Searching for Autoimmune Epilepsy: Why, Where, and When?
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ABSTRACT:
SUBMITTER: Jehi L
PROVIDER: S-EPMC5706358 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders-and specifically factors predisposing these patients-are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness.
| S-EPMC3639560 | biostudies-other
Project description:In a cohort of 34 patients with autoimmune limbic encephalitis and/or epilepsy, we identified 4 patients exhibiting claustrum fluid-attenuated inversion recovery (FLAIR) hyperintensities. All 4 patients presented with explosive onset of seizures and developed medically intractable epilepsy, and 2 exhibited a marked response to immunotherapy. Associated features included cognitive and behavioral disturbances (4/4), cerebrospinal fluid (CSF) lymphocytic pleocytosis (3/4), and a neural autoantibody (2/4). Electroencephalogram (EEG) features consisted of slow wave activity and epileptiform discharges in frontal and parasagittal regions, where ictal patterns were captured in 1 patient. In 1 patient, magnetoencephalographic source imaging of interictal spikes revealed dipole sources in anterior insular or subinsular localizations, mirroring claustrum FLAIR hyperintensities, which developed after a short lag from presentation and resolved in all but 1 patient. These MRI abnormalities were isolated (2/4) or associated with mesial temporal hyperintensities (2/4). Claustrum FLAIR hyperintensities may be a useful MRI marker of autoimmune epilepsy.
| S-EPMC5862111 | biostudies-literature
Project description:Epilepsy affects ~50 million people. In ~30% of patients the etiology is unknown, and ~30% are unresponsive to anti-epileptic drugs. Intractable epilepsy often leads to multiple seizures daily or weekly, lasting for years, and accompanied by cognitive, behavioral, and psychiatric problems. This multidisciplinary scientific (not clinical) 'Perspective' article discusses Autoimmune Epilepsy from immunological, neurological and basic-science angles. The article includes summaries and novel discoveries, ideas, insights and recommendations. We summarize the characteristic features of the respective antigens, and the pathological activity in vitro and in animal models of autoimmune antibodies to: Glutamate/AMPA-GluR3, Glutamate/NMDA-NR1, Glutamate/NMDA-NR2, GAD-65, GABA-R, GLY-R, VGKC, LGI1, CASPR2, and β2 GP1, found in subpopulations of epilepsy patients. Glutamate receptor antibodies: AMPA-GluR3B peptide antibodies, seem so far as the most exclusive and pathogenic autoimmune antibodies in Autoimmune Epilepsy. They kill neural cells by three mechanisms: excitotoxicity, Reactive-Oxygen-Species, and complement-fixation, and induce and/or facilitate brain damage, seizures, and behavioral impairments. In this article we raise and discuss many more topics and new insights related to Autoimmune Epilepsy. 1. Few autoimmune antibodies tilt the balance between excitatory Glutamate and inhibitory GABA, thereby promoting neuropathology and epilepsy; 2. Many autoantigens are synaptic, and have extracellular domains. These features increase the likelihood of autoimmunity against them, and the ease with which autoimmune antibodies can reach and harm these self-proteins. 3. Several autoantigens have 'frenetic character'- undergoing dynamic changes that can increase their antigenicity; 4. The mRNAs of the autoantigens are widely expressed in multiple organs outside the brain. If translated by default to proteins, broad spectrum detrimental autoimmunity is expected; 5. The autoimmunity can precede seizures, cause them, and be detrimental whether primary or epiphenomenon; 6. Some autoimmune antibodies induce, and associate with, cognitive, behavioral and psychiatric impairments; 7. There are evidences for epitope spreading in Autoimmune Epilepsy; 8. T cells have different 'faces' in the brain, and in Autoimmune Epilepsy: Normal T cells are needed for the healthy brain. Normal T cells are damaged by autoimmune antibodies to Glutamate/AMPA GluR3, which they express, and maybe by additional autoantibodies to: Dopamine-R, GABA-R, Ach-R, Serotonin-R, and Adrenergic-R, present in various neurological diseases (summarized herein), since T cells express all these Neurotransmitter receptors. However, autoimmune and/or cytotoxic T cells damage the brain; 9. The HLA molecules are important for normal brain function. The HLA haplotype can confer susceptibility or protection from Autoimmune Epilepsy; 10. There are several therapeutic strategies for Autoimmune Epilepsy.
| S-EPMC8790247 | biostudies-literature
Project description:Epilepsy is a debilitating condition, often with neither a known etiology nor an effective treatment. Autoimmune mechanisms have been increasingly identified.To conduct a population-level study investigating the relationship between epilepsy and several common autoimmune diseases.A retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. Participants were beneficiaries enrolled between 1999 and 2006 (N?=?2?518?034).We examined the relationship between epilepsy and 12 autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease.The risk of epilepsy was significantly heightened among patients with autoimmune diseases (odds ratio, 3.8; 95% CI, 3.6-4.0; P?<?.001) and was especially pronounced in children (5.2; 4.1-6.5; P?<?.001). Elevated risk was consistently observed across all 12 autoimmune diseases.Epilepsy and autoimmune disease frequently co-occur; patients with either condition should undergo surveillance for the other. The potential role of autoimmunity must be given due consideration in epilepsy so that we are not overlooking a treatable cause.
| S-EPMC4324719 | biostudies-literature
Project description:Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n?=?12) in comparison to a healthy control group (n?=?16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.
| S-EPMC6015084 | biostudies-other
Project description: Not available
| S-EPMC5716492 | biostudies-literature
Project description:IntroductionLate-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another possible cause of recurrent seizures in the elderly, and may account for a proportion of cases of LOE of unknown origin (LOEUO). This 24-h ambulatory electroencephalography (AEEG)-based study compared patients with LOEUO and AE to identify features suggestive of immune-mediated seizures in the elderly.Materials and methodsWe retrospectively reviewed 232 AEEG examinations performed in patients over 55 years with ≥6-month follow-up, and selected 21 subjects with AE and 25 subjects with LOEUO. Clinical charts and AEEG recordings were carefully analyzed.ResultsTwenty-five patients with LOEUO (12 women, mean age at onset 67.9 years) and 21 AE subjects (8 women, mean age at onset 65.7 years) were enrolled. High-frequency seizures were reported in 20/21 AE and 7/25 LOEUO cases (p < 0.00001). Focal aware seizures were more common in AE (14/21 vs. 6/25, p = 0.00058), whereas "isolated" focal-to-bilateral tonic-clonic seizures occurred in 5/25 patients with LOEUO only (p = 0.053). AE subjects reported ictal autonomic manifestations more frequently (p = 0.0033). Three-hundred-seventy and 24 seizures were recorded in 13/21 patients with AE and 3/25 patients with LOEUO, respectively (p = 0.0006). Interictal epileptiform discharges were observed in 70% of both groups, but their sleep activation was more common in AE (p = 0.06).ConclusionOur study shows that high-frequency focal seizures with autonomic manifestations should raise the suspicion of AE in the elderly with new-onset seizures. It also highlights the relevant contribution of AEEG, which might reduce the diagnostic delay and provide useful clues to recognize AE.
| S-EPMC9412019 | biostudies-literature
Project description: Not available
| S-EPMC8277215 | biostudies-literature
Project description:OBJECTIVE:Drug-resistant seizures are common in patients with leucine-rich, glioma-inactivated 1 (LGI1)-IgG associated and contactin-associated protein-like 2 (CASPR2)-IgG associated encephalitis. We performed the first randomized double-blind placebo-controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency. METHODS:Our enrollment goal was 30 LGI1/CASPR2-IgG-seropositive adult patients with ?2 seizures per week. Patients were randomized to receive IVIG (0.5g/kg day 1, 1g/kg day 2, 0.6g/kg weeks 3 and 5) or volume-matched intravenous normal saline. Following the blinded phase, the nonresponders in the placebo group received IVIG. The primary clinical outcome was 50% reduction in seizure frequency from baseline to 5?weeks. RESULTS:After enrollment of 17 patients (LGI1-IgG, 14; CASPR2-IgG, 3) over 34 months, the study was terminated due to slow enrollment. Six of 8 patients in the IVIG group were responders, compared to 2 of 9 in the placebo group (p =?0.044, odds ratio = 10.5, 95% confidence interval = 1.1-98.9). For the LGI1-IgG seropositive subgroup, 6 of 8 patients in the IVIG group were responders, compared to zero of 6 in the placebo group. Two LGI1-IgG-seropositive patients receiving IVIG, but none receiving placebo, were seizure-free at the end of the blinded phase. Four of the 6 patients entering the open-label IVIG arm reported ?50% reduction in seizure frequency. There were no correlations with LGI1/CASPR2-IgG1-4 subclasses. INTERPRETATION:Superiority of IVIG to placebo reached statistical significance for the primary endpoint for all patients and the subset with LGI1-IgG. These results have to be interpreted with the caveat that the study did not reach its originally selected sample size. ANN NEUROL 2020;87:313-323.
| S-EPMC7003900 | biostudies-literature
Project description:The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size.This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period.A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%), anti-GABAB-R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures.This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new-onset seizures in isolation or with a seizure-predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural-specific autoantibodies does not rule out AE.
| S-EPMC5817820 | biostudies-literature