This issue of Epilepsy Research News includes summaries of articles on:
- The Cerebellum as a Source of Generalized Convulsive Seizures
- Examining the Benefit of Rapid Genome Sequencing for Infantile Epilepsy
- Large Genetic Study Provides Insights on Why Epilepsy Develops and Potential Treatments
- Preventive Epilepsy Treatment with Vigabatrin Does Not Improve Neurocognitive Development in Infants with Tuberous Sclerosis Complex (TSC)
- Advances in Cannabidiol (CBD) for Epilepsy Treatment and Prevention
A recent study provides new insights into how convulsive seizures happen, implicating a “circuit” in the brain, specifically a connection of neurons between the cerebellum and thalamus, in driving convulsive seizures. To investigate the importance of this circuit in causing seizures, the team utilized a technique called optogenetic imaging to record the activity of neurons in the brain before, during, and after convulsive seizures. The team found that a group of neurons in a specific area of the thalamus called the ventral posteromedial nucleus were initiating convulsive seizures. The team then found that neurons in the cerebellum that connect to this area of the thalamus not only significantly contribute to the seizures, but that blocking activity from the cerebellum to the thalamus blocked seizures from occurring. The team noted that the findings not only deepen the understanding of how seizures originate but also create the possibility of targeting this cerebellum-thalamus circuit to treat convulsive seizures.
A recent study shows that rapid genome sequencing (a process that looks for changes across the entire genome) can provide a rapid diagnosis of genetic mutations and influence clinical care of infants with new-onset epilepsy. As part of this study, researchers sequenced the genomes of 100 infants with unexplained seizures along with their parents to better understand the potential diagnostic value of this approach for infantile epilepsy. The researchers found that across all children enrolled in the study, 43% received a diagnosis within weeks, and that diagnosis impacted the medical outcomes in nearly 90% of those cases, guiding treatment options for over half. This study provides an initial framework for further investigation of the long-term benefits of early genetic diagnosis in infants, and the potential use of targeted “precision” treatments that are specific to an infant’s genetic diagnosis.
The largest genetic study of its kind has discovered specific changes in our DNA that increase the risk of developing epilepsy. The research advances our knowledge of why epilepsy develops and may inform the development of new treatments for the condition. The researchers identified 26 distinct areas in our DNA that appear to be involved in epilepsy. This included 19 which are specific to a particular form of epilepsy called genetic generalized epilepsy. They were also able to identify 29 genes within these DNA regions that probably contribute to epilepsy. The researchers also showed that many of the current medications for epilepsy work by targeting the same epilepsy risk genes that were highlighted in the study. Furthermore, based on their data, the researchers were able to propose some potentially effective alternative drugs. The researchers noted that these discoveries, only achieved through international collaboration, help us to better understand the genetics of this type of epilepsy and potential treatments.
In new study results, researchers found that administering the preventive epilepsy treatment vigabatrin (Sabril ®) prior to seizure onset did not improve neurocognitive outcomes in TSC infants at two years of age. In the original results, this study (known as the PREVeNT trial) showed that preventative treatment delayed the start and lowered the number of infantile spasms in infants with TSC. This study enrolled 84 infants with TSC between 2016 and 2020, who had been diagnosed with TSC either through prenatal testing, physical examination, or genetic testing, but had yet to have any seizures. Infants who developed a specific EEG biomarker that indicates a risk of developing seizures were then placed in two groups, one receiving preventative vigabatrin treatment and one receiving a placebo. In this new study, the researchers found that infants who received vigabatrin still had drug-resistant epilepsy at 24 months, that focal seizures remained prominent in the infants, and there was no benefit in cognitive outcomes. The researchers state that these findings indicate the need to develop more effective therapies to treat cognitive and behavioral dysfunction in TSC.
A series of recently published articles details new breakthroughs in the field of medical cannabinoids for epilepsy and seizure disorders. Two publications review the effectiveness of CBD, a compound found in cannabis, in treating epilepsy and seizures. Another publication in the series describes the results of a meta-analysis (a type of study that reviews and combines the results of multiple other studies) to determine the overall effectiveness and safety of CBD treatment in children with genetic epilepsies such as Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis Complex. This analysis revealed that CBD was effective in managing these genetic epilepsies, albeit with an increase in adverse events such as diarrhea, somnolence, sedation, and potential drug interactions. A separate publication showed potential effects of CBD as a prevention against seizures that are similar to those associated with temporal lobe epilepsy. Together, these publications provide information on the use of CBD in the treatment of epilepsy and open up the possibility of utilizing CBD in individuals at risk for developing epilepsy.