Determining the Correlation Between Antiphospholipid Antibodies and Epilepsy: A Systematic Review

Seizures are frequently found in patients with autoimmune diseases such as lupus and APS. Recent publications concluded that APLAs are associated with seizures and their presence results in more poor control. Conversely, the presence of auto-antibodies directed against different targets, including APLA, voltage-gated potassium channels, c-aminobutyric acid B receptor, GAD, and others, have been identified in up to 20% of newly-diagnosed epilepsy patients and there is increasing evidence of their pathogenic role.

We sought to evaluate the relationship between epilepsy and antiphospholipid antibodies (APLA) and/or antiphospholipid antibody syndrome (APS). This was done by means of a systematic review of the literature. We sought to answer four questions: 1) Are epilepsy and seizure disorders more prevalent among pts. with aPLAS/aPLAs?; 2) Is aPLAS more prevalent among patients with epilepsy or seizure disorders?; 3) In those with seizure disorders, is there a heightened prevalence of aPLAs?; 4) Does the presence and titre of aPLAs determine the severity and/or frequency of seizures, in these patients?

We conducted a systematic review to evaluate the relationship between APLA (including anticardiolipin Ab, anti beta-2-glycoprotein-1 Ab, and lupus anticoagulant) and epilepsy. We searched MEDLINE, EMBASE, Healthstar, the Cochrane library, LILACS, Scopus and grey literature. We included cohort, case-control, and cross-sectional studies studying the prevalence of epilepsy in patients with APS and/or +APLA, the prevalence of +APLA and/or APS in patients with epilepsy, and the severity of the seizures in patients with +APLA and/or APS.

The search retrieved 837 relevant references and 79 were retrieved for full review. We included in the final review 24 studies (19 case-control, 3 cohort and 2 cross-sectional). In 3 cohorts, including 1585 patients with APS, the frequency of epilepsy ranged between 3.4 and 8.5%. In 16 case-control studies, including 3893 patients, the OR for +APLA and/or APS in patients with epilepsy ranged from 0.60 to 13.3 in individual studies. In 2 case-control studies, including 804 patients, the OR for epilepsy in patients with +APLA and/or APS ranged from 0.83 to 2.82 in individual studies.

An OR or RR could be calculated in only 17 studies, and within this group, twelve positive and five negative studies were identified. No meta-analysis was conducted due to the high heterogeneity of designs. In 4 studies, an association was found between +APLA and seizure frequency and severity. In positive studies there was no correlation between +APLA, epilepsy and cerebral ischemia.

We conclude that +APLA/APS might be related with higher risk and severity of epilepsy, however further studies using accepted consensus definitions for APLA positivity, more stringent methodology and appropriate subgroup analysis are needed.

Lazo-Langner:Pfizer: Honoraria; Leo Pharma: Honoraria.