Epilepsy research in 2022: clinical advances

In 2022, epilepsy research has made advances across a range of clinically important areas, from self-management, genetics, imaging, and surgical planning to understanding febrile seizures and coma-related periodic patterns. Most notably, in May 2022, the World Health Assembly adopted the Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders, which aims to address gaps in health care delivery, with epilepsy as a core focus.¹

Many research groups have previously investigated how to use enhanced imaging technologies to produce clinically useful data for the characterisation of individual outcomes and prognosis for epilepsy, but these efforts have typically had little success. In a prospective study, Lee and colleagues² studied patients with temporal lobe epilepsy using neuropsychological testing and MRI. They used an unsupervised machine learning technique to derive four latent or unseen disease factors, and these factors reflected whole-brain changes and predicted cognitive outcomes in individual patients.

Other research groups have worked on methods to predict post-surgical outcomes in epilepsy. Astner-Rohracher and colleagues³ developed and externally validated a score to assess whether a potentially resectable focus could be identified if a patient had stereoelectroencephalography. This score can help identify patients who might not benefit from intracranial EEG and could reduce their diagnostic and health-care burdens by considering therapies such as neuromodulation. Similar modelling work has been done to help improve diagnosis of SCN1A-related epilepsies in children. Brunklaus and colleagues⁴ showed that their model, which incorporated clinical and genetic data, could distinguish between Dravet syndrome and other genetic epilepsies with febrile seizures. Early and accurate identification of rare epilepsies is crucial as therapeutic progress for these populations continues. Trials are ongoing for several rare epilepsies, including some assessing early safety and efficacy of ganaxolone in children with CDKL5 deficiency disorder.⁵

Improvements in diagnostic techniques for paediatric epilepsy have also included a clinical proof of utility for magnetoencephalography. This imaging technique has technical limitations, particularly in paediatric patients, because of the fixed-sized helmets that are required to accommodate the cooling devices in the standard superconducting quantum interference device sensors. Optically pumped magnetometers developed in 2018 do not require this bulky cooling equipment. Feys and colleagues⁶ showed that in children with epilepsy, these new sensors were similarly able to localise interictal discharges and had improved signal-to-noise ratio and amplitude compared with magnetoencephalography.

Progress has also been made in understanding psychiatric comorbidities in epilepsy. Meador and colleagues⁷ used data from the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs cohort study, including women with epilepsy and their children, to investigate mood disorders during pregnancy and the post-partum period. Although major depressive episodes were not more prevalent in women with epilepsy than in those without epilepsy, subsyndromic depressive episodes were more frequent. These findings have implications for how women are screened and supported during their pregnancies and the post-partum period. Studies are needed to identify high-risk populations who could benefit from targeted behavioural interventions. An example of such an intervention was assessed by Streltzov and colleagues,⁸ who showed the effectiveness of a home-based virtual version of an epilepsy self-management programme at improving quality of life. A virtual programme could be more widely and easily disseminated to at-risk groups than a clinic-based programme.

Other developments in 2022 have increased our understanding of febrile seizures and periodic EEG patterns in coma. Skotte and colleagues⁹ did a genome-wide association study in children with febrile seizures. They found that variants in several fever-response genes and some known epilepsy genes (eg, SCN1A and ANO3) seemed to be associated with febrile seizures. They developed a polygenic risk score which was associated with epilepsy and with a history of hospital admission for febrile seizures, but polygenic risk was low in patients with febrile seizures and neuropsychiatric disease compared with people with febrile seizures in a general population sample. These findings might inform risk stratification of children with febrile seizures and suggest that both neuronal hyperexcitability and inflammatory pathways might contribute to febrile seizures.

The need and aggressiveness with which to treat EEG periodic patterns in survivors of cardiac arrest who are comatose is clinically debated. Ruijter and colleagues¹⁰ did an open-label randomised trial in which rhythmic periodic patterns were suppressed in these patients. In survivors of cardiac arrest who were comatose, the incidence of poor neurological outcome 3 months after hospital admission did not differ between individuals who had their periodic pattern suppressed for at least 48 h and those who received standard care.

Overall, the advances in epilepsy research in 2022 have improved our understanding of the CNS, and much progress has been made in discovery and translation of experimental findings towards clinical implementation.

Biography

Justin Paget