Chronobiology of epilepsy: diagnostic and therapeutic implications of chrono-epileptology.

The combination of chronobiology and epilepsy offers novel diagnostic and therapeutic management options. Knowledge of the interactions between circadian periodicity, entrainment, sleep patterns, and epilepsy may provide additional diagnostic options beyond sleep deprivation and extended release medication formulations. It may also provide novel insights into the physiologic, biochemical, and genetic regulation processes of epilepsy and the circadian clock, rendering new treatment options. Temporal fluctuations of seizure susceptibility based on sleep homeostasis and circadian phase in selected epilepsies may provide predictability based on mathematical models. Chrono-epileptology offers opportunities for individualized patient-oriented treatment paradigms based on chrono-pharmacology, differential medication dosing, chrono-drug delivery systems, and utilization of "zeitgebers" such as chronobiotics or light-therapy and desynchronization strategies among others.

Treatment of cataplexy in Niemann-Pick disease type C with the use of miglustat.

Cataplexy is the sudden muscle weakness brought on by strong emotions, particularly joking, laughter, or anger. Cataplexy may involve only certain group of muscles or the entire voluntary musculature. In rare cases, symptoms of cataplexy can be seen during the course of some inherited diseases (Niemann-Pick type C (NPC), Prader-Willi syndrome, myotonic dystrophy, Norrie disease). We report the successful use of miglustat, a reversible inhibitor of the enzyme glucosylceramide synthase, approved for use in Gaucher's disease, and which catalyses the first step in the biosynthesis of most glycosphingolipid, in a boy with NPC with cataplexy. A 9-year-old boy was admitted for assessments of frequent "drop attacks" while laughing. The filipin fluorescence tests of cultured skin fibroblasts revealed massive accumulation of unesterified cholesterol, confirming the diagnosis of NPC disease. Molecular studies confirmed the diagnosis of NPC too. After approval from the bioethics committee, miglustat was initiated on the child at 100mg three times a day. Cataplectic attacks disappeared completely after 6 months on treatment, and patient continues to be in remission from the cataplectic attacks at 16 months follow-up. There was no further progression of neurological signs or symptoms or splenomegaly, with some improvement in cognitive function as well as social, affective and attention problems, up-gaze, and gait. Miglustat was well tolerated with no side effects observed. In summary, this is the first report of miglustat treatment of cataplexy in NPC. Long-term follow-up for continuing efficacy and tolerability in a larger cohort with NPC is needed to substantiate our observation.

Vagus nerve stimulation in children with refractory epilepsy: unusual complications and relationship to sleep-disordered breathing.

BACKGROUND: Vagus nerve stimulation (VNS) is approved for use in patients with refractory epilepsy over the age of 12 years. While this procedure is widely used, there is little data on adverse events in young children. MATERIALS AND METHODS: A retrospective chart review was conducted on 26 children who had VNS implantation for refractory epilepsy from 1998 to 2004. RESULTS: Ages ranged from 3 to 17 years (16 boys and 10 girls). Seventy-seven percent had moderate to severe mental retardation. Sixty-five percent had more than 30 seizures per month. Symptomatic-generalized epilepsy was the predominant epilepsy syndrome seen in 77% of children. The duration of VNS treatment ranged from 1 month to 8 years (mean = 3.5 years). Twenty of 26 patients (77%) were on rapid-cycling mode. More than 50% reduction in seizure frequency was noted in 54% with two patients achieving seizure freedom. Twenty-three percent had less than 50% seizure reduction. Four patients were able to terminate seizures with use of the magnet. VNS was removed from one patient because of intractable cough persisting in spite of stimulation being turned off for 1 month. Another patient had it removed twice for infection. Obstructive sleep apnea (OSA) was observed in four patients (15%) after placement of VNS. CONCLUSION: VNS appears to be an effective treatment for children with refractory epilepsy. Development of intractable cough in one patient in spite of device being turned off and recurrent infection-related removal in another are unusual complications. Polysomnography before implantation of VNS should be considered to identify patients with pre-existing OSA.