Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LGI1 mutations predispose to a rare epilepsy syndrome and when inactivated in mice leads to early onset seizures and premature death. Histopathology of the mature brain soon after birth shows cortical dysplasia in Lgi1 null mice with hypercellularity in the outer cortical layers. Here we show extensive gene expression changes in neuronal precursor cells from Lgi1 null mice compared with wild type mice. The most significantly dysregulated pathway involves canonical axon guidance signaling with multiple networks involved in cell movement, adhesion and invasion related to actin cytoskeleton reorganization. The Lgi1 null NPCs show increased cell motility in vitro compared with normal counterparts. Dysregulation of genes critical to cell movement/migration and critical transcription factors involved in early neuronal development is a prominent feature. These studies provide a critical mechanistic link to the observation of increased cellularity in the outer layers of the developing cortex in Lgi1 null mice.
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PMID:Inactivation of Lgi1 in murine neuronal precursor cells leads to dysregulation of axon guidance pathways. 3127 52

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.
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PMID:[Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2]. 3128 28

BACKGROUND Anti-LGI1 encephalitis is a type of autoimmune limbic encephalitis. This case report elucidates features of anti-LGI1 limbic encephalitis, focusing on clinical findings and outcome as well as on rarely reported sinus arrest and its pathophysiology. CASE REPORT A 49-year-old female patient presented at the Emergency Department (ED) because of twitching and an acute confusional state. Initial neurological examination revealed cognitive disturbance with disorientation, inattention, and amnestic deficits. While in the ED, twitching of the right arm was observed and shortly thereafter she experienced a sinus arrest. A temporary cardiac pacemaker was implanted. Laboratory investigations demonstrated mild hyponatremia and positive LGI1-IgG antibodies in serum. An initial head MRI was unremarkable and electroencephalography showed epileptic seizure activity starting focally in the left hemisphere synchronous with the intermittent twitching of the right arm. A seizure-suppressant therapy with levetiracetam, valproate, and gabapentin was initiated, as well as an immunosuppressive pulse therapy with methylprednisolone followed by a tapering oral regimen of prednisolone. Within a few days, the seizures ceased. One month later, neurocognitive test results were back to normal. At 2 years, mild depressive symptoms and anxiety disorder were the main clinical problems, as well as episodic migraine-like headaches. CONCLUSIONS Repetitive focal dystonic seizures, confusion, amnestic deficits, sinus arrest, and mild-to-moderate hyponatremia are pathognomonic features of anti-LGI1 limbic encephalitis. Sinus arrest may occur because of a direct pathophysiological dysfunction of the structures involved in autonomic cardiac rhythm control or as an ictal or postictal phenomenon. Early diagnosis and initiation of immunosuppressive therapy are both of utmost importance for favorable clinical outcome.
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PMID:Syncope and Twitching at the Emergency Department. 3144 80

Background and purpose: We retrospectively analyzed the clinical characteristics of children with autoimmune encephalitis (AE) in two Chinese tertiary pediatric neurology centers. We also compared anti-NMDAR encephalitis with and without co-positive MOG antibody, as well as specific autoantibody-positive AE and autoantibody-negative but probable AE. Methods: A retrospective study of children (0-18 years old) with AE in Peking University First Hospital and Children's Hospital Affiliated to Capital Institute of Pediatrics was carried out from May 2012 to January 2017. Demographics, clinical features, laboratory, and imaging findings, outcome, and co-positivity with MOG antibody were analyzed. Results: A total of 103 children had AE, 89 (86.4%) had anti-NMDAR encephalitis, 2 (1.9%) had anti-LGI1 encephalitis, 1 (0.9%) had anti-CASPR2 encephalitis, and 11 (10.7%) were diagnosed as autoantibody-negative but probable AE. Among the 89 children with anti-NMDAR encephalitis, 35 were males and 54 were females. The follow-up time was 1-3 years. A total of 15 cases (15/89, 16.9%) with anti-NMDAR encephalitis had co-positive MOG antibody (serum or cerebrospinal fluid or both). These patients were more likely to experience relapse later in life (P = 0.014). We had two cases with anti-LGI1 encephalitis, that is, one with sleep disorder onset, and the other one with seizure onset, both of whom recovered after treatment. One case with anti-CASPR2 encephalitis was treated with an antiepileptic drug and fully recovered. There were 11 cases diagnosed as autoantibody-negative but probable AE who had relatively poorer outcome than those with autoantibody-positive AE (15.2%, 14/89). However, the difference was not significant (P = 0.08). Only one 12-year-old girl with NMDAR-antibody AE had ovarian teratoma. Conclusion: Most subjects with AE in our Chinese cohort had anti-NMDAR AE, which had relatively good prognosis. Children with anti-LGI1 or anti-CASPR2 encephalitis were rare and showed good response on immunotherapy. Co-positive MOG antibody was relatively common in anti-NMDAR encephalitis, which was related to high relapse rate. In our study, the prognosis of autoantibody-negative but probable AE seemed worse than that of specific autoantibody-positive AE.
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PMID:Pediatric Autoimmune Encephalitis: Case Series From Two Chinese Tertiary Pediatric Neurology Centers. 3150 15

Autoimmune encephalitides, with an estimated incidence of 1.5 per million population per year, although described only 15 years ago, have already had a remarkable impact in neurology and paved the field to autoimmune neuropsychiatry. Many patients traditionally presented with aberrant behavior, especially of acute or subacute onset, and treated with anti-psychotic therapies, turn out to have a CNS autoimmune disease with pathogenic autoantibodies against synaptic antigens responding to immunotherapies. The review describes the clinical spectrum of these disorders, and the pathogenetic role of key autoantibodies directed against: a) cell surface synaptic antigens and receptors, including NMDAR, GABAa, GABAb, AMPA and glycine receptors; b) channels such as AQP4 water-permeable channel or voltage-gated potassium channels; c) proteins that stabilize voltage-gated potassium channel complex into the membrane, like the LGI1 and CASPR2; and d) enzymes that catalyze the formation of neurotransmitters such as Glutamic Acid Decarboxylase (GAD). These antibodies, effectively target excitatory or inhibitory synapses in the limbic system, basal ganglia or brainstem altering synaptic function and resulting in uncontrolled neurological excitability disorder clinically manifested with psychosis, agitation, behavioral alterations, depression, sleep disturbances, seizure-like phenomena, movement disorders such as ataxia, chorea and dystonia, memory changes or coma. Some of the identified triggering factors include: viruses, especially herpes simplex, accounting for the majority of relapses occurring after viral encephalitis, which respond to immunotherapy rather than antiviral agents; tumors especially teratoma, SCLC and thymomas; and biological cancer therapies (immune-check-point inhibitors). As anti-synaptic antibodies persist after viral infections or tumor removal, augmentation of autoreactive B cells which release autoantigens to draining lymph nodes, molecular mimicry and infection-induced bystander immune activation products play a role in autoimmunization process or perpetuating autoimmune neuroinflammation. The review stresses the importance of early detection, clinical recognition, proper antibody testing and early therapy initiation as these disorders, regardless of a known or not trigger, are potentially treatable responding to systemic immunotherapy with intravenous steroids, IVIg, rituximab or even bortezomid.
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PMID:The immunobiology of autoimmune encephalitides. 3161 Nov 42

The autoimmune encephalitis (AE) syndromes have been characterised by the detection of autoantibodies in serum and/or cerebrospinal fluid which target the extracellular domains of specific neuroglial antigens. The clinical syndromes have phenotypes which are often highly characteristic of their associated antigen-specific autoantibody. For example, the constellation of psychiatric features and the multi-faceted movement disorder observed in patients with NMDAR antibodies are highly distinctive, as are the faciobrachial dystonic seizures observed in close association with LGI1 antibodies. These typically tight correlations may be conferred by the presence of autoantibodies which can directly access and modulate their antigens in vivo. AE remains an under-recognised clinical syndrome but one where early and accurate detection is critical as prompt initiation of immunotherapy is closely associated with improved outcomes. In this review of a rapidly emerging field, we outline molecular observations with translational value. We focus on contemporary methodologies of autoantibody detection, the evolution and distinctive nature of the clinical phenotypes, generalisable therapeutic paradigms, and finally discuss the likely mechanisms of autoimmunity in these patients which may inform future precision therapies.
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PMID:The autoantibody-mediated encephalitides: from clinical observations to molecular pathogenesis. 3165 89

Anti-leucine-rich glioma inactivated-1 (anti-LGI1) encephalitis is a subgroup of autoimmune encephalitis. We herein report the case of a 60-year-old man who presented with typical symptoms, including short-term memory loss, mental abnormalities, hyponatremia and seizures characterized by faciobrachial dystonic seizures and who was diagnosed with anti-LGI1 encephalitis. At the same time, he was diagnosed with essential thrombocythemia. A significant improvement was obtained by treatment with corticosteroid, immunoglobulin, mycophenolate mofetil, and hydroxyurea. Autoimmune diseases are associated with a significantly increased risk of developing myeloproliferative neoplasms, which may explain the coexistence of anti-LGI1 encephalitis and essential thrombocythema in this patient; however, but more cases and studies are needed to determine whether there is any correlation between these conditions.
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PMID:Anti-leucine-rich Glioma Inactivated-1 Encephalitis Associated with Essential Thrombocythemia. 3194 73

Autoantibodies to leucine-rich glioma-inactivated protein 1 (LGI-1) are associated with inflammation of the limbic system. Faciobrachial dystonic seizures are pathognomonic for LGI1-antibiodies and their treatment with immunotherapy is effective in seizure control with a potential to prevent cognitive decline. We report a 57-year-old man who presented to the emergency department with recurrent seizures, visual hallucinations and severe memory impairment over a seven-week period; he reported a background of alcohol excess. Initial investigations revealed hyponatremia, indicating syndrome of inappropriate anti-diuretic hormone secretion. Magnetic resonance imaging of the brain revealed bilateral asymmetrical high-T2 and low-T1 signal in the medial temporal lobes. Serum immunofluorescence assay tested positive for LGI-1 antibody. Patient responded to treatment with levetiracetam, intravenous methylprednisolone and five plasma exchange sessions. Patient remains on a maintenance dose of prednisolone and azathioprine. It is imperative that clinicians recognize signs of autoimmune encephalitis in order to curb long-term sequelae and improve clinical outcomes.
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PMID:Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report. 3203 79

In recent years, there have been many developments in the field of autoimmune encephalitis. Autoimmune encephalitis is often treatable, and fast recognition and treatment are essential to prevent irreversible damage. Identification of patients with autoimmune encephalitis is challenging because patients display various symptoms and consequently present to different medical specialists. We describe 3 cases of autoimmune encephalitis due to different antibodies. A 23-year-old woman presented with acute psychosis, followed by seizures and autonomic dysfunction. She was diagnosed with anti-NMDAR encephalitis caused by antibodies that were triggered by ovarian teratoma. A 59-year-old man developed severe behavioural changes, memory deficits, and subtle faciobrachial dystonic seizures. He had anti-LGI1 encephalitis and recovered completely. The third patient was a 57-year-old man who presented with diarrhea and weight loss, and gradually developed progressive rigidity, myoclonus and ataxia over the course of several months. He was ultimately diagnosed with anti-DPPX encephalitis. All patients responded well to immunotherapy with (near-)complete recovery within months to years.
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PMID:[Clinical symptoms of patients with autoimmune encephalitis: a guide to timely recognition and treatment]. 3207 82

Primary schizophreniform psychoses are thought to be caused by complex gene-environment interactions. Secondary forms are based on a clearly identifiable organic cause, in terms of either an etiological or a relevant pathogenetic factor. The secondary or "symptomatic" forms of psychosis have reentered the focus stimulated by the discovery of autoantibody (Ab)-associated autoimmune encephalitides (AEs), such as anti-NMDA-R encephalitis, which can at least initially mimic variants of primary psychosis. These newly described secondary, immune-mediated schizophreniform psychoses typically present with the acute onset of polymorphic psychotic symptoms. Over the course of the disease, other neurological phenomena, such as epileptic seizures, movement disorders, or reduced levels of consciousness, usually arise. Typical clinical signs for AEs are the acute onset of paranoid hallucinatory symptoms, atypical polymorphic presentation, psychotic episodes in the context of previous AE, and additional neurological and medical symptoms such as catatonia, seizure, dyskinesia, and autonomic instability. Predominant psychotic courses of AEs have also been described casuistically. The term autoimmune psychosis (AP) was recently suggested for these patients. Paraclinical alterations that can be observed in patients with AE/AP are inflammatory cerebrospinal fluid (CSF) pathologies, focal or generalized electroencephalographic slowing or epileptic activity, and/or suspicious "encephalitic" imaging findings. The antibody analyses in these patients include the testing of the most frequently found Abs against cell surface antigens (NMDA-R, CASPR2, LGI1, AMPA-R, GABAB-R), intracellular antigens (Hu, Ri, Yo, CV2/CRMP5, Ma2 [Ta], amphiphysin, GAD65), thyroid antigens (TG, TPO), and antinuclear Abs (ANA). Less frequent antineuronal Abs (e.g., against DPPX, GABAA-R, glycine-R, IgLON5) can be investigated in the second step when first step screening is negative and/or some specific clinical factors prevail. Beyond, tissue-based assays on brain slices of rodents may detect previously unknown antineuronal Abs in some cases. The detection of clinical and/or paraclinical pathologies (e.g., pleocytosis in CSF) in combination with antineuronal Abs and the exclusion of alternative causes may lead to the diagnosis of AE/AP and enable more causal therapeutic immunomodulatory opportunities.
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PMID:Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations. 3216 3


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