Investigation of neuronal autoantibodies in two different focal epilepsy syndromes

Abstract

SUMMARYObjective: Neuronal antibodies have been identified in patients with seizures as the main or sole symptom. Our aim was to investigate the prevalence of these autoantibodies in patients with focal epilepsy of unknown cause (FEoUC) and in the group having mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Methods: We studied anti-neuronal antibodies of consecutive adult patients diagnosed with FEoUC and MTLE-HS in our epilepsy center. The clinical and laboratory features of antibody-positive patients were compared with those of seronegative patients. The responses to therapy have also been investigated. Results: Sera from 81 patients with epilepsy were tested. We found antibodies against glycine receptor (GLY-R) in 5 (6.2%), contactin-associated protein 2 (CASPR-2) in 4 (4.9%), N-methyl-D-aspartate receptor (NMDA-R) in 2 (2.5%), and voltage-gated potassium channel (VGKC)-complex in 2 (2.5%) of our patients with epilepsy. Psychotic attacks and nonspecific magnetic resonance imaging (MRI) white matter changes (WMCs) showed significant associations in seropositive patients (p = 0.003 and p = 0.03, respectively). Poor drug-response rates and total seizure counts were also higher in the seropositive patients but without reaching statistical significance. Three seropositive patients with previous epilepsy surgery showed typical histopathologic results for MTLE-HS, but not inflammatory changes. Moreover, some patients harboring these antibodies partly benefited from immunotherapy. Significance: We detected neuronal antibodies in one sixth of patients with focal epilepsy, GLY-R antibodies being the leading one. Psychosis or nonspecific MRI WMCs were frequent in the seropositive group. Our results suggested that relevant antibodies should be screened for a treatment possibility in these groups. KEY WORDS: Epilepsy, Autoantibodies, Glycine receptor, Voltage-gated potassium channel, N-methyl-D-aspartate receptor.Epilepsy is a common neurologic disorder showing resistance to antiepileptic drugs (AEDs) in at least 25-30% of the cases, and its etiology is still unknown.1,2 On the other hand, there is growing evidence that autoimmunity might play a role in epilepsy. A variety of serum antibodies to specific neuronal proteins has recently been identified in ordinary patients with epilepsy. Other than the first reported typical cases with limbic encephalitis or encephalopathy,

Brain Infiltration of Immune Cells in CASPR2–Antibody Associated Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

“…These findings corroborate the previously established significance of autoimmunity in the pathogenesis of TLE (3,4,5,6). Although MTLE-HS and TLE patients might present with a wide variety of neuronal cell surface antibodies, contactin-associated protein-like 2 (CASPR2) antibody is by far the most prevalently found antibody in this epilepsy subgroup (2). To find further evidence for the potential autoimmune nature of CASPR2-related MTLE-HS, we examined surgically removed temporal lobe specimens of treatment-resistant CASPR2 antibody-positive and -negative MTLE-HS patients using immunohistochemical methods.…”

“…Among diverse epilepsy syndromes, focal temporal lobe epilepsy (TLE) of unknown cause and mesial TLE with hippocampal sclerosis (MTLE-HS) particularly stand out with their high anti-neuronal antibody positivity rates and favorable response to immunosuppressive treatment (2). These findings corroborate the previously established significance of autoimmunity in the pathogenesis of TLE (3,4,5,6).…”

“…We had previously reported a TLE patient with glycine receptor antibodies and treatment-resistant seizures, who gave remarkable response to pulse steroid and intravenous immunoglobulin treatment; thus, epilepsy surgery was avoided (2). Therefore, investigation of the potentially immunosuppressant-responsive subtypes of MTLE-HS through further examination of anti-neuronal antibodies and surgically removed brain specimens is highly recommended.…”

“…Neuronal cell surface antibodies directed against ion channels or synaptic membrane proteins have recently been shown in several epilepsy cohorts (1,2). Among diverse epilepsy syndromes, focal temporal lobe epilepsy (TLE) of unknown cause and mesial TLE with hippocampal sclerosis (MTLE-HS) particularly stand out with their high anti-neuronal antibody positivity rates and favorable response to immunosuppressive treatment (2).…”

Anti-Neuronal Autoantibodies Associated with Epilepsy and Related Neurological Syndromes

“…[2, 47,48] VGKC-kompleksi antikorları ile ilişkili otoimmün ensefalit ile başvurup izlemi sırasında aylar içerisinde mezial temporal skleroz geliştiren çok sayıda olgu tanımlanmıştır. Ayrıca mezial temporal skleroz olgularında yüksek oranda anti-nöro-nal antikor (genellikle CASPR2, GlyR ve NMDAR antikorları) saptanmış ve bu olguların bir kısmının immünoterapi ile nö-bet sıklıklarının azaldığı gösterilmiştir.…”