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Background: Long-term outcomes following febrile seizures in African children are not well described, but ma- laria-associated seizures are a risk factor for epilepsy. Design/Methods: 107 consecutive children admitted with febrile seizures (FS group) were age-matched to concurrently admitted children with febrile illness and no seizure, or febrile illness only (FIO). Quarterly follow-up assessments deter- mined interim seizures and developmental outcomes. Results: 214 children were enrolled and followed for mean 20.4 months (median 24, mode 27). The most common diag- nosis was clinical malaria. During follow-up, children in the FS group were more likely to have recurrent febrile seizures (29.9 vs. 11.3%; RR1.27; CI 1.10-1.46), an unprovoked seizure (27.1 vs. 1.9%; RR 1.35; CI 1.20-1.52) and epilepsy (11.2 vs. 0.9; RR 1.16; CI 1.04-1.20). Risk factors for unprovoked seizures during follow-up included younger age at enroll- ment (25.5 v. 34.6 months, p=0.04) and developmental delay preceding the index illness (33.3 vs. 13.1%, p=0.009). Within the FS group, children with focal seizures at enrollment were more likely to experience unprovoked seizures (52.9 vs. 20%, p=0.007) and epilepsy (41.7 vs. 7.8%, p=0.03). Conclusions: Children admitted with febrile seizures in rural Zambia have a high risk of subsequent epilepsy. Further re- search is needed to determine if specific infectious etiologies (e.g. malaria) are associated with epilepsy development in such children. Where access to healthcare services are limited, febrile seizure admission may also be a marker for a pre- existing propensity toward later epilepsy. Regardless, follow- up is warranted to facilitate early initiation of treatment if recurrent, unprovoked seizures occur.

The neuropeptide galanin has been implicated in inhibiting seizures and protecting hippocampal neurons from excitotoxic injury. In the hippocampus galanin acts through two receptor subtypes, GalR1, expressed in CA1, and GalR2, abundant in dentate gyrus. We developed an approach to induce and to study selective semichronic knockdown of GalR2 in the rat hippocampus. A 50% reduction of GalR2 binding was achieved by continuous infusion of complementary peptide nucleic acid antisense oligonucleotide into the dentate gyrus. This resulted in an increase in the severity of self-sustaining status epilepticus induced by electrical stimulation of the perforant path, induced mild neuronal injury in the dentate hilus, augmented seizure-induced hilar injury and inhibited seizure-induced neurogenesis in the subgranular zone of the dentate gyrus. Our data suggest that in the dentate gyrus, galanin, acting through GalR2, inhibits seizures, promotes viability of hilar interneurons and stimulates seizure-induced neurogenesis. These results are important for understanding the role of galanin and galanin receptor subtypes in the hippocampus both under normal conditions and in excitotoxic injury.