Autoimmune Encephalitis Research Articles

Anti-CASPR2 antibody-associated autoimmune encephalitis with GFAP Α IGG: A first report

Anti-CASPR2 antibody-associated autoimmune encephalitis with GFAP Α IGG: A first report

Improving Early Recognition of Potentially Treatable Causes of Rapidly Progressive Dementia

AbstractBackgroundRapidly progressive dementia (RPD) includes patients with less than two years from the onset of cognitive impairment to incapacitation due to dementia. Although RPD is often associated with fatal neurodegenerative diseases, including early‐onset Alzheimer disease or Creutzfeldt‐Jakob disease, treatable forms of RPD are increasingly recognized. Early recognition of patients with potentially treatable causes of RPD is key to the timely provision of therapies required to achieve the best possible long‐term outcomes.Method155 patients with RPD were prospectively enrolled from February 2016 to August 2022 via two tertiary care centers. Etiologic diagnoses were independently assigned by two neurologists with good agreement (>90%). Causes of RPD were further classified as treatment‐responsive or nonresponsive, referencing the extant literature. Demographic, clinical, and paraclinical features associated with treatable causes of RPD were identified using stepwise multivariate logistic regression and validated with 5‐fold cross validation.Result87/155 patients (56.1%) had a potentially treatable cause of RPD, including autoimmune/inflammatory disease (n = 52, 59.8%), vasculitis (n = 13, 14.9%), primary psychiatric disease (n = 4, 4.6%), or nutritional deficiency (n = 4, 4.6%). Multivariable analyses identified seven features that were independently associated with treatment‐responsiveness: age‐at‐symptom onset (OR: 0.62 per decade, 95%CI: 0.42‐0.93), seizures (OR: 9.81, 95%CI: 2.84‐33.89), MRI suggestive of autoimmune encephalitis (OR: 23.08, 95%CI: 2.28‐233.40), CSF white blood cell count ≥10 cells/mm3 (OR: 32.24, 95%CI:5.80‐179.21), movement abnormalities (OR: 4.99, 95%CI: 1.76‐14.10), presence of disease‐associated tumor (OR: 13.82, 95%CI: 2.25‐85.11), and mania (OR: 18.47, 95%CI: 1.76‐193.61). Model performance was excellent (c‐statistic = 0.88, 95%CI: 0.82‐0.94; p<0.001): 71 patients (81.6%) with potentially treatable causes of RPD and 56 patients (82.4%) with non‐treatable causes of RPD were correctly classified (PPV = 85.5%; NPV = 77.8%).ConclusionTreatment‐responsive causes of RPD were common in our series. Younger age, seizures, movement abnormalities, or mania at presentation, and paraclinical tests suggesting inflammation (MRI or CSF) or tumor in patients with RPD should prompt consideration of treatable causes of RPD and initiation of treatment when indicated.

Comparison of intravenous immunoglobulin and plasma exchange in the treatment of autoimmune encephalitis in a tertiary care hospital

Comparison of intravenous immunoglobulin and plasma exchange in the treatment of autoimmune encephalitis in a tertiary care hospital

Clinico-radiological response to immunomodulatory therapy in seronegative autoimmune encephalitis (SAIE): A case series in a tertiary care center of Northern India

Clinico-radiological response to immunomodulatory therapy in seronegative autoimmune encephalitis (SAIE): A case series in a tertiary care center of Northern India

Clinical Spectrum, Serological Pattern and Outcome of Seropositive Autoimmune Encephalitis at King Abdulaziz Medical City, MNGHA, Riyadh, KSA

Clinical Spectrum, Serological Pattern and Outcome of Seropositive Autoimmune Encephalitis at King Abdulaziz Medical City, MNGHA, Riyadh, KSA

Autoimmune encephalitis associated with anti-N-methyl-D-aspartate receptor and anti-HU antibodies successfully treated with carboplatin and etoposide for small-cell lung cancer: A case report

Autoimmune encephalitis associated with anti-N-methyl-D-aspartate receptor and anti-HU antibodies successfully treated with carboplatin and etoposide for small-cell lung cancer: A case report

Neutropaenia complications from Ocrelizumab and Rituximab treatment

Ocrelizumab is an anti-CD20 monoclonal antibody (mAb) that has been shown in phase 3 clinical trials to reduce relapses and disease progression in multiple sclerosis (MS) patients. Prior to the approval of ocrelizumab, rituximab, a chimeric anti-CD20 mAb was used to treat MS. Rituximab is still used to treat MS in many countries outside of Australia and remains mainstay of treatment of many non-MS neuroimmunological and systemic inflammatory diseases. Rituximab is currently used in neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis, in addition to its widespread usage in hematological malignancies and systemic inflammatory diseases. Ocrelizumab is currently approved in Australia for treatment of relapsing-remitting MS (RRMS). Neutropaenia is a rare complication of both ocrelizumab and rituximab treatment. This case series reports 12 patients who have experienced neutropaenia following ocrelizumab or rituximab treatment and aims to characterize the clinical parameters of neutropaenia experienced by these patients, including the severity and duration of neutropaenia, length of hospital admission, the types of subsequent infections experienced and types of treatment necessary before patients reached count recovery. The unpredictability of neutropaenia and potential for serious infections highlight the need for continued hematological monitoring for patients on B-cell depleting therapies and calls for careful patient counselling to provide guidance on whether to continue such therapies in patients who have experienced related neutropaenia.

Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay

Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1β signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1β converting enzyme (ICE)/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.

Role of FDG PET/CT in definitive and presumed autoimmune encephalitis.

F-18 Fluorodeoxyglucose PET/CT (FDG-PET) is emerging as a useful imaging adjunct to MRI in the initial diagnostic evaluation of autoimmune encephalitis (AIE)-though presently it is not included in the diagnostic criteria. In this prospective study we enrolled a total of 52 patients with clinically diagnosed and treated AIE. MRI evaluation was done in each case along with CSF and EEG where feasible. FDG-PET was done for all and images were interpreted visually and using SPM. The mean age group of patients included was 38.5 ± 22.6 years with 31 females and 21 males. 23 antibody-positive cases underwent PET, the most common antibody detected was anti-NMDAR type followed by anti-LGI 1. Most common metabolic pattern in NMDARE was hypermetabolism in basal ganglia and hypometabolism in parieto-occipital cortices and ovarian teratoma was detected in two of these patients on whole-body PET. A metabolic pattern consistent with AIE was demonstrated in 22/29 (75.8%) antibody-negative patients with hypermetabolism in basal ganglia and mesial temporal cortices. The overall sensitivity of FDG PET was 86% (45/52). MRI abnormalities were detected in 22/52 (42%) cases, 10/23 antibody positive and 12/29 antibody negative cases. PET was positive in 23/30 (76%) MRI negative cases. Sensitivity of FDG PET for supporting a diagnosis of AIE was higher compared to MRI in both antibody-positive (definitive) and antibody-negative (presumed) AIE. Specific metabolic patterns can be demonstrated on FDG PET in AIE, prompting an early diagnosis so that timely treatment can be instituted.

Enhancing the clinical diagnosis of the acute and subacute phases of autoimmune encephalitis and predicting the risk factors: the potential advantages of 18F-FDG PET/CT

Background2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) could help evaluate metabolic abnormalities by semi-quantitative measurement to identify autoimmune encephalitis (AE). Few studies have been conducted to analyze the prognostic factors of AE. The study aimed to explore the values of diagnosis and treatment evaluation by 18F-FDG PET and preliminarily discussed the potential value in predicting the prognosis of AE patients.MethodsAE patients underwent 18F-FDG PET/CT and magnetic resonance imaging (MRI). There were two steps to analyse 18F-FDG PET imaging data. The first step was visual assessment. The second step was to analyse 18F-FDG PET parameters using Scenium software (Siemens Molecular Imaging Ltd). The mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) of brain relative regional metabolism (BRRM) were quantified in the case and control groups according to the anatomical automatic labeling (AAL) partition. The main statistical method was the Kruskal–Wallis test. Finally, the simple linear regression method was used to analyse the relationships between 18F-FDG PET parameters and the modified Rankin Scale (mRS) scores before and after treatment.ResultsThe results on 18F-FDG PET showed that visual assessment abnormalities were in the mesial temporal lobe (MTL) (70.8%), (mainly infringing on the hippocampus and amygdala), basal ganglia (62.5%), frontal lobes (37.5%), occipital lobes (29.2%), and parietal lobes (12.5%). The positive rate of abnormalities on 18F-FDG PET was more sensitive than that on MRI (95.5% vs 32.2%, p = 0.001). The number of lesions on PET was positively correlated with the mRS scores before and after treatment, and the correlation before treatment was more significant. Before treatment, the SUVmean of the left occipital lobe was the most remarkable (SUVmean, R2 = 0.082, p > 0.05) factor associated with the mRS score, and the correlation was negative. With regard to prognosis, the SUVmax of the MTL was the most notable (R2 = 0.1471, p > 0.05) factor associated with the mRS score after treatment, and the correlation was positive.Conclusions18F-FDG PET could be more sensitive and informative than MRI in the early phases of AE. The common pattern of AE was high MTL metabolism on 18F-FDG PET, which was associated with hypometabolism of the occipital lobe, and the number of lesions on PET before treatment may be significant factors in assessing disease severity. The SUVmax of MTL hypermetabolism may serve as a prognostic biomarker in AE.

Systematic review: clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis.

The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no uniform treatment guidelines. To summarize the clinical characteristics of patients with anti-NMDAR encephalitis and to analyze the factors affecting the disease prognosis. A systematic analysis of medical records was conducted, and PubMed, Embase, and Cochrane Library were searched from January 1, 2011, to December 31, 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. This study included 472 case reports. Most patients had prodromal symptoms of about 2 weeks, including psychiatric symptoms (53.2%), flu-like symptoms (51.5%), and seizures (23.9%), among others. Poor prognoses were associated with patients who had autonomic instability (p = 0.010), central hypoventilation (p = 0.014), and ICU support (p = 0.002). Patients with a higher age of onset were more likely to develop central hypoventilation (OR 1.024, CI 1.006-1.042, p = 0.009), cognitive impairment (OR 1.023, CI 1.009-1.037, p = 0.001), and memory impairment (OR 1.034, CI 1.017-1.050, p < 0.001), whereas patients with a lower age were more likely to have seizures (OR 0.979, CI 0.965-0.993, p = 0.003). In this study, 97.0% of patients received immunotherapy, with the most commonly used treatment regimen being intravenous methylprednisolone (IVGC) and intravenous immunoglobulin (IVIG). When compared with other treatment regimens, the IVGC+IVIG regimen (p < 0.001) resulted in better prognoses. When encountering patients with fever, headache, and initial psychiatric symptoms of unknown etiology, clinicians should test their CSF for antibodies to distinguish autoimmune encephalitis. Patients with autonomic instability, central hypoventilation, and ICU support had poorer prognoses. Clinicians should be aware that older patients are more likely to develop central hypoventilation, cognitive impairment, and memory impairment, while younger patients are more likely to develop seizures. The IVGC+IVIG treatment regimen has better prognoses than others. This study includes case reports, which have obvious selection bias, and there are no unified standards to measure the severity of the disease. Therefore, in the future, larger samples and randomized controlled trials are needed to evaluate the efficacy of different treatment regimens.

Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis.

Autoimmune encephalitis (AE) is a distinct neuro-immunological disorder associated with the production of autoantibodies against neuronal proteins responsible for pharmacoresistant seizures, cognitive decline and behavioral problems. To establish the causal link between leucine-rich glioma inactivated 1 (LGI1) antibody and seizures, we developed an in-vivo antibody-mediated AE rat model in which serum antibodies (IgG) obtained from blood samples of leucine-rich glioma inactivated 1 (LGI1) protein antibody (IgG) positive encephalitis patients were passively transferred into non-epileptic Wistar rats. Serum IgG of N-methyl-d-aspartate receptor (NMDAR) antibody positive patients were used as positive control since the pathogenicity of this antibody has been previously shown in animal models. Total IgG obtained from the pooled sera of NMDAR and LGI1-IgG positive patients with epileptic seizures and healthy subjects was applied chronically every other day for 11 days into the cerebral lateral ventricle. Spontaneous seizure development was followed by electroencephalography. Behavioral tests for memory and locomotor activity were applied before and after the antibody infusions. Then, pentylenetetrazol (PTZ) was administered intraperitoneally to evaluate seizure susceptibility. Immunohistochemistry processed for assessment of hippocampal astrocyte proliferation and expression intensity of target NMDAR and LGI1 antigens. No spontaneous activity was observed during the antibody infusions. PTZ-induced seizure stage was significantly higher in the NMDAR-IgG and LGI1-IgG groups compared to control. Besides, memory deficits were observed in the NMDAR and LGI1-IgG groups. We observed enhanced astrocyte proliferation in NMDAR- and LGI1-IgG groups and reduced hippocampal NMDAR expression in NMDAR-IgG group. These findings suggest that neuronal surface auto-antibody administration induces seizure susceptibility and disturbed cognitive performance in the passive transfer rat model of LGI1 AE, which could be a potential in-vivo model for understanding immune-mediated mechanisms underlying epileptogenesis and highlight the potential targets for immune-mediated seizures in AE patients.

Antibody Investigations in 2,750 Children With Suspected Autoimmune Encephalitis.

To assess the frequency and types of neuronal and glial (neural) antibodies in children with suspected autoimmune encephalitis (AE). Patients younger than 18 years with suspected AE other than acute disseminated encephalomyelitis, whose serum or CSF samples were examined in our center between January 1, 2011, and April 30, 2022, were included in this study. Samples were systematically examined using brain immunohistochemistry; positive immunostaining was further investigated with cell-based assays (CBA), immunoblot, or live neuronal immunofluorescence. Of 2,750 children, serum or CSF samples of 542 (20%) showed brain immunoreactivity, mostly (>90%) against neural cell surface antigens, and 19 had antibodies only identified by CBA. The most frequent targets were N-methyl-d-aspartate receptor (NMDAR, 76%) and myelin oligodendrocyte glycoprotein (MOG, 5%), followed by glutamic acid decarboxylase 65 (2%) and γ-aminobutyric acid A receptor (2%). Antibodies against other known cell surface or intracellular neural antigens (altogether 6% of positive cases) and unknown antigens (9%) were very infrequent. The repertoire of antibodies in children with AE is different from that of the adults. Except for NMDAR and MOG antibodies, many of the antibodies included in diagnostic panels are rarely positive and their up-front testing in children seems unneeded.

Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study

Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival. This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors. From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively). Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. The Instituto de Salud Carlos III and the European Union.

Neurological complexity in systemic lupus erythematosus: insights into autoimmune encephalitis

Background: Autoimmune encephalitis (AE) is an inflammatory syndrome characterized by autoantibodies targeting the central nervous system (CNS), leading to a wide range of neurological and psychiatric manifestations. Objective: This systematic review aims to investigate the coexistence of AE and systemic lupus erythematosus (SLE) to shed light on potential underlying mechanisms. Materials and Methods: Following PRISMA guidelines, a comprehensive search was conducted using Boolean logic in research databases i.e., PubMed, ProQuest, ScienceDirect, and Web of Science to identify relevant studies on AE, SLE, and their potential correlation. After the initial screening, exclusion, and quality assessment using the Joanna Briggs Institute Critical Appraisal Checklist, 14 studies were included for analysis. Among 18 patients, 88.9% were female whose an average age was 31.9 ± 12.7 years. Clinical presentations were varied, including cognitive impairment (66.67%), seizures (61.1%), altered mental status (50%), and movement disorders. Neuroimaging and neurophysiological findings consistently aligned with encephalitis, with MRI abnormalities observed in 94.4% of cases. Various autoantibodies were identified, including anti-NMDAR, anti-AMPA-R2, and anti-GluR antibodies. Conclusion: The identification of neuronal antibodies is crucial, particularly in scenarios involving both neuropsychiatric SLE (NPSLE) and encephalitis. This investigation aims to reveal etiological insights. The ongoing debate revolves around whether SLE-related encephalitis is associated with NPSLE through SLE antibodies or involves distinct antibodies. Further clinical research is essential to clarify the pathogenic role of autoantibody in SLE-linked AE.

Anti- NMDAR Encephalitis in a 28 years old female: Revisited

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the prevailing subtype of autoimmune encephalitis, commonly misdiagnosed initially as infectious encephalitis due to its symptomatology resembling that of viral encephalitis and meningitis. The condition exhibits a higher incidence in females, with a gender ratio of 4:1 compared to males. While electroencephalogram (EEG) and magnetic resonance imaging (MRI) aid in the diagnostic process, the presence of antibodies in the cerebrospinal fluid (CSF) serves as the definitive confirmation. Autoimmune encephalitis typically presents with a spectrum of neuropsychiatric symptoms

Cerebral glucose hypometabolism and hypoperfusion of cingulate gyrus: an imaging biomarker of autoimmune encephalitis with psychiatric symptoms

BackgroundAbout 60% of autoimmune encephalitis (AE) patients present psychiatric symptoms, but the underlying mechanism remains unknown. This study examined the role of the cingulate cortex in such patients to identify predictive poor psychiatric factors.MethodsIn this study, 49 AE patients and 39 healthy controls were enrolled. AE patients were further divided into two groups based on the presence/absence of psychiatric symptoms. The ratio of the standardized uptake value (SUVR) and relative cerebral blood flow (rCBF) in different regions of the cingulate cortex were calculated through positron emission tomography–computed tomography (PET/CT) and arterial spin labeling (ASL) MRI, and the results were compared among the three groups. In addition, we followed-up on the psychiatric outcomes and identified the risk factors for poor psychiatric prognosis, focusing on the cingulate cortex.ResultsMore than half of the AE patients (27/49) exhibited psychiatric symptoms. Agitation and thought blocking were typical psychiatric phenotypes, except for anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, which mainly presented with catatonia and a depressed mood. AE patients with psychiatric symptoms experienced reduced metabolism and perfusion of the anterior cingulate cortex (ACC), midcingulate cortex (MCC), and posterior cingulate cortex (PCC). The SUVR of ACC can be used as an independent risk factor of poor psychiatric outcomes, which had an area under the ROC curve (AUC) of 0.865.ConclusionImpaired cingulate cortex function in AE may be the potential mechanism of psychiatric symptoms. Hypometabolism of ACC is an independent prognostic factor predicting an unfavorable psychiatric prognosis in AE.

Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke

BackgroundAnti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). MethodsData were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers ≥1:10, thereof low titers as ≤1:100 and high titers as >1:100. We used the Center for Epidemiological Studies–Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points. ResultsNMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1–4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (βcrude = 2.56 [95%CI = −0.34 to 5.45]; βadjusted = 2.26 [95%CI = −0.68 to 5.20]) and effects were highest in patients with high titer (low titers: βcrude = 1.42 [95%CI = −1.79 to 4.62], βadjusted = 0.53 [95%CI = −2.47 to 3.54]; high titers: βcrude = 5.85 [95%CI = 0.20 to 11.50]; βadjusted = 7.20 [95%CI = 0.98 to 13.43]). ConclusionPatients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients.

Abstract 14677: Surgical Thymectomy for Autoimmune Encephalitis With CRMP-5 and AMPAR Antibodies Induced by SARS-CoV-2 Infection

Introduction: SARS-CoV-2 has been linked to development of autoimmune diseases. We describe a case of a patient with untreated thymoma who developed 2 cross-reactive autoantibodies between thymus and brain: collapsing response mediator protein-5 (CRMP-5) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid receptor (AMPAR), triggered by SARS-CoV-2, inducing encephalitis and coma. Emergency thymectomy reduced anti-CRMP-5 and anti-AMPAR antibodies and restored patient neurologic function within 3 months. Description of Case: A 31-year-old male with a known history of thymoma with myasthenia gravis presented with a 1-day history of memory loss, hallucinations, ataxia, involuntary movements, and tachypnea. Rapid nasal swab COVID-19 test was positive. Over several hours, the patient became unresponsive, requiring urgent intubation for airway protection. Brain computed tomography and magnetic resonance imaging with gadolinium showed no abnormalities. Cerebrospinal fluid (CSF) analysis revealed leukocytosis with lymphocytic predominance. Four days later, CSF and serum were tested for and demonstrated high levels of CRMP-5 and AMPAR antibodies, consistent with autoimmune encephalitis. Complete robotic thymectomy was performed. Pathologic analysis revealed type B2 thymoma with negative resection margins. Three months after surgical intervention, antibody titers normalized, the patient regained consciousness, and had no neurologic deficits. Discussion: Surgical thymectomy effectively treats autoimmune encephalitis in patients with thymoma and positive CRMP-5 and AMPAR antibodies in the setting of SARS-CoV-2 infection. This rare condition is typically seen in patients with thymoma or small cell lung cancer who experience acute viral infection. Although autoantibodies to CRMP-5 and AMPAR are known to be induced by viral infection, this is the first time it has been reported for SARS-CoV-2. Timely surgical intervention is necessary to reverse obtundation and acute encephalitis by removing the cross reactive epitopes in the thymus gland. Future studies are needed to explore the molecular mechanism of SARS-CoV-2 induced immune dysfunction and autoimmunity involving cross-reactive epitopes in this deadly syndrome.

Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review

ObjectivesSymptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. MethodsA literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. ResultsA total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. ConclusionRadiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.