Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy.

Summary:Purpose: To study the effects of cathodal DC polarization in patients with refractory epilepsy and malformations of cortical development (MCDs) as indexed by seizure frequency and epileptiform EEG discharges.Methods: Nineteen patients with MCDs and refractory epilepsy underwent one session of DC polarization (20 min, 1 mA) targeting the epileptogenic focus. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after, and 15 and 30 days after either sham or active DC polarization. Seizure frequency after the treatment was compared with baseline.Results: Active compared with sham DC polarization was associated with a significant reduction in the number of epileptiform discharges [mean ED reduction of −64.3% (95% CI, −122.5% to −6.0%) for the active treatment group and −5.8% (95% CI, −26.8% to 15.2%) for the sham treatment group]. A trend (p = 0.06) was noted for decrease in seizure frequency after active compared with sham treatment [mean seizure frequency decrease of −44.0% (95% CI, −95.0% to 7.1%) for the active treatment group and −11.1% (95% CI, −22.2% to 44.4%) for the sham treatment group].Conclusions: This randomized, controlled study shows that cathodal DC polarization does not induce seizures and is well tolerated in patients with refractory epilepsy and MCDs. Furthermore, the results suggest that this technique might have an antiepileptic effect based on clinical and electrophysiological criteria. Key Words: Cathodal DC polarization-Transcranial direct current stimulation-EEG-Epilepsy-Malformations of cortical development.Modification of dysfunctional electrical brain activity by using electrical stimulation seems to be a potentially valuable alternative for epilepsy treatment that should be further explored. For instance, evidence exists that direct stimulation of subcortical and cortical mesotemporal structures can reduce seizure frequency in some forms of epilepsy (1,2). A few animal (3) and human studies (4-6) suggest that noninvasive low-frequency repetitive transcranial magnetic stimulation (rTMS) might also be clinically effective in seizure control in patients with refractory epilepsy. DC polarization provides an alternative means of modifying brain excitability noninvasively, and its effects on the cortical excitability appear to be similar to those of rTMS (7-10). Furthermore, animal studies showed that direct-current (DC) stimulation can indeed induce a local suppression of the epileptiform activity (11-13). A number of studies using DC polarization in humans suggest that this technique is safe (14-17). In DC polarization, the cerebral cortex is stimulated through a weak constant electric current in a noninvasive and painless manner. This weak current induces focal changes of cortical excitability-increase or decrease depending on the electrode polarity-that last beyond the period of stimulation. Several studies have shown that this technique might modulate cortical excitability in the human motor (18-20), prefrontal (21), and...

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Objective: To study the effects of repetitive transcranial magnetic stimulation (rTMS) on epileptic EEG discharges in patients with refractory epilepsy and malformations of cortical development (MCDs). Methods: Eight patients with MCD and refractory epilepsy underwent 1 session of low-frequency rTMS (0.5 Hz, 600 pulses) focally targeting the MCD. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after as well as 15 and 30 days after rTMS treatment. Results: Stimulation significantly decreased the number of EDs 15 and 30 days after rTMS treatment (mean reduction of 46.4%, 95% CI 12.7–80.2%, and mean reduction of 42.1%, 95% CI 8.2–75.7%, respectively). This was associated with a significant reduction in the number of seizures reported as compared with the 4-week period preceding rTMS (mean reduction of 57.3%, 95% CI 33.1–80.3%, and mean reduction of 51.2%, 95% CI 27.9–74.9%, respectively). Conclusion: This open study shows a significant antiepileptic effect of rTMS based on clinical and electrophysiological criteria and supports the therapeutic utility of rTMS for patients with well-localized epileptogenic cortical malformations.

Approximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatile drug delivery or in the form of ‘zeitgebers’ that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacology may provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacology in the treatment of epilepsy as well as future treatment avenues.

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