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immunotherapy and autoimmune epilepsy

Sonal Bhatia, Sarah E Schmitt
PURPOSE OF REVIEW: This review explores different treatment modalities for immune-mediated epilepsy, including epilepsy caused by autoantibodies as well as epilepsy in the context of systemic autoimmune disease. RECENT FINDINGS: Autoimmune epilepsy is an increasingly recognized entity. Conventional treatments for epilepsy, such as antiseizure medications and epilepsy surgery, are less successful in treating epilepsy caused by autoimmune disease. Immunomodulatory therapies such as corticosteroids, intravenous immunoglobulin, and plasma exchange are generally more successful in treating immune-mediated epilepsy than conventional epilepsy therapies...
February 14, 2018: Current Neurology and Neuroscience Reports
Yating Wu, Aihua Liu
Epilepsy is a common chronic brain disorder with multiple causes, and now autoimmune factors are believed to be an independent cause for epilepsy. Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures. Moreover, systemic autoimmune diseases and epilepsy co-occur frequently. Neural specific autoantibodies can also mediate the process of seizures through different pathways. The diagnosis of autoimmune epilepsy is based on frequency of antiepileptic drug-resistant seizures, the presence of neural specific autoantibodies, inflammatory changes in serum or spinal fluid or on magneticresonanceimaging, the change in electroencephalogram, a personal or family history of autoimmunity...
December 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Eric Lancaster
PURPOSE OF REVIEW: Paraneoplastic neurologic syndromes target specific areas of the nervous system with pathogenic autoantibodies or T-cell responses. Each syndrome conveys a risk of particular tumors. Expanded paraneoplastic antibody testing has led to improved diagnosis but created challenges involving appropriate interpretation of test results. RECENT FINDINGS: Peripheral nervous system paraneoplastic disorders such as myasthenia gravis and Lambert-Eaton myasthenic syndrome involve pathogenic autoantibodies...
December 2017: Continuum: Lifelong Learning in Neurology
Junzhao Cui, Hui Bu, Junying He, Zeyan Zhao, Weixin Han, Ruiping Gao, Xiaoqing Li, Qing Li, Xiaosu Guo, Yueli Zou
PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years)...
December 6, 2017: International Journal of Neuroscience
Anusha K Yeshokumar, Carlos A Pardo
Autoimmune epilepsies describe clinical syndromes wherein the immune system is suspected to be involved in the pathogenesis of seizures or as a mechanism for neuronal injury following seizures. These diseases typically affect otherwise healthy children and are characterized by explosive onset of focal seizures, encephalopathy, cognitive deterioration, or other focal neurological deficits, or all of these. Traditional neurological diagnostics lack sensitivity and specificity in the diagnosis of autoimmune epilepsies, and results must be considered in the clinical context...
August 2017: Seminars in Pediatric Neurology
Riki Matsumoto, Mitsuhiro Sakamoto, Akio Ikeda
The recent discovery of autoimmune antibodies to the neuronal cell surface membrane and extra- or intra-cellular proteins, such as NMDAR and LGI1, shed light on a proposed new etiology of epilepsy, namely, "autoimmune epilepsy". A large part of this entity most likely belongs to a forme fruste of autoimmune (limbic) encephalitis. Seizures are usually subacute in onset and refractory to antiepileptic medications. Patients occasionally manifest multiple seizure semiologies, such as autonomic or faciobrachial dystonic seizures...
October 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
Xueping Chen, Fan Liu, Jin-Mei Li, Xiao-Qi Xie, Qiong Wang, Dong Zhou, Huifang Shang
OBJECTIVE: Autoimmune encephalitis associated with antibodies against gamma-aminobutyric-acid B receptor (GABABR) has not been described in detail in Chinese patients. METHODS: Patients with anti-GABABR encephalitis treated between January 2013 and December 2015 were analyzed in terms of clinical characteristics, laboratory findings, tumor presence, autoantibody patterns, treatment response and outcomes. RESULTS: Eleven patients were identified (male, N = 8; female, N = 3), with the median age of 51 years...
November 2017: Neurological Research
Raffaele Iorio, Valentina Damato, Amelia Evoli, Marco Gessi, Simona Gaudino, Vincenzo Di Lazzaro, Gregorio Spagni, Jacqueline A Sluijs, Elly M Hol
OBJECTIVE: To report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies. METHODS: From January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients' serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot...
February 2018: Journal of Neurology, Neurosurgery, and Psychiatry
José Fidel Baizabal-Carvallo, Marlene Alonso-Juarez
Several neurological syndromes have been recognized associated to GAD antibodies. Among those disorders, cerebellar ataxia (CA) is one of the most common, along with stiff-person syndrome. Patients with GAD associated CA present with a progressive pancerebellar syndrome, with a subacute or chronic evolution, along with other neurological manifestations such as stiffness, oculomotor dysfunction, epilepsy, and cognitive dysfunction. These symptoms may be preceded by the so-called "brainstem attacks", where manifestations consistent with transient dysfunction of the brainstem may be observed...
October 2017: Journal of Neural Transmission
Christian G Bien, Martin Holtkamp
Autoimmune encephalitides may account for epilepsies of so far unknown cause. These "autoimmune epilepsies" may respond well to immunotherapy. More than a dozen autoantibodies have been found with this constellation; therefore, broad autoantibody testing of serum-CSF pairs offers the best diagnostic yield. Several particular features raise the suspicion of an autoimmune cause in otherwise unexplained seizure disorders.
May 2017: Epilepsy Currents
Anteneh M Feyissa, A Sebastian López Chiriboga, Jeffrey W Britton
OBJECTIVE: We aimed to report the pattern of usage and efficacy of antiepileptic drugs (AEDs) in patients with autoimmune epilepsy (AE). METHODS: We retrospectively studied the Mayo Clinic's electronic medical record of patients with AE in which seizures were the main presenting feature. Clinical data, including demographics, seizure characteristics, type of AED and immunotherapy used, presence of neural antibody, and treatment outcomes, were reviewed. RESULTS: The medical records of 252 adult patients diagnosed with autoimmune encephalitis and paraneoplastic disorders were reviewed...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
Gokcen Gozubatik-Celik, Cigdem Ozkara, Canan Ulusoy, Aysegul Gunduz, Sakir Delil, Naz Yeni, Erdem Tuzun
BACKGROUND: and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients. METHOD: Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies...
September 2017: Epilepsy Research
Jan Bauer, Albert J Becker, Wassim Elyaman, Jukka Peltola, Stephan Rüegg, Maarten J Titulaer, James A Varley, Ettore Beghi
Inflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies...
July 2017: Epilepsia
Divyanshu Dubey, Jaysingh Singh, Jeffrey W Britton, Sean J Pittock, Eoin P Flanagan, Vanda A Lennon, Jan-Mendelt Tillema, Elaine Wirrell, Cheolsu Shin, Elson So, Gregory D Cascino, Dean M Wingerchuk, Matthew T Hoerth, Jerry J Shih, Katherine C Nickels, Andrew McKeon
OBJECTIVE: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. METHODS: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient...
July 2017: Epilepsia
Zhiwei Fang, Yunqi Yang, Xuan Chen, Weiwang Zhang, Yangmei Xie, Yinghui Chen, Zhenguo Liu, Weien Yuan
In this comprehensive article, we present an overview of some most common autoimmune antibodies believed to be potentially pathogenic for autoimmune epilepsies and elaborate their pathogenic mode of action in molecular levels based on the existing knowledge. Findings of the studies of immunemodulatory treatments for epilepsy are also discussed, and guidelines for immunotherapy are sorted out. We aim to summarize the emerging understanding of different pathogenic mechanisms of autoantibodies and clinical immunotherapy regimens to open up therapeutic possibilities for future optimum therapy...
2017: Frontiers in Immunology
Claudia Varrasi, Domizia Vecchio, Luca Magistrelli, Gionata Strigaro, Laura Tassi, Roberto Cantello
In its classic presentation, Hashimoto's encephalopathy is an acute-subacute complex neuropsychiatric syndrome with cognitive impairment, hallucinations, myoclonus, tremor or ataxia, associated with elevated anti-thyroid antibodies. Corticoids and immunotherapy are dramatically effective. However, in some cases, not all the associated features are presented and this delays diagnosis and appropriate treatment. We describe a man with abrupt onset of recurrent auditory seizures resulting in refractory non-convulsive status epilepticus...
March 1, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
Divyanshu Dubey, Abdulradha Alqallaf, Ryan Hays, Matthew Freeman, Kevin Chen, Kan Ding, Mark Agostini, Steven Vernino
Importance: Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. Objective: To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Design, Setting, and Participants: Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified...
April 1, 2017: JAMA Neurology
Andrew McKeon, Jennifer A Tracy
The glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibody is a biomarker of autoimmune central nervous system (CNS) disorders and, more commonly, nonneurological autoimmune diseases. Type 1 diabetes, autoimmune thyroid disease, and pernicious anemia are the most frequent GAD65 autoimmune associations. One or more of these disorders coexists in approximately 70% of patients with GAD65 neurological autoimmunity. Neurological phenotypes have CNS localization and include limbic encephalitis, epilepsy, cerebellar ataxia, and stiff-person syndrome (SPS), among others...
July 2017: Muscle & Nerve
Penelope Fouka, Harry Alexopoulos, Ioanna Chatzi, Skarlatos G Dedos, Martina Samiotaki, George Panayotou, Panagiotis Politis, Athanasios Tzioufas, Marinos C Dalakas
OBJECTIVE: To describe newly identified autoantibodies associated with cerebellar disorders. DESIGN/METHODS: We first screened the sera of 15 patients with cerebellar ataxia, without any known associated autoantibodies, with immunocytochemistry on mouse brain. After characterization and validation of a newly identified antibody, 85 additional patients with suspected autoimmune cerebellar disease were screened using a cell-based assay. RESULTS: Immunoglobulin G from one of the first 15 patients demonstrated a distinct staining pattern on Purkinje neurons...
January 2017: Neurology® Neuroimmunology & Neuroinflammation
M Zhang, H J Hao, L P Liu, H H Zhang, Y Y Zhou
Autoimmune encephalitis with GABAB receptor antibodies has been rarely reported. Two cases of GABAB receptor antibodies encephalitis were presented here.Epilepsy was the onset symptom, followed by declined consciousness and frequent seizures. Fever was presented in the whole course of the disease. Myorhythmia of the two hands and pilomotor seizures were shown in the later course of the disease. No specificity was demonstrated in electroencephalograms and magnetic resonance imaging. Sensitive response was shown to the first-line immunotherapy...
October 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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