Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy.

As a result, everolimus recently received approval for the adjunctive treatment of patients aged ?2 years with refractory TSC-associated focal and secondary generalized seizures. However, efficacy and safety data for infants with TSC-associated WS are still lacking. Therefore, a prospective open-label observational study was initiated at our center, to evaluate everolimus add-on treatment in infants with TSC-associated WS, previously refractory to standard treatment.

For this preliminary report, data from four male infants with TSC2 and a median observation period of 13 (range = 8-42) months after treatment initiation were analyzed. Two infants showed electroclinical remission until day 14 after everolimus treatment initiation. In one additional infant, hypsarrhythmia resolved. No relapse after initial response was documented. Developmental progress improved in three infants. Tolerability was similar to that described in older children.

According to these preliminary results, everolimus appears to have the potential to treat successfully both spasms and hypsarrhythmia in infants with TSC-associated WS, contributing to better developmental progress.

A compound isolated from spider venom called Hm1a helps reduce seizure susceptibility and mortality in mice with Dravet syndrome, according to researchers.

Their study, “Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death,” was published in PNAS.

Dravet syndrome is resistant to several pharmaceutical therapies that are geared toward treatment of other types of epilepsy. This creates an urgent need to develop new therapeutic strategies to treat this genetic disease.

Most patients with Dravet syndrome have a mutation in the SCN1A gene which results in a deficiency in the sodium channel NaV1.1. In the brain, NaV1.1 is expressed on the surface of nerve cells and plays a critical role in nerve-nerve cell signaling.

Spider venom is a rich source of compounds that target ion channels, much like Nav1.1.

Hm1a is a peptide — short chains of amino acids, which are the building blocks of proteins — present in spider venom that selectively improves the functioning of Nav1.1.

Abstract
In a study that applied a nonlinear mixed effect model to evaluate factors affecting steady-state serum carbamazepine concentrations in elderly nursing home residents, co-administration of iron supplements was reported to reduce serum carbamazepine concentrations by approximately one third. Although these findings suggest that iron ions reduce the oral bioavailability of carbamazepine, the influence of confounders cannot be excluded. Further studies are required to confirm this interaction.

Biologist Suzanne Paradis’ lab suppressed seizures in mice by changing the connections between neurons.

Researchers in the lab of Associate Professor of Biology Suzanne Paradis have discovered a novel treatment for reducing seizure activity in the brains of rodents, a discovery they hope might one day help people living with epilepsy. The research was published this spring in the journal Epilepsia.

Paradis’s lab researches synapses, the connections between brain cells. Most synapses are excitatory — they facilitate the passage of signals from one brain cell to another. Others though are inhibitory, thwarting transmission.

In the latest research, the Paradis group worked with mice with symptoms resembling those found in epileptic humans. They applied an infusion of Sema4D into the animals’ brains. The mice experienced a reduction in the severity of their seizures.

Women who take epilepsy drugs while they are pregnant may have a lower risk of having a child with delays in language skills if they take folic acid supplements before and early in pregnancy, according to a study published in the August 1, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study found that among children whose mothers took epilepsy drugs while they were pregnant, those whose mothers did not take folic acid supplements were four times more likely to have delays in their language skills when they were 18 months old compared to children of mothers without epilepsy whose mothers did not take folic acid supplements. By three years old, those whose mothers took no supplements were nearly five times as likely to have language delays compared to children of mothers without epilepsy.

The study was conducted in Norway, where the government does not require foods to be fortified with folic acid, which is required in the United States. Even with folic acid added to foods, taking additional supplements is recommended for pregnant women in the United States.

OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE).

METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ?12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included.

RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after ?2 prior AEDs) than late (?3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent.

SIGNIFICANCE: In routine clinical care of patients with idiopathic generalized epilepsy, perampanel improved seizure outcomes for generalized tonic-clonic seizures, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in idiopathic generalized epilepsy.

BACKGROUND: Variants within the CDKL5 gene result in a severe epileptic encephalopathy now known as the CDKL5 Deficiency Disorder. Phenotypic characteristics include global developmental delay and early seizure onset with poor response to anti-epileptic medications. Vagus nerve stimulation (VNS) has been used in other populations as an adjunct treatment for refractory epilepsy with seizure reduction reported in over half of patients. This study aimed to investigate the role of VNS in the CDKL5 Deficiency Disorder.

METHODS: The International CDKL5 Disorder Database collects information on individuals with the CDKL5 Deficiency Disorder. Families provide information regarding seizure characteristics and their pharmaceutical and non-pharmaceutical management including VNS use. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided from patients attending the CDKL5 Center of Excellence at Children’s Hospital Colorado.

RESULTS: Individuals who had a pathogenic CDKL5 variant and on whom information regarding VNS treatment was available were identified (n?=?222). Previous or current use of VNS was reported for 38 (17.1%), with a median age at implantation of 4.9 years. Improvements in seizure control were reported in over two-thirds (25/36, 69%); including reduction in frequency (17/25, 68%), duration (18/25, 72%) and intensity (15/25, 60%) of seizures. Median duration of VNS use before any seizure improvement was 73 days. Behavioural changes such as improved mood and alertness were reported in nine individuals. Early termination of VNS secondary to side effects was reported in three cases. There was no reduction in number of AEDs for those with VNS treatment.

CONCLUSION: This study suggests that VNS is a generally safe and effective adjunct treatment for CDKL5-associated epilepsy. Additional benefits such as mood and behavioural improvements provide further support of its use in the CDKL5 Deficiency Disorder. Future studies are required to determine the optimal settings and therapeutic potential for this treatment.

Takeda Pharmaceutical Company Limited and Ovid Therapeutics Inc. provided an overview of their TAK-935/OV935 broad clinical development program. The companies plan to initiate three clinical trials: in pediatric patients with Dravet syndrome and Lennox-Gastaut syndrome, in pediatric patients with CDKL5 deficiency disorder (CDD) and Duplication 15q (Dup15q) syndrome, and an extension trial for patients with developmental and epileptic encephalopathies (DEEs) who participated in a previous TAK-935/OV935 clinical study.

These trials join the clinical development program that includes a fully enrolled Phase 1b/2a trial of adults with DEE. Together, these trials will further investigate the potential of TAK-935/OV935 to modulate the N-Methyl-D-Aspartate (NMDA) signaling receptor, which has been implicated in several neurologic disorders.