Epilepsy continues to remain one of the most common chronic neurological disorders,
associated with significant morbidity, affecting more than 50 million people globally.[1] The understanding of epileptogenesis has taken large strides, but still epilepsy
continues to evoke challenges and fascination in equal measure. This contributes to
continuously drive innovations, which have spanned pharmacological therapies, surgical
and neurostimulation techniques, as well as technological developments aimed at seizure
prediction and monitoring.
In the pharmacological front, newer antiepileptic drugs have expanded treatment options
with improved efficacy and tolerability. Cenobamate, approved in 2019, emerged as
an effective agent acting through dual mechanisms—modulating sodium channels and GABA-A
receptors[2] for refractory focal seizures. Azetukalner (XEN1101), a next-generation Kv7 potassium
channel opener, currently undergoing phase 3 trials has shown promise for both focal
and generalized seizures, with once-daily dosing and no need for titration.[3] Repurposed agents like Fenfluramine, a drug with dual-action sigma-1 receptor and
serotonergic activity,[4] were approved for Dravet syndrome in 2020.[5] Ganaxolone is also another new development, approved in 2022, which marks the first
neuroactive steroid used in epilepsy management with its mechanism—enhancing tonic
and phasic inhibition via GABA-A modulation[6]
[7]—offering a new therapeutic avenue for syndromic epilepsies in infants and children.
Surgical and diagnostic innovations have further transformed the landscape of care.
Techniques like laser interstitial thermal therapy, a minimally invasive alternative
to open respective surgery, provide effective ablation of seizure foci with shorter
recovery times. Magnetic resonance imaging–guided thermal ablation has proven effective
in patients with mesial temporal lobe epilepsy, hypothalamic hamartomas, and focal
cortical dysplasia.[8] Neurostimulation therapies have become vital tools, especially for patients not
amenable to surgery. Vagus nerve stimulation, deep brain stimulation of the anterior
thalamic nucleus, and responsive neurostimulation[9]
[10]
[11]—which delivers targeted electrical pulses upon detecting abnormal brain activity—have
shown meaningful reductions in seizure frequency and are being used more regularly.
Noninvasive neuromodulation techniques like transcranial magnetic stimulation are
also being explored, though evidence for their efficacy remains variable.[12] Focused ultrasound, a noninvasive technique capable of lesioning epileptogenic zones
or opening the blood–brain barrier for drug delivery, remains in its early stages.[13]
In cases where surgical intervention in epilepsy may be limited by factors such as
bilateral seizure foci, involvement of eloquent brain regions, or multifocal epileptic
networks, invasive techniques like stereo-electroencephalography (SEEG) and subdural
electrodes have become key tools. SEEG, in particular, allows for high-resolution,
three-dimensional mapping of epileptic activity through depth electrode implantation,
offering critical localization in cases where noninvasive methods fall short. Advances
in the conducting mediums including the utilization of polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic
acid) (PEDOT:PSS) show promise for electrode modification due to their high conductivity,
mechanical flexibility, and biocompatibility, making them particularly suitable for
integration into neural devices for brain science research.[14]
Technological advances have enabled real-time seizure detection and prediction. Wearable
devices like smart watches, accelerometers, and subcutaneous electroencephalogram
(EEG) monitors can alert caregivers to convulsive seizures, improving safety during
high-risk periods such as sleep.[15] Machine learning algorithms are now capable of predicting seizures with >85% sensitivity
using preictal EEG and multimodal data.[16]
[17] Experimental systems such as NeuroVista[18] aim to predict seizures by analyzing continuous EEG patterns, potentially allowing
for preventive intervention—all driven by artificial intelligence (AI)-based seizure
prediction. Apps are transforming patient engagement, improving treatment adherence,
and enhancing data collection for clinical trials.
Innovation in epilepsy should not only occur isolated to treating and preventing seizures,
rather it has to be comprehensive involving psychiatric, cognitive, and systemic comorbidities
associated with epilepsy. In that regard, there is more awareness in recognizing depression
and anxiety as a risk factor and a consequence of epilepsy. There has also been global
radicalization, with the World Health Organization's Intersectoral Global Action Plan
(2022–2031) for epilepsy and other neurological disorders emphasizing the integration
of epilepsy services into primary care, training nonspecialists in diagnosis and treatment,
access to essential medicines and diagnostic tools, and community-based rehabilitation
and social support. The convergence of precision medicine, digital therapeutics, and
patient-centered care marks the next frontier. Key trends to watch include: gene therapy
and antisense oligonucleotides for monogenic epilepsies (e.g., SCN1A, STXBP1); microbiome-targeted
therapies and dietary modulation beyond ketogenic diets; immune-modulating therapies
for autoimmune epilepsies, supported by novel biomarkers (e.g., LGI1, CASPR2 antibodies);
personalized polytherapy algorithms using AI-driven decision models.
The landscape of epilepsy care is being innovated, from molecular biology to wearable
devices and neurosurgical precision, with research findings being converted effectively
to clinical tools. Yet, it is imperative that these advances are equitably distributed
across geographies and socioeconomic strata. The future is promising and demands persistent
investment, interdisciplinary collaboration, and unwavering patient focus.
