Case report: Successful treatment of an anti-D2R and DPPX antibody-associated autoimmune encephalitis patient with high-dose methylprednisolone and intravenous immunoglobulin.

Background: Autoimmune encephalitis is a neurological condition caused by abnormal immune responses, manifesting as cognitive impairments, behavioral abnormalities, and seizures. Its diagnosis depends on the detecting neuronal surface antibodies in serum or cerebrospinal fluid. Despite recent advances in understanding, clinical recognition remains challenging, especially with rare antibodies such as anti-dopamine D2 receptor (D2R) and anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibodies. Delayed diagnosis can lead to severe complications. This case presentation emphasizes the diagnostic intricacies and effective treatment of the anti-D2R and DPPX antibody-associated autoimmune encephalitis. Case description: The patient presented with a 3-day history of fatigue and limb soreness followed by a 3-h episode of confusion and limb convulsions. Upon admission to our facility, the initial diagnosis included status epilepticus, aspiration pneumonia, metabolic acidosis, respiratory alkalosis, and suspected encephalitis. Despite receiving antiepileptic, anti-infection, and antivirus therapy, the patient's condition deteriorated. Both computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed no significant abnormalities. No pathogen was identified in the cerebrospinal fluid (CSF). However, further CSF and serum examination revealed positive results of anti-D2R and anti-DPPX antibodies, confirming a diagnosis of anti-D2R and DPPX antibody-associated autoimmune encephalitis. The patient underwent a comprehensive treatment regimen, including high-dose methylprednisolone pulse therapy combined with intravenous immunoglobulin (IVIG), antiviral and anti-infection treatments, and antiepileptic medications. Significant clinical improvement was observed, and by the 18th day of admission, the patient was stable and coherent. Conclusions: The current patient represents the first reported case of double-positive autoimmune encephalitis for anti-D2R and DPPX antibodies, with epilepsy as a prominent feature. High-dose methylprednisolone pulse therapy combined with IVIG has shown significant safety and efficacy in treating anti-D2R and DPPX antibody-positive autoimmune encephalitis-associated epilepsy.

Autoimmune encephalitis related to LGI1 antibodies with negative MRI study: Description of two cases / Encefalitis autoinmune relacionada con anticuerpos LGI1 con estudio de RM negativo: descripción de dos casos

Background Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. Case description The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. Conclusion Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings (AU)

Antecedentes La encefalitis autoinmunitaria relacionada con anticuerpos LGI1 puede ser fácilmente mal diagnosticada clínicamente debido a sus manifestaciones clínicas complejas y diversas. Presentamos dos casos de encefalitis relacionada con anticuerpos LGI1 con hallazgos de imágenes negativas y realizamos una revisión de la literatura sobre esta entidad patológica. Descripción de casos El primer caso fue el de un hombre de 60años que presentó movimientos involuntarios del miembro derecho paroxístico. El segundo caso fue el de un hombre de 66años que presentó alucinaciones auditivas, temblores involuntarios del miembro derecho y un deterioro cognitivo progresivo. Ambos pacientes en este estudio mostraron resultados negativos de imágenes por resonancia magnética (RM). Los exámenes rutinarios de líquido cefalorraquídeo (LCR) y bioquímicos no mostraron anomalías significativas, pero se detectaron anticuerpos LGI1 positivos en ambos: LCR y suero. Conclusión Basándonos en nuestra experiencia y en la revisión de la literatura, recomendamos considerar la posibilidad de encefalitis relacionada con anticuerpos LGI1 cuando aparezcan crisis distónicas faciobraquiales, convulsiones de inicio agudo o subagudo, hiponatremia (posiblemente con hipoclorhidria del LCR) y trastornos cognitivo-psiquiátricos, incluso en ausencia de hallazgos radiográficos específicos o modificaciones en el LCR (AU)

Aetiology and Prognosis of Encephalitis in Korean Children: A Retrospective Single-Centre Study, 2005-2020.

PURPOSE: Encephalitis is a heterogeneous syndrome that occurs in childhood and is not rare. However, epidemiological studies of encephalitis based on the International Encephalitis Consortium (ICS) and expert recommendations are lacking. We investigated the aetiology and prognosis of encephalitis in Korean children. MATERIALS AND METHODS: This retrospective study included children aged <19 years hospitalised for encephalitis at Severance Children's Hospital between 2005 and 2020. The 2013 ICS criteria were used to diagnose encephalitis, and causality was classified according to the site from which the specimen was obtained. Neurological sequelae were categorised using the modified Rankin Scale (mRS) score. RESULTS: In total, 551 children were included, with 7% classified as possible, 77% as probable, and 15% as proven cases. A cause was identified in 42% of the cases (n=222), with viruses being the most common (42%), followed by bacteria (38%) and autoimmune encephalitis (12%). In cases of proven/probable encephalitis (n=65), bacteria accounted for 52%, followed by viruses (25%) and autoimmune encephalitis (22%). In cases with a single pathogen, the anti-N-methyl-D-aspartate receptor autoantibody (n=14) was the most common, followed by Group B streptococcus (n=13), herpes simplex virus (n=11), enterovirus (n=4), and others. Approximately 37% of patients had severe sequelae (mRS score ≥3) at discharge, which decreased to 31% 6 months after discharge. CONCLUSION: This large-scale study showed that autoimmune and infectious causes accounted for a significant proportion of encephalitis in Korean children. Further studies are needed to determine whether early targeted treatment following early diagnosis leads to a favourable prognosis in these populations.

Autoimmune encephalitis related to LGI1 antibodies with negative MRI study: Description of two cases.

BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. CASE DESCRIPTION: The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. CONCLUSION: Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings.

General features, pathogenesis, and laboratory diagnostics of autoimmune encephalitis.

Autoimmune encephalitis (AE) is a group of inflammatory conditions that can associate with the presence of antibodies directed to neuronal intracellular, or cell surface antigens. These disorders are increasingly recognized as an important differential diagnosis of infectious encephalitis and of other common neuropsychiatric conditions. Autoantibody diagnostics plays a pivotal role for accurate diagnosis of AE, which is of utmost importance for the prompt recognition and early treatment. Several AE subgroups can be identified, either according to the prominent clinical phenotype, presence of a concomitant tumor, or type of neuronal autoantibody, and recent diagnostic criteria have provided important insights into AE classification. Antibodies to neuronal intracellular antigens typically associate with paraneoplastic neurological syndromes and poor prognosis, whereas antibodies to synaptic/neuronal cell surface antigens characterize many AE subtypes that associate with tumors less frequently, and that are often immunotherapy-responsive. In addition to the general features of AE, we review current knowledge on the pathogenic mechanisms underlying these disorders, focusing mainly on the potential role of neuronal antibodies in the most frequent conditions, and highlight current theories and controversies. Then, we dissect the crucial aspects of the laboratory diagnostics of neuronal antibodies, which represents an actual challenge for both pathologists and neurologists. Indeed, this diagnostics entails technical difficulties, along with particularly interesting novel features and pitfalls. The novelties especially apply to the wide range of assays used, including specific tissue-based and cell-based assays. These assays can be developed in-house, usually in specialized laboratories, or are commercially available. They are widely used in clinical immunology and in clinical chemistry laboratories, with relevant differences in analytic performance. Indeed, several data indicate that in-house assays could perform better than commercial kits, notwithstanding that the former are based on non-standardized protocols. Moreover, they need expertise and laboratory facilities usually unavailable in clinical chemistry laboratories. Together with the data of the literature, we critically evaluate the analytical performance of the in-house vs commercial kit-based approach. Finally, we propose an algorithm aimed at integrating the present strategies of the laboratory diagnostics in AE for the best clinical management of patients with these disorders.

Autonomic nervous system involvement in autoimmune encephalitis and paraneoplastic neurological syndromes.

In autoimmune neurological diseases, the autonomic nervous system can be the primary target of autoimmunity (e.g. autoimmune autonomic ganglionopathy), or, more frequently, be damaged together with other areas of the nervous system (e.g. Guillain-Barré syndrome). Patients with autoimmune encephalitis and paraneoplastic neurological syndromes (PNS) often develop dysautonomia; however, the frequency and spectrum of autonomic signs and symptoms remain ill defined except for those scenarios in which dysautonomia is a core feature of the disease. Such is the case of Lambert-Eaton myasthenic syndrome, Morvan syndrome or anti-NMDAR encephalitis; in the latter, patients with dysautonomia have been reported to carry a more severe disease and to retain higher disability than those without autonomic dysfunction. Likewise, the presence of autonomic involvement indicates a higher risk of death due to neurological cause in patients with anti-Hu PNS. However, in anti-Hu and other PNS, as well as in the context of immune checkpoint inhibitors' toxicities, the characterization of autonomic involvement is frequently overshadowed by the severity of other neurological symptoms and signs. When evaluated with tests specific for autonomic function, patients with autoimmune encephalitis or PNS usually show a more widespread autonomic involvement than clinically suggested, which may reflect a potential gap of care when it comes to diagnosing dysautonomia. This review aims to revise the autonomic involvement in patients with autoimmune encephalitis and PNS, using for that purpose an antibody-based approach. We also discuss and provide general recommendations for the evaluation and management of dysautonomia in these patients.

Mechanisms and Emerging Therapies for Treatment of Seizures in Pediatric Autoimmune Encephalitis and Autoinflammatory/Autoimmune-Associated Epilepsy.

There has been increasing understanding of the role of inflammation in seizures and epilepsy, as well as targeted immunomodulatory treatments. In children, immune-mediated seizures often present acutely in the setting of autoimmune encephalitis and are very responsive to immunotherapy with low rates of subsequent epilepsy. Conversely, seizures in autoimmune-associated epilepsies, such as Rasmussen syndrome, can remain refractory to multimodal therapy, including immunomodulation. In this review, the authors discuss the presentations of immune-mediated seizures in children, underlying mechanisms, and emerging therapies.

Validation of different predictive scoring scales in patients with new-onset epileptic seizures or epilepsy related to neuronal surface antibody-mediated autoimmune encephalitis.

OBJECTIVE: To validate the different predictive scoring scales in the Chinese population with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface antibody (Ab)-mediated autoimmune encephalitis (AE). METHODS: We retrospectively reviewed the charts of 174 consecutive patients from October 2018 to December 2022, whose serum and cerebrospinal fluid samples were tested for neuronal surface Abs. The antibody prevalence in epilepsy and encephalopathy (APE2), antibodies contributing to focal epilepsy signs and symptoms (ACES), "obvious" indications for neural antibody testing in epilepsy or seizures (ONES) checklist, and the combinations were used to validate the predictive models of neuronal surface Ab-mediated AE. RESULTS: A total of 139 patients with new-onset epileptic seizures or epilepsy of unknown etiology were enrolled. Abs were detected in 37 patients (26.6%). The APE2/ONES reflex score had the highest sensitivity (89.2%) and lowest specificity (41.7%). The ACES score had the lowest sensitivity (67.5%) and highest specificity (64.7%). Variations in the performance were observed in the different types of AE. 100% of patients with anti-γ-aminobutyric acid B-B receptor encephalitis were predicted by ONES, APE2/ONES reflex, and ACES/ONES reflex scores. Only 75% of patients with anti-N-methyl-D-aspartate receptor encephalitis were predicted by the APE2/ONES and ACES/ONES reflex scores. CONCLUSION: Our study was the first to validate various predictive scoring scales in the Chinese cohort of patients with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface Ab-mediated AE. Based upon clinical suspicion, more than one scoring scale should be performed to predict the chance of AE in those patients.

Diagnostic Superiority of 18 F-FDG PET Over MRI in Detecting Anti-LGI1 Autoimmune Encephalitis : A Comparative Study With Insights Into Faciobrachial Dystonic Seizures Mechanisms and Recurrence Identification.

OBJECTIVE: Our study aimed to investigate the utility of 18 F-FDG PET imaging in diagnosing and monitoring patients with anti-leucine-rich glioma-inactivated 1 antibody autoimmune encephalitis (anti-LGI1 AE). We also sought to understand the mechanisms of faciobrachial dystonic seizures (FBDSs). PATIENTS AND METHODS: We analyzed 18 F-FDG PET scans from 50 patients with anti-LGI1 AE, using visual and semiquantitative methods, and compared these with 24 healthy controls. All patients tested positive for anti-LGI1 antibodies in serum or cerebrospinal fluid before PET imaging. The patients were divided into FBDS and non-FBDS groups to compare metabolic differences using voxel-based semiquantitative analysis. Finally, we separately analyzed PET images of patients with symptom recurrence. RESULTS: The sensitivity of 18 F-FDG PET was superior to MRI (97.9% vs 63.8%, respectively; P < 0.001). Semiquantitative analysis revealed hypermetabolism in the basal ganglia, medial temporal lobe, and brainstem, and hypometabolism in most neocortical regions compared with healthy controls. The FBDS group exhibited hypometabolism in the frontal and temporal lobes compared with the non-FBDS group. Among 7 recurrent patients, 3 were confirmed as recurrence and 3 as sequelae by PET. One patient relapsed shortly after discontinuing corticosteroids when PET indicated active lesions. CONCLUSIONS: 18 F-FDG PET scans were more sensitive than MRI in detecting anti-LGI1 AE, which displayed a pattern of hypermetabolism in the basal ganglia and medial temporal lobe, as well as neocortex hypometabolism. Hypometabolism in the frontal and temporal lobes was associated with FBDS. Furthermore, 18 F-FDG PET scans can differentiate recurrence from sequelae and guide the timing of immunotherapy cessation.

Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy.

We describe three cases of overlapping Epstein-Barr virus (EBV) Encephalitis and Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A). The three cases all presented with initial symptoms of fever, headache, coma, and posture tremor of the upper limbs, then followed by limb weakness and dysuria. All of the three cases were on ventilators. Case 1 and 2 improved dramatically after intravenous methylprednisoloneand immunoglobulin treatment. However, case 3 presented dyspneic, and died from gastrointestinal hemorrhage. The GFAP-A triggered by EBV intracranial infection could initially masquerade as EBV encephalitis only, and the detection of GFAP antibody is essential for differentiation.

Leucine-rich glioma-inactivated protein 1 antibody-associated encephalitis in a 22-month-old girl: a case report.

BACKGROUND: LGI-1 antibody-associated encephalitis is a type of autoimmune encephalitis with a lower prevalence than NMDAR antibody-associated encephalitis. LGI-1 antibody-associated encephalitis is the second most prevalent of all autoimmune encephalitides. LGI-1 antibodies interfere with the interactions of inter-synaptic proteins to produce clinical manifestations (N Engl J Med 378:840-851, 2018). CASE PRESENTATION: Leucine-rich glioma-inactivated protein 1 (LGI-1) antibody-associated encephalitis is a subtype of autoimmune encephalitis with a low incidence. We report a case of a girl aged 22 months with convulsive seizures, psycho-behavioral abnormalities, sleep disorders, and limb tremors. This patient was diagnosed with LGI-1 antibody-associated encephalitis based on electroencephalography (EEG) examinations and autoimmune encephalitis antibody analyses. A combined therapy of anti-epileptic and immunosuppressant drugs was effective in controlling the patient's neurological symptoms. CONCLUSIONS: The incidence of LGI-1 antibody-associated encephalitis is low and it occurs mostly in middle-aged and elderly patients, although it occasionally occurs in pediatric patients. To the best of our knowledge, this report describes the youngest patient with LGI-1 antibody-associated encephalitis. Following timely diagnosis, administration of anti-epileptic and immunosuppressant therapy was remarkably effective.

Contactin-associated protein-2 and anti-aquaporin-4 antibody positive autoimmune encephalitis secondary to herpes simplex encephalitis: A case report.

RATIONALE: Recurrent herpes simplex encephalitis (HSE) can easily induce autoimmune encephalitis (AE). However, there are few reports of anti-contactin-associated protein-2 (CASPR2)-related encephalitis, especially with positive anti-aquaporin 4 (AQP4) antibodies. PATIENT CONCERNS: A 14-year-old boy was admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University for "headache, dizziness, and fever for four days" with positive anti-CASPR2 and anti-AQP4 antibodies in the cerebrospinal fluid. DIAGNOSES: Cranial MRI showed lesions in the right hippocampus, amygdala, and insular lobe, with local sulcus enhancement in the right insular, temporal, and frontal lobes. The fluid-attenuated inversion recovery was significantly enhanced. Human herpes virus type I was detected by cerebrospinal fluid metagenomic testing. The patient was diagnosed with AE secondary to HSE, with positive anti-CASPR2 and anti-AQP4 antibodies. INTERVENTIONS: After 2 weeks of immunoglobulin and methylprednisolone immunomodulatory therapy, acyclovir antivirus, mannitol dehydration, reducing intracranial pressure, and other symptomatic support therapy. OUTCOMES: The patient's symptoms significantly improved, with no complaints of discomfort, and he was discharged for observation. The patient was followed up a month after discharge and had no complaints of discomfort. LESSONS: CASPR2 and anti-aquaporin-4 antibody-positive AE have not been reported to be positive. This case will raise awareness of CASPR2 and anti-aquaporin-4 antibody-positive AE secondary to HSE, strengthen diagnostic capacities, and provide advice to treat it.

What is autoimmune encephalitis-associated epilepsy? Proposal of a practical definition.

Seizures resulting from cerebral autoimmunity are either acutely symptomatic in the context of autoimmune encephalitis (AIE) with neural surface antibodies, or they are indicative of an enduring predisposition to seizures, that is, epilepsy. Here, we propose a practical definition for autoimmune encephalitis-associated epilepsy (AEAE): Seizures associated with antibodies against glutamic acid decarboxylase, paraneoplastic syndromes, or Rasmussen encephalitis are classified as AEAE. AEAE secondary to AIE with antibodies against the N-methyl-D-aspartate receptor, leucine-rich glioma inactivated protein 1, contactin-associated protein-2, or γ-aminobutyric acid-B receptor can be diagnosed if the following criteria are met: seizures persist for at least 2 years after immunotherapy initiation; no signs of encephalitis on magnetic resonance imaging and no fluorodeoxyglucose positron emission tomography hypermetabolism; normal cerebrospinal fluid cell count; and a substantial decrease in antibody titers. This classification corresponds to different disease mechanisms. While AIE results from the pathogenic effects of neural antibodies, AEAE is probably the consequence of encephalitis-related tissue damage and thereby mainly structurally mediated. The distinction between AIE and AEAE also has practical consequences: In AIE, immunotherapy is usually highly beneficial, whereas anti-seizure medication has little effect. In AEAE, immunotherapy is less promising and the usual anti-seizure interventions are preferable. In addition, the diagnosis of AEAE has social consequences in terms of driving and professional limitations.

Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia.

BACKGROUND & OBJECTIVES: Autoimmune encephalitis (AIE) may present with prominent cognitive disturbances without overt inflammatory changes in MRI and CSF. Identification of these neurodegenerative dementia diagnosis mimics is important because patients generally respond to immunotherapy. The objective of this study was to determine the frequency of neuronal antibodies in patients with presumed neurodegenerative dementia and describe the clinical characteristics of the patients with neuronal antibodies. METHODS: In this retrospective cohort study, 920 patients were included with neurodegenerative dementia diagnosis from established cohorts at 2 large Dutch academic memory clinics. In total, 1,398 samples were tested (both CSF and serum in 478 patients) using immunohistochemistry (IHC), cell-based assays (CBA), and live hippocampal cell cultures (LN). To ascertain specificity and prevent false positive results, samples had to test positive by at least 2 different research techniques. Clinical data were retrieved from patient files. RESULTS: Neuronal antibodies were detected in 7 patients (0.8%), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX, and anti-NMDAR. Clinical symptoms atypical for neurodegenerative diseases were identified in all 7 and included subacute deterioration (n = 3), myoclonus (n = 2), a history of autoimmune disease (n = 2), a fluctuating disease course (n = 1), and epileptic seizures (n = 1). In this cohort, no patients with antibodies fulfilled the criteria for rapidly progressive dementia (RPD), yet a subacute deterioration was reported in 3 patients later in the disease course. Brain MRI of none of the patients demonstrated abnormalities suggestive for AIE. CSF pleocytosis was found in 1 patient, considered as an atypical sign for neurodegenerative diseases. Compared with patients without neuronal antibodies (4 per antibody-positive patient), atypical clinical signs for neurodegenerative diseases were seen more frequently among the patients with antibodies (100% vs 21%, p = 0.0003), especially a subacute deterioration or fluctuating course (57% vs 7%, p = 0.009). DISCUSSION: A small, but clinically relevant proportion of patients suspected to have neurodegenerative dementias have neuronal antibodies indicative of AIE and might benefit from immunotherapy. In patients with atypical signs for neurodegenerative diseases, clinicians should consider neuronal antibody testing. Physicians should keep in mind the clinical phenotype and confirmation of positive test results to avoid false positive results and administration of potential harmful therapy for the wrong indication.

[Long-term cognitive impairment in autoimmune encephalitis]. / Troubles cognitifs séquellaires dans le cadre d'une encéphalite auto-immune.

Autoimmune encephalitis (AE) are a group of rare inflammatory diseases of the central nervous system that can manifest as subacute cognitive impairment. Despite the presence of diagnostic criteria, it can be challenging to identify this disease in certain age groups. In this article, we present the two main clinical phenotypes of AE associated with cognitive impairment, the factors contributing to the long-term cognitive outcome and its management after the acute phase.

Les encéphalites auto-immunes (EAI) sont un groupe de maladies inflammatoires rares du système nerveux central (CNS) pouvant se manifester par une atteinte cognitive d'apparition subaiguë. Malgré la présence des critères diagnostiques, leur identification peut représenter un défi dans certains groupes d'âge. Dans cet article, nous exposons les deux principaux phénotypes cliniques d'EAI s'associant à des troubles cognitifs, les facteurs contribuant au pronostic cognitif et la prise en charge après la phase aiguë.

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature.

Background: Only 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease. Objective: We initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies. Methods: Observational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed. Results: We identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease. Conclusions: In patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.

Thymoma-associated autoimmune encephalitis: Analysis of factors determining prognosis.

INTRODUCTION: Autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders caused by a misdirected immune response against self-antigens expressed in the central nervous system. The thymus is a central organ in the immune system and thymic tumors are thought to be possible initiators of many neurological disorders. Recently, there is growing evidence that thymomas are associated with autoimmune encephalitis. AIMS: Our study initially explored the characteristics of patients with autoimmune encephalitis combined with thymoma. METHODS: We used patient data from January 1, 2011 to October 1, 2021 from the PubMed, Web of Science, Ovid, and CNKI platforms to analyze overall demographics, frequency of symptoms and associations, and treatment prognosis outcomes. RESULTS: A total of 68 patients were included. There were 39 female cases (57.4%). The mean age was 50 years (IQR 40-66 years). All had acute and subacute onset. The clinical manifestations were mostly cognitive changes (70.6%), mental disorders (57.4%), and epilepsy (50.0%). The most common neuronal antibody was alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Magnetic resonance imaging (MRI) abnormalities were present in 81.0% of patients, mostly in the hippocampus, temporal lobe, and some in cortical and subcortical areas. Abnormalities in the electroencephalogram (EEG) in 69.8% of patients. Treatment involved immunotherapy and thymoma treatment, with 79.7% of patients improving after treatment. While 20.3% of patients had a poor prognosis. Further, 14.8% of patients relapsed. Mental disorders, autonomic dysfunction, sleep disturbances, anti-Ma2, and thymoma untreated were more frequent in patients with poor prognosis. CONCLUSION: Thymoma-associated autoimmune encephalitis is a unique disease entity. Long-term follow-up of chest CT findings is recommended for patients with autoimmune encephalitis.

Metabolic phenotyping of pilomotor seizures in autoimmune encephalitis.

OBJECTIVES: Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP are still unclear. To have a better understanding of IP underlying mechanisms, the current study investigated whole-brain metabolic networks for the analysis of AE-associated IP. METHODS: Patients with AE and IP diagnosed at our Institute between 2018 and 2022 were selected. We then investigated the brain regions associated with AE-associated IP using positron emission tomography (PET). Anatomometabolic changes (interictal 18 F fluorodeoxyglucose PET) in AE patients with IP were compared with those of AE patients of similar age without IP (p-voxel <0.001, uncorrected). RESULTS: Sixteen patients showed significant IP. The overall IP prevalence was 4.09% of patients with AE and 12.9% of patients with limbic encephalitis. The most common autoantibodies were against LGI1 (68.8%) followed by GAD65 (6.3%), NMDA (6.3%), GABAb (6.3%), CASPR2 (6.3%), and antibodies recognizing both GAD65 and mGLUR5 (6.3%). Most patients responded well to immunotherapy. Analysis of the imaging results at the voxel level showed that patients with IP had hypermetabolic changes in the right inferior temporal gyrus, suggesting involvement of this brain region in IP. CONCLUSIONS: Our findings indicate that IP as an uncommon AE-associated manifestations should be recognized. We observed that the metabolic pattern of IP was conspicuous in the right inferior temporal gyrus.