus, European subtype, genome, amino acid sequence, virulence determinants

West Nile virus encephalitis: Clinical characteristics and a comparison to other infectious encephalitides

PurposeTo compare functional outcomes and help differentiate between important causative agents of acute infectious encephalitis in adults, focusing on West Nile virus encephalitis (WNVE). MethodsThe electronic database of Tel Aviv Medical Center was screened for patients admitted during 2010–2020 with acute encephalitis. Additionally, patient laboratory results during the same period were screened for CSF samples positive for common pathogens causing encephalitis. The main patient groups were compared in terms of clinical characteristics and functional outcomes. ResultsOne hundred and five infectious encephalitis patients were identified. WNVE patients (n = 31) and VZV encephalitis (VZVE) patients (n = 31) were older than HSV1 encephalitis (HSV1E) patients (n = 15) (median ages 73, 76, 51, respectively). WNVE patients had a more prominent inflammatory profile. CSF characteristics significantly differed between groups, with an extreme mononuclear white blood cell predominance in VZVE patients (median 98%).Functional outcomes at discharge were significantly worse in WNVE patients (median modified Rankin Scale score 4 at hospital discharge, 2.5 at last follow-up) when compared with HSV1E patients (2.5, 1, respectively) and VZVE patients (1.5, 1, respectively). ConclusionIn odds with previous reports, WNVE and VZVE in this study were far more prevalent than HSV1E. Differences in clinical characteristics could prove clinically useful early in encephalitis, including an association of WNVE with a relatively prominent inflammatory profile (somewhat resembling a bacterial infection) and an extreme mononuclear white blood cell predominance in VZVE. The detrimental outcome of WNVE emphasizes the need to advance research on WNV infection.

Association of ovarian teratoma with anti-N-methyl-D-aspartate receptor encephalitis: a case report and narrative review.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a potentially life-threatening autoimmune disorder which is strongly associated with ovarian teratomas in young female patients. The primary aim is to highlight the importance of considering NMDAR encephalitis in the differential diagnosis of young female patients presenting with acute or subacute neuropsychiatric symptoms, especially when accompanied by ovarian teratomas. This case report and literature review detail the presentation, diagnosis, and treatment of a 35-year-old G4P3 Indigenous woman who initially presented with neuropsychiatric symptoms and fever, having a history of extensive drug and alcohol use. Misdiagnosed initially, the patient's lack of response to standard treatments led to further investigations, revealing paraneoplastic anti-NMDAR encephalitis secondary to a left ovarian teratoma. The report examines the treatment regimen followed, including prednisolone, intravenous immunoglobulin, rituximab injections, and laparoscopic bilateral salpingo-oophorectomy. This case underscores the critical need for increased clinical vigilance for anti-NMDAR encephalitis in patients, particularly young females, presenting with neuropsychiatric symptoms and potential ovarian teratomas. The literature review accompanying the case report provides valuable insights into the presentation, diagnosis, and management of this complex condition. Lastly, this study emphasised the diagnostic challenges inherent in paraneoplastic neuropsychiatric syndromes, advocating for a multidisciplinary approach in similar clinical scenarios.