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.

Limbic Encephalitis and Autoimmune Encephalitides: Pathophysiology, Classification, Clinical Presentation, and Treatment

Limbic encephalitis represents a cluster of autoimmune disorders, with inflammation in the medial temporal lobe characterised by the subacute onset of neuropsychiatric symptoms such as anxiety, affective symptoms, psychosis, short-term memory impairment, as well as faciobrachial and grand mal seizures. The limbic system is a complex anatomical structure which this paper seeks to explain in terms of its anatomy and physiology, before exploring what happens when it is impaired as is the case of autoimmune and limbic encephalitis. We will discuss the pathophysiology, clinical symptomatology and diagnosis of autoimmune encephalitis, a cluster of symptoms which can be easily overlooked or misdiagnosed within psychiatric settings. Characteristic indicators of autoimmune encephalitis include neurologic symptoms such as facial twitching, seizures, confusion, and cognitive decline;however, our experience realises that autoimmune encephalitis is not easy to identify as most patients initially present with psychiatric symptomatology rather than these neurological symptoms. Furthermore, immunological and laboratory testing take a long time to diagnose the condition. Importantly, few psychiatrists consider the autoimmune nature of the neuropsychiatric presentation. It is hence vital to consider autoimmune encephalitis in all patients with atypical presentations.

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.

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 encephalitis after surgery for appendiceal cancer:A case report

BACKGROUND Primary cancer of the appendix is rare and often difficult to diagnose preoperatively due to the lack of specific clinical symptoms. Autoimmune encephalitis(AIE) is the most common cause of non-infectious encephalitis. The etiologies of AIE include tumors(paraneoplastic), infections(parainfections), or recessive infections. The tumors that have been reported to cause AIE include thymomas, ovarian teratomas, lung cancers, and breast cancers. However, there are no reports of AIE occurring after surgery for appendiceal cancer. This report describes the diagnosis and treatment of a patient with an appendiceal cancer and postoperative AIE.CASE SUMMARY We report the case of a 47-year-old man who was transferred to our hospital due to a recurrent low intestinal obstruction. Abdominal enhanced computed tomography was used to consider the possibility of a terminal ileal tumor with serous infiltration and lymph node metastasis. A right hemi-colectomy was performed under general anesthesia with an ileo-transcolon anastomosis and laparoscopic exploration. The postoperative pathologic evaluation revealed a high-grade goblet cell carcinoma of the appendix, accompanied by mesangial and abdominal lymph node metastases, and neural tube and vascular infiltration. The operation was completed without complication. The patient developed restlessness on postoperative day 4, and gradually developed a disturbance of consciousness on postoperative day 6. He was transferred to West China Hospital of Sichuan University and diagnosed with AIE.CONCLUSION Albeit rare, the occurrence of neurologic and psychiatric symptoms in patients with an appendiceal cancer postoperatively suggests the possibility of AIE.

Challenges to associate early onset epilepsy with COVID-19 autoimmune encephalitis:A case

BACKGROUND Diagnosis of coronavirus disease 2019(COVID-19)-related neurological events in the pediatric population is challenging.Overlapping clinical picture of children with altered neurological state and inborn errors of metabolism,in addition to the frequency of asymptomatic COVID-19 cases,pose the main challenges for diagnosis.Diagnostic approaches to the onset post-COVID 19 subacute encephalopathy are still troublesome as seronegative autoimmune encephalitis(AIE)is reported.CASE SUMMARY A 27-mo-old boy was admitted for stormy refractory seizure of polymorphic semiology and altered mental status followed by various neuropsychiatric features that were suggestive of AIE.Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal.Neither the immunological assessment,including viral serologies,antinuclear antibodies,autoimmune antibodies(NMDA,AMPA,CASPR2,LG11,GABARB,Hu,Yo,Ri,CV2,PNMA2,SOX1,Titin,amphiphysin,Recoverin),nor the metabolic assessment for lactate and pyruvate showed significant anomaly.Both positive history of COVID-19 infection and the findings of characteristic repetitive extreme delta brush played a key role in the diagnosis of COVID-19-related AIE.A remarkable improvement in the state of the child was noted after two pulse doses of intravenous Veinoglobulin and high dose of intravenous Corticosteroid.CONCLUSION Diagnostic biomarkers for AIE might aid effective treatment.

Can Autoimmune Encephalitis Occur with Negative Markers? A Rare Case Report

In our case, we present a case of a 27-year-old male who presented with progressively worsening altered mental status and seizures. Over the course of his admission to the hospital and intensive care unit, laboratory testing failed to find an offending agent to his presentation. Testing did result in the diagnosis of encephalitis, but an underlying cause was not found. After careful exclusion of bacterial, viral, and other types of encephalopathy, autoimmune encephalopathy was diagnosed despite the absence of commonly used markers of autoimmune encephalopathy. The presentation and symptoms of our patient led to a wide range of differentials, and a high index of suspicion was needed throughout his admission in order to obtain the appropriate tests. Although appropriate testing might be ordered, due to the sensitivities and specificities of all laboratory tests, these objective tests do produce false negative results at times. It is in these times that one must weigh the physical exam, clinical judgment, and the process of elimination to diagnose an underlying pathology. Autoimmune Encephalitis diagnosis can be broken down into possible, probable, and definitive diagnoses based on antibody testing results. In this case, we present a patient with probable autoimmune encephalitis that failed to yield positive autoimmune markers after extensive testing of other possible causes of encephalitis.

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.

Four kinds of antibody positive paraneoplastic limbic encephalitis: A rare case report

BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.

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.

Serial Brain Positron Emission Tomography Fused to Magnetic Resonance Imaging in Post-Infectious and Autoantibody-Associated Autoimmune Encephalitis

Serial positron emission tomography fused to magnetic resonance imaging showed progression of GAD65 autoimmune encephalitis.

Stiff-Person Syndrome Associated with Anti-Glutamic Acid Decarboxylase Autoimmune Encephalitis in a Young Woman: A Case Report

A 34-year-old female with stiff-person syndrome(SPS)is reported in this paper.She experienced short-term memory impairment and was diagnosed with anti-glutamic add decarboxylase(GAD)autoimmune encephalitis(AE)at the local hospital.However,after the treatment with intravenous immunoglobulin and highdose glucocorticoids,her symptoms unchanged.Two months later,she was admitted to our hospital due to an unstable gait and persistent leg stiffness,at which point she was diagnosed as anti-GAD AE concomitant with SPS.Her clinical symptoms improved with an increased dose of y-aminobutyric acid(GABA)-enhancing drug and plasma exchange.Anti-GAD antibody-associated AE combined with SPS is extremely rare.Treatment with GABA-enhancing drugs and appropriate immunotherapy can improve the neurological function of patients suffering from the combination of SPS and limbic encephalitis.

Autoimmune encephalitis with posterior reversible encephalopathy syndrome:A case report

BACKGROUND Posterior reversible encephalopathy syndrome(PRES)is a neuroimaging-based syndrome and is associated with multifocal vasogenic cerebral edema.Patients with PRES frequently demonstrate headache,seizure,encephalopathy,altered mental function,visual loss and so on.We here report a patient who showed persistent neurologic deficits after PRES and was ultimately diagnosed with autoimmune encephalitis(AE).CASE SUMMARY This case exhibits a rare imaging manifestation of anti-casper 2 encephalitis which was initially well-matched with PRES and associated vasogenic edema.CONCLUSION AE should be further considered when the etiology,clinical manifestations,and course of PRES are atypical.

Glutamic acid decarboxylase 65-positive autoimmune encephalitis presenting with gelastic seizure, responsive to steroid: A case report

BACKGROUND Anti-glutamic acid decarboxylase(GAD)antibody is known to cause several autoimmune-related situations.The most known relationship is that it may cause type I diabetes.In addition,it was also reported to result in several neurologic syndromes including stiff person syndrome,cerebellar ataxia,and autoimmune encephalitis.Decades ago,isolated epilepsy associated with anti-GAD antibody was first reported.Recently,the association between temporal lobe epilepsy and anti-GAD antibody has been discussed.Currently,with improvements in examination technique,many more autoimmune-related disorders can be diagnosed and treated easier than in the past.CASE SUMMARY A 44-year-old female Asian with a history of end-stage renal disease(without diabetes mellitus)under hemodialysis presented with diffuse abdominal pain.The initial diagnosis was peritonitis complicated with sepsis and paralytic ileus.Her peritonitis was treated and she recovered well,but seizure attack was noticed during hospitalization.The clinical impression was gelastic seizure with the presentation of frequent smiling,head turned to the right side,and eyes staring without focus;the duration was about 5–10 s.Temporal lobe epilepsy was recorded through electroencephalogram,and she was later diagnosed with anti-GAD65 antibody positive autoimmune encephalitis.Her seizure was treated initially with several anticonvulsants but with poor response.However,she showed excellent response to intravenous methylprednisolone pulse therapy.Her consciousness returned to normal,and no more seizures were recorded after 5 d of intravenous methylprednisolone treatment.CONCLUSION In any case presenting with new-onset epilepsy,in addition to performing routine brain imaging to exclude structural lesion and cerebrospinal fluid studies to exclude common etiologies of infection and inflammation,checking the autoimmune profile has to be considered.In the practice of modern medicine,autoimmune-related disorders are relatively treatable and should not be missed.

Structural mechanisms of GABA A receptor autoimmune encephalitis

Autoantibodies targeting neuronal membrane proteins can cause encephalitis,seizures,and severe behavioral abnormalities.While antibodies for several neuronal targets have been identified,structural details on how they regulate function are unknown.Here we determined cryo-electron microscopy structures of antibodies derived from an encephalitis patient bound to theγ-aminobutyric acid type A(GABAA)receptor.

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.

White matter connectivity damage secondary to hippocampal and amygdala target injuries in acute limbic encephalitis Diffusion tensor image and voxel-based morphometry paired study

BACKGROUND： Limbic encephalitis is a rare syndrome that specifically affects the limbic system. Magnetic resonance imaging （MRI） has been typically used to detect brain changes in this disease. However, the mechanisms of limbic encephalitis-related white matter damage remain poorly understood. OBJECTIVE： To characterize white matter connectivity changes secondary to injuries of the limbic system in limbic encephalitis through combined application of diffusion tensor imaging （DTI） and voxel-based morphometry. DESIGN, TIME AND SETTING： A non-randomized, controlled, clinical, neuroimaging, DTI study was performed at the Department of Radiology, West China Hospital in December 2008. PARTICIPANTS： A male, 46-year-old, limbic encephalitis patient, as well as 11 age- and gender-matched healthy volunteers, were enrolled in the present study. METHODS： MRI was performed on the limbic encephalitis patient using a 3.0T MR scanner. Three-dimensional SPGR Tl-weighted images and DTI were acquired in the patient and controls. Data were analyzed using Matlab 7.0 and SPM2 software. MAIN OUTCOME MEASURES： Results from routine MRI scan with contrast enhancement of patient, as well as fractional anisotropy and mean diffusivity value map differences between patient and controls. RESULTS： Significant symmetric MRI signal intensity abnormalities were observed with routine MRI Affected bilateral hippocampi and amygdala exhibited hypointense signals in TIWI and hyperintense signals in T2 images. The DTI study revealed decreased fractional anisotropy values in the bilateral alveus and fimbria of the hippocampus, bilateral internal and external capsules, white matter of the right prefrontal area, and left corona radiate in the patient compared with normal controls （P 〈 0.001） Significantly increased fractional anisotropy, mean diffusivity, or decreased mean diffusivity were not observed in the patient, compared with controls. CONCLUSION： Secondary white matter damage to the hippocampal afveus and fimbria was apparent in the limbic encephalitis patient. In addition, other white matter fiber injuries surrounded the limbic structures, which were not attributed to secondary limbic system injuries.

Case Study on Focal Retrograde Amnesia due to Limbic Encephalitis

This case study addresses episodic memory impairment or focal retrograde amnesia related to limbic encephalitis. The patient in question was a right-handed man in his 60s who developed focal retrograde amnesia due to limbic encephalitis. An abnormal MRI signal was observed in the right medial temporal lobe. Immediately after the encephalitis onset, mental symptoms—including impaired consciousness, disorientation, hallucinations, and delusions—appeared;however, his condition improved with medical treatment. After transfer to a convalescent and rehabilitation hospital, various neuropsychological tests were conducted but no apparent functional decline was observed in intellectual function, attention, memorization, or retention. However, the patient exhibited impairments related to autobiographical memory and memory of events 4?-?5 years before the onset of limbic encephalitis. Based on these observations, the patient was considered to exhibit focal retrograde amnesia due to limbic encephalitis. Despite exhibiting retrograde amnesia, he had no difficulty in his daily life in the ward. Moreover, after discharge from hospital, smooth work reinstatement was possible. This case demonstrates that, even after exhibiting retrograde amnesia, if its duration is relatively short and physical function and other higher-order brain functions are sustained, social rehabilitation—including work reinstatement—is feasible.

Limbic Encephalitis Associated with Voltage-Gated Potassium Channel-Complex Antibodies: Patient Report and Literature Review

Background: The family of disorders associated with antibodies against neuronal surface antigens is a rapidly expanding category of autoimmune neurologic disease. Methods: Clinical and laboratory findings of a patient with voltage-gated Kv1 potassium channel (VGKC)-complex autoantibodies are reported and the literature is reviewed. Results: New-onset faciobrachial dystonic seizures, distal large and painful small fiber peripheral neuropathy, dysautonomia, cognitive and memory disturbances were associated with hypometabolism of the left temporal lobe without evidence of systemic malignancy in whole-body positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography. Brain MRI and cerebrospinal fluid were normal with absent intrathecal VGKC-complex antibodies consistent with extrathecal production. Epidermal nerve fiber studies confirmed small fiber neuropathy in association with abnormal autonomic laboratory testing. Discussion: Neurologic involvement associated with VGKC complex autoimmunity is a precisely delineated disorder involving the central, peripheral, and autonomic nervous system.

Autoimmune Encephalitides

Autoimmune encephalitis is a potentially severe disorder of the brain of diverse causes with a complex differential diagnosis. Recent advances in the past decade have led to the elucidation of new syndromes and biological markers transforming the approach to diagnosis and management of autoimmune encephalitis. Limbic encephalitis, the commonest form of autoimmune encephalitis, combines common presentations of cognitive, psychiatric, and epileptic disorders and has until recently been considered paraneoplastic or postinfectious in origin. The autoimmune encephalitides are clinically and histopathologically associated with serum and intrathecal antibodies to intracellular and surface neuronal antigens, and constituents of the limbic system neuropil. This has led to a reconsideration of a number of neuropsychiatric and neurocognitive disorders as having shared mechanisms of origin. This chapter reviews their historical background, clinical presentation, laboratory evaluation, histopathology, diagnosis and management.