Seizures and epilepsy of autoimmune origin: A long-term prospective study

Abstract

To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy. Methods: Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown. Results: One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy. Significance: ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time.

Association between autoimmune encephalitis and epilepsy: Systematic review and meta-analysis

“…Our present meta-analysis showed that the pooled-period prevalence of AE in epilepsy was approximately 1%. Another study, however, found a prevalence of 24.8%, which is much higher than the findings of our present meta-analysis, as well as that reported by others [41]. This discrepancy may be due to the patients in this previous study including patients with new-onset seizures of unknown etiology.…”

“…Therefore, we calculated the incidence/prevalence of NMDAR, IGL1, and CAPSR2 in epilepsy, which are the common antibodies associated with AE. Eleven studies examined NMDAR antibodies [41,42,45,46,50,53,54,[56][57][58]60]. After excluding one study that focused only on anti-NMDAR encephalitis [53], we found that the pooled-period prevalence of anti-NMDAR in epilepsy was 1% (95% CI: 0.01-0.02, p < 0.0001, Z = 4.74, I 2 = 88.8%) (Fig.…”

“…The types of epilepsy included in the various studies were inconsistent, including new-onset epilepsy, unknown-etiology epilepsy, SE, and refractory-status epilepticus. Two studies reported that patients had a positive outcome following immunotherapy and AED treatment [41,45]. The prevalence of AE in epilepsy obtained from the pooled period was 1% (95% CI: 0.01-0.02).…”

“…AE was reported as one of the etiologies of epilepsy in six studies [41][42][43][44][45][46]. Two studies were conducted on adults and pediatrics, three studies on adults, and one study on pediatric patients only.…”

“…Nineteen studies reported the incidence or prevalence of antibody positivity in patients with epilepsy [47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Five of the studies included an epilepsy group with AE, since they also tested for autoantibodies [41][42][43][44][45][46]. Both adult and pediatric populations were included in six studies, only adults in five studies, and only pediatrics in another three studies.…”