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.

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.

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.

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.

Heterogeneity of clinical features, EEG and brain imaging findings in anti‑leucine‑rich glioma‑inactivated protein 1 autoimmune encephalitis: a retrospective case series study and review of the literature

Background Anti-leucine-rich glioma-inactivated 1(LGI-1)autoimmune encephalitis(AE),characterized by rapid decline of memory,seizures,and neuropsychiatric abnormalities,is a rare but devastating disorder.Early diagnosis and treatment are essential to prevent long-term sequelae.In this report,we provide a detailed description of clinical characteristics,laboratory test results,imaging,and electroencephalography(EEG)findings,as well as treatment responses of eight patients with anti-LGI-1 AE treated at our center.Case presentation At the onset,all eight patients presented with confusion/memory deterioration,seizures(including faciobrachial dystonic seizures or other types of seizure),and behavioral changes such as hallucination,paranoia,and anxiety.Four patients were found with severe hyponatremia.Anti-LGI1 antibodies were detected in the cerebrospinal fluid and/or serum of all patients.For patients with faciobrachial dystonic seizures,no discernible scalp EEG change was detected,while EEG recording of patients experiencing other types of seizure showed focal slowing,focal epileptiform discharges,and focal onset seizures.All patients showed abnormal brain magnetic resonance imaging signals,mainly involving the mesial temporal lobe and the hippocampus.In addition,one patient also experienced fulminant cerebral edema during the acute phase of the illness.All patients received immunotherapy and anti-seizure medications and achieved good seizure control.Nevertheless,these patients continued to experience cognitive impairment during their long-term follow-ups.Conclusions The care of anti-LGI1 AE patients requires rapid evaluation,prompt initiation of immunotherapy,and long-term follow-up.The long-term presence of neurocognitive complications observed in these patients underline the importance of developing reliable biomarkers that can distinguish between different subtypes of this disease with heterogeneous clinico-electrographico-radiological features.Further research is needed to understand the molecular mechanisms underlying the heterogeneity,in order to facilitate development of more effective treatments for anti-LGI1 AE.

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.

Autoimmune Encephalitis： An Expanding Frontier of Neuroimmunology

INTRODUCTIONDiscovery of the spectrum ofautoimmune encephalitis （ALE） is among the most attractive events of neurology in the past decade. AIE includes a heterogeneous group of encephalitic syndromes, which generally include two major categories： classic paraneoplastic limbic encephalitis （LE） associated with the so-called well-characterized onconeural autoantibodies against intracellular neuronal antigens （e.g., Hu, Ma2, etc.） and new-type AIE associated with autoantibodies to the neuronal surface or synaptic antigens.

Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a 4-year-old girl:a case report

Background:Leucine-rich glioma-inactivated protein 1(LGI1)antibody-mediated encephalitis is a rare subtype of autoimmune encephalopathy,which is associated with autoimmunity against the neuronal plasma membrane proteins.The characteristic symptoms of this disease are memory dysfunction,seizures,faciobrachial dystonic seizures,cognitive deficits,neuropsychiatric disturbances,and intractable hyponatremia.The diagnosis of this disease mainly depends on the presence of anti-LGI1 antibody in serum or cerebrospinal fluid of patients.LGI1 antibody encephalitis has been reported mostly in adults,with rare occurrences in children.Case presentation:In this report,we described a 4-year-old girl with typical seizures.Seizure types included focal seizures and generalized tonic-clonic seizures.The electroencephalogram findings showed focal discharges.Brain magnetic resonance imaging(MRI)showed normal.The cerebrospinal fluid(CSF)levels of cells,glucose,and chloride were within the normal range,and the culture did not reveal growth of any pathogen.Test of serum LGI1-Ab was positive,while the tests for autoimmune encephalitis antibody series in CSF were negative.The seizures of the patient were completely controlled after the therapy of immunoglobulin,methylprednisolone and antiepileptic drugs(AEDs),and the mental state almost returned to normal.Conclusion:To our knowledge,the patient described here may be the youngest case of LGI1 antibody encephalitis reported to date.Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures and have good response to the therapy of immunoglobulin,methylprednisolone and antiepileptic drugs.Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1-antibody encephalitis.

Psychotic and nonpsychotic mood disorders in autoimmune encephalitis:diagnostic issues and research implications

Recent research on autoimmune disorders suggests additional links between systemic and central nervous system(CNS)pathophysiology,among which the identification of antibody-induced limbic encephalitis provided the strongest evidence for the potential involvement of autoimmunity in the pathogenesis of severe mood and psychotic symptoms.In these illnesses,psychiatric symptoms predominate in the initial phase of the disorder in up to 70%of the cases,and they often lead patients to early psychiatric evaluation.For this reason,it is very important to increase the limited knowledge among psychiatrists about these autoimmune neuropsychiatric diseases,which can mimic psychiatric syndromes,in particular,those typically presented in severe mood disorders and schizophrenia.On the other hand,similarities in clinical presentation suggest that neuroinflammation and systemic immune dysregulation may play a role in the pathophysiology of severe mood and psychotic disorders.A complex interaction between periphery and immune cells of the CNS may result in cellular damage through mechanisms involving excitotoxicity,oxidative stress,and mitochondrial dysfunction.These pathways are possibly shared between comorbid medical disorders and severe mood and psychotic disorders and may reflect common underlying vulnerability.

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.

Diagnostic algorithms in autoimmune encephalitis

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized.Recognition of clinical syndromes,consistent methods of diagnosis,and early targeted immunotherapy can lead to a favorable outcome in diseases that may be associated with significant disability or death if left untreated.Here the conditions associated with neuronal surface antibodies are briefly reviewed,some general aspects of these syndromes are considered and guidelines that could help in the recognition of these disorders are suggested.Furthermore,a diagnostic algorithm to detect and characterize neuronal cell surface autoantibodies is suggested and some of the caveats of serum testing are outlined.Future directions will involve the identification of novel autoantibodies,the standardization of methods to detect and characterize them,as well as evaluation of the most efficacious therapeutic strategies in patients with established diagnosis of autoimmune encephalitis.

Unremitting diarrhoea in a girl diagnosed anti-N-methyl-D-aspartatereceptor encephalitis:A case report

BACKGROUND Asymptomatic cytomegalovirus(CMV)infection is common in children;in contrast,in children with a weakened immune system,invasive CMV can occur.This is the first case report of a severe manifestation of CMV esophagoenterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor(antiNMDAR)encephalitis who received only a moderate dose of corticosteroid therapy.CASE SUMMARY A 12-year-old-Thai girl presented with acute behavioural change and headache for 6 d.Electroencephalogram and positivity for NMDAR autoantibodies were compatible with anti-NMDAR encephalitis.Hence,she received pulse methylprednisolone 10 mg/kg per day for 4 d and continued with prednisolone 1.2 mg/kg per day.On day 42 of corticosteroid therapy,she developed unremitting vomiting and diarrhoea.Endoscopy showed multiple ulcers and erythaematous mucosa along the gastrointestinal tract.Tissue CMV viral load and viral-infected cells confirmed CMV esophago-enterocolitis.Therefore,the patient received ganciclovir 5 mg/kg per dose every 12 h for 3 wk and then 5 mg/kg per dose once daily for 3 wk.Unremitting diarrhoea slowly improved from stool output 1-4 L per day to 1-2 L per day after 3 wk of treatment.Pulse methylprednisolone 20 mg/kg for 5 d was initiated and continued with prednisolone 1 mg/kg per day.After this repeated pulse methylprednisolone treatment,surprisingly,diarrhoea subsided.Immunologic work-up was performed to rule out underlying immune deficiency with unremarkable results.CONCLUSION Unremitting diarrhoea from CMV esophago-enterocolitis subsided with antiviral and methylprednisolone therapy,implying the immune and NMDAR dysregulation in anti-NMDAR encephalitis.

Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases:A case report

BACKGROUND Anti-N-methyl-D-aspartate receptor encephalitis(NMDARe)is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease,whereas it has been relatively rare.We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease.CASE SUMMARY A 29-year-old man was initially admitted with headache,fever,intermittent abnormal behavior,decreased intelligence,limb twitching and loss of consciousness on July 16,2018.On admission,examination reported no abnormality.During his presentation,he experienced aggravated symptoms,and the reexamination of cranial magnetic resonance imaging(MRI)indicated punctate abnormal signals in the left parietal lobe.External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody(Ab)(-),cerebrospinal fluid NMDAR-Ab(+)1:10 and Epstein-Barr virus capsid antigen antibody Ig G(+).Due to the imaging findings,anti-NMDARe was our primary consideration.The patient was treated with methylprednisolone and gamma globulin pulse therapy,mannitol injection dehydration to reduce intracranial pressure,sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms.The patient was admitted to the hospital for the second time for“abnormal mental behavior and increased limb movements”on December 14,2018.Re-examination of electroencephalography and cranial MRI showed no abnormality.The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive.Considering comprehensive recurrent anti-NMDARe,the patient was treated with propylene-hormone pulse combined with immunosuppressive agents(mycophenolate mofetil),and the symptoms were relieved.The patient was admitted for“hoarseness and double vision”for the third time on August 23,2019.Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe,and synoptophore examination indicated concomitant esotropia.The patient’s visual acuity further decreased,and the reexamination of cranial MRI+enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata,left pons arm,left cerebellum and right midbrain,thalamus.The patient was diagnosed with an accompanying demyelinating disease.Serum antimyelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive.The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome.The patient was successfully treated with methylprednisolone,gamma globulin pulse therapy and rituximab treatment.The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion.CONCLUSION We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

Anti-IgLON5 disease: a novel topic beyond neuroimmunology

Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the antiIgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in antiIgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.

Anti-NMDAR encephalitis with seizure-like activity and hemiplegia-a case report and literature review

Background Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis accounts for the vast majority of cases of autoimmune encephalitis.Its common clinical symptoms are psychiatric symptoms,behavioral dysfunction,seizures,speech impairment,cognitive impairment,movement disorders,decreased consciousness,and autonomic instability.This report was aimed to provide evidence for anti-NMDAR encephalitis with seizure-like activity,based on the clinical presentations,brain magnetic resonance imaging(MRI),and electroencephalogram(EEG)recordings.Case presentation We report a 11-year-old girl who suffered epigastric pain after vigorous physical activity.She felt weakness of the muscles.She had syncope only once and urinary incontinence on the way to the hospital and vomited at the arrival.The entire procedure lasted approximately 15 min.The next night she had recurrent headache attacks along with irritability,like someone“tapping”to the right occipital region.She experienced numbness in the left upper limbs and shallowing of the frontal lines on the left side.Holter monitoring showed normal findings,but brain MRI,EEG recording,and cerebrospinal fluid(CSF)antibody testing showed abnormal results.The patient was finally diagnosed with anti-NMDAR encephalitis.After treatment with glucocorticoids and acyclovir,she fully recovered and was discharged from the hospital.Conclusions Although the patient presented with pain and impaired limb movements,she did not have respiratory or(and)circulatory failure,and the symptoms entirely resolved.Early accurate diagnosis and timely treatment are essential for patients with anti-NMDAR encephalitis.

Encephalitis associated with autoantibodies binding toγ-aminobutyric acid-A,γ-aminobutyric acid-B and glycine receptors:immunopathogenic mechanisms and clinical characteristics

Recent,discoveries of neural antibodies have facilitated the diagnosis of immune-mediated,immunotherapy-responsive neurologic disorders.Antibodies that target inhibitory central nervous system receptors,such asγ-aminobutyric acid-B,γ-aminobutyric acid-A,and glycine receptors,disrupt inhibitory regulatory synaptic functions,and lead to neuronal hyperexcitability.The myriad of neurologic,manifestations associated with these antibodies includes seizures,encephalopathy,muscle rigidity and stiffness.This article provides a review of the immunopathogenic mechanisms and the clinical and therapeutic implications of autoimmune encephalitis associated with these antibodies that target inhibitory receptors.

Autoimmune encephalopathies in children:diagnostic clues and therapeutic challenges

Neuronal surface antibody syndromes(NSAS)encompass a variety of disorders associated with“neuronal surface antibodies”.These share clinical and neuroradiological features that pose challenges related to their recognition and treatment.Recent epidemiological studies show a clear predominance for the glutamate-N-methyl-D-aspartate receptor encephalitis in both adults and pediatric population.Despite this,the overall NSAS’s incidence remains underestimated,and diagnosis persists to be not always easy to achieve.Based on current literature data,in this paper the authors propose a diagnostic pathway to approach and treat pediatric NSAS.An autoimmune etiology can be suggested through the integration of clinical,immunological,electrophysiological and neuroradiological data.On that basis,a target treatment can be started,consisting of corticosteroids and intravenous immunoglobulin or plasma exchange as a first-line immunotherapy,followed by second-line drugs including rituximab,cyclophosphamide or mycophenolate mophetil,if the case.In children a prompt diagnosis and a targeted treatment may lead to a better clinical outcome.Nevertheless further studies are required to assess the need of more tailored treatments according to long-term outcome findings and prognostic factors in different NSAS.

Limbic Encephalitis Associated with Anti-y-aminobutyric Acid B Receptor Antibodies： A Case Series from China

Background： Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor （GABABR） in patients with limbic encephalitis （LE） was first described in 2010. We present a series of klan Chinese patients tbr further clinical refinement. Methods： Serum and cerebrospinal fluid （CSF） samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABABR antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results： All eighteen anti-GABABR antibody-positive cases had limbic syndromes, and electroencephalogram （EEG） or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen （17/18） patients presented with new-onset refractory seizure or status epileptics. Twelve （12/18） patients had memory deficits, 11 （11/18） patients had personality change, 7 （7/18） patients had disturbance of consciousness, and 3 （3/18） patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 （6/18） patients. Ten （10/18） patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten （10/18） patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications. Conclusions： Our study demonstrates that most Han Chinese patients with anti-GABABR antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABABR antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.