Abstract Details

Neuronal antibodies in a prospective, multicenter cohort of patients with focal epilepsy of unknown origin
Autoimmune Neurology
S11 - Autoimmune CNS Inflammatory Disorders: Clinical Advances (3:30 PM-3:41 PM)
001
Autoimmune encephalitis (AIE) has emerged the last decade as a severe but treatable neurological condition. Most patients have clear encephalitis signs, including seizures. However, patients can also have less fulminant symptoms, and some might even have chronic epilepsy without other encephalitis signs.

To determine  frequencies of antibody-mediated encephalopathies in patients with focal epilepsy of unknown origin, and to assess outcome.

In this Dutch multicenter, prospective cohort study, performed from 2014-2017,  adults with focal epilepsy of unknown origin, and no suspicion of AIE, were included by epileptologists. Data about patient and seizure characteristics were obtained at enrollment. Data about seizures frequency, treatment, and mRS were obtained prospectively one, four, eight and twelve months after inclusion. Serological analysis was done, and if available, CSF analysis. To detect neuronal antibodies samples were tested using immunohistochemistry (IHC), cell-based assay (CBA), live hippocampal neurons (LN) and ELISA. 

Informed consent was obtained in 634 patients, and 590 patients were included.

Antibodies were detected in 19 patients (3,2%): fourteen high titer anti-GAD65 (>10000 IU/ml, confirmed in CSF), one anti-LGI1, two anti-Caspr2, and two anti-GlycineR. In 16 patients IHC was positive, and two also had positive LN, without known antibodies. These samples are currently being analyzed. Focusing on the patients with known antibodies, all 19 patients had subtle encephalitis signs (i.e. cognitive dysfunction, stiff person syndrome, autonomic disturbances). Drug-resistant seizures occurred in 17/19 patients (89%), 13 of them were treated with immunotherapy. All three patients with anti-LGI1 or anti-Caspr2 became seizure-free, while 6/14 GAD65 patients had >50% seizure reduction without becoming seizure-free. Other follow-up data are currently being collected.

In this large patient cohort we found a low prevalence of antibody-mediated encephalopathies, including anti-LGI1, anti-Caspr2, anti-GAD65 and anti-GlycineR. All patients with neuronal antibodies had subtle other encephalitis signs, and most patients had drug-resistant seizures.

                                                                                         

Authors/Disclosures

PRESENTER 		No disclosure on file
Roland Thijs No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Paul Wirtz, MD, PhD No disclosure on file
Anna Bastiaansen Anna Bastiaansen has nothing to disclose.
Agnes Van Sonderen No disclosure on file
No disclosure on file
Peter Sillevis Smitt, MD (Erasmus MC) The institution of Dr. Sillevis Smitt has received research support from Euroimmun. Dr. Sillevis Smitt has received intellectual property interests from a discovery or technology relating to health care.
Maarten J. Titulaer, MD, PhD (Erasmus Medical Center) The institution of Dr. Titulaer has received research support from Dutch Epilepsy Foundations (NEF 19-08). The institution of Dr. Titulaer has received research support from CSL Behring. The institution of Dr. Titulaer has received research support from UCB. The institution of Dr. Titulaer has received research support from Netherlands Organisation for Scientific Research (ZonMW, Memorabel initiative and E-RARE UltraAIE) . The institution of Dr. Titulaer has received research support from Horizon Therapeutics / Amgen. The institution of Dr. Titulaer has received research support from Dioraphte (charity). The institution of Dr. Titulaer has received research support from Guidepoint Global LLC. The institution of Dr. Titulaer has received research support from ArgenX. Dr. Titulaer has received publishing royalties from a publication relating to health care.