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.

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.

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.

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.

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.

Chikungunya encephalitis:A case report

Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous system appears to be the most common severe complication of CHIKV infection.Patient’s Concern:A seventy-five-year-old patient from India presented to the hospital with fever,chills,rigors,and multiple joint pains for which he was worked up.Diagnosis:CHIKV encephalitis.Interventions:The patient was treated initially on supportive therapy with antipyretics,intravenous fluids;however,during his hospital stay,the patient had altered sensorium during which he was managed in the intensive care unit;required mechanical ventilation.Outcomes:The patient sccumbed to his illness.Lessons:Treating clinicians should keep CHIKV disease in the differential diagnosis in cases of febrile exanthems associated with disabling arthritis,especially in a CHIKV-endemic country like India.

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.

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.

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.

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.

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.

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.

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.

Survey on Vaccination of Foxes Against Encephalitis

[Objective] This study was conducted to survey the vaccination of foxes against encephalitis in Changli. [Method] A total of 85 fox blood samples were col- lected from four farmers in Changli County. The serum antibody titer against fox encephalitis was detected by enzyme-linked immunosorbent assay （ELISA）. The OD values were measured to determine the presence of CAV-1 antibody in samples. [Result] 93% of the 15 serum samples from Farmer 1, 86% of the 14 serum sam- ples from Farmer 2, 97% of the 30 serum samples from Farmer 3 and 92% of 26 serum samples from farmer 4 were CAV-1 antibody-positive. In summary, among the 85 serum samples from the four farmers, six were CAV-1 antibody-negative, and 79 were CAV-1 antibody-positive, namely 93% of the foxes were successfully immunized. [Conclusion] The results revealed that vaccination against fox encephali- tis in Changli was run well, but the immunization in several foxes should be strengthened.

Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management

Tick-borne encephalitis is an infection of central nervous system caused by tick-borne encephalitis virus transmitted to humans predominantly by tick bites. During the last few decades the incidence of the disease has been increasing and poses a growing health problem in almost all endemic European and Asian countries. Most cases occur during the highest period of tick activity, in Central Europe mainly from April to November. Tickborne encephalitis is more common in adults than in children. Clinical spectrum of the disease ranges from mild meningitis to severe meningoencephalitis with or without paralysis. Rare clinical manifestations are an abortive form of the disease and a chronic progressive form. A post-encephalitic syndrome, causing long-lasting morbidity that often affects the quality of life develops in up to 50% of patients after acute tick-borne encephalitis. Clinical course and outcome vary by subtype of tick-borne encephalitis virus(the disease caused by the European subtype has milder course and better outcome than the disease caused by Siberian and Far-Easter subtypes), age of patients(increasing age is associated with less favorable outcome), and host genetic factors. Since clinical features and laboratory results of blood and cerebrospinal fluid are nonspecific, the diagnosis must be confirmed by microbiologic findings. The routine laboratory confirmation of the tick-borne encephalitis virus infection is based mainly on the detection of specific Ig M and Ig G antibodies in serum(and cerebrospinal fluid), usually by enzyme-linked immunosorbent assay. There is no specific antiviral treatment for tick-borne encephalitis. Vaccination can effectively prevent the disease and is indicated for persons living in or visiting tick-borne encephalitis endemic areas.

Mechanism of Japanese encephalitis virus genotypes replacement based on human,porcine and mosquito-originated cell lines model

Objective:To examine the multiplication efficiency Japanese encephalitis virus(JEV)genotype Ⅰ(G Ⅰ) and genotype Ⅲ(GⅢ) of different cell lines which originated from human,porcine,mosquitoes in order to prove mechanism of JEV G Ⅰ replacement JEV GⅢ since it emerging in nature recent decades.Methods:The mixture of Gi and GⅢ JEV isolates was inoculated on human rhabdomyosarcoma(RD).pig kidney epithelial(PS) and Aedes albopictus C6/36 clone(C6/36) which originated from human,porcine and mosquitoes,respectively.Plaque assays were performed to calculate virus titer and real-time RT-PCR with GⅠand GⅢspecific primer sets to quantify the number of GⅠ and GUI RNA copies.Results:The highest virus titer reached at the 3rd day of post infection when G Ⅰand GⅢ mixture was inoculated on RD and PS and that of C636 was at the 4^(th)day.JEVs were amplified and maintained by C6/36 cells after 10 passages whereas that by RD and PS only limited within 8 and 6 passages,respectively.GⅠ strain amplified and maintained more efficiently on C6/36 and PS but not RD.whereas GⅢ strain amplified and maintained more efficiently on RD.Conclusions:There is a correlation between the multiplication efficiency of GⅠ and GⅢ JEV strains when these two genotype strains co-infected on different cell lines with the predominance of GⅠstrains in C6/36 and PS and the limited detection of G 1 strains in RD cells proving a possible mechanism of shift JEV genotypes in nature recent decades since GⅠ emerging.

A Reverse-transcription Recombinase-aided Amplification Assay for the Rapid Detection of the Far-Eastern Subtype of Tick-borne Encephalitis Virus

Objective Tick-borne encephalitis virus(TBEV) is an emerging pathogen in Europe and North Asia that causes tick-borne encephalitis(TBE). A simple, rapid method for detecting TBEV RNA is needed to control this disease. Methods A reverse-transcription recombinase-aided amplification(RT-RAA) assay was developed. This assay can be completed in one closed tube at 39℃ within 30 minutes. The sensitivity and specificity of RT-RAA were validated using non-infectious synthetic RNA representing a fragment of the NS5 region of the wild-type(WT) TBEV genome and the Senzhang strain. Additionally, 10 batches of tick samples were used to evaluate the performance of the RT-RAA assay. Results The analytical limit of detection of the assay was 20 copies per reaction of the TBEV synthetic transcript and 3 plaque-forming units(pfu) per reaction of TBEV titers. With the specific assay, no signal due to other arboviruses was observed. Of the 10 batches of tick samples obtained from the Changbai Mountains of China, three were TBEV-positive, which was consistent with the results of the quantitative real-time PCR assay. Conclusion A rapid, highly sensitive, specific, and easy-to-use method was developed for the detection of the TBEV Far-Eastern subtype.

Electroconvulsive therapy and/or plasmapheresis in autoimmune encephalitis?

Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a variety of clinical syndromes-anti-N-Methyl-D-Aspartate receptor(NMDAR) is the commonest. Currently, the most widely used therapy is prompt plasmapheresis and steroid treatment(and tumour resection if indicated), followed by second line immunosuppression if this fails. Given the growing awareness of autoimmune encephalitis as an entity, it is increasingly important that we consider it as a potential diagnosis in order to provide timely, effective treatment. We discuss several previously published case reports and one new case. These reports examined the effects of electroconvulsive therapy(ECT) on patients with autoimmune encephalitis, particularly those in whom psychiatric symptoms are especially debilitating and refractory to standard treatment. We also discuss factors predicting good outcome and possible mechanisms by which ECT may be effective. Numerous cases, such as those presented by Wingfield, Tsutsui, Florance, Sansing, Braakman and Matsumoto, demonstrate effective use of ECT in anti-NMDAR encephalitis patients with severe psychiatric symptoms such as catatonia, psychosis, narcolepsy and stupor who had failed to respond to standard treatments alone. We also present a new case of a 71-year-old female who presented to a psychiatric unit initially with depression, which escalated to catatonia, delusions, nihilism and auditory hallucinations. After anti-NMDAR antibodies were isolated, she was treated by the neurology team with plasmapheresis and steroids, with a partial response. She received multiple sessions of ECT and her psychiatric symptoms completely resolved and she returned to her premorbid state. For this reason, we suggest that ECT should be considered, particularly in those patients who are non-responders to standard therapies.

TaqMan Real-time RT-PCR Assay for Detecting and Differentiating Japanese Encephalitis Virus

Objective To detect Japanese encephalitis virus（JEV） rapidly and distinguish its genotypes, a TaqMan-based reverse transcriptase quantitative polymerase chain reaction（RT-PCR） detection system was developed.Methods By aligning the full-length sequences of JEV（G1-G5）, six sets of highly specific TaqMan real-time RT-PCR primers and probes were designed based on the highly conserved NS1, NS2, and M genes of JEV, which included one set for non-specific JEV detection and five sets for the detection of specific JEV genotypes. Twenty batches of mosquito samples were used to evaluate our quantitative PCR assay.Results With the specific assay, no other flavivirus were detected. The lower limits of detection of the system were 1 pfu/mL for JEV titers and 100 RNA copies/μL. The coefficients of variation of this real-time RT-PCR were all 〈 2.8%. The amplification efficiency of this method was between 90% and 103%.Conclusion A TaqMan real-time RT-PCR detection system was successfully established to detect and differentiate all five JEV genotypes.