Autoimmune Encephalitis Research Articles

Autoimmune encephalitis with coexisting antibodies to GABABR, GAD65, SOX1 and Ma2.

Autoimmune encephalitis (AE) is a disease caused by an abnormal reaction between the body's autoimmunity and the central nervous system, in which the abnormal immune response targets antigenic components within or on the surface of neuronal cells. The main manifestations are mental and behavioural changes, cognitive impairment, impaired consciousness, seizures, movement disorders, etc. Most cell surface antibodies respond well to immunotherapy, intracellular antibodies, on the other hand, are usually associated with more tumours and are relatively difficult to treat with a poor prognosis. In recent years, autoimmune encephalitis that is positive for multiple anti-neuronal antibodies has been gradually recognized in the clinic, with complex and varied clinical manifestations, especially in combination with malignant tumours, which have worse treatment and prognosis. Current clinical studies on the coexistence of multiple anti-neuronal antibodies in patients with AE are mainly disseminated case reports. Patients with AE in which four anti-neuronal antibodies coexist are even rarer. We report a patient who initially presented with an irritating dry cough and hyponatraemia and a chest CT suspicious for malignancy, followed by progressive deterioration of persistent status epilepticus, consciousness and cognitive deficits, and psycho-behavioural abnormalities. Serum and cerebrospinal fluid antibodies against neuronal surface or intracellular antigens were detected using a cell-based assay (CBA) method. Serum and cerebrospinal fluid were found to be positive for anti-GABABR, GAD65, SOX1 and Ma2 antibodies. And a definitive diagnosis of small cell lung cancer was made by immunohistochemistry. He eventually received gammaglobulin, steroid pulsed therapy and tumour chemotherapy. The coexistence or overlap of multiple anti-neuronal surface antibodies with anti-neuronal intracellular antibodies is rare and increases the likelihood of underlying malignancy. Elucidating the impact of individualized immunotherapy and coexisting antibodies on the clinical presentation of patients has the potential to improve long-term prognosis.

Caloric requirement targets for nutritional support in adult autoimmune encephalitis: a retrospective cohort study.

Autoimmune encephalitis (AE) is a severe neurological disease often accompanied by consciousness disturbances, severe swallowing difficulties, and gastrointestinal dysfunction, increasing the risk of malnutrition. However, the optimal caloric intake target during the acute phase of AE remains unclear. This study aims to evaluate the impact of caloric intake on short-term clinical outcomes in AE patients, specifically focusing on the improvement in Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, to provide recommendations for nutritional support during the acute phase. A retrospective study analyzed clinical data from 128 adult AE patients requiring nutritional support, admitted to West China Hospital, Sichuan University, from January 2020 to January 2024. Patients were categorized into low-calorie intake (below 70% of requirements), standard-calorie intake (70-100% of requirements), and high-calorie intake (above 100% of requirements) groups. Multivariate linear and logistic regression models were used to quantify the associations. Higher caloric intake was significantly associated with improved CASE scores (β = 8.58, SE = 3.75, 95% CI = 1.14 to 16.03, p = 0.02). Low caloric intake negatively impacted the improvement of CASE scores (p = 0.049), particularly in seizures and speech problems. The low-calorie intake group had significantly longer hospital stays and nutrition therapy durations (45.79 ± 30.98 days, p < 0.01; 40.39 ± 31.92 days, p = 0.02). Adequate caloric intake has a significant positive impact on the short-term clinical outcomes of AE patients, suggesting that meeting or exceeding caloric requirements may promote neurological recovery in AE patients. Future prospective studies are needed to validate these findings and further optimize nutritional support strategies.

Lack of Comprehensive Neural Antibody Testing: A Contributor to Diagnostic Delay in Autoimmune Encephalitis.

Lack of Comprehensive Neural Antibody Testing: A Contributor to Diagnostic Delay in Autoimmune Encephalitis.

Musical and verbal memory dissociation in a patient with autoimmune encephalitis

Music is emotionally arousing and activates different brain areas. Musicians with encephalitis spare musical memory. However, no prior studies have used delayed verbal and musical memory tasks in a patient with thalamic damage. The aim of the present study is to analyse a possible dissociation between verbal and musical memory in a patient with autoimmune encephalitis, who was an amateur musician. JC is a 67- years-old amateur musician with autoimmune encephalitis. He and 8 participants (musicians and non-musicians) were assessed through musical (novel excerpt recognition) and verbal memory tasks (word learning, recall and recognition), including a delayed memory task, a week later. The results showed JC had spared musical memory and impaired verbal memory, and a significant dissociation between them. The dissociation found could be due to the musical training brain plasticity. These findings support the idea of music stimuli as therapeutic tools for these patients.

Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance.

Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) encompass a heterogeneous group of antibody-associated disorders. Both the number of syndromes and commercially available antibody tests have increased considerably over the past decade. High-quality population-based data on epidemiology of these disorders and real-world performance of antibody tests are needed. In this nationwide retrospective cohort study, we identified all serum and CSF samples tested for antibodies against intracellular antigens (IAs: Hu [ANNA1], Yo [PCA1], CV2 [CRMP5], Ri [ANNA2], Ma1, Ma2 [Ta], amphiphysin, GAD65, GFAP, KLHL11, CARP VIII) or extracellular antigens (EAs: NMDAR, LGI1, Caspr2, GABA-B-R, GABA-A-R, AMPAR, DPPX, GlyR, mGluR1, VGCC, IgLON5, Tr [DNER]) between January 2016 and December 2021 in the Netherlands. Nationwide coverage was guaranteed for all antibodies except anti-GAD65 and anti-VGCC. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV); obtained clinical information about patients who tested positive; assigned diagnosis of AIE/PNS according to diagnostic criteria; and calculated incidence rates for IA, EA, and individual antibody-associated syndromes. In the study period, 2,877 (9.5%) of 30,246 samples, belonging to 1,228 patients, tested positive. Sensitivity and specificity were high (>95%) to very high (>99%) for most tests in both serum and CSF. PPVs for several tests were moderate to poor, especially for serum testing of IA antibodies (25%-80%). Clinical data were available for 940 (76.5%) of 1,228 patients. A total of 578 AIE/PNS diagnoses were made. The incidence rate for AIE/PNS (per million person-years) increased from 4.70 (95% CI 3.72-5.85) in 2016 to 5.76 (4.69-7.00) in 2021. Overall, the incidence rate was 5.57 (5.13-6.05), 2.96 (2.64-3.31) for the EA and 2.61 (2.31-2.94) for the IA subgroup. The 4 most common AIE/PNS types were anti-NMDAR, anti-LGI1, anti-Hu, and anti-GAD65, together comprising almost two-thirds of all diagnoses (364/578, 63.0%). Most commercial antibody tests perform well overall, but important pitfalls remain. Although almost all tests had high specificity, PPV was only modest in the setting of these rare diseases and mass testing. We observe trends toward increasing incidence of antibody-associated AIE/PNS.

Distinguishing seizures in autoimmune limbic encephalitis from mesial temporal lobe epilepsy with hippocampal sclerosis: Clues of a temporal plus network

ObjectiveDiagnosing autoimmune limbic encephalitis (ALE) in adults with new-onset seizures can be challenging, especially when seizures represent the predominant manifestation and MRI findings are not straightforward. By comparison with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), this study aimed to identify ictal electro-clinical features that might help clinicians recognize ALE-related seizures. MethodsThis retrospective, multi-centre study analysed the ictal semiology and EEG correlate of 116 video-EEG-captured seizures in 40 ALE patients and 45 ones recorded in 21 MTLE-HS subjects. The proportion of patients presenting each clinical feature on at least one occasion was compared between the study groups. Latent class analysis (LCA) was also performed. ResultsIctal features were overall more numerous in ALE than in MTLE-HS (33 vs 22), and LCA confirmed the intrinsic variability of ALE-related seizures. Hyperventilation served as a trigger only in ALE (4/40). Awareness impairment (p = 0.032), limb dystonic posturing (p = 0.009) and manual automatisms (p < 0.001) were significantly less common in ALE cases. Conversely, piloerection was observed only in ALE subjects, although it did not reach statistical significance (p = 0.289), as was the case for déjà-vu (p = 0.084), and sensory symptoms (p = 0.079). Regarding EEG, the type of ictal pattern differed significantly (p = 0.007). SignificanceThis study shows that, despite the wide overlap with MTLE-HS, some ictal electro-clinical features could help clinicians suspect the autoimmune origin of adult-onset seizures. Moreover, autoimmune limbic seizures apparently shared similarities with ‘temporal plus’ epilepsy, which could partly account for the poor surgical outcomes and provide an interesting conceptual framework for future research.

Catatonia in anti-NMDA receptor encephalitis: a case series and approach to improve outcomes with electroconvulsive therapy

BackgroundAnti-N-methyl-D-aspartate (NMDA) receptor encephalitis has been recognised to present with the syndrome of catatonia. In severe cases dysautonomia is representative of malignant catatonia. The treatment with benzodiazepines (BZDs) and electroconvulsive therapy (ECT) may decrease morbidity and mortality in patients presenting with anti-NMDA receptor encephalitis and catatonia.MethodsThis is a retrospective case series of eight patients with anti-NMDA receptor encephalitis treated with ECT. We use clinical prediction scores (Clinical Assessment Scale for Autoimmune Encephalitis [CASE] and anti-NMDAR Encephalitis One-Year Functional Status scores) to compare expected outcomes and observed outcomes.ResultsCASE scores in our group ranged between 5 and 19, with a mean score of 13.8 (median 15.5). NEOS scores ranged from 2 to 4, with a mean and median of 3. Of the eight patients, six had a favourable modified Rankin Score (0–2) at a follow-up of 8 to 12 months. Patients received an average of 29.9 ECT treatments in total.ConclusionsBased on clinical prediction scores, this cohort had better than expected functional outcomes. We discuss the use of BZDs and ECT in these cases and propose a treatment algorithm for patients who present with catatonic syndrome in anti-NMDA receptor encephalitis.

A Case Report on Anti-N-Methyl-D-Aspartate Encephalitis

Aim: The case study aims to describe and evaluate the initial neuropsychiatric symptoms, therapeutic methods, and diagnostic criteria, of a 3-year-old girl who had been diagnosed with anti-N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis. This case study implies the importance of early detection and treatment in pediatric autoimmune encephalitis, highlighting its diagnostic challenges and the successive use of immunotherapy and outcomes. Presentation of Case: A 3-year-old developmentally normal girl child was brought to the hospital with C/O fever for 2 days. Following this she had seizures lasting for around 2 minutes and followed by shivering movements in the right leg for 15 minutes and then she regained consciousness after 25 minutes. CSF analysis showed pleocytosis. Serological tests (Typhoid IgM, Rapid Malaria, Scrub IgM, Dengue IgM, Japanese Encephalitis, and Herpes Simplex Virus IgM) were negative. MRI indicated diffuse encephalopathy, and EEG detected epileptic activity. Further antibody testing in serum and CSF revealed positive Anti-NMDAR antibodies. The patient was treated with amoxicillin-clavulanate(400mg), ceftriaxone(750mg), and acyclovir(130mg) intravenously initially. Once the definitive diagnosis was made, she was treated with IVIG(26g), methylprednisolone(390mg), and levetiracetam(280mg). Discussion: Anti-N-Methyl-D-Aspartate Receptor Encephalitis is an autoimmune encephalitis characterized by complicated neuropsychiatric symptoms and immunoglobulin G (IgG) antibodies against the NR1 subunit of the NMDA receptors in the central nervous system. Conclusion: The appropriate diagnosis and treatment of autoimmune encephalitis necessitate an organized approach. A wide range of autoantibody tests can be performed to identify or rule-out specific autoimmune causes. Patients may relapse and require appropriate follow-up care.

Clinical characteristics and prognosis analysis of acute symptomatic seizures secondary to autoimmune encephalitis.

This study aimed to analyze the clinical characteristics and prognosis of patients with autoimmune encephalitis (PWAE) who experienced seizures during the acute phase. Clinical data were collected from 84 patients diagnosed with AE at the General Hospital of Ningxia Medical University between January 2015 and January 2023. Patients were divided into seizure and non-seizure groups. Clinical characteristics of both groups were compared, including differences between anti-NMDAR and anti-LGI1 encephalitis within the seizure group. Due to the limited sample size and to avoid overfitting, we focused on univariate logistic regression analysis to identify individual prognostic factors. A total of 84 patients were enrolled, with 76.19% (64/84) in the seizure group and 23.81% (20/84) in the non-seizure group. The seizure group had a longer hospital stay (p = 0.013), higher rates of impaired consciousness (p = 0.001), and more frequent intensive care unit (ICU) admission (p = 0.011). They also had higher peripheral blood neutrophil-to-lymphocyte ratio (NLR), leukocyte count, and uric acid levels (p = 0.038, p = 0.006, p = 0.020), and were more likely to show slow-wave rhythms on electroencephalography (EEG) (p = 0.031). At 2-year follow-up, there was no significant difference in prognosis between the seizure and non-seizure groups (p = 0.653), with 35.94% (23/64) of the seizure group having a poor prognosis. Status epilepticus (SE), complications, endotracheal intubation, mRS score at discharge, APE2, and RITE2 scores increased the risk of poor prognosis (OR > 1), while intensive care and albumin reduced the risk (OR < 1). Seizures are common in the early stages of AE, with faciobrachial dystonic seizures (FBDS) characteristic of anti-LGI1 encephalitis and SE and super-refractory status epilepticus (Sup-RSE) frequently observed in anti-NMDAR encephalitis. Seizure semiology across AE subtypes lacks specificity, and no symptoms clearly distinguish immune-mediated from non-immune causes. While seizures are linked to AE severity, particularly in anti-NMDAR encephalitis, they do not appear to impact overall prognosis. SE, complications, endotracheal intubation, modified Rankin Scale (mRS) score at discharge, Antibody-Prevalence in Epilepsy and Encephalopathy (APE2) score, Response to Immunotherapy in Epilepsy and Encephalopathy (RITE2) score, intensive care, and albumin were identified as significant prognostic factors.

Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesised the presence of additional genetic predispositions. In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively. Outside the known major HLA signal, we found two single nucleotide polymorphisms (SNPs) at genome-wide significance (p < 5 x 10-8), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23. Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses.

Adult-onset neuronal ceroid lipofuscinosis misdiagnosed as autoimmune encephalitis and normal-pressure hydrocephalus: A 10-year case report and case-based review.

Neuronal ceroid lipofuscinoses (NCLs) are rare, fatal, inherited neurodegenerative disorders characterized by myoclonic epilepsy, cognitive decline, brain atrophy, and retinopathy. The pathogenesis and clinical manifestations of NCL are not well understood and frequently result in misdiagnosis and overtreatment. The aim of this case report and review is to improve our understanding of the clinical features and management of NCL. A 36-year-old woman initially presented with refractory epilepsy. Initially diagnosed with autoimmune encephalitis, the patient was later diagnosed with normal-pressure hydrocephalus. A definitive diagnosis of adult-onset neuronal ceroid lipofuscinosis (ANCL) was established after 10 years of observation, utilizing biopsy and genetic testing. High-dose intravenous immunoglobulin and methylprednisolone were administered, along with the insertion of a ventriculoperitoneal shunt. Despite various treatments, the patient's condition did not improve. ANCL typically presents with the clinical triad of refractory seizures, progressive cognitive decline, and movement disorders. Neuroimaging often reveals progressive brain atrophy on magnetic resonance imaging, while electroencephalograms frequently show epileptiform discharges. The prognosis is generally poor. Improved understanding of ANCL from both clinical and radiological perspectives, coupled with early consideration of differential diagnoses, could minimize unnecessary interventions and optimize patient care.

Specific and Polyfunctional T Cell Response Against N-Methyl-d-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model

Background: Anti-N-Methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1359–378 peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment. Results: In this mouse model, we identified anti-GluN1-specific CD4+ but also CD8+ T cells in both spleen and meninges. T helper cells have a polyfunctional profile, arguing for a T and B cell crosstalk to generate anti-GluN1 pathogenic Abs. Interestingly, proteomic analysis of AE meninges showed enrichment of differentially expressed proteins in biological processes associated with B cell activation and cytokine signalling pathways. Conclusions: This study identified, for the first time, a potential contribution of T helper cells in the pathology of NMDAR AE and paved the way for the development of future tolerogenic approaches to treat relapses.

Causal relationship between circulating inflammatory proteins and risk of different types of encephalitis: A two-sample Mendelian randomization study

BackgroundCytokines are potent molecules of the immune response. They act at the site of inflammation and circulate in the bloodstream. However, there are few studies on encephalitis and circulating inflammatory proteins. MethodsIn this study, Mendelian randomization (MR) was used to explore the potential causal effect of 91 circulating inflammatory proteins on 3 different types of encephalitis. Causal effects were examined using Steiger, MR-Egger, weighted median, and inverse variance weighting (IVW) methods. IVW methods were primarily used for results interpretation. In addition, sensitivity analyses were performed, including assessment of heterogeneity, horizontal pleiotropy, and Leave-one-out techniques. ResultsWe subjected 91 circulating inflammatory proteins to MR analysis of causality with each of the three types of encephalitis. The results suggested that the inflammatory factors with a potential causal relationship with viral encephalitis were caspase 8, C-X-C motif chemokine 6, interleukin-10, interleukin-15 receptor subunit alpha, interleukin-7, and TNF-beta. Inflammatory factors potentially causally associated with acute disseminated encephalomyelitis are beta-nerve growth factor, cystatin D, interleukin-7,Latency-associated peptide transforming growth factor beta 1,and neurotrophin-3.Inflammatory factors potentially causally associated with autoimmune encephalitis are C–C motif chemokine 25, hepatocyte growth factor, latency-associated peptide transforming growth factor beta 1, programmed cell death 1 ligand 1, sulfotransferase 1A1, and tumor necrosis factor. ConclusionThis finding identifies potential causal effects of certain circulating inflammatory factors on susceptibility to three types of encephalitis. It also suggests the therapeutic potential of modulating the levels of these cytokines. A basis for further research is provided.

Polygenic Landscape of Cryptogenic New-Onset Refractory Status Epilepticus: A Comprehensive Whole-Genome Sequencing Study.

Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole-genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024.

Prevalence & clinical outcome of autoimmune encephalitis versus viral encephalitis in children with acute encephalitis syndrome: A prospective observational study.

Background & objectives Acute encephalitic syndrome (AES), encompasses a wide spectrum of potential causes, clinical presentations, and outcomes. While infectious encephalitis is generally considered more prevalent, autoimmune encephalitis is emerging as a significant aetiology. Neuronal autoantibodies have been identified independently or in association with acute viral encephalitis. The primary objective of this study was to ascertain the prevalence and clinical manifestation of autoimmune encephalitis as well as of coexisting viral markers in children with AES. Methods This study was a prospective observational investigation conducted in a hospital setting. It involved enrolling children with AES who were admitted to specific tertiary hospitals. Children were subjected to examinations to detect the presence of viral markers and neuronal autoantibodies in both their blood and cerebrospinal fluid (CSF). All the participants received treatment based on established guidelines and was followed for six months for outcome assessment. Results During the study period, 867 children with AES were examined. Among these cases, 37 children (4.2%) were diagnosed with autoimmune encephalitis, and all of them tested positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibodies. Evidence of viral infection was seen in 409 (47.1%) of cases, out of which nearly 254 (29.2%) children had detectable HSV IgM antibodies. Among the 37 children with autoimmune encephalitis, 25 (67.5%) had evidence of a viral trigger, with eight of them tested positive for HSV IgM antibodies. The clinical presentation of autoimmune-associated AES was similar to those with viral aetiology. Interpretation & conclusions Autoimmune encephalitis triggered by neurotropic (HSV) viral infection was more prevalent in this study than in the earlier reports. Typically, these children show positive responses to immunosuppressive treatments if administered promptly. It is hence advisable to assess children who exhibit behavioural issues and movement disorders for possible autoimmune encephalitis.

Characteristic analysis of autoimmune encephalitis with antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

The clinical data of 7 patients with anti-α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor (AMPAR) encephalitis admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2024 were retrospectively collected, and 87 cases with complete literature data were included for summary analysis. Seven casess exhibited limbic encephalitis, including 3 with lung cancer and 1 with thymoma. All cases were treated with glucocorticoids and/or human immunoglobulin. Four cases with concurrent tumors were followed up for 1 to 25 months and all died. Among the 94 patients (7 admitted cases and 87 documented cases), there were 76 cases with tumor (80.9%), including 33 cases of thymoma (43.4%), 23 cases of lung cancer (30.3%), 9 cases of breast cancer (11.8%), and 6 cases of ovarian tumor (7.9%). The tumor was diagnosed in 13 cases (18.8%) before encephalitis, 40 cases (58.0%) within 1 month after encephalitis, 13 cases (18.8%) within 1-6 months, 2 case (2.9%) within 6-12 months, and 1 case (1.4%) after 1 year. Compared to the 18 patients without tumors who were followed up for>1 year, the 76 patients with tumors showed an increase in age and incidence of mental disorders (both P<0.05), while follow-up time and proportion of good prognosis were decreased (both P<0.05). Closely follow-up should be conducted within 1 year after anti-AMPAR encephalitis, especially in the lungs, thymus, breast, and ovaries. The prognosis of patients with tumors is poor, and older age and mental disorders may indicate the occurrence of tumors.

Anti-dopamine receptor 2 antibody encephalitis in adults: a case report

BackgroundAnti-dopamine receptor 2 (D2R) antibody encephalitis (D2R encephalitis) is a subtype of autoimmune encephalitis (AE). Lesions in affected patients primarily involve the basal ganglia, resulting in a range of psychiatric and movement disorders. A majority of cases reported to date have impacted children or adolescents, whereas we here describe a case of adult-onset D2R encephalitis.Case presentationA 30-year-old female patient affected by insomnia, recent memory impairment, bradykinesia, decreased responsivity, increased muscular tone of the extremities, and involuntary shaking of the right limb. Magnetic resonance imaging (MRI) of the basal ganglia did not reveal any notable findings, and both serum and cerebrospinal fluid were positive for antibodies specific for D2R. D2R encephalitis was diagnosed following the exclusion of other diseases. The patient’s symptoms improved significantly with immunotherapeutic treatment, and she recovered fully over a 6-month follow-up period.ConclusionsD2R is a new form of AE that can develop in adults and can be effectively treated via immunotherapy.

MiR-147-3p in pathogenic CD4 T cells controls chemokine receptor expression for the development of experimental autoimmune diseases

Incomplete Freund's adjuvant (IFA) has long been used to trigger autoimmune diseases in animal models, such as experimental autoimmune encephalitis and collagen-induced arthritis. However, the molecular mechanisms that control CD4 T cell effector functions and lead to the development of autoimmune diseases are not well understood. A self-antigen and heat-killed Mycobacterium tuberculosis emulsified in IFA augmented the activation of CD4 T cells, leading to the differentiation of pathogenic CD4 T cells in the draining lymph nodes. In contrast, IFA emulsification did not elicit Foxp3+ regulatory T cell expansion. We found that pathogenic Th1 cells expressed miR-147-3p, which targets multiple genes to affect T cell function. Finally, miR-147-3p expressed in CXCR6+SLAMF6– Th1 cells was required for the onset of neurological symptoms through the control of CXCR3 expression. Our findings demonstrate that miR-147-3p expressed in pathogenic CD4 T cells regulates the migratory potential in peripheral tissues and impacts the development of autoimmune diseases.

C9orf72 Gene-Associated Frontotemporal Dementia Mimicking Autoimmune Pathology.

The C9orf72 mutation can manifest in diverse clinical ways, including rapid cognitive decline, parkinsonism, or late-life neuropsychiatric symptoms, sometimes mimicking autoimmune encephalitis. A 64-year-old female presented to the autoimmune neurology clinic with rapidly progressive dementia (RPD) associated with episodes of headache, confusion, auditory hallucinations, and abnormal electroencephalogram. She was treated empirically at an outside hospital for possible autoimmune encephalitis with intravenous methylprednisolone, but there was no improvement, and rapid cognitive decline continued. Family history was notable for RPD with akinetic mutism in her sister, sudden severe depression followed by parkinsonism with progressive dementia in her father in his 60s, and late-life gradually progressive dementia in her mother. Additional testing revealed a low titer positive contactin-associated protein-like 2 (CASPR2) immunoglobulin G (IgG) in the serum and elevated CSF 14-3-3 protein. CSF CASPR2 IgG and real-time quaking-induced conversion for Creutzfeldt-Jakob disease were negative. Brain MRI showed normal parenchymal volume. Genetic testing was conducted, which identified a heterozygous pathogenic hexanucleotide tandem repeat expansion in the C9orf72 gene. This case underscores the phenotypic variability of C9orf72 mutation and the importance of a detailed family history exploring young or atypical deaths and neuropsychiatric symptoms or behavioral changes. Genetic etiologies are crucial to consider in those with a family history concerning autosomal dominant inheritance patterns of early-onset dementia, parkinsonism, or late-onset psychiatric disease. Emphasis is placed on considering alternative etiologies early, particularly when there is no response to first-line immunomodulation for suspected autoimmune dementia.

Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes with Progressive Supranuclear Palsy-like Manifestations.

Advances in diagnostic procedures have led to an increasing rate of diagnosis of autoimmune encephalitis or paraneoplastic neurological syndrome (AE/PNS) among patients with progressive supranuclear palsy (PSP)-like manifestations. In this narrative review, we first discuss the clinical characteristics of AE/PNS in comparison to those of PSP, followed by a discussion of diagnosis and treatment. The antibodies involved in these conditions include anti-IgLON5, -Ma2, and -Ri antibodies, each of which has a characteristic clinical presentation. The steps in the diagnosis of AE/PNS in patients with PSP-like manifestations include (i) suspicion of AE/PNS based on clinical presentations atypical of PSP and (ii) antibody detection measures. Methods used to identify antibodies include a combination of tissue-based assays and confirmatory tests. The primary confirmatory tests include cell-based assays and immunoblotting. Treatments can be divided into immunotherapy and tumor therapies, the former of which includes acute and maintenance therapies. One of the major challenges of diagnosis is that existing reports on PSP-like patients with AE/PNS include only case reports, with the majority discussing antibodies other than anti-IgLON5 antibody. As such, more patients need to be evaluated to establish the relationship between antibodies and PSP-like manifestations.