Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations

Anti-N-methyl-D-aspartate receptor-associated encephalitis(NMDARE)is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction.The mechanism of pathogenesis remains incompletely understood,but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways.Young adults are most frequently affected;the median age at diagnosis is 21 years.There is a strong female predilection with a female sex predominance of 4:1.NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma.However,NMDARE has also been described in patients with small cell lung cancer,clear cell renal carcinoma,and other benign and malignant neoplasms.Diagnosis is based on correlation of the clinical presentation,electro-encephalography,laboratory studies,and imaging.Computed tomography,positron emission tomography,and magnetic resonance imaging are essential to identify an underlying tumor,exclude clinicopathologic mimics,and predict the likelihood of long-term functional impairment.Nuclear imaging may be of value for prognostication and to assess the response to therapy.Treatment may involve high-dose corticosteroids,intravenous immunoglobulin,and plasma exchange.Herein,we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria,treatment regimens,and proposed pathogenetic mechanisms.

Meningoencephalitis due to Listeria monocytogenes in a Young Immunocompetent Patient: Case Report with Literature Review

Meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompetent individuals. We present the case of a young adult patient without immunocompromise, who developed meningoencephalitis due to L. monocytogenes;This case is exceptional, since it occurred in an individual outside the classic age group, in addition to not having risk factors, which is why it should be considered an atypical causal agent.

Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune disease.AE was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May 2018.Currently,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

A case of Rickettsia felis infection-induced encephalitis in a pregnant woman

Rickettsia felis is an exclusively cytozoic Gram-negative prokaryote with cat fleas as the major vectors.[1]As early as 1918,Rickettsia felis was detected in cat fleas in Europe and named Rickettsia ctenocephali.[2]Symptoms of fever,malaise,headache,maculopapular rash and eschar are observed in patients with Rickettsia felis infection.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing.Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing.Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing.Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Herpes Simplex Virus Encephalitis Complicated by Acute Ischemic Stroke

Introduction: Herpes simplex virus is the most common etiology for life-threatening sporadic encephalitis worldwide. Antiviral therapy with acyclovir has been shown to reduce mortality and should be started promptly in patients with clinically suspected viral encephalitis before serological confirmation of the diagnosis. Despite antiviral treatment, it is associated with significant mortality and a wide range of neurologic sequelae or neuropsychiatric disorders. Clinical presentation includes fever, headache, altered mental status, and focal or generalized seizures. In some cases, it can present with focal neurological deficits, such as an acute stroke. The aim of this study is to identify rare complications of HSVE. Presentation: We present a case of a 71-year-old female patient with herpes virus encephalitis and an ischemic cerebral accident. The findings of CT scan of the brain revealed an extensive right temporal hypodensity. CSF findings include an elevated protein level, normal glucose level and pleocytosis with lymphocyte predominance. The lumbar tap confirmed the presence of herpes simplex virus type 1 with polymerase chain reaction (PCR) in the CSF. Neurological manifestations include focal neurological deficit with left-sided hemiparesis and coma. After 40 days of complex therapy, an improvement in the mental state was observed. Conclusion: There are varying degrees of neurologic sequelae among survivors in children and adults despite the antiviral treatment. Herpes simplex encephalitis has significant morbidity and high mortality due to the lack of prophylactic treatment and preventable strategies.

Serological Investigation into the Infected Genotypes of Patients with Japanese Encephalitis in the Coastal Provinces of China

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains unknown.We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of China.Methods In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and G5.Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to 2020.Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV.Two cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 JEV.Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.

The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

Objective: This study aims to explore the differences in cerebrospinal fluid oligoclonal band (CSF-OCB) expression among different age groups in viral encephalitis and its reference value for diagnosis. Methods: Forty-two patients with viral encephalitis were divided into two groups: 25 adults and 17 children. The presence of oligoclonal bands in the cerebrospinal fluid (CSF) was detected using polyacrylamide gel electrophoresis, and CSF routine analysis was conducted for comparative analysis. Results: The CSF-OCB positivity rate was higher in the adult group (48%) compared with the pediatric group (11.76%), with a statistically significant difference (P Conclusion: 1) The expression of CSF-OCB positivity in patients with viral encephalitis is age-related, with higher positivity rates observed in adults compared to children. 2) Although CSF oligoclonal band detection is not a specific diagnostic marker for viral encephalitis in adults, it still holds certain reference value.

Anti-contact protein-associated protein 2 antibody encephalitis in children:A case report

BACKGROUND Anti-contactin-associated protein-like 2(CASPR2)antibody encephalitis is an autoimmune disorder characterized by the presence of antibodies against the voltage-gated potassium channel.This leads to neurological symptoms,such as seizures,cognitive decline,and neuropathic pain,primarily affecting the limbic system.The prognosis of this disorder varies among individuals.CASE SUMMARY The patient,a girl aged nine years and nine months,underwent treatment for 14 to 21 d.The main clinical manifestations were vomiting and unclear consciousness,positive pathological signs,normal cranial computed tomography and magnetic resonance imaging,and abnormal electroencephalogram.The child was discharged after receiving immunoglobulin and hormone treatment.Subsequent follow-up over a period of 15 months after discharge,conducted through telephone and outpatient visits,showed no recurrence of symptoms.CONCLUSION Anti-CASPR2 antibody autoimmune encephalitis in children is rare,mainly manifested as convulsions,mental abnormalities,cognitive impairment,and neuropathic pain,among others.Timely evaluation for autoimmune encephalitis antibodies is crucial,especially in cases of recurrent central nervous system involvement in children.

Isolated Hyperacute T-Waves in West Nile Encephalitis Indicating Atypical Variant of Stress-Induced Cardiomyopathy

Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.

Two Cases of Autoimmune Encephalitis with Multiple Anti-neuronal Antibodies

Autoimmune encephalitis(AE)can arise from various etiologies and present with complex clinical manifestations,especially in cases involving multiple anti-neuronal antibodies.This report presents two cases of AE with multiple anti-neuronal antibodies admitted to Ningbo Medical Center Li Huili Hospital on October 9,2020,and March 12,2024.Case 1 is a 15-year-old boy with positive anti-N-methyl-D-aspartate receptor(NMDAR)and anti-metabotropic glutamate receptor 5(mGluR5)antibodies in his serum and cerebrospinal fluid(CSF).Case 2 is a 14-year-old boy with positive NMDAR and myelin oligodendrocyte glycoprotein(MOG)antibodies in his CSF.Patients with AE who have multiple anti-neuronal antibodies present significant diagnostic and therapeutic challenges,warranting close clinical attention.

Varicella-Zoster Virus Encephalitis with Hyponatremia in an Immunocompetent Elderly Patient:A Case Report

As a common cause of viral encephalitis,varicella-zoster virus(VZV)may invade the central nervous system of immunosuppressed patients during reactivation.Herein,we report a rare case of an immunocompetent patient with VZV encephalitis who developed severe hyponatremia and was considered to have a suspected primary infection.The patient was diagnosed with the support of second-generation sequencing and had persistent hyponatremia after being cured.Although rare,this case suggests that VZV encephalitis may occur in unexpected patients and present with unusual clinical manifestations,requiring advanced detection methods and clinical expertise for resolution.

Analysis of the Effectiveness of Targeted Nursing in Children with Severe Viral Encephalitis Complicated with Respiratory Failure

Objective:To explore and analyze the effectiveness of targeted nursing in children with severe viral encephalitis complicated with respiratory failure.Methods:From April 2021 to April 2023,74 children with severe viral encephalitis complicated with respiratory failure admitted to the Department of Pediatrics of our hospital were selected as the research objects and divided into the target group(n=37)and the reference group(n=37).Targeted nursing was given to the target group,while general nursing was given to the reference group.Physical rehabilitation,motor scores,and lung function were compared between the groups.Results:The recovery time of limb abnormalities,convulsions,abnormal consciousness,and cranial nerve disorders in the target group was significantly better than that in the reference group(P<0.05).The motor function,joint activity and pain,sensory function,and total score of the target group were significantly lower than those of the reference group(P<0.05).After the intervention,lung function indicators including VC(vital capacity),FVC(forced vital capacity),and MVV(maximum voluntary ventilation)of the target group were better than those of the reference group(P<0.05).Conclusion:Targeted nursing can shorten the recovery period of severe viral encephalitis complicated with respiratory failure in children,speed up the recovery of motor function,and improve lung function.This nursing model has a significant application effect in children with severe viral encephalitis complicated with respiratory failure.

Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Anti-leucine-rich glioma inactivated protein 1 encephalitis with sleep disturbance as the first symptom: A case report and review of literature

BACKGROUND Anti-leucine-rich glioma inactivated protein 1(anti-LGI1) encephalitis is an infrequent type of autoimmune encephalitis(AE) characterized by acute or subacute cognitive and psychiatric disturbance, facio-brachial dystonic seizures(FBDSs), and hyponatremia. Anti-LGI1 AE has increasingly been considered a primary form of AE. Early identification and treatment of this disease are clearly very important.CASE SUMMARY Here, we report that a male patient developed severe anti-LGI1 encephalitis, which was initially misdiagnosed as a sleep disturbance. He was hospitalized for epileptic seizures and typical FBDSs half a month after he developed sleep disturbances. LGI1 antibodies were detected in his cerebrospinal fluid and serum(1:100 and 1:3.2, respectively), which led to the diagnosis of classic anti-LGI1 AE. No obvious abnormality was observed on brain computed tomography images. T2-weighted fluid-attenuated inversion recovery and T2-weighted scans of brain magnetic resonance imaging(MRI) showed slightly elevated signals within the left basal ganglia area. No tumor was detected within the brain of this patient using MRI. After hormone and antiepileptic drug treatment, the patient’s symptoms improved significantly.CONCLUSION Anti-LGI1 antibody-associated encephalitis has characteristic clinical manifestations, such as cognitive impairment, psychiatric symptoms, seizures, sleep disorders, hyponatremia, and FBDSs. LGI1 antibodies are present in the serum and/or cerebrospinal fluid, but their production is sensitive to immunosuppressants, and this disease has a relatively good prognosis. In particular, we should be aware of the possibility of anti-LGI1 antibody-associated encephalitis in adolescents with sleep disorders to avoid missed diagnoses and misdiagnoses.

Discrimination between leucine-rich glioma-inactivated 1 antibody encephalitis and gamma-aminobutyric acid B receptor antibody encephalitis based on ResNet18

This study aims to discriminate between leucine-rich glioma-inactivated 1(LGI1)antibody encephalitis and gammaaminobutyric acid B(GABAB)receptor antibody encephalitis using a convolutional neural network(CNN)model.A total of 81 patients were recruited for this study.ResNet18,VGG16,and ResNet50 were trained and tested separately using 3828 positron emission tomography image slices that contained the medial temporal lobe(MTL)or basal ganglia(BG).Leave-one-out cross-validation at the patient level was used to evaluate the CNN models.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were generated to evaluate the CNN models.Based on the prediction results at slice level,a decision strategy was employed to evaluate the CNN models’performance at patient level.The ResNet18 model achieved the best performance at the slice(AUC=0.86,accuracy=80.28%)and patient levels(AUC=0.98,accuracy=96.30%).Specifically,at the slice level,73.28%(1445/1972)of image slices with GABAB receptor antibody encephalitis and 87.72%(1628/1856)of image slices with LGI1 antibody encephalitis were accurately detected.At the patient level,94.12%(16/17)of patients with GABAB receptor antibody encephalitis and 96.88%(62/64)of patients with LGI1 antibody encephalitis were accurately detected.Heatmaps of the image slices extracted using gradient-weighted class activation mapping indicated that the model focused on the MTL and BG for classification.In general,the ResNet18 model is a potential approach for discriminating between LGI1 and GABAB receptor antibody encephalitis.Metabolism in the MTL and BG is important for discriminating between these two encephalitis subtypes.

Epidemic Japanese B encephalitis combined with contactinassociated protein-like 2 antibody-positive autoimmune encephalitis:A case report

BACKGROUND It is not uncommon to develop viral encephalitis.Epidemic Japanese B encephalitis infection combined with contactin-associated protein-like 2(CASPR-2)antibody-positive autoimmune encephalitis has not been reported at present.In clinical work,we need to consider more options.CASE SUMMARY A 32-year-old male worker presented with headache,fever and call-unresponsive presentation.Complete cranial magnetic resonance image showed symmetrical abnormal signals in bilateral medial temporal lobe,bilateral thalamus and basal ganglia.Improved lumbar puncture showed that cerebrospinal fluid protein and cell count increased significantly.Viral encephalitis was considered,and the patient's consciousness still increased rapidly after antiviral treatment.Further detection of Cerebrospinal fluid Japanese B encephalitis virus Polymerase Chain Reaction positive,serum autoimmune encephalitis antibody showed CASPR-2 antibody positive(1:320),the patient's condition gradually improved after plasma exchange treatment.3 mo later,the serum CASPR-2 antibody was negative and the patient's condition was stable.CONCLUSION This article reports the world’s first case of Epidemic Japanese B encephalitis infection combined with CASPR-2 antibody-positive autoimmune encephalitis,with a view to raising awareness.

Autoimmune complications and clinical outcomes of herpes simplex encephalitis in children: A case series

Objective:To report the neurologic prognosis and autoimmune complications of 16 cases of childhood herpes simplex virus encephalitis.Methods:The study was conducted atŞanlıurfa Training and Research Hospital,Turkey from June 2017 to August 2019.The study included 16 pediatric patients aged between 6 months and 17 years(median age 77.7 months)who were diagnosed with herpes simplex virus type 1 encephalitis by pediatric infectious disease and pediatric neurology clinics.Patients were followed using patient records,and interviews at the pediatric neurology clinic or via the telephone.Clinical and demographic data,received therapies,neurologic prognosis and complications were evaluated.Results:Patients with and without autoimmune encephalitis were compared in terms of age,sex,symptom duration before treatment,initial cerebrospinal fluid protein,glucose,red blood count and white blood count but no significant difference was found.Autoimmune complications were seen in four patients.N-methyl-D-aspartate encephalitis was observed in three patients and choreoathetosis was seen in one patient.The average follow-up period was 48.3 months.Twenty-five percent of the patients were receiving multiple antiepileptic drug(AED)treatment,43.8%were receiving single AED treatment and 31.3%were not receiving AED treatment at the end of the follow-up.Motor disability was observed in 12.5%and drug-resistant epilepsy was observed in 6.3%who had autoimmune complications.Conclusions:Seizures and movement disorders were controlled with immunotherapy and autoantibodies should be studied routinely.Treatment should be started early upon recognition of autoimmune complications through follow-up by measuring autoantibody levels and clinical examination results.Effective prevention and curative treatment modalities are needed to avoid herpes simplex virus encephalitis complications.

Late-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with mitochondrial DNA 3243A>G mutation masquerading as autoimmune encephalitis:A case report

BACKGROUND Here,we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)syndrome,which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation.CASE SUMMARY A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations,symmetrical bitemporal lobe abnormalities,clinical and laboratory findings,and a lack of relevant prodromal history,which suggested diagnosis of autoimmune encephalitis.Further work-up,in conjunction with the patient’s medical history,family history,and lactate peak on brain lesions on magnetic resonance imaging,suggested a mitochondrial disorder.Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene,which led to a diagnosis of MELAS syndrome.CONCLUSION This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age,as the symptoms and signs are atypical for MELAS syndrome.

Laryngospasm as an uncommon presentation in a patient with anti-N-methyl-D-aspartate receptor encephalitis:A case report

BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory deficits,among others.However,laryngospasm is rare.We present the case of a patient with anti-NMDAR antibodies and severe laryngospasms.CASE SUMMARY The patient was a 15-year-old female with normal psychomotor development.She was initially admitted to our neurological intensive care unit with seizures.She received anti-epilepsy treatment,and the seizures disappeared.However,2 wk later,she developed behavioral problems and speech impairment.Then,she developed severe laryngospasms,which were treated with intubation and a tracheotomy.Antibodies against the NMDAR were detected in the patient’s cerebrospinal fluid.Therefore,she was diagnosed with anti-NMDAR encephalitis.In addition,she received intravenously administered immunoglobulins,and methylprednisolone was administered.The patient’s symptoms gradually improved,and she was discharged from our hospital.Approximately 9 mo later,the patient could speak sentences,walk independently,and carry out activities of daily living independently.Through our case report,we highlighted laryngospasm as an uncommon presentation in patients with anti-NMDAR encephalitis.CONCLUSION Laryngospasm may be an uncommon clinical manifestation of anti-NMDAR encephalitis.