Ferulic Acid Inhibits Catamenial Epilepsy Through Modulation of Female Hormones

Approximately 40% of women with epilepsy experience perimenstrual seizure exacerbation, referred to as catamenial epilepsy. These seizures result from cyclic changes in circulating progesterone and estradiol levels and there is no effective treatment for this form of intractable epilepsy. We artificially increased progesterone levels and neurosteroid levels (pseudo-pregnancy) in adult Swiss albino female mice (19-23 g) by injecting them with pregnant mares' serum gonadotropin (5 IU s.c.), followed by human chorionic gonadotropin (5 IU s.c.) after 46 hours. After this, ferulic acid (25, 50, 100 mg/kg i.p.) treatment was observed for 10 days. During treatment, progesterone, estradiol, and corticosterone levels were estimated in blood on days 1, 5, and 10. Neurosteroid withdrawal was induced by finasteride (50 mg/kg, i.p.), a 5 α-reductase inhibitor on treatment day 9. Twenty-four hours after finasteride administration (day 10 of treatment), seizure susceptibility was evaluated with the sub-convulsant pentylenetetrazol (PTZ) dose (40 mg/kg i.p.). Four to six hours after PTZ, animals were assessed for depression like phenotypes using tail-suspension test (TST). Four to six hours following TST, animals were euthanized, and discrete brain parts (cortex and hippocampus) were separated for estimation of norepinephrine, serotonin, and dopamine as well as glutamic acid decarboxylase enzyme activity. PMSG and HCG treatment elevated progesterone and estradiol levels, assessed on days 1, 5, and 10 causing a state of pseudo-pregnancy. Treatment with finasteride increases seizure susceptibility and depression-like characteristics possibly due to decreased progesterone levels and elevated estrogen levels coupled with decreased monoamine and elevated corticosterone levels. Ferulic acid treatment, on the other hand, significantly decreased seizure susceptibility and depression like behaviours, possibly as a result of increased progesterone, restored estradiol, corticosterone, monoamine, and glutamic acid decarboxylase enzyme activity. We concluded that ferulic acid exhibited antiepileptic effects in a mouse model of catamenial epilepsy and comorbid depression due to its restorative effects on circulating hormones and cerebral monoamine and glutamic acid decarboxylase enzyme activity.

A surgical solution for a catamenial epilepsy medical therapy-resistant: A presumed case of cerebral endometriosis?

The presence of catamenial epilepsy in patients diagnosed with endometriosis is the symptom that would direct towards a suspected cerebral endometriotic localization. However, data research of medical literature supporting this diagnosis shows a small number of studies and the specific research on medline led to the finding of only four case reports. Hence forward, we will report a case of a patient with the surgical diagnosis of ovarian endometriosis, whom had signs of catamenial epilepsy resistant to medical therapy, and with contraindication to hormone therapy because of cerebral ischemic episodes, subjected to laparoscopic bilateral ovarosalpingectomy.

Development and validation of a predictive model of drug-resistant genetic generalized epilepsy

ObjectiveTo develop and validate a clinical prediction model for antiepileptic drug (AED)–resistant genetic generalized epilepsy (GGE).MethodWe performed a case-control study of patients with and without drug-resistant GGE, nested within ongoing longitudinal observational studies of AED response at 2 tertiary epilepsy centers. Using a validation dataset, we tested the predictive performance of 3 candidate models, developed from a training dataset. We then tested the candidate models' predictive ability on an external testing dataset.ResultsOf 5,189 patients in the ongoing longitudinal study, 121 met criteria for AED-resistant GGE and 468 met criteria for AED-responsive GGE. There were 66 patients with GGE in the external dataset, of whom 17 were cases. Catamenial epilepsy, history of a psychiatric condition, and seizure types were strongly related with drug-resistant GGE case status. Compared to women without catamenial epilepsy, women with catamenial epilepsy had about a fourfold increased risk for AED resistance. The calibration of 3 models, assessing the agreement between observed outcomes and predictions, was adequate. Discriminative ability, as measured with area under the receiver operating characteristic curve (AUC), ranged from 0.58 to 0.65.ConclusionCatamenial epilepsy, history of a psychiatric condition, and the seizure type combination of generalized tonic clonic, myoclonic, and absence seizures are negative prognostic factors of drug-resistant GGE. The AUC of 0.6 is not consistent with truly effective separation of the groups, suggesting other unmeasured variables may need to be considered in future studies to improve predictability.