Efficacy of levetiracetam at 12 months in children classified by seizure type, cognitive status, and previous anticonvulsant drug use.

In a retrospective study of 59 children (ages 9 months to 23 years; mean age 11 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of levetiracetam therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications (range 0-5), and the number of previous anticonvulsant drugs (range 1-12). Good to excellent seizure control (50-100% reduction) was attained in 6 (40%) patients with focal seizures, 16 (55%) patients with generalized seizures, and 8 (61%) patients with mixed seizures; these efficacy rates were not significantly different. The efficacy of levetiracetam was independent of cognitive status. Adverse effects were not associated with higher mean doses. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of levetiracetam and zonisamide had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of the mechanisms of action of levetiracetam and zonisamide and/or their pharmacodynamic interactions.

Broad-spectrum efficacy of zonisamide at 12 months in children with intractable epilepsy.

In a retrospective study of 35 children (ages 8 months to 22 years; mean age 9 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of zonisamide therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications, and the number of previous anticonvulsant drugs. Good to excellent seizure control (50-100% reduction) was attained in seven (54%) patients with generalized seizures, two (40%) patients with focal seizures, five (35%) patients with mixed seizures, and one (33%) patient with infantile spasms. In this group of children, the efficacy of zonisamide was comparable for focal, generalized, and mixed seizures. The efficacy of zonisamide was independent of cognitive status. Adverse effects were not associated with a higher mean dose. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of zonisamide and levetiracetam had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of mechanisms of action of zonisamide and levetiracetam and/or their pharmacodynamic interactions.

Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium syndrome).

Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. Here, we report the first patient heterozygous for 2 novel mutations in VLDLR. An 18-month-old girl presented with significant hypotonia, global developmental delay, and truncal and peripheral ataxia. Magnetic resonance imaging of the brain demonstrated hypoplasia of the inferior cerebellar vermis and hemispheres, small pons, and a simplified cortical sulcation pattern. Sequence analysis of the VLDLR gene identified a nonsense and missense mutation. Six mutations in VLDLR have now been identified in 5 families with a phenotype characterized by moderate-to-profound mental retardation, delayed ambulation, truncal and peripheral ataxia, and occasional seizures. Neuroanatomically, the loss-of-function effect of the different mutations is indistinguishable. VLDLR-associated cerebellar hypoplasia is emerging as a panethnic, clinically, and molecularly well-defined genetic syndrome.

Relationship between significant perinatal events and migraine severity.

OBJECTIVE: Nociceptive neuronal circuits are formed during embryonic and postnatal times, so insult during these periods may result in long-term alterations to pain circuitry via synaptic plasticity. One possible long-term result of plasticity is central hyperexcitability, which is suspected to be involved in chronic headache. This study aimed to establish whether there is an association between early pain experiences and the experience of migraines in later childhood. METHODS: In a retrospective study, we examined the charts of 280 pediatric migraineurs at the Division of Pediatric Neurology at Robert Wood Johnson Medical School and documented their perinatal history and migraine characteristics. RESULTS: Analysis revealed that there was a significant relationship between patients who had been in the NICU at birth and the type of pain medication prescribed when compared with patients who had not been in the NICU (chi2 test, chi2(2) = 23.304; N = 30250). Findings also suggested that pediatric migraine patients who had been in the NICU at birth had a significantly earlier age of onset of their migraines (chi2 +/- SD = 7.83 +/- 3.23; N = 30) when compared with patients who did not remain in the NICU (chi2 +/- SD = 9.68 +/- 3.57; N = 250; Kolmogorov-Smirnov Test, chi2 = 10.699). CONCLUSION: On the basis of these findings, we speculate that pain experience as a neonate, through neuronal plasticity and resulting central hyperexcitability, can alter the later experience of pain. However, this observational study cannot validate these links. Other potential explanations that work either synergistically or alone include other forms of stimulation and greater parental vigilance that may occur when neonates spend time in the NICU. This study would prompt additional development of a larger prospective study to establish a link between early pain experience and subsequent pain syndromes and also future investigation into the treatment of pain in neonates as a preventive measure for avoiding long-lasting neuronal alterations.