Postdoctoral fellow Massachusetts General Hospital and Harvard Medical School
Rationale: Seizures manifest with a variety of pathologies and exhibit great diversity. Although many studies have dealt with seizure initiation, few have investigated the underlying mechanisms that lead to seizure termination. At first glance seizures appear to have similar terminations, but a subset of these do not show this regular pattern. In these seizures, an ictal event may terminate in some locations but not in others, and in some cases, this can lead to status epilepticus. Our current work seeks to determine whether seizure termination can reflect clinically relevant information and be predictive of the responses to proposed treatment.
Methods: Seizures (n=466 from 70 patients) were recorded from patients with medical refractory epilepsy who underwent presurgical evaluation with intracranial electrodes. Each seizure was visually examined and classified into focal or secondarily generalized seizures. Seizures were classified into two groups: (a) those that end simultaneously on all recorded channels (synchronous termination, ST), and (b) those for which seizure activity terminates on some channels while continuing for longer on others (asynchronous termination, AT). To account for the differences in the number of seizures in each patient, we have randomly selected one representative seizure from each seizure type in each patient for further analysis, yielding 137 seizures. We then evaluated whether the patient’s response to the treatment (indicated as either favorable: Engel I/II; or ineffective: Engel III/IV) can be validated based on whether their seizures exhibited synchronous or asynchronous endings. Patients were classified into three groups: patients that only exhibited ST-type seizures (G1), patients that only exhibited AT-type seizures (G2), and patients that exhibited a mix of ST- and AT-type seizures (G3). In G3 patients, we further assessed whether there is a difference in network connectivity between seizures that share the same onset region and spread (focal or secondarily generalized) but end differently (ST versus AT).
Results: We analyzed 137 seizures, of which 32% were focal and 68% were secondarily generalized. Most focal seizures (93%) were ST-type. Among seizures that propagated to further regions, 64% of these were ST-type and 32% were AT-type, with 4% going into status epilepticus. Of the 70 patients in this study, 46 of them had ST-type-only seizures (G1), 5 patients had AT-type-only seizures (G2), and 19 had both ST- and AT-type seizures (G3). In G1 patients, 35 of them had surgery with 25/35 (71%) having favorable outcomes, in G2 patients, four had resective surgery and all benefited from the surgery. Finally, 11 patients from G3 had surgery with 9/11 (81%) having favorable outcomes. We compared the connectivity between different channels in a subset (n=6) of G3 patients, selected such that their seizures started from the same region and were secondarily generalized. In this group we compared connectivity between ST- and AT-type seizures. Our analysis demonstrated that the connectivity between channels during an ST-type seizure is different to that of an AT-type seizure. In all patients we observed that there are fewer connections between regions during ST-type seizures compared to the seizures that showed asynchronous ending.
Conclusions: Through our findings, we demonstrate that there is no difference in response to treatment in patients that have only ST-type seizures compared to the patients with both ending types. Further, we showed that there exists more connectivity between regions during AT-type seizures. This may explain how the connectivity between different brain areas can lead to a stronger network in generating seizures or persistence in ictal activity.
Funding: Please list any funding that was received in support of this abstract.: NIH R01-NS062092