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With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders.

BACKGROUND: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. OBJECTIVES: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. METHODS: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. RESULTS: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2-39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy (p = 0.001), seizures (p = 0.045), and leptomeningeal enhancement (p = 0.045). CONCLUSION: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.

OBJECTIVE: The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS. METHODS: A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project. RESULTS: The panel proposed to substitute "classical syndromes" with the term "high-risk phenotypes" for cancer and introduce the concept of "intermediate-risk phenotypes." The term "onconeural antibody" was replaced by "high risk" (>70% associated with cancer) and "intermediate risk" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided. CONCLUSIONS: The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.

INTRODUCTION: Catatonia is classically associated with psychiatric conditions but may occur in medical and neurologic disorders. Status epilepticus (SE) is a seizure lasting more than five minutes or two or more seizures within a five-minute period without interictal recovery of consciousness. Non-convulsive status epilepticus (NCSE) is SE without prominent motor activity that may present with catatonic symptoms. The relevance of NCSE as a potential etiology for catatonia is not clear in the literature. METHODS: A systematic review was completed to evaluate the literature on NCSE presenting with catatonia. PubMed and PsycInfo databases were searched and articles were reviewed for the presence of catatonia and NCSE. RESULTS: 15 articles describing 27 cases meeting inclusion criteria were identified. The authors add 1 case to the literature. The most common catatonic symptoms identified in NCSE were mutism and stupor. Clinical features frequent in NCSE presenting with catatonia included new catatonic symptoms, age over 50 years, comorbid neurological conditions, or a change in medications that affect seizure threshold. A documented psychiatric history was also common and may contribute to delayed diagnosis. DISCUSSION/CONCLUSION: It is important to consider NCSE in the differential diagnosis of new catatonic symptoms. A suggested approach to diagnostic evaluation is provided.

A 37-year-old man with a history of seminoma presented with vertigo, ataxia, and diplopia. An autoantibody specific for kelch-like protein 11 (KLHL11) was identified with the use of programmable phage display. Immunoassays were used to identify KLHL11 IgG in 12 other men with similar neurologic features and testicular disease. Immunostaining of the patient's IgG on mouse brain tissue showed sparse but distinctive points of staining in multiple brain regions, with enrichment in perivascular and perimeningeal tissues. The onset of the neurologic syndrome preceded the diagnosis of seminoma in 9 of the 13 patients. An age-adjusted estimate of the prevalence of autoimmune KLHL11 encephalitis in Olmsted County, Minnesota, was 2.79 cases per 100,000 men. (Funded by the Rochester Epidemiology Project and others.).

Background: Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n = 10), patients with SPS (n = 20), and patients with T1D (n = 42). Results: GAD65Ab epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10 patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive epilepsy patients. One of these patients responded well to anti-epileptic drugs (AEDs), while another patient did not require medication for seizure control. The third patient was refractory due to a diagnosis of meningioma. The response of the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients with T1D and epilepsy showed profiles similar to those in epilepsy patients. Conclusions: Different autoimmune responses associated with T1D, epilepsy and SPS are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic etiology in patients diagnosed with both T1D and epilepsy may present two different etiologies regarding their epileptic condition. In one group T1D co-occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an autoimmune epileptic condition., SCOPUS: ar.j, info:eu-repo/semantics/published