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. 2014 May 6;82(18):1578-86.
doi: 10.1212/WNL.0000000000000383. Epub 2014 Apr 4.

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

M Toledano  1 , J W Britton, A McKeon, C Shin, V A Lennon, A M L Quek, E So, G A Worrell, G D Cascino, C J Klein, T D Lagerlund, E C Wirrell, K C Nickels, S J Pittock
Affiliations

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

M Toledano et al. Neurology. .

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 = 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 = 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.

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Conflict of interest statement

M. Toledano and J. Britton report no disclosures relevant to the manuscript. A. McKeon receives research support from the Guthy-Jackson Charitable Foundation. C. Shin reports no disclosures relevant to the manuscript. V. Lennon is a named inventor on a patent (#7101679 issued 2006) relating to aquaporin-4 antibodies for diagnosis of neuromyelitis optica and receives royalties for this technology; is a named inventor on patents (#12/678,350 filed 2010 and #12/573,942 filed 2008) that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; and receives research support from the NIH (NS065829). A. Quek, E. So, and G. Worrell report no disclosures relevant to the manuscript. G. Cascino serves as associate editor of Neurology® and receives honoraria from the American Academy of Neurology. He receives research support from NeuroPace, Inc. and the NIH (RO1 NS053998). C. Klein and T. Lagerlund report no disclosures relevant to the manuscript. E. Wirrell serves on the editorial boards of Epilepsia, Journal of Child Neurology, and Canadian Journal of Neurological Sciences and receives research support from the Mayo Foundation. K. Nickels receives research support from NeuroPace, Inc. S. Pittock is a named inventor on patents (#12/678,350 filed 2010 and #12/573,942 filed 2008) that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; and receives research support from Alexion Pharmaceuticals, Inc., the Guthy-Jackson Charitable Foundation, and the NIH (NS065829). Go to Neurology.org for full disclosures.

Figures

Figure 1
Figure 1. Clinical features suggestive of autoimmune epilepsy
AED = antiepileptic drug.
Figure 2
Figure 2. Patient selection
*Multiple sclerosis 1, possible cerebroretinal microangiopathy with calcifications and cysts 1, gliomatosis cerebri 2, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) 1, nonepileptic behavioral spells 2, alcohol withdrawal seizures 1. AED = antiepileptic drug.
Figure 3
Figure 3. Immunotherapy trial response
(A) Flow chart of response to immunotherapy trial according to antibody type. (B) Flow chart of response to immunotherapy trial according to immunotherapeutic agent tried. (C) Percent of responders by antibody type. (D) Percent of responders to first and second immunotherapeutic agent tried. Abs = antibodies; CC N and CC P/Q = voltage-gated calcium channel N-type and P/Q-type; gAChR = neuronal ganglionic nicotinic acetylcholine receptor antibody; GAD65 = glutamic acid decarboxylase 65; IVIg = IV immune globulin; IVMP = IV methylprednisolone; PMA Ab = plasma membrane antigen antibodies; VGKC = voltage-gated potassium channel.
Figure 4
Figure 4. Suggested algorithm for the management of patients with suspected autoimmune epilepsy
AED = antiepileptic drug; IVIg = IV immune globulin; IVMP = IV methylprednisolone; PLEX = plasma exchange.
See this image and copyright information in PMC

Comment in

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