Original Article
13
Epilepsy and Autoimmunity in Pediatric Patients Hüseyin Tutkak3
1 Department of Pediatric Neurology, Ankara University Medical
School, Ankara, Turkey 2 Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom 3 Department of Immunology and Allergy, Ankara University Medical School, Ankara, Turkey 4 Department of Medical Biochemistry, Ankara University Medical School, Ankara, Turkey
Sema Karagöl4
Bethan Lang2
Linda Clover2
Address for correspondence Ömer Bektaş, MD, Department of Pediatric Neurology, Ankara University Medical School, Ankara Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları A.B.D. 06100 ebeci/Ankara, Turkey (e-mail: [email protected]).
Neuropediatrics 2015;46:13–19.
Abstract
Keywords
► ► ► ►
epilepsy autoimmune pediatric onconeural antibodies ► VGKC antibodies
Our aim was to determine the presence and possible role of autoantibodies in epileptic patients with an undetermined etiology. Eighty epilepsy patients, who were referred to the Pediatric Neurology Department at Ankara University between November 2011 and April 2012, were enrolled in the study. Antinuclear antibodies (ANA), anticardiolipin IgG, antiphospholipid, antithyroid peroxidase, paraneoplastic, glutamic acid decarboxylase (GAD), and N-methyl-D -aspartate (NMDA) receptor antibodies were studied in our university laboratory. In addition, NMDA receptor (NMDAR), voltagegated potassium channel (VGKC)-complex, leucine-rich, glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2) antibodies were studied at the Oxford University Immunology Laboratory. The study included 35 girls (44%) and 45 boys (56%) with a mean symptom age of 8.6 4.53 years. ANA was detected in 15 (18.8%), antiphospholipid Ab in 3 (3.75%), anticardiolipin Ab in 1 (1.25%), and antithyroid peroxidase in 3 (3.75%) epileptic patients. In addition, anti-GAD Ab was detected in 7 (8.75%), anti-Yo Ab in 3 (3.75%), and anti-Ma2 in 3 (3.75%) epileptic patients. Anti-VGKC was positive in 13 (16.25%) epileptic patients. We performed a pioneer study to investigate the association between autoimmunity and pediatric epilepsy and we conclude that autoimmunity should be considered in epileptic patients with an undetermined etiology.
Introduction Epilepsy is the most common serious neurological disorder. “Structural/metabolic” and “genetic” causes of epilepsy are regularly being identified; however, the majority of epilepsies are classified as having an “unknown cause.”1 Autoimmune processes have been hypothesized as a potential cause of these etiologically undetermined epilepsies.2–4 There is recent accumulating evidence that specific neuronal autoanti-
received December 4, 2013 accepted after revision July 8, 2014 published online October 7, 2014
bodies (auto-Abs) with pathogenic potential could be present in a subset of patients with epilepsy.5 Seizures are also a common symptom, particularly in limbic encephalitis and multifocal paraneoplastic disorders.6–14 Auto-Ab specificities recognized in the setting of paraneoplastic limbic encephalitis include antineuronal nuclear Ab type 1 (Hu), collapsin response-mediator protein 5 (CRMP-5), and Ma2. The voltage-gated potassium channel (VGKC) complex, glutamic acid decarboxylase (GAD) Abs, and
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1389895. ISSN 0174-304X.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Ömer Bektaş1 Leslie Jacobson2 Angela Vincent2 Gülhis Deda1
Pediatric Autoimmune Epilepsy
Bektaş et al.
N-methyl-D-aspartate (NMDA), often nonparaneoplastic in etiology, have been reported in patients with limbic encephalitis14,15 and idiopathic epilepsy with antiepileptic-resistant seizures.16–19 In addition, several Abs have been reported to be associated with epilepsy, such as Abs against cardiolipin, nuclear antigens, phospholipids, and thyroid peroxidase20–23; however, the results from some of these studies could have been confounded by the nonspecific binding of human sera in the assays, which are not always well controlled. Autoimmune Abs were detected in 1.7 to 14% of adult patients with epilepsy.5,16–20,24 However, although neuronal auto-Abs have been detected in case reports and case series,25,26 there is only a prospective study performed in children.27 The purpose of this study was to examine the autoimmune Ab levels in pediatric epileptic patients with an undetermined etiology to determine a possible relationship between autoimmunity and epilepsy via neuronal auto-Abs.
Methods Study Population A total of 80 epilepsy patients at Ankara University Pediatric Neurology Department between November 2011 and April 2012 were enrolled in the study. Their ages ranged from 9 months to 18 years (mean: 8.6 451/median: 9). The 80 enrolled epilepsy patients (45 males and 35 females) were chosen from among epilepsy patients with undetermined etiology and susceptible autoimmunity who were referred or followed. The study was approved by the Ankara University Local Ethics Committee, and informed consent was obtained from the parents. Patients who met one of the following inclusion criteria were included in this study: (1) epilepsy that responded well to steroids or immunomodulatory agents and (2) epilepsy with an acute or subacute (
13
Epilepsy and Autoimmunity in Pediatric Patients Hüseyin Tutkak3
1 Department of Pediatric Neurology, Ankara University Medical
School, Ankara, Turkey 2 Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom 3 Department of Immunology and Allergy, Ankara University Medical School, Ankara, Turkey 4 Department of Medical Biochemistry, Ankara University Medical School, Ankara, Turkey
Sema Karagöl4
Bethan Lang2
Linda Clover2
Address for correspondence Ömer Bektaş, MD, Department of Pediatric Neurology, Ankara University Medical School, Ankara Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları A.B.D. 06100 ebeci/Ankara, Turkey (e-mail: [email protected]).
Neuropediatrics 2015;46:13–19.
Abstract
Keywords
► ► ► ►
epilepsy autoimmune pediatric onconeural antibodies ► VGKC antibodies
Our aim was to determine the presence and possible role of autoantibodies in epileptic patients with an undetermined etiology. Eighty epilepsy patients, who were referred to the Pediatric Neurology Department at Ankara University between November 2011 and April 2012, were enrolled in the study. Antinuclear antibodies (ANA), anticardiolipin IgG, antiphospholipid, antithyroid peroxidase, paraneoplastic, glutamic acid decarboxylase (GAD), and N-methyl-D -aspartate (NMDA) receptor antibodies were studied in our university laboratory. In addition, NMDA receptor (NMDAR), voltagegated potassium channel (VGKC)-complex, leucine-rich, glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2) antibodies were studied at the Oxford University Immunology Laboratory. The study included 35 girls (44%) and 45 boys (56%) with a mean symptom age of 8.6 4.53 years. ANA was detected in 15 (18.8%), antiphospholipid Ab in 3 (3.75%), anticardiolipin Ab in 1 (1.25%), and antithyroid peroxidase in 3 (3.75%) epileptic patients. In addition, anti-GAD Ab was detected in 7 (8.75%), anti-Yo Ab in 3 (3.75%), and anti-Ma2 in 3 (3.75%) epileptic patients. Anti-VGKC was positive in 13 (16.25%) epileptic patients. We performed a pioneer study to investigate the association between autoimmunity and pediatric epilepsy and we conclude that autoimmunity should be considered in epileptic patients with an undetermined etiology.
Introduction Epilepsy is the most common serious neurological disorder. “Structural/metabolic” and “genetic” causes of epilepsy are regularly being identified; however, the majority of epilepsies are classified as having an “unknown cause.”1 Autoimmune processes have been hypothesized as a potential cause of these etiologically undetermined epilepsies.2–4 There is recent accumulating evidence that specific neuronal autoanti-
received December 4, 2013 accepted after revision July 8, 2014 published online October 7, 2014
bodies (auto-Abs) with pathogenic potential could be present in a subset of patients with epilepsy.5 Seizures are also a common symptom, particularly in limbic encephalitis and multifocal paraneoplastic disorders.6–14 Auto-Ab specificities recognized in the setting of paraneoplastic limbic encephalitis include antineuronal nuclear Ab type 1 (Hu), collapsin response-mediator protein 5 (CRMP-5), and Ma2. The voltage-gated potassium channel (VGKC) complex, glutamic acid decarboxylase (GAD) Abs, and
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1389895. ISSN 0174-304X.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Ömer Bektaş1 Leslie Jacobson2 Angela Vincent2 Gülhis Deda1
Pediatric Autoimmune Epilepsy
Bektaş et al.
N-methyl-D-aspartate (NMDA), often nonparaneoplastic in etiology, have been reported in patients with limbic encephalitis14,15 and idiopathic epilepsy with antiepileptic-resistant seizures.16–19 In addition, several Abs have been reported to be associated with epilepsy, such as Abs against cardiolipin, nuclear antigens, phospholipids, and thyroid peroxidase20–23; however, the results from some of these studies could have been confounded by the nonspecific binding of human sera in the assays, which are not always well controlled. Autoimmune Abs were detected in 1.7 to 14% of adult patients with epilepsy.5,16–20,24 However, although neuronal auto-Abs have been detected in case reports and case series,25,26 there is only a prospective study performed in children.27 The purpose of this study was to examine the autoimmune Ab levels in pediatric epileptic patients with an undetermined etiology to determine a possible relationship between autoimmunity and epilepsy via neuronal auto-Abs.
Methods Study Population A total of 80 epilepsy patients at Ankara University Pediatric Neurology Department between November 2011 and April 2012 were enrolled in the study. Their ages ranged from 9 months to 18 years (mean: 8.6 451/median: 9). The 80 enrolled epilepsy patients (45 males and 35 females) were chosen from among epilepsy patients with undetermined etiology and susceptible autoimmunity who were referred or followed. The study was approved by the Ankara University Local Ethics Committee, and informed consent was obtained from the parents. Patients who met one of the following inclusion criteria were included in this study: (1) epilepsy that responded well to steroids or immunomodulatory agents and (2) epilepsy with an acute or subacute (
