Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings

Abstract

Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis

“…Patients 1, 2, 3, 4, 13 and 21 were previously reported by Ekizoglu et al 1; patients 6, 7, 12, 16 and 17 were previously reported by Baysal-Kirac et al 24 in this table 1.…”

“…Patients 1, 2, 3, 4, 13 and 21 were previously reported by Ekizoglu et al 1; patients 6, 7, 12, 16 and 17 were previously reported by Baysal-Kirac et al 24 in this table 1.*Numbers indicate the antibody binding intensity scored visually on a range from 0 (negative) to 4 (very strong).†Indicates patients with a benign course and unexplained remission. ‡Seizure free after operation for 3 years one F- BCS during AED tapering, afterwards seizure-free again since 2007.…”

“…However, it was curious that three of the four patients had psychotic features and two achieved seizure freedom without surgery, suggesting that this subgroup could be of interest. In a recent study, we showed low level VGKC-complex antibody positive epilepsy patients with serum antibodies exhibiting strong reactivity with hippocampal axons and dendrites 24. Thus, VGKC-complex antibody positivity might be an indicator of neuroinflammation, especially in the setting of chronic epilepsy.…”

Seizures and Epilepsies due to Channelopathies and Neurotransmitter Receptor Dysfunction: A Parallel between Genetic and Immune Aspects

“…FBDS seems to be related with LGI1 antibodies, since no FBDS was reported in 5 Korean patients with CASPR2 antibodies [Sunwoo et al, 2015]. Even though ictal and peri-ictal dysautonomic features such as tachychardia, blood pressure abnormalities, or hypersalivation are primarily observed in anti-NMDAR encephalitis (see above, Part 1) or Caspr2 encephalitis [Baysal-Kirac et al, 2016], pilomotor seizures [Rocamora et al, 2014] and bradycardia [Naasan et al, 2014] were respectively described in 3/5 and in 3/14 patients in association with LGI1 antibodies.…”

Searching for Autoimmune Epilepsy: Why, Where, and When?

“…In a thoroughly detailed position statement, Graus et.al lay out the clinical scenarios that should raise suspicion for autoimmune encephalitis/epilepsy, thereby identifying patients with the highest expected yield for antibody testing, but more importantly, those with a clinical picture that would justify treatment for autoimmune encephalitis even while waiting to receive the results of antibody testing. Such efforts to define autoimmune epilepsy on clinical grounds are even more critical as we recognize that patients may be "seronegative" but still have autoimmune epilepsy, given the lag of our knowledge as we are only starting to scratch the surface of this entity and still have many more pathogenic antibodies to discover [2][3][4]8 .…”