Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy

Abstract

Objective: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy. Method:We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of $1 neural autoantibody (n 5 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6-to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency.Results: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p 5 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%).Conclusions: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy. Classification of evidence:This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control. Neurology ® 2014;82:1578-1586 GLOSSARY AED 5 antiepileptic drug; CASPR2 5 contactin-associated protein-like 2; CC 5 calcium channel; gAChR 5 neuronal acetylcholine receptor, ganglionic-type; GAD65 5 glutamic acid decarboxylase 65; IgG 5 immunoglobulin G; IVIg 5 IV immune globulin; IVMP 5 IV methylprednisolone; LGI1 5 leucine-rich, glioma-inactivated 1; PMA Abs 5 antibodies to neural plasma membrane antigen; VGKC 5 voltage-gated potassium channel.Approximately one-third of epilepsy cases are intractable to antiepileptic drug (AED) therapy.

Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy

“…Patients with anti‐VGKC included 21 patients with anti‐LGI1 and two patients with anti‐CASPR2 antibodies. FBDS only appeared in patients with anti‐LGI1, among whom six patients (28.57%) had FBDS, consistent with a previous study 11. Eight patients (20.51%) included in the study had an underlying malignancy: 2 had adenocarcinoma of the lung, 5 had small cell lung cancer, and 1 had hepatic mass (refused further investigation).…”

“…These seizures are manifested by sudden onset of flexion contraction of one upper extremity, accompanied by contraction of the ipsilateral face, head, and neck 12. These seizures, which typically last for approximately 1 sec, and occur multiple times per day, are present in approximately one fourth of VGKC complex antibody epilepsy patients 11. Except for FBDS, patients with VGKC complex antibodies mainly experience mesial temporal lobe seizures, including simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized tonic‐clonic (SGTC) seizures 13.…”

Immunotherapy Responsive Epilepsies: General Clinical Features, Commonly Detected Antibodies and Treatment Studies

“…[53,54] mayan hastaların ise %33'ünde immün tedaviye yanıt alın-mıştır. [60] Seronegatif hastalarda görülen bu yanıtın henüz keşfedilmemiş antikor tipleri ile ilişkili olduğu öne sürülmek-tedir. [57] Bununla birlikte benzer klinik ve radyolojik bulgular görülse de farklı antikorların varlığında immün tedaviye…”

“…[56] Diğer yandan GAD, Ma1 ve Ma2'ye karşı gelişmiş antikorların saptandığı olgularda immün tedaviye yanıtın kötü olduğu görülmüştür. [60] Benzer şekilde çocuk hastalarda nöronal yüzey antikoru saptanan hastaların tümü immün tedaviye yanıt verirken, antikor negatif hastaların ancak yarısında yanıt alınabilmiştir. [57] Ayrıca tedaviye yanıtsız olgularda, nöbet başlangıcı ile immün tedaviye başlanması arasında geçen sürenin uzunluğu negatif bir prognostik faktör olarak bildirilmiştir.…”

“…[57] Ayrıca tedaviye yanıtsız olgularda, nöbet başlangıcı ile immün tedaviye başlanması arasında geçen sürenin uzunluğu negatif bir prognostik faktör olarak bildirilmiştir. [60] Nöronal yüzey antikoru ilişkili ensefalitlerde hastaların çoğu birinci basamak tedaviye haftalar içinde yanıt vermişlerdir. Ancak NMDA-R ensefalitinde bu yanıt daha da yavaş gelişebilmektedir.…”