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• W2149405816 endingPage "3999" @default.
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• W2149405816 abstract "Heterozygous loss-of-function mutations in the α subunit of the type I voltage-gated sodium channel Na V 1.1 cause severe myoclonic epilepsy in infancy (SMEI), an infantile-onset epileptic encephalopathy characterized by normal development followed by treatment-refractory febrile and afebrile seizures and psychomotor decline. Mice with SMEI (mSMEI), created by heterozygous deletion of Na V 1.1 channels, develop seizures and ataxia. Here we investigated the temperature and age dependence of seizures and interictal epileptiform spike-and-wave activity in mSMEI. Combined video-EEG monitoring demonstrated that mSMEI had seizures induced by elevated body core temperature but wild-type mice were unaffected. In the 3 age groups tested, no postnatal day (P)17–18 mSMEI had temperature-induced seizures, but nearly all P20–22 and P30–46 mSMEI had myoclonic seizures followed by generalized seizures caused by elevated core body temperature. Spontaneous seizures were only observed in mice older than P32, suggesting that mSMEI become susceptible to temperature-induced seizures before spontaneous seizures. Interictal spike activity was seen at normal body temperature in most P30–46 mSMEI but not in P20–22 or P17–18 mSMEI, indicating that interictal epileptic activity correlates with seizure susceptibility. Most P20–22 mSMEI had interictal spike activity with elevated body temperature. Our results define a critical developmental transition for susceptibility to seizures in SMEI, demonstrate that body temperature elevation alone is sufficient to induce seizures, and reveal a close correspondence between human and mouse SMEI in the striking temperature and age dependence of seizure frequency and severity and in the temperature dependence and frequency of interictal epileptiform spike activity." @default.
• W2149405816 created "2016-06-24" @default.
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• W2149405816 date "2009-03-10" @default.
• W2149405816 modified "2023-09-30" @default.
• W2149405816 title "Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy" @default.
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• W2149405816 doi "https://doi.org/10.1073/pnas.0813330106" @default.
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