Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder

Scheffer, Ingrid E.; Bhatia, KP; Lopes-Cendes, Íscia; Fish, D. R.; Marsden, C. D.; Andermann, Frédérick; Andermann, Eva; Desbiens, Richard; Cendes, Fernando; Manson, J. I.

doi:10.1016/s0140-6736(94)91463-x

Cited by 302 publications

(193 citation statements)

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“…If this suggestion is correct, mice are able to compensate functionally for this hyperactivity: they show seizures only after nicotine injections. Humans with ␣4*-or ␤2*-linked ADNFLE compensate slightly less completely: they have subtle seizures that escaped clinical description until 1994 (Scheffer et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4^*Nicotinic Receptors

Fonck¹,

Cohen²,

Nashmi³

et al. 2005

J. Neurosci.

120

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A leucine to alanine substitution (L9ЈA) was introduced in the M2 region of the mouse ␣4 neuronal nicotinic acetylcholine receptor (nAChR) subunit. Expressed in Xenopus oocytes, ␣4(L9ЈA)␤2 nAChRs were Ն30-fold more sensitive than wild type (WT) to both ACh and nicotine. We generated knock-in mice with the L9ЈA mutation and studied their cellular responses, seizure phenotype, and sleepwake cycle. Seizure studies on ␣4-mutated animals are relevant to epilepsy research because all known mutations linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) occur in the M2 region of ␣4 or ␤2 subunits. Thalamic cultures and synaptosomes from L9ЈA mice were hypersensitive to nicotine-induced ion flux. L9ЈA mice were ϳ15-fold more sensitive to seizures elicited by nicotine injection than their WT littermates. Seizures in L9ЈA mice differed qualitatively from those in WT: L9ЈA seizures started earlier, were prevented by nicotine pretreatment, lacked EEG spike-wave discharges, and consisted of fast repetitive movements. Nicotine-induced seizures in L9ЈA mice were partial, whereas WT seizures were generalized. When L9ЈA homozygous mice received a 10 mg/kg nicotine injection, there was temporal and phenomenological separation of mutant and WT-like seizures: an initial seizure ϳ20 s after injection was clonic and showed no EEG changes. A second seizure began 3-4 min after injection, was tonic-clonic, and had EEG spike-wave activity. No spontaneous seizures were detected in L9ЈA mice during chronic video/EEG recordings, but their sleep-wake cycle was altered. Our findings show that hypersensitive ␣4* nicotinic receptors in mice mediate changes in the sleep-wake cycle and nicotineinduced seizures resembling ADNFLE.

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Section: Discussionmentioning

confidence: 99%

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4^*Nicotinic Receptors

Fonck¹,

Cohen²,

Nashmi³

et al. 2005

J. Neurosci.

120

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“…Clinical features of the nine eligible participants from a single large family [14,18] are summarized in Table 1. At the current assessment, a detailed clinical history and neurological examination were obtained by M.F.…”

Section: Participantsmentioning

confidence: 99%

Neuropsychological function in patients with a single gene mutation associated with autosomal dominant nocturnal frontal lobe epilepsy

Wood¹,

Saling²,

Fedi³

et al. 2010

Epilepsy & Behavior

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a b s t r a c tAutosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a nonlesional condition associated with mutation of the gene coding for the a4 nicotinic acetylcholine receptor (nAChR). The nAChR modulates aspects of memory and attention. We examined the neuropsychological phenotype of ADNFLE, with a particular emphasis on understanding the impact on frontal lobe functions. We used standard clinical tests as well as focused measures of frontal lobe function in a well-defined group of patients with ADN-FLE. Their performance was compared with that of a group of age-, sex-, and education-matched control participants. Patients with ADNFLE showed impairments on tasks requiring cognitive flexibility against a background of well-preserved intellectual abilities. In accord with existing research, verbal memory impairments were identified in the patient group; the level of impairment on these tasks correlated with disease-related factors. In our study of ADNFLE associated with one mutation, cognitive flexibility appears to be the core cognitive deficit.Crown

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“…To answer this question, we propose a set of validation criteria for genetic animal models of epilepsy, composed of face, construct and predictive validities. The first genetic abnormality of idiopathic epilepsy was documented for ADNFLE in 1994 [16]. We recently generated four genetic animal models of ADNFLE, and evaluated their validities according to the above validation criteria.…”

Section: Introductionmentioning

confidence: 99%

Validation criteria for genetic animal models of epilepsy

Okada

Zhu

Yoshida

et al. 2010

E&S

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In the past decades, several mutant genes that encode ion channel subunit proteins or their functionally-related proteins have been identified in pedigrees of idiopathic epilepsy. To explore the pathogenesis and pathophysiology of epilepsy syndrome, the functional abnormalities of transmission in genetic animal models bearing the mutant genes identified in pedigrees of idiopathic epilepsy should be analyzed. In spite of these efforts, it is important to identify the most suitable genetic animal models for exploration of epileptogenesis and ictogenesis, as well as the development of novel antiepileptic drugs. In the literature on genetic epileptic animal models, there is no systematic discussion on how to assess the validation criteria for such models. In this review, we describe the validation criteria for genetic animal models of epilepsy.

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Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder

Cited by 302 publications

References 10 publications

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4^*Nicotinic Receptors

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4^*Nicotinic Receptors

Neuropsychological function in patients with a single gene mutation associated with autosomal dominant nocturnal frontal lobe epilepsy

Validation criteria for genetic animal models of epilepsy

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Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder

Cited by 302 publications

References 10 publications

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4*Nicotinic Receptors

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4*Nicotinic Receptors

Neuropsychological function in patients with a single gene mutation associated with autosomal dominant nocturnal frontal lobe epilepsy

Validation criteria for genetic animal models of epilepsy

Contact Info

Product

Resources

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Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4^*Nicotinic Receptors

Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive α4^*Nicotinic Receptors