Autoimmune epilepsy: clinical characteristics and response to immunotherapy

Abstract

Objective: To describe clinical characteristics and immunotherapy responses in patients with autoimmune epilepsy.

Design: Observational, retrospective case series.

Setting: Mayo Clinic Health System.

Patients: Thirty-two patients with an exclusive (n=11) or predominant (n=21) seizure presentation in whom an autoimmune etiology was suspected (on the basis of neural autoantibody [91%], inflammatory cerebrospinal fluid [31%], or magnetic resonance imaging suggesting inflammation [63%]) were studied. All had partial seizures: 81% had failed treatment with 2 or more antiepileptic drugs and had daily seizures and 38% had seizure semiologies that were multifocal or changed with time. Head magnetic resonance imaging was normal in 15 (47%) at onset. Electroencephalogram abnormalities included interictal epileptiform discharges in 20; electrographic seizures in 15; and focal slowing in 13. Neural autoantibodies included voltage-gated potassium channel complex in 56% (leucine-rich, glioma-inactivated 1 specific, 14; contactin-associated proteinlike 2 specific, 1); glutamic acid decarboxylase 65 in 22%; collapsin response- mediator protein 5 in 6%; and Ma2, N-methyl-D-aspartate receptor, and ganglionic acetylcholine receptor in 1 patient each.

Intervention: Immunotherapy with intravenous methylprednisolone; intravenous immune globulin; and combinations of intravenous methylprednisolone, intravenous immune globulin, plasmapheresis, or cyclophosphamide.

Main outcome measure: Seizure frequency.

Results: After a median interval of 17 months (range, 3-72 months), 22 of 27 (81%) reported improvement postimmunotherapy; 18 were seizure free. The median time from seizure onset to initiating immunotherapy was 4 months for responders and 22 months for nonresponders (P<.05). All voltage-gated potassium channel complex antibody-positive patients reported initial or lasting benefit (P<.05). One voltage-gated potassium channel complex antibody-positive patient was seizure free after thyroid cancer resection; another responded to antiepileptic drug change alone.

Conclusion: When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome.

Figure

Representative neuroimaging abnormalities and evolution. Patient 18 presented with a 10-month history of daily episodes of complex partial seizures. Despite normal magnetic resonance imaging (MRI) findings at presentation (A), subsequent preimmunotherapy MRI performed 9 months after seizure onset revealed left amygdala swelling (B) and bilateral hippocampal hyperintensity and atrophy (C). Radiolabeled fluorodeoxyglucose positron emission tomography brain scan showed hypermetabolism within the left amygdala (D) (arrow). Patient 27 had a 4-month history of daily complex partial seizures. Brain MRI revealed T2 hyperintensity within the right amygdalohippocampal region 3 months following seizure onset (E), which evolved to include the contralateral region 2 months later (F). Repeated MRI 3 months later before immunotherapy initiation demonstrated radiographic evidence of bilateral mesial temporal sclerosis (G) and residual left amygdala swelling and hyperintensity (H). Patient 3 presented with partial and secondary generalized seizures. There was signal abnormality in the right lateral temporal lobe (I) (arrow) after her first generalized tonic-clonic seizure, which occurred several weeks after the onset of partial seizures. Patient 11 was diagnosed with epilepsia partialis continua and had abnormal signal in the left precentral gyrus (arrow) 2 months after seizure onset (J). Patient 7 developed status epilepticus after a 3-month history of complex partial seizures. Admission MRI revealed right thalamic and medial temporal hyperintensities (K). Patient 32 presented with generalized tonic-clonic seizure and subsequently developed antiepileptic drug–intractable aphasic seizures. Presentation MRI demonstrated pronounced signal abnormality in the left frontoparietal region (L).