Cenobamate and Clobazam Combination as Personalized Medicine in Autoimmune-Associated Epilepsy With Anti-Gad65 Antibodies.

BACKGROUND AND OBJECTIVES: Autoimmune-associated epilepsy (AAE) with antiglutamic acid decarboxylase 65 (GAD65) antibodies is considered a T-cell-mediated encephalitis that evolves to drug-resistant epilepsy. We do not have an effective therapeutic strategy for these patients. Because the GAD enzyme is primarily responsible for the conversion of glutamate to GABA, the mechanism of epileptogenesis in this condition predicts decreased levels of GABA content in synaptic vesicles. Cenobamate (CNB) acts as a positive allosteric modulator at synaptic and extra synaptic GABAA receptors, producing increased inhibitory neurotransmission in the brain. This mechanism could be especially beneficial in AAE with anti-GAD65 antibodies because it would be able to correct the imbalance due to the GABAergic stimulation deficit in postsynaptic neurons. METHODS: We recruit a retrospective multicentric consecutive case series of AAE with anti-GAD65 antibodies from 5 epilepsy units in Spain who have received treatment with CNB. RESULTS: A total of 8 patients were recruited. This cohort of highly refractory patients have failed a mean of 9.50 (SD = 3.20) ASM without control of seizures for sustained periods of time. The average number of seizures per month during the previous 3 months before CNB treatment was 19.63 (SD = 17.03). After the introduction of CNB improvement was achieved in all our patients, with a median reduction in the number of seizures of 92.22% (interquartile range [IQR]: 57.25-98.75). The mean follow-up was 156.75 days (SD = 68.23). In patients with concomitant treatment with clobazam (CLB), the median percentage of seizure reduction was higher than those not taking CLB: 94.72% (IQR: 87.25-100) vs 41.50% (p = 0.044) and also higher than the control group of patients with refractory epilepsy not related to anti-GAD65 treated with the same combination: 94.72% (IQR: 87.25-100) vs 45.00% (IQR: 25.00-87.00) (p = 0.019). DISCUSSION: Treatment with the combination CNB + CLB could be a type of personalized medicine in patients with AAE with anti-GAD65. Our preliminary data will need to be endorsed with new prospective and controlled studies.

Is the double gene dose of DQ2.5 or DQ2.5/DQ2.2 an involved factor in the clinical features of celiac disease?

Objectives: Celiac disease (CD) is barely known if the quantitative effect of DQB1*02 (DQ2) double dose in antigen presentation to T-cells has translation into the clinic. For this, we have conducted a case-control study in a cohort of two hundred and nineteen patients with CD. Material and methods: For the control group, individuals were enrolled with single dose of DQ2, carrying DQ2.5 heterodimers in heterozygous state (n = 109). The cases with CD were diving into three groups: cases with overall DQ2 double dose (n = 110), DQ2.5 homozygous (n = 33) and DQ2.5/DQ2.2 heterozygous (n = 77). Prevalence and associations of demographic, laboratory, histological and clinical characteristics between the control group and cases were studied. Results: No differences were found for the total of 16 variables analyzed between the control group and overall DQ2 double dose as well as DQ2.5 homozygous cases. In contrast to DQ2.5/DQ2.2, heterozygous cases presented a protection factor for developing allergy to airway allergens regarding the control group (OR = 0.210, p = .019). Conclusions: To date, this negative association has not been described. Further studies will be necessary to elucidate the implication of this protection factor in CD. Since, until now the association between CD and allergic diseases has been poorly studied.