Seizure freedom after functional hemispherectomy and a possible role for the insular cortex: the Dutch experience.

OBJECT: The authors undertook this study to identify predictors of persistent postoperative seizures in their group of 28 Dutch pediatric and adolescent patients with medically intractable epilepsy who underwent functional hemispherectomy. METHODS: The records of 28 pediatric and adolescent patients who underwent a functional hemispherectomy in the University Medical Center Utrecht were retrospectively analyzed. The authors performed a Cox regression analysis, using the first postoperative seizure as the event. Pathology, age at surgery, age at seizure onset, duration of epilepsy, type of surgery, surgeon, possible incomplete disconnection on MR images, and presence of residual insular cortex were analyzed as potential associated variables during the follow-up period. RESULTS: The patients' mean age at surgery was 69.9 months (range 3.0-294.2 months) and mean duration of follow-up was 39.0 months (range 6.0-132.0 months). Six patients had postoperative seizures (21%). One patient had persistent bilateral status epilepticus and died 4 months after surgery. The Cox regression analysis showed presence of insular cortex to be the only variable statistically associated with postoperative seizures (p = 0.021) in this group of 28 patients. CONCLUSIONS: In this group of Dutch pediatric and adolescent patients, residual insular cortex was positively correlated with persistent postoperative seizures. Given the small sample size in this study, however, caution should be used in drawing conclusions about the role of the insular cortex.

Persistent sodium current in subicular neurons isolated from patients with temporal lobe epilepsy.

The persistent sodium current is a common target of anti-epileptic drugs and contributes to burst firing. Intrinsically burst firing subicular neurons are involved in the generation and spread of epileptic activity. We measured whole-cell sodium currents in pyramidal neurons isolated from the subiculum resected in drug-resistant epileptic patients and in rats. In half of the cells from both patients and rats, the sodium current inactivated within 500 ms at -30 mV. Others displayed a tetrodotoxin-sensitive slowly or non-inactivating sodium current of up to 53% of the total sodium current amplitude. Compared with the transient sodium current in the same cells, this persistent sodium current activated with normal kinetics but its voltage-dependent activation occurred 7 mV more hyperpolarized. Depolarizing voltage steps that lasted 10 s completely inactivated the persistent sodium current. Its voltage dependence did not differ from that of the transient sodium current but its slope was less steep. The voltage dependence and kinetics of the persistent sodium current in cells from patients were not different from that in subicular cells from rats. The current density and the relative amplitude contribution were 3-4 times greater in neurons from drug-resistant epilepsy patients. The abundant presence of persistent sodium current in half of the subicular neurons could lead to a larger number of neurons with intrinsic burst firing. The extraordinarily large amplitude of the persistent sodium current in this subset of subicular neurons might explain why these patients are susceptible to seizures and hard to treat pharmacologically.

Material-specific recognition memory deficits elicited by unilateral hippocampal electrical stimulation.

Although the medial temporal lobe is thought to be critical for recognition memory (RM), the specific role of the hippocampus in RM remains uncertain. We investigated the effects of transient unilateral hippocampal electrical stimulation (ES), subthreshold for afterdischarge, on delayed item RM in epilepsy patients implanted with bilateral hippocampal depth electrodes. RM was assessed using a novel computer-controlled test paradigm in which ES to left or right hippocampus was either absent (baseline) or synchronized with item presentation. Subsequent yes-no RM performance revealed a double dissociation between material-specific RM and the lateralization of ES. Left hippocampal ES produced word RM deficits, whereas right hippocampal ES produced face RM deficits. Our findings provide the first demonstration in humans that selective unilateral stimulation-induced hippocampal disruption is sufficient to produce impairments on delayed RM tasks and provide support for the material-specific laterality of hippocampal function with respect to RM.