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Introduction: Acute viral encephalitis syndrome including dengue encephalitis (DE) is an important tropical illness with a guarded prognosis. The cerebral blood flow may be affected in acute viral encephalitis. Transcranial Doppler (TCD) sonography can quantitatively determine intracranial vascular flow dynamics in acute viral encephalitis. Aim: We aimed to investigate the intracranial blood flow characteristics in patients with DE and compare with nondengue acute viral encephalitis patients. Materials and Methods: In this prospective study, all the cases of acute viral encephalitis including dengue were enrolled over 18 months and followed up at 3 months. TCD was performed to determine the mean velocity pulsatility index (PI) and resistive index (RI) across the middle cerebral artery, anterior cerebral artery, posterior cerebral artery (PCA), vertebral artery, and basilar artery and compared it among dengue versus nondengue group as well as outcome at 3 months. Results: Out of 39 patients, 19 were diagnosed with DE, whereas 20 patients suffered from the nondengue group. The elevated PI and RI in the left PCA were found to statistically significant (P = 0.001 and 0.008, respectively) in the DE group. There was no significant difference in any other TCD indices in any other vessel among both the groups. In addition, an initial low Glasgow Outcome Scale (GOS) and higher brain imaging abnormality were significantly associated with poor GOS of

Acute disseminated encephalomyelitis (ADEM) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) involving the spinal cord and white matter of the brain, usually affecting children and young adults after vaccination or an infection. Neuropsychiatric manifestations are common but are less frequently reported in literature. This case details a young man with no previous comorbidities, who presented with a range of neuropsychiatric manifestations including blank stares, catatonic-like symptoms, selective mutism, irritability, aggression, and visual hallucination. Magnetic resonance imaging showed focal abnormal signal intensity at the splenium of the corpus callosum, notably mildly hypointense on T1W, hyperintense on T2W/FLAIR with restricted diffusion on ADC/DWI. Minimal patchy enhancement was noted postcontrast. Subtle T2/FLAIR hyperintensities were also seen involving the right medial thalamus. He was diagnosed with monophasic ADEM and initiated on intravenous methylprednisolone 1 g daily; however, he developed potential steroid-induced psychosis and was subsequently changed to orodispersible olanzapine and intravenous immunoglobulin (IVIG) 0.4 g/kg/h for 5 days to which he responded satisfactorily. This case report highlights the importance of treating ADEM with steroids and immunoglobulins as it can result in high psychiatric and physical morbidity and mortality if untreated early.

Encephalitis and acute disseminated encephalomyelitis (ADEM) are often caused or triggered by viruses—but the specific pathogen commonly remains unidentified in routine care. We explored the use of viral metagenomic next-generation sequencing (mNGS) in addition to PCR testing of non-invasive stool samples to see if unbiased testing could potentially increase diagnostic yield. To identify specific clinical cases at the point of care, we took advantage of a previously published digital app allowing instant clinical case classification based on consensus case criteria, the VACC-Tool. This hospital-based prospective digital surveillance program assessed 100 pediatric patients (mean age: 11 years, range: 0.15–17.85; 49% male) with case-confirmed encephalitis and/or ADEM. Analysis of case classification at the point of care revealed that in routine care, 96% of confirmed encephalitis/ADEM cases had been missed. Overall agreement of routine care diagnoses with digital encephalitis/ADEM case classification was n = 8) and enterovirus infection (n = 5). Use of mNGS increased the yield of virus detection by 77% (n = 23 virus hits). Specifically, mNGS identified 10 additional virus species beyond herpes- and enteroviruses. Of the additional 23 virus hits detected with mNGS, PCR confirmation was possible post hoc in 14 cases (61%). Linking digital case classification, mNGS, and PCR testing may not be feasible in routine care at this point but may help to provide hints to the pathogenesis of encephalitis/ADEM in childhood, warranting further research and exploration.

Objective To summarize the clinical characteristics of patients with anti- contactin - associated protein 2 (CASPR2) antibody-associated encephalitis. Methods and Results Total 13 patients diagnosed and treated for anti-CASPR2 antibody-associated encephalitis at The Third Affiliated Hospital, Sun Yat-Sen University from August 2017 to August 2022 were collected. Initial manifestations: 9 patients exhibited limbic system symptoms, 2 patients presented with peripheral nerve symptoms (both with limb pain), one patient had cerebellar ataxia, and one patient had limb weakness. Anti - CASPR2 antibody detection: all the 13 patients underwent serum anti- CASPR2 antibody testing, which was positive in all cases; 10 patients underwent cerebrospinal fluid (CSF) anti-CASPR2 antibody testing, with 5 cases testing positive; 3 patients had other concomitant positive autoimmune antibodies. Head MRI examination: among the 13 patients, 2 patients head T2 - FLAIR showed hyperintensity in the medial temporal lobes either unilaterally or bilaterally; 2 patients had cerebral microbleeds. Treatment: 2 patients were treated only with steroids, 4 patients received only intravenous immunoglobulin (IVIg), 5 patients were treated with steroids and IVIg, one patient received rituximab only, and one patient received a combination of IVIg, steroids, protein A immunoadsorption and rituximab. Follow-up: follow-up ranged from 1-5 years, with 2 patients lost to follow - up; one patient relapsed after self - discontinuation of medication and achieved a modified Rankin Scale (mRS) score of 0 after treatment; of the remaining 10 patients, one patient showed no symptom improvement, one patient had some symptoms preventing normal life, 6 patients had normal life, 2 patients died. Conclusions Anti-CASPR2 antibody-associated encephalitis has complex clinical characteristics, and serum antibody testing is crucial for diagnosis.

Objective To report and analyze the clinical features of the first documented case in China of anti-neurofilament heavy chain (NfH) antibody-associated encephalitis. Methods and Results A 63-year-old female presented with cognitive impairment, recurrent epileptic episodes, and aphasia. Head MRI showed multiple abnormal signals in bilateral frontal and parietal lobes, and slight swelling in some gyri, dilatation of the supratentorial ventricular system and brain atrophy, especially in bilateral temporal lobes and hippocampus. 18F-DPA714 PET/MRI showed abnormal uptake in multiple brain regions in the frontal, temporal, parietal and occipital lobes, suggesting neuroinflammation in the brain. EEG showed frequent epileptiform discharges. Cerebrospinal fluid white cell count and glucose were elevated. Serum and cerebrospinal fluid antibodies related to autoimmune encephalitis were negative. Serum tissue-based indirect immunofluorescence assay showed cerebellar neurofilament-like fluorescence surrounding Purkinje cells, further detection of neurofilament protein-related antibodies, it suggested high titer of serum NfH-IgG (1∶1000). The patient was diagnosed with anti-NfH antibody-associated encephalitis. After treatment with intravenous immunoglobulin and methylprednisolone, the prognosis was improved. Conclusions Anti-NfH antibody - associated encephalitis is a rare and clinically complex condition. The myriad of symptoms complicates early diagnosis and differential identification. Early initiation of immunomodulatory therapy may offer prognostic advantages.

Abstract Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020–December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms.

Abstract Background Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1–2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). Objective To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. Methods This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. Results Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. Conclusion This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported. Case presentation A 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis. Conclusion This case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly.

Abstract Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection.

We presented a case of a 66-year-old female whose initial symptom was headache without obvious inducement. The patient's condition progressed rapidly to a semi-coma state after symptomatic treatment. The 18F-FDG PET/CT scan revealed circular FDG hypermetabolism and central metabolic defect of the pons and left frontal lobe lesions. The combination of clinical findings, MRI, and Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid led to the diagnosis of Balamuthia mandrillaris encephalitis. The patient died 5 days after discharge.

Objective To summarize the clinical features of infection - associated autoimmune encephalitis (IAE) with different antibodies in Xinjiang region, and to explore the diagnostic value of relevant laboratory indicators for IAE. Methods A total of 47 patients with IAE diagnosed and treated in People's Hospital of Xinjiang Uiger Autonomous Region from January 2018 to October 2023 were enrolled, including 18 cases (38.30%) of anti - leucine - rich glioma - inactivated 1 (LGI1) antibody - associated encephalitis, 16 cases (34.04%) of anti - N - methyl - D - aspartate receptor (NMDAR) encephalitis, 8 cases (17.02%) of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated encephalitis, and 5 cases (10.64%) of anti-γ -aminobutyric acid receptor type B (GABABR) encephalitis. Social demographic data, clinical manifestations, laboratory and other examinations were collected, and receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of relevant laboratory indicators for IAE. Results The age of onset (χ2 = 9.500, P = 0.023), myasthenia (χ2 = 9.967, P = 0.019), vision loss (χ2 = 9.967, P = 0.019) and seizures (χ2 = 8.046, P = 0.045), cerebrospinal fluid (CSF) white blood cell count (χ2 = 15.237, P = 0.002) and chloride (F = 4.156, P = 0.011) in patients with anti - LGI1 antibody - associated encephalitis, anti - NMDAR encephalitis, anti - MOG antibody - associated encephalitis and anti - GABABR encephalitis were statistically significant. The age of onset in patients with anti-LGI1 antibody-associated encephalitis was larger than that in patients with anti-NMDAR encephalitis (Z = - 2.384, P = 0.017) and anti- MOG antibody-associated encephalitis (Z = - 2.420, P = 0.016). The CSF white blood cell count in patients with anti - NMDAR encephalitis was higher than that in patients with anti - LGI1 antibody - associated encephalitis (Z = - 3.307, P = 0.001) and anti-MOG antibody-associated encephalitis (Z = - 2.835, P = 0.005). CSF chloride was higher in patients with anti-NMDAR encephalitis (t = 3.159, P = 0.007) and anti-GABABR encephalitis (t = - 4.592, P = 0.007) than in patients with anti-LGI1 antibody-associated encephalitis. ROC curve showed that the area under the curve (AUC) of age of onset for diagnosis of anti-LGI1 antibodyassociated encephalitis was 0.722 (95%CI: 0.569-0.875, P = 0.012), the sensitivity was 0.556, the specificity was 0.821, and the cut-off value was 54.50 years old. The AUC of CSF white blood cell count in the diagnosis of anti-LGI1 antibody-associated encephalitis was 0.706 (95%CI: 0.558-0.855, P = 0.019), the sensitivity was 0.889, the specificity was 0.571, and the cut-off value was 4.50 × 106/L. The AUC in the diagnosis of anti - NMDAR encephalitis was 0.790 (95%CI: 0.643-0.937, P = 0.002), the sensitivity was 0.600, the specificity was 0.967, and the cut-off value was 13.50 × 106/L. The AUC of CSF chloride for the diagnosis of anti-LGI1 antibody-associated encephalitis was 0.748 (95%CI: 0.598-0.898, P = 0.005), with a sensitivity of 0.722 and a specificity of 0.714, and a cut-off value of 122.70 mmol/L. Conclusions IAE with different antibodies in Xinjiang region has specific clinical features. Age of onset, CSF white blood cell count and chloride have important value in the diagnosis of anti-LGI1 antibody-associated encephalitis, and CSF white blood cell count has important value in the diagnosis of anti-NMDAR encephalitis.

Objective To summarize the clinical characteristics of Vogt-Koyanagi-Harada syndrome (VKHS) combing with meningitis/encephalitis patients. Methods and Results The clinical data of the inpatients of Beijing Tongren Hospital, Capital Medical University from January 2009 to December 2022 with VKHS combing with meningitis/encephalitis were retrospectively analyzed. A total of 23 patients were included in the study, of which 20 patients (86.96%) had neurological symptoms, with headache being the most common (19 cases, 82.61%), 11 patients (47.83%) had increased cerebrospinal fluid (CBF) pressure, 14 patients (60.87%) had increased CBF white blood cells, and 11 patients (47.83%) had increased CBF protein. The brain MRI mainly showed white matter demyelination (8/14 cases). Optic nerve MRI showed inflammatory lesions of optic nerve and optic papilla (12/14 cases). The visual evoked potential (VEP) mainly showed prolonged latency (10/16 cases). The optical coherence tomography (OCT) showed retinal exudation (8/15 cases) and retinal neurocortical detachment (7/15 cases). The main results of fundus photography were disc edema (17/18 cases). The main manifestation of fundus fluorescein angiography (FFA) was uveitis (9/15 cases). After intravenous hormone and intravenous immunoglobulin (IVIg) treatment, 14 patients were followed up, and neurological symptoms were completely relieved, 11 patients had good visual prognosis, and 3 patients had no obvious visual improvement. Conclusions VKHS might present with meningitis/encephalitis symptoms, and the CSF characteristics of these patients were similar to those of viral meningitis. For those with early suspicions of VKHS, CBF examination and imaging examination might assist in early diagnosis and treatment.

Abstract Background There are few thorough studies assessing predictors of severe encephalitis, despite the poor prognosis and high mortality associated with severe encephalitis. The study aims to evaluate the clinical predictors of mortality and poor outcomes at hospital discharge in patients with severe infectious encephalitis in intensive care units. Method In two Chinese hospitals, a retrospective cohort study comprising 209 patients in intensive care units suffering from severe infectious encephalitis was carried out. Univariate and multivariate logistic regression analyses were used to identify the factors predicting mortality in all patients and poor outcomes in all survivors with severe infectious encephalitis. Results In our cohort of 209 patients with severe encephalitis, 22 patients died, yielding a mortality rate of 10.5%. Cerebrospinal fluid pressure ≥ 400mmH2O (OR = 7.43), abnormal imaging (OR = 3.51), abnormal electroencephalogram (OR = 7.14), and number of rescues (OR = 1.12) were significantly associated with an increased risk of mortality in severe infectious encephalitis patients. Among the 187 survivors, 122 (65.2%) had favorable outcomes, defined as the modified Rankine Scale (mRS) score (0 ~ 3), and 65(34.8%) had poor outcomes (mRS scores 4 ~ 5). Age (OR = 1.02), number of rescues (OR = 1.43), and tubercular infection (OR = 10.77) were independent factors associated with poor outcomes at discharge in all survivors with severe infectious encephalitis. Conclusions Multiple clinical, radiologic, and electrophysiological variables are independent predictive indicators for mortality and poor outcomes in patients with severe encephalitis in intensive care units. Identifying these outcome predictors early in patients with severe encephalitis may enable the implementation of appropriate medical treatment and help reduce mortality rates.

Herpes simplex encephalitis (HSE) is a common viral encephalitis that can be fatal if not adequately treated. Fever, cerebrospinal fluid (CSF) pleocytosis, and typical neuroimaging findings are commonly observed in HSE cases. We encountered a patient with HSE who did not exhibit these classic clinical features. A 63-year-old male presented with his first-ever seizure. Fever did not develop until the fourth day of admission, and neither neuroimaging nor CSF analysis revealed abnormalities. Under suspicion of autoimmune encephalitis, methylprednisolone was administered. Subsequently, when the patient developed fever, a follow-up neuroimaging study was performed and revealed abnormalities consistent with HSE. The patient was promptly treated with acyclovir, which led to a full recovery. Diagnosing HSE in patients who present without fever or CSF pleocytosis and with typical neuroimaging findings poses a challenge. Therefore, prior to initiating immunosuppressive treatment, it is crucial to closely observe patients and to conduct follow-up tests, including neuroimaging and CSF analysis.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disorder with diverse clinical manifestations including myelitis, meningitis, encephalitis, and optic neuritis. MOGAD rarely presents with unilateral cerebral cortical encephalitis (CCE), rendering the diagnosis difficult in these cases. Furthermore, MOGAD is frequently accompanied by other autoimmune diseases such as thyroid disease or inflammatory bowel disease. Herein, we report a case of unilateral CCE with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. In addition, our patient presented with systemic symptoms as well as neurologic symptoms and was finally diagnosed with ulcerative colitis (UC). A 60-year-old female was admitted to the hospital with an acute onset of headache and fever. Neurological examination revealed left-sided homonymous hemianopsia with intermittent visual hallucinations as flickering red-circular spots in the left visual field. Brain magnetic resonance imaging showed focal hyperintensities and enhancement in the right temporo-parieto-occipital cortex. Electroencephalography indicated a focal seizure in the right occipital cortex. After the administration of an antiepileptic drug, the patient showed clinical and radiological improvements. She tested positive for serum anti-MOG antibodies and was diagnosed with anti-MOG-associated unilateral CCE. However, the gastrointestinal symptoms persisted, thus, a sigmoidoscopy was performed. The patient was diagnosed with comorbid UC. Steroids were administered to treat the UC and the gastrointestinal symptoms improved. To the best of our knowledge, this is the first case of MOGAD presenting as a unilateral CCE in Korea. This case highlights the clinical phenotypes of MOGAD and the need to assess comorbid autoimmune diseases in patients with MOGAD.

Abstract Background Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. Results One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p

Abstract Background Hepatitis A is the most common cause of acute hepatitis around the globe, especially in developing countries. It often presents with signs and symptoms related to the gastrointestinal system. However, it rarely presents extrahepatic manifestations, which can be more common in adults than in children. Case presentation We report a unique case of hepatitis A presenting with encephalitis that was resolved conservatively. Before attributing the neurological features to hepatitis A, we had to rule out other etiologies with similar presentations. Clinical discussion Many viruses cause encephalitis, such as herpes simplex virus types 1 and 2, varicella zoster virus and enteroviruses. A few cases of hepatitis A complicated by encephalitis have been reported in the literature. In our case, developing a tonic-clonic seizure with no past seizure history demanded more investigations to exclude other etiologies. Ultimately, clinical signs and laboratory investigations led us to consider hepatitis A as the main cause of the patient’s symptoms of encephalitis. Conclusion Hepatitis A virus may present with extrahepatic manifestations more than expected, so more studies and research should be done to increase physicians’ knowledge of these manifestations, make early diagnosis, and administer the effective treatment.

Abstract Background Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, we sought to evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population. Methods We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from the Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With day 0 defined as the date of vaccination, risk window was defined as days 1–28 and the control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type. Results From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08–1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03–2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (IRR 1.03; 95% CI 0.91–1.16). Conclusions Our findings suggest an overall increased risk of encephalitis after COVID-19 vaccination. However, the absolute risk was small and should not impede COVID-19 vaccine confidence. No significant association was found between the risk of meningitis and COVID-19 vaccination.

Abstract Background The raccoon roundworm, Baylisascaris procyonis, can cause a meningoencephalitis as neural larva migrans which is known in avian species, including rainbow lorikeets in North America, but has not been described in Old World parrots in Germany yet. Case presentation A 2-month-old, male rainbow lorikeet from a zoo in Germany was submitted for necropsy. Prior to death the animal had progressive neurological signs like apathy and torticollis. In the cerebrum a focally extensive severe granulomatous to necrotizing encephalitis with an intralesional larval nematode was diagnosed. Based on the clinical and pathological findings, the larval morphology and the epidemiological background, the larva was identified as Baylisascaris procyonis. Conclusions Cerebral baylisascariosis should be considered as a differential diagnosis in zoo and pet birds with neurological signs having contact to racoons or rather racoon faeces in Germany due to the high prevalence of Baylisascaris procyonis in the German raccoon population.

West Nile virus (WNV) is transmitted via mosquito bites and causes ubiquitous zoonosis. Most infections in humans are asymptomatic, approximately 20% present as fever, and less than 1% as neuroinvasive disease. Central nervous system involvement is presented as meningitis, encephalitis, acute flaccid paralysis, or a combination of them. West Nile neuroinvasive disease (WNND) has a severe clinical course, potentially fatal outcome and frequent neurological sequelae in survivors. Risk factors for neurological impairment are advanced age and immunosuppression. Here we present a clinical case of meningoencephalitis caused by WNV and a brief literature review. Clinical and epidemiological data, laboratory, microbiological, molecular methods and imaging techniques were used. The cytokine levels of IL-6, IL-8, IL-10, IL-12(p40) and TNF-α in cerebrospinal fluid (CSF) and serum were also measured. We present a 55-year-old man with a sudden onset of headache, vomiting and fever. The symptoms appeared after a recent trip to Türkiye and involved multiple mosquito bites. Neck stiffness, disturbances in consciousness, signs of cerebral edema and subsequently focal neurological deficits were observed. The etiological diagnosis was verified by positive polymerase chain reaction for WNV and the presence of specific IgM antibodies in the CSF. After a 28-day hospital stay, the patient was discharged and referred to a Physiotherapy Unit due to residual motor deficits. WNV etiology should be suspected in patients with clinical and laboratory signs of viral neuroinfection, mosquito bites, and/or travel to endemic regions.

ABSTRACTBorna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies.ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has very rapidly become a global pandemic with millions of confirmed cases worldwide. In early 2021, viral encephalitis was the first neurological complication associated with COVID-19 and since then rise in cases has been reported with this association. A review highlighting 3 potential mechanisms linking a correlation between seizures and COVID-19 was previously reported. Herein described is a unique case of SARS-CoV2 infection that presented with focal seizure with impaired awareness.

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020–December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms. [ABSTRACT FROM AUTHOR]

Repeated and uncontrolled seizures in epilepsy result in brain cell loss and neural inflammation. Current anticonvulsants primarily target ion channels and receptors implicated in seizure activity. Identification of neurotherapeutics that can inhibit epileptiform activity and reduce inflammation in the brain may offer significant benefits in the long-term management of epilepsy. Fenamates are unique because they are both non-steroidal anti-inflammatory drugs (NSAIDs) and highly subunit selective modulators of GABAA receptors. In the current study we have investigated the hypothesis that fenamates have antiseizure properties using mature human stem cell-derived neuro-glia cell cultures, maintained in long-term culture, and previously shown to be sensitive to first, second and third generation antiepileptics. Mefenamic acid, flufenamic acid, meclofenamic acid, niflumic acid, and tolfenamic acid (each tested at 10-100 µM) attenuated 4-aminopyridine (4-AP, 100 µM) evoked epileptiform activity in a dose-dependent fashion. These actions were as effective diazepam (3-30 µM) and up to 200 times more potent than phenobarbital (300-1,000 µM). The low (micromolar) concentrations of fenamates that inhibited 4-AP evoked epileptiform activity correspond to those reported to potentiate GABAA receptor function. In contrast, the fenamates had no effect on neural spike amplitudes, indicating that their antiseizure actions did not result from inhibition of sodium-channels. The antiseizure actions of fenamates were also not replicated by either of the two non-fenamate NSAIDs, ibuprofen (10-100 µM) or indomethacin (10-100 µM), indicating that inhibition of cyclooxygenases is not the mechanism through which fenamates have anticonvulsant properties. This study therefore shows for the first time, using functionally mature human stem cell-derived neuroglial circuits, that fenamate NSAIDs have powerful antiseizure actions independent of, and in addition to their well-established anti-inflammatory properties, suggesting these drugs may provide a novel insight and new approach to the treatment of epilepsy in the future. [ABSTRACT FROM AUTHOR]

Objective. To explore whether the new‐onset refractory status epilepticus caused by autoimmune encephalitis has a better prognosis. Methods. This retrospective observational study enrolled patients with NORSE who were admitted from January 2015 to February 2024. The clinical data and clinical outcomes of the patients were collected and analyzed, and the primary outcome was seizures still at follow‐up. Statistical analyses were performed using SPSS software V.22.0. Results. Among the 42 patients with NORSE, 15 (35.7%) had autoimmune encephalitis (AE), 3 (7.1%) patients had central nervous system infections, 24 (57.1%) patients had an unknown etiology, and 4 (9.5%) patients died in the hospital. Modified Rankin scale (MRS) scores at discharge of NORSE patients in the autoimmune encephalitis group and non‐AE group were compared (P = 0.339). After 4 years of follow‐up, analysis of patients who still had seizures showed that the only risk factor was etiology and that patients with nonautoimmune encephalitis etiology were more prone to later epilepsy (P = 0.030 (OR = 16.767, 95% CI: 1.454‐213.395)). The MRS scores of the AE group and non‐AE group were compared (P ≤ 0.001), with the autoimmune group having a better functional outcome. Significance. The overall prognosis of patients with autoimmune encephalitis may be better than that of patients with other etiologies, and later epilepsy is more likely in patients with nonautoimmune encephalitis. However, this result requires further validation in larger studies with more data. [ABSTRACT FROM AUTHOR]

[Display omitted] • RBM3 showed neuroprotective role in acute brain injury. • RBM3 ameliorated inflammatory level and oxidative stress. • RBM3 interacted with GAS6 to promote its mRNA stability. • Silencing GAS6 reversed the Nrf2 signaling pathway activated by RBM3. RNA-binding motif protein 3 (RBM3), as a cold-inducible protein, exhibits neuroprotective function in brain disorders. This study was conducted to investigate the effects of RBM3 on acute brain injury (ABI) and its underlying mechanism. The cerebral injury (CI) rat model and oxygen-glucose deprivation (OGD) cell model were established. The neurological severity score, wire-grip score, morris water maze test, and Y-maze test were used to detect the neurological damage, vestibular motor, learning, and memory functions. Cerebral injury, apoptosis, oxidative stress, and inflammatory level were evaluated by hematoxylin-eosin and TUNEL staining and specific kits. Flow cytometry was used to analyze the apoptosis rate. The relationship between RBM3 and growth arrest specific (GAS) 6 was analyzed by RNA immunoprecipitation assay. The results indicated that RBM3 recovered of neurological function and behaviour impairment of CI rats. Additionally, RBM3 reversed the increased oxidative stress, inflammatory level, and apoptosis induced by CI and OGD. RBM3 interacted with GAS6 to activate the Nrf2 signaling pathway, thus playing neuroprotection on ABI. Besides, the results of RBM3 treatment were similar to those of mild hypothermia treatment. In summary, RBM3 exerted neuroprotection and ameliorated inflammatory levels and oxidative stress by stabilizing GAS6 mRNA through the Nrf2 signaling pathway, suggesting that RBM3 might be a potential therapeutic candidate for treating ABI. [ABSTRACT FROM AUTHOR]

Introduction: Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments differ. Utilizing single-cell RNA sequencing (scRNA-seq) data from mice, we tested the hypothesis that retinal and brain microglia exhibit distinct transcriptional profiles due to their unique microenvironments. Methods: Eyes and brains from 2-4 month wildtype mice were combined (20 eyes; 3 brains) to yield one biologically diverse sample per organ. Each tissue was digested into single cell suspensions, enriched for immune cells, and sorted for scRNA-seq. Analysis was performed in Seurat v3 including clustering, integration, and differential expression. Multi-parameter flow cytometry was used for validation of scRNA-seq results. Lymphocytic choriomeningitis virus (LCMV) Clone 13, which produces a systemic, chronic, and neurotropic infection, was used to validate scRNA-seq and flow cytometry results in vivo. Results: Cluster analysis of integrated gene expression data from eye and brain identified 6 Tmem119+P2ry12+ microglial clusters. Differential expression analysis revealed that eye microglia were enriched for more pro-inflammatory processes including antigen processing via MHC class I (14.0-fold, H2-D1 and H2-K1) and positive regulation of T-cell immunity (8.4-fold) compared to brain microglia. Multi-parameter flow cytometry confirmed that retinal microglia expressed 3.2-fold greater H2-Db and 263.3-fold more H2-Kb than brain microglia. On Day 13 and 29 after LCMV infection, CD8+ T-cell density was greater in the retina than the brain. Discussion: Our data demonstrate that the microenvironment of retina and brain differs, resulting in microglia-specific gene expression changes. Specifically, retinal microglia express greater MHC class I by scRNA-seq and multi-parameter flow cytometry, resulting in a possibly enhanced capability to stimulate CD8+ T-cell inflammation during LCMV infection. These results may explain tissue-specific differences between retina and brain during systemic viral infections and CD8+ T-cell driven autoimmune disease. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia is an uncommon and atypical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient. [ABSTRACT FROM AUTHOR]

Cross-sectional studies have demonstrated strong associations between physical frailty and depression. However, the evidence from prospective studies is limited. Here, we analyze data of 352,277 participants from UK Biobank with 12.25-year follow-up. Compared with non-frail individuals, pre-frail and frail individuals have increased risk for incident depression independent of many putative confounds. Altogether, pre-frail and frail individuals account for 20.58% and 13.16% of depression cases by population attributable fraction analyses. Higher risks are observed in males and individuals younger than 65 years than their counterparts. Mendelian randomization analyses support a potential causal effect of frailty on depression. Associations are also observed between inflammatory markers, brain volumes, and incident depression. Moreover, these regional brain volumes and three inflammatory markers—C-reactive protein, neutrophils, and leukocytes—significantly mediate associations between frailty and depression. Given the scarcity of curative treatment for depression and the high disease burden, identifying potential modifiable risk factors of depression, such as frailty, is needed. Identifying modifiable risk factors that could prevent depression is important. Here, the authors show increased risks of incident depression in pre-frail and frail individuals and highlight the mediating role of brain structure and inflammation. [ABSTRACT FROM AUTHOR]

Fatigue can lead to several health issues and is particularly prevalent among elderly individuals with chronic inflammatory conditions. Ninjin'yoeito, a traditional Japanese herbal medicine, is used to address fatigue and malaise, anorexia, and anemia. This study aimed to examine whether relieving inflammation in the brain and skeletal muscle of senescence-accelerated mice prone 8 (SAMP8) could reduce fatigue-like conditions associated with aging. First, SAMP8 mice were divided into two groups, with and without ninjin'yoeito treatment. The ninjin'yoeito-treated group received a diet containing 3% ninjin'yoeito for a period of 4 months starting at 3 months of age. At 7 months of age, all mice underwent motor function, treadmill fatigue, and behavioral tests. They were then euthanized and the skeletal muscle weight, muscle cross-sectional area, and concentration of interleukin (IL)-1β and IL-1 receptor antagonist (IL-1RA) in both the brain and skeletal muscle were measured. The results showed that the ninjin'yoeito-treated group had higher motor function and spontaneous locomotor activity than the untreated group did and ran for significantly longer in the treadmill fatigue test. Moreover, larger muscle cross-sectional area, lower IL-1β concentrations, and higher IL-1RA concentrations were observed in both the brain and skeletal muscle tissues of the ninjin'yoeito-treated group than in the untreated group. The results suggest that ninjin'yoeito improves age-related inflammatory conditions in both the central and peripheral tissues and reduces fatigue. [ABSTRACT FROM AUTHOR]

Background: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1–2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). Objective: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. Methods: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. Results: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. Conclusion: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide-induced (LPS) inflammation is used as model to understand the role of inflammation in brain diseases. However, no studies have assessed the ability of peripheral low-level chronic LPS to induce neutrophil activation in the periphery and brain. Subclinical levels of LPS were injected intraperitoneally into mice to investigate its impacts on neutrophil frequency and activation. Neutrophil activation, as measured by CD11b expression, was higher in LPS-injected mice compared to saline-injected mice after 4 weeks but not 8 weeks of injections. Neutrophil frequency and activation increased in the periphery 4–12 h and 4–8 h after the fourth and final injection, respectively. Increased levels of G-CSF, TNFa, IL-6, and CXCL2 were observed in the plasma along with increased neutrophil elastase, a marker of neutrophil extracellular traps, peaking 4 h following the final injection. Neutrophil activation was increased in the brain of LPS-injected mice when compared to saline-injected mice 4–8 h after the final injection. These results indicate that subclinical levels of peripheral LPS induces neutrophil activation in the periphery and brain. This model of chronic low-level systemic inflammation could be used to understand how neutrophils may act as mediators of the periphery–brain axis of inflammation with age and/or in mouse models of neurodegenerative or neuroinflammatory disease. [ABSTRACT FROM AUTHOR]

Objective: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. Methods: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. Results: The average age at diagnosis was 45.93 ± 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on 18F-fluorodeoxyglucose positronemission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. Conclusion: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis. [ABSTRACT FROM AUTHOR]

Introduction: Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. Method: A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. Results: The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLADRB* 10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Discussion: Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms. [ABSTRACT FROM AUTHOR]

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported. Case presentation: A 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis. Conclusion: This case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly. [ABSTRACT FROM AUTHOR]

Encephalitis is a rare and potentially fatal manifestation of herpes simplex type 1 infection. Following genome-wide genetic analyses, we identified a previously uncharacterized and very rare heterozygous variant in the E3 ubiquitin ligase WWP2, in a 14-month-old girl with herpes simplex encephalitis. The p.R841H variant (NM_007014.4:c.2522G > A) impaired TLR3 mediated signaling in inducible pluripotent stem cells-derived neural precursor cells and neurons; cells bearing this mutation were also more susceptible to HSV-1 infection compared to control cells. The p.R841H variant increased TRIF ubiquitination in vitro. Antiviral immunity was rescued following the correction of p.R841H by CRISPR-Cas9 technology. Moreover, the introduction of p.R841H in wild type cells reduced such immunity, suggesting that this mutation is linked to the observed phenotypes. Encephalitis is a rare and severe complication of Herpes Simplex type 1 infection. Here, Bibert et al describe a genetic variant in a 2-year-old affected child that impairs interferon production in neuronal cells and enhances viral replication. [ABSTRACT FROM AUTHOR]