A comparison of glutamic acid decarboxylase serum autoantibody levels in pediatric intractable and non-intractable epilepsy

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Ratumbuysang" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 609 "Ancho" => 1500 "Tamanyo" => 73402 ] ] "descripcion" => array:1 [ "en" => "Diagram of alternative groups based on cost utilities." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nety Daud Karaeng, Andi Ilham Makhmud, Kristian Liaury" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Nety Daud" "apellidos" => "Karaeng" ] 1 => array:2 [ "nombre" => "Andi Ilham" "apellidos" => "Makhmud" ] 2 => array:2 [ "nombre" => "Kristian" "apellidos" => "Liaury" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2603924921000471?idApp=UINPBA00004N" "url" => "/26039249/00000004000000S1/v1_202104281119/S2603924921000471/v1_202104281119/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "A comparison of glutamic acid decarboxylase serum autoantibody levels in pediatric intractable and non-intractable epilepsy" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Novi Dwi Anggraini, Prastiya Indra Gunawan, Darto Saharso, Irwanto" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Novi Dwi" "apellidos" => "Anggraini" "email" => array:1 [ 0 => "novidwianggraini@yahoo.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Prastiya Indra" "apellidos" => "Gunawan" ] 2 => array:2 [ "nombre" => "Darto" "apellidos" => "Saharso" ] 3 => array:1 [ "apellidos" => "Irwanto" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Pediatrics, College of Medicine, Airlangga University, Soeteomo Hospital, Indonesia" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "IntroductionIntractable epilepsy is defined as inadequate seizure control despite compliance with effective AEDs and excluding non-epileptic events and poor compliance or failure of two adequate AEDs, either monotherapy or combination therapy, to achieve sustained seizure-free status, the occurrence of one seizure per month, and no more than a 3-month seizure-free period.<a class="elsevierStyleCrossRefs" href="#bib0105">1,2</a> Glutamic acid decarboxylase (GAD) is the main enzyme catalyst for the conversion of glutamic acid to gamma aminobutyric acid (GABA), the main neurotransmitter inhibitor in the GABAergic terminal in the brain. The presence of GAD have influence in balance equilibrium between inhibitors and excitation of neurotransmitters.<a class="elsevierStyleCrossRef" href="#bib0115">3</a> Autoantibodies to glutamic acid decarboxylase (GAD-Ab) as one of the causes of epilepsy are found in patients with acute and chronic epilepsy. Most of the published reports concern adult patients, and the frequency of these antibodies in the pediatric epileptic population is unknown.<a class="elsevierStyleCrossRef" href="#bib0120">4</a> In regard to intractable epilepsy, we found a higher concentration compared to the control as an effect of uncontrolled seizure activity. A previous study found 6.7% with autoantibodies>1000iu/ml in intractable epilepsy.<a class="elsevierStyleCrossRef" href="#bib0125">5</a>The prevalence of GAD-Ab has been found to increase in adult epilepsy and temporal lobe epilepsy.<a class="elsevierStyleCrossRef" href="#bib0130">6</a> Autoimmunity as an epilepsy etiology has a significant clinical impact, with immune therapy as part of a treatment plan that can offer the patient clinical improvement.<a class="elsevierStyleCrossRef" href="#bib0135">7</a> Several studies have demonstrated the remission of epileptic seizures following the administration of immunosuppressant therapy, a finding that confirmed that epilepsy patients with GAD-Ab have a positive effect from immunosupressant therapy.<a class="elsevierStyleCrossRefs" href="#bib0140">8–11</a>Failure to control seizures in children has medical, social, and economic effects, as well as potential behavioral problems that may result in a negative effect on their education. Uncontrolled seizure activity has also been associated with cognitive impairment.<a class="elsevierStyleCrossRef" href="#bib0160">12</a> Most clinicians do not consider autoimmunity as one of the causes of intractable epilepsy. Clinicians must consider that an immune etiology may be present, especially in patients with subacute seizures who do not appear to have structural abnormalities on magnetic resonance imaging.<a class="elsevierStyleCrossRef" href="#bib0165">13</a>Materials and methodsPatientsThis study was conducted from November to December 2018. The author received written informed consent from the patient parent. Data collection included age, gender, regional AEDs prescribed, dosage and medication frequency, type of therapy and its duration, and seizure frequency. Inclusion criteria were children from 1 month to 17 years old, previously diagnosed with intractable epilepsy or non-intractable epilepsy, currently receiving anti-epileptic drug treatment, and a parent who agreed to have his/her child participate and who signed the informed consent. Exclusion criteria were a history of an autoimmune disease (e.g., type 1 DM, Crohn's disease, Hashimoto thyroiditis), neurological disease (e.g., encephalitis), chronic inflammatory disease, a history of refractory related to non-epileptic seizures, inadequate AEDs, non-compliance, and high-dose steroid therapy. Autoantibodies to glutamic acid decarboxylase serum were analyzed from peripheral blood collection. A total of 90 patients met the inclusion criteria for this study, but 10 refused blood collection and dropped out. The Institutional Review Board (IRB) at Dr. Soetomo Hospital, Surabaya, approved all protocols in this study (number 0585/KEPK/IX/2018).MethodsThis was a case control study conducted at Dr. Soetomo Hospital, Surabaya. Data were collected in the pediatric neurology outpatient clinic)MeasurementAll patients in this study were evaluated for GAD-Ab in serum. As a cut-off for increased GAD-Ab, we referred to a previous study that used>100mg/dl in serum.<a class="elsevierStyleCrossRef" href="#bib0110">2</a> The evaluation of GAD-Ab was carried out using AED245Hu 96 Tests Enzyme-linked Immunosorbent Assay Kit For Anti-Glutamic Acid Decarboxylase Antibodies (Anti-GAD) (Cloud-Clone Corp., Houston, TX, USA) with a standard curve range of 2–600ng/ml. The examination results were in the form of quantitative data.Statistical analysisIBM SPSS Statistics version 21.0 (IBM Co., Armonk, NY, USA) was used for statistical analysis. The Mann–Whitney U test was used to compare GAD-Ab levels in serum; a p value of <0.05 was considered to have statistical significance.ResultA sample of 80 patients diagnosed with epilepsy were interviewed. Their parents also completed data collection sheets. Patients were divided into two groups, namely intractable epilepsy and non-intractable epilepsy. This study showed no differences between males and females. Patients whose ages were between 1 and 5 years old outnumbered other age categories. In the intractable group, the type of seizure experienced most often is the general tonic–clonic seizure, and all patients used 2 or 3 anti-epileptic drugs (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Based on the non-parametric Mann–Whitney U test, intractable epilepsy serum GAD-Ab levels were higher compared to those in the non-intractable epilepsy group, with p values=0.000 (p significant<0.05) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiscussionAutoantibodies to glutamic acid decarboxylase have been detected in CSF and serum in patients with epilepsy. Increased GAD-Ab is strongly associated with epilepsy and indicative of ongoing immune dysregulation.<a class="elsevierStyleCrossRef" href="#bib0110">2</a> This study showed that GAD-Ab serum is higher in children with intractable epilepsy compared to children with non-intractable epilepsy. Although there were several neuronal autoantibodies suspected as etiologies of epilepsy, we compared GAD-Ab specifically between children with intractable and controlled forms of epilepsy. The increased prevalence of autoantibodies is more strongly associated with epilepsy, perhaps indicating that immune dysregulation may be commonly associated with this disorder.<a class="elsevierStyleCrossRef" href="#bib0170">14</a>This study found a significant difference in GAD-Ab levels between the two groups, with a higher level of GAD autoantibodies in the group with intractable epilepsy. This result supports previous studies that found similar results; both found significantly higher levels of GAD-Ab in the intractable epilepsy group compared to the control group.<a class="elsevierStyleCrossRefs" href="#bib0110">2,15</a> One study confirmed that GAD-Ab was associated with several forms of epilepsy such as idiopathic and cryptogenic temporal epilepsy, and another found GAD-Ab up to 100 iu/ml, especially in drug-resistant patients with epilepsy.<a class="elsevierStyleCrossRefs" href="#bib0145">9,16</a>The highest GAD-Ab level was found in patients with intractable epilepsy, providing evidence for an autoimmune etiology and active immunological processes in the brain.<a class="elsevierStyleCrossRef" href="#bib0180">16</a> Antibodies to glutamic acid decarboxylase induce suppression of GABA release, modulate inhibitory potential in interneurons, down-regulate GABA synthesis in neuronal cell terminals, decrease GABA release in post-synaptic purkinje cells, disrupt neuronal activity, and intervene in the regulation of brain neurotransmitters.<a class="elsevierStyleCrossRefs" href="#bib0135">7,17</a> This leads directly to intercellular protein mediated by T cell cytotoxicity, which causes inflamation and burnout in the hippocampal region.<a class="elsevierStyleCrossRefs" href="#bib0125">5,18</a> Antibodies to GAD play a role in the cerebellar pathway where irreversible lesions cause permanent neuronal damage and cerebellar atrophy.<a class="elsevierStyleCrossRef" href="#bib0195">19</a>Our study has limitations that must be considered. The study examined GAD-Ab in blood. A high level of GAD-Ab is reported to have been found in cerebral spinal fluid; however, we did not use CSF for this study because the procedure for collecting it is invasive and uncomfortable, and the number of parents who would have rejected this procedure would, understandably, be quite high. The blood–brain barrier leak due to inflammation results in antineuronal antibodies being found in the blood; thus, we considered blood for the research material.<a class="elsevierStyleCrossRef" href="#bib0200">20</a> In this study, the variation of epilepsy samples is wide, where the range of age is 1 month to 17 years; therefore, it required a larger sample number.In conclusion, the GAD-Ab serum level is higher in children with intractable epilepsy compared to children with non-intractable epilepsy. Further studies of other neurological autoimmune antibodies to reveal autoimmunity in the etiology of epilepsy should be conducted.ConclusionChildren suffering from intractable epilepsy have higher levels of GAD-Ab compared to children with non-intractable epilepsy.Data availabilityThe data used to support the findings of this study are available from the corresponding author upon request.Ethical approvalAll procedures in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The ethical approval of this study was granted from Ethical Committee, Faculty of Medicine, Universitas Airlangga.ConsentInformed consent was obtained from all individual subjects included in the study.Conflicts of interestNo potential conflict of interest relevant to this article was reported." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1504162" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Result" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1365125" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Measurement" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Result" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusion" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Data availability" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Ethical approval" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Consent" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-09-24" "fechaAceptado" => "2020-10-15" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1365125" "palabras" => array:3 [ 0 => "Autoantibodies to glutamic acid decarboxylase" 1 => "Intractable epilepsy" 2 => "Children" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveThe purpose of this study was to compare autoantibodies to glutamic acid decarboxylase serum levels in children suffering from intractable and non-intractable epilepsy at Dr. Soetomo General Hospital Surabaya, Indonesia. MethodsA case–control study was conducted with children suffering from intractable and non-intractable epilepsy from November to December 2018 in the pediatric neurology outpatient clinic. Autoantibodies to glutamic acid decarboxylase serum levels were examined from both groups using ELISA; statistical analysis was performed using the Mann–Whitney U test non-parametric tests. ResultA sample of 80 children was divided into two groups of 40 children each. Their average age was 5.4 years (range of 4 months–17 years). The average anti-epileptic drug treatment duration was 2.3 years (3 months–13 years). Glutamic acid decarboxylase autoantibody levels in the intractable group were higher compared to levels in the non-intractable group, ranging from 140 to 410ng/ml (median 243.3) and 10–120ng/ml (median 98.10) respectively with p values<0.05. ConclusionChildren suffering from intractable epilepsy have higher levels of GAD-Ab compared to children with non-intractable epilepsy." 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Full-text and the content of it is under responsibility of authors of the article." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intractable epilepsy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non intractable epilepsy \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, median±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5y±4.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4y±4.95 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of therapy, median±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2y±0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2y±0.75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (57.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6–10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (17.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11–17 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (22.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Seizure type n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">General tonic clonic seizure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Partial seizure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (27.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atonic seizure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2583978.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patient characteristic." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">GAD autoantibibodies (ng/ml) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Intractable epilepsy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Non intractable epilepsy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rangemedian±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140–410235.34±94.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10–12091.05±27.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2583977.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Antibodies to glutamic acid decarboxylase serum levels comparison between groups." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glutamic acid decarboxylase autoantibodies in controlled and uncontrolled epilepsy: a pilot study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. 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Novi Dwi Anggraini

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novidwianggraini@yahoo.com

Corresponding author.

, Prastiya Indra Gunawan, Darto Saharso, Irwanto

Department of Pediatrics, College of Medicine, Airlangga University, Soeteomo Hospital, Indonesia

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Intractable epilepsy is defined as inadequate seizure control despite compliance with effective AEDs and excluding non-epileptic events and poor compliance or failure of two adequate AEDs&#44; either monotherapy or combination therapy&#44; to achieve sustained seizure-free status&#44; the occurrence of one seizure per month&#44; and no more than a 3-month seizure-free period&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;2</span></a> Glutamic acid decarboxylase &#40;GAD&#41; is the main enzyme catalyst for the conversion of glutamic acid to gamma aminobutyric acid &#40;GABA&#41;&#44; the main neurotransmitter inhibitor in the GABAergic terminal in the brain&#46; The presence of GAD have influence in balance equilibrium between inhibitors and excitation of neurotransmitters&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> Autoantibodies to glutamic acid decarboxylase &#40;GAD-Ab&#41; as one of the causes of epilepsy are found in patients with acute and chronic epilepsy&#46; Most of the published reports concern adult patients&#44; and the frequency of these antibodies in the pediatric epileptic population is unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> In regard to intractable epilepsy&#44; we found a higher concentration compared to the control as an effect of uncontrolled seizure activity&#46; A previous study found 6&#46;7&#37; with autoantibodies<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1000<span class="elsevierStyleHsp" style=""></span>iu&#47;ml in intractable epilepsy&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of GAD-Ab has been found to increase in adult epilepsy and temporal lobe epilepsy&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Autoimmunity as an epilepsy etiology has a significant clinical impact&#44; with immune therapy as part of a treatment plan that can offer the patient clinical improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> Several studies have demonstrated the remission of epileptic seizures following the administration of immunosuppressant therapy&#44; a finding that confirmed that epilepsy patients with GAD-Ab have a positive effect from immunosupressant therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">8&#8211;11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Failure to control seizures in children has medical&#44; social&#44; and economic effects&#44; as well as potential behavioral problems that may result in a negative effect on their education&#46; Uncontrolled seizure activity has also been associated with cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> Most clinicians do not consider autoimmunity as one of the causes of intractable epilepsy&#46; Clinicians must consider that an immune etiology may be present&#44; especially in patients with subacute seizures who do not appear to have structural abnormalities on magnetic resonance imaging&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This study was conducted from November to December 2018&#46; The author received written informed consent from the patient parent&#46; Data collection included age&#44; gender&#44; regional AEDs prescribed&#44; dosage and medication frequency&#44; type of therapy and its duration&#44; and seizure frequency&#46; Inclusion criteria were children from 1 month to 17 years old&#44; previously diagnosed with intractable epilepsy or non-intractable epilepsy&#44; currently receiving anti-epileptic drug treatment&#44; and a parent who agreed to have his&#47;her child participate and who signed the informed consent&#46; Exclusion criteria were a history of an autoimmune disease &#40;e&#46;g&#46;&#44; type 1 DM&#44; Crohn&#39;s disease&#44; Hashimoto thyroiditis&#41;&#44; neurological disease &#40;e&#46;g&#46;&#44; encephalitis&#41;&#44; chronic inflammatory disease&#44; a history of refractory related to non-epileptic seizures&#44; inadequate AEDs&#44; non-compliance&#44; and high-dose steroid therapy&#46; Autoantibodies to glutamic acid decarboxylase serum were analyzed from peripheral blood collection&#46; A total of 90 patients met the inclusion criteria for this study&#44; but 10 refused blood collection and dropped out&#46; The Institutional Review Board &#40;IRB&#41; at Dr&#46; Soetomo Hospital&#44; Surabaya&#44; approved all protocols in this study &#40;number 0585&#47;KEPK&#47;IX&#47;2018&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This was a case control study conducted at Dr&#46; Soetomo Hospital&#44; Surabaya&#46; Data were collected in the pediatric neurology outpatient clinic&#41;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Measurement</span><p id="par0030" class="elsevierStylePara elsevierViewall">All patients in this study were evaluated for GAD-Ab in serum&#46; As a cut-off for increased GAD-Ab&#44; we referred to a previous study that used<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg&#47;dl in serum&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> The evaluation of GAD-Ab was carried out using AED245Hu 96 Tests Enzyme-linked Immunosorbent Assay Kit For Anti-Glutamic Acid Decarboxylase Antibodies &#40;Anti-GAD&#41; &#40;Cloud-Clone Corp&#46;&#44; Houston&#44; TX&#44; USA&#41; with a standard curve range of 2&#8211;600<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; The examination results were in the form of quantitative data&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Statistical analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">IBM SPSS Statistics version 21&#46;0 &#40;IBM Co&#46;&#44; Armonk&#44; NY&#44; USA&#41; was used for statistical analysis&#46; The Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test was used to compare GAD-Ab levels in serum&#59; a <span class="elsevierStyleItalic">p</span> value of &#60;0&#46;05 was considered to have statistical significance&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Result</span><p id="par0040" class="elsevierStylePara elsevierViewall">A sample of 80 patients diagnosed with epilepsy were interviewed&#46; Their parents also completed data collection sheets&#46; Patients were divided into two groups&#44; namely intractable epilepsy and non-intractable epilepsy&#46; This study showed no differences between males and females&#46; Patients whose ages were between 1 and 5 years old outnumbered other age categories&#46; In the intractable group&#44; the type of seizure experienced most often is the general tonic&#8211;clonic seizure&#44; and all patients used 2 or 3 anti-epileptic drugs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Based on the non-parametric Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#44; intractable epilepsy serum GAD-Ab levels were higher compared to those in the non-intractable epilepsy group&#44; with <span class="elsevierStyleItalic">p</span> values<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000 &#40;<span class="elsevierStyleItalic">p</span> significant<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">Autoantibodies to glutamic acid decarboxylase have been detected in CSF and serum in patients with epilepsy&#46; Increased GAD-Ab is strongly associated with epilepsy and indicative of ongoing immune dysregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> This study showed that GAD-Ab serum is higher in children with intractable epilepsy compared to children with non-intractable epilepsy&#46; Although there were several neuronal autoantibodies suspected as etiologies of epilepsy&#44; we compared GAD-Ab specifically between children with intractable and controlled forms of epilepsy&#46; The increased prevalence of autoantibodies is more strongly associated with epilepsy&#44; perhaps indicating that immune dysregulation may be commonly associated with this disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">This study found a significant difference in GAD-Ab levels between the two groups&#44; with a higher level of GAD autoantibodies in the group with intractable epilepsy&#46; This result supports previous studies that found similar results&#59; both found significantly higher levels of GAD-Ab in the intractable epilepsy group compared to the control group&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#44;15</span></a> One study confirmed that GAD-Ab was associated with several forms of epilepsy such as idiopathic and cryptogenic temporal epilepsy&#44; and another found GAD-Ab up to 100 iu&#47;ml&#44; especially in drug-resistant patients with epilepsy&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#44;16</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The highest GAD-Ab level was found in patients with intractable epilepsy&#44; providing evidence for an autoimmune etiology and active immunological processes in the brain&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> Antibodies to glutamic acid decarboxylase induce suppression of GABA release&#44; modulate inhibitory potential in interneurons&#44; down-regulate GABA synthesis in neuronal cell terminals&#44; decrease GABA release in post-synaptic purkinje cells&#44; disrupt neuronal activity&#44; and intervene in the regulation of brain neurotransmitters&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">7&#44;17</span></a> This leads directly to intercellular protein mediated by T cell cytotoxicity&#44; which causes inflamation and burnout in the hippocampal region&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;18</span></a> Antibodies to GAD play a role in the cerebellar pathway where irreversible lesions cause permanent neuronal damage and cerebellar atrophy&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Our study has limitations that must be considered&#46; The study examined GAD-Ab in blood&#46; A high level of GAD-Ab is reported to have been found in cerebral spinal fluid&#59; however&#44; we did not use CSF for this study because the procedure for collecting it is invasive and uncomfortable&#44; and the number of parents who would have rejected this procedure would&#44; understandably&#44; be quite high&#46; The blood&#8211;brain barrier leak due to inflammation results in antineuronal antibodies being found in the blood&#59; thus&#44; we considered blood for the research material&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> In this study&#44; the variation of epilepsy samples is wide&#44; where the range of age is 1 month to 17 years&#59; therefore&#44; it required a larger sample number&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion&#44; the GAD-Ab serum level is higher in children with intractable epilepsy compared to children with non-intractable epilepsy&#46; Further studies of other neurological autoimmune antibodies to reveal autoimmunity in the etiology of epilepsy should be conducted&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Children suffering from intractable epilepsy have higher levels of GAD-Ab compared to children with non-intractable epilepsy&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data availability</span><p id="par0070" class="elsevierStylePara elsevierViewall">The data used to support the findings of this study are available from the corresponding author upon request&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ethical approval</span><p id="par0075" class="elsevierStylePara elsevierViewall">All procedures in this study were in accordance with the ethical standards of the institutional and&#47;or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards&#46; The ethical approval of this study was granted from Ethical Committee&#44; Faculty of Medicine&#44; Universitas Airlangga&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Consent</span><p id="par0085" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all individual subjects included in the study&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">No potential conflict of interest relevant to this article was reported&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The purpose of this study was to compare autoantibodies to glutamic acid decarboxylase serum levels in children suffering from intractable and non-intractable epilepsy at Dr&#46; Soetomo General Hospital Surabaya&#44; Indonesia&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A case&#8211;control study was conducted with children suffering from intractable and non-intractable epilepsy from November to December 2018 in the pediatric neurology outpatient clinic&#46; Autoantibodies to glutamic acid decarboxylase serum levels were examined from both groups using ELISA&#59; statistical analysis was performed using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test non-parametric tests&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Result</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A sample of 80 children was divided into two groups of 40 children each&#46; Their average age was 5&#46;4 years &#40;range of 4 months&#8211;17 years&#41;&#46; The average anti-epileptic drug treatment duration was 2&#46;3 years &#40;3 months&#8211;13 years&#41;&#46; Glutamic acid decarboxylase autoantibody levels in the intractable group were higher compared to levels in the non-intractable group&#44; ranging from 140 to 410<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;median 243&#46;3&#41; and 10&#8211;120<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;median 98&#46;10&#41; respectively with <span class="elsevierStyleItalic">p</span> values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Children suffering from intractable epilepsy have higher levels of GAD-Ab compared to children with non-intractable epilepsy&#46;</p></span>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;12 months&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#8211;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;57&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>6&#8211;10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>11&#8211;17 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Seizure type n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>General tonic clonic seizure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Partial seizure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;27&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Atonic seizure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">GAD autoantibibodies &#40;ng&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Rangemedian<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
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                    0 => array:2 [
                      "titulo" => "Glutamic acid decarboxylase autoantibodies in controlled and uncontrolled epilepsy&#58; a pilot study"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Kwan"
                            1 => "G&#46;J&#46; Sills"
                            2 => "K&#46; Kelly"
                            3 => "E&#46; Butler"
                            4 => "M&#46;J&#46; Brodie"
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                    0 => array:2 [
                      "doi" => "10.1016/s0920-1211(00)00180-7"
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                        "tituloSerie" => "Epilepsy Res"
                        "fecha" => "2000"
                        "volumen" => "42"
                        "paginaInicial" => "191"
                        "paginaFinal" => "195"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11074191"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antinuclear antibodies and glutamic acid decarboxylase antibodies in children with refractory epilepsy"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;E&#46; Abd El-Aziz"
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                      "Revista" => array:3 [
                        "tituloSerie" => "Egypt Pediatr Assoc Gaz"
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                        "volumen" => "61"
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              "identificador" => "bib0115"
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                0 => array:2 [
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                      "titulo" => "Localization and quantitation of expression of two glutamate decarboxylase genes in pancreatic beta-cells and other peripheral tissues of mouse and rat"
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                          "etal" => false
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                      "doi" => "10.1210/endo.133.6.8243324"
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                    0 => array:2 [
                      "titulo" => "Abnormal autoantibodies in pediatric refractory epilepsies"
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                            0 => "C&#46;M&#46; Korff"
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Epileptologie"
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                      "titulo" => "Autoantibodies and epilepsy"
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                        0 => array:2 [
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                    0 => array:2 [
                      "doi" => "10.1111/j.1528-1167.2011.03031.x"
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                      "titulo" => "Newly-diagnosed pediatric epilepsy is associated with elevated autoantibodies to glutamic acid decarboxylase but not cardiolipin"
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                          "etal" => true
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                    0 => array:2 [
                      "doi" => "10.1016/j.eplepsyres.2013.02.009"
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                0 => array:2 [
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                      "titulo" => "Non-paraneoplastic limbic encephalitis associated with anti-glutamic acid decarboxylase antibodies"
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                          "etal" => true
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                      "doi" => "10.1016/j.jneuroim.2008.05.015"
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                      "doi" => "10.1007/s10072-011-0566-8"
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                      "titulo" => "Cyclophosphamide for anti-GAD antibody-positive refractory status epilepticus"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46;C&#46; Kanter"
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                            2 => "D&#46; Staykov"
                            3 => "T&#46; Biermann"
                            4 => "T&#46; Struffert"
                            5 => "F&#46; Kerling"
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Article information

ISSN: 26039249
Original language: English

DOI:10.1016/j.mcpsp.2021.100237

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Year/Month	Html	Pdf	Total

2024 October	12	0	12
2024 September	23	2	25
2024 August	29	1	30
2024 July	9	4	13
2024 June	20	2	22
2024 May	19	3	22
2024 April	36	3	39
2024 March	26	6	32
2024 February	8	8	16
2024 January	13	4	17
2023 December	9	13	22
2023 November	13	5	18
2023 October	12	7	19
2023 September	15	7	22
2023 August	17	5	22
2023 July	25	2	27
2023 June	48	5	53
2023 May	52	4	56
2023 April	58	6	64
2023 March	51	7	58
2023 February	48	7	55
2023 January	13	11	24
2022 December	13	6	19
2022 November	21	9	30
2022 October	48	9	57
2022 September	18	4	22
2022 August	8	8	16
2022 July	12	7	19
2022 June	16	4	20
2022 May	9	8	17
2022 April	8	9	17
2022 March	14	7	21
2022 February	7	8	15
2022 January	6	7	13
2021 December	10	10	20
2021 November	9	13	22
2021 October	4	11	15
2021 September	6	5	11
2021 August	1	2	3
2021 July	2	0	2
2021 June	8	11	19
2021 May	6	4	10

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