Early‐onset Absence Epilepsy and Paroxysmal Dyskinesia

Guerrini, Renzo; Sánchez-Carpintero, Rocı́o; Deonna, Thierry; Santucci, Margherita; Bhatia, Kailash P.; Moreno, T.; Parmeggiani, Lucio; Bernardina, Bernardo Dalla

doi:10.1046/j.1528-1157.2002.13802.x

Cited by 70 publications

(57 citation statements)

References 28 publications

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“…An interesting and increasingly recognized phenomenon is the coexistence of epilepsy and paroxysmal dyskinesia in the same individual (Guerrini 2001;Guerrini et al 2002). Despite the fact that the basic pathophysiology underlying that coexistence is unknown, both neurological disorders seems to be the clinical consequence from a gain-of-function mutation of BK channels leading to an increase in neuronal excitability (Du et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Ca2+-activated K+ channels of the BK-type in the mouse brain

Sausbier

Sailer

et al. 2005

Histochem Cell Biol

141

128

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An antibody against the 442 carboxy-terminal amino acids of the BK channel alpha-subunit detects high immunoreactivity within the telencephalon in cerebral cortices, olfactory bulb, basal ganglia and hippocampus, while lower levels are found in basal forebrain regions and amygdala. Within the diencephalon, high density was found in nuclei of the ventral and dorsal thalamus and the medial habenular nucleus, and low density in the hypothalamus. The fasciculus retroflexus and its termination in the mesencephalic interpeduncular nucleus are prominently stained. Other mesencephalic expression sites are periaquaeductal gray and raphe nuclei. In the rhombencephalon, BK channels are enriched in the cerebellar cortex and in the locus coeruleus. Strong immunoreactivity is also contained in the vestibular nuclei, but not in cranial nerves and their intramedullary course of their roots. On the cellular level, BK channels show pre- and postsynaptic localizations, i.e., in somata, dendrites, axons and synaptic terminals.

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Section: Discussionmentioning

confidence: 99%

Ca2+-activated K+ channels of the BK-type in the mouse brain

Sausbier

Sailer

et al. 2005

Histochem Cell Biol

141

128

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“…Epilepsy and PD have been reported to co-occur in various forms. Characteristically, epilepsy manifests as idiopathic syndrome, making a genetic cause plausible [Guerrini et al 2000]. A family with Rolando epilepsy with PED and writer's cramp with autosomal recessive inheritance was described by Guerrini and colleagues [1999] and has been linked to chromosome 16p, which is within the ICCA region.…”

Section: Geneticsmentioning

confidence: 99%

Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Unterberger

Trinka

2008

Ther Adv Neurol Disord

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Paroxysmal dyskinesias (PDs) are a rare group of hyperkinetic movement disorders mainly characterized by their episodic nature. Neurological examination may be entirely normal between the attacks. Three main types of PDs can be distinguished based on their precipitating events -(i) paroxysmal kinesigenic dyskinesias (PKD), (ii) paroxysmal non-kinesigenic dyskinesias (PNKD) and (iii) paroxysmal exercise-induced (exertion-induced) dyskinesias (PED). The diagnosis of PDs is based on their clinical presentation and precipitating events. Substantial progress has been made in the field of genetics and PDs. Treatment options mainly include anticonvulsants and benefit of treatment is depending on the type of PD. Most important differential diagnosis are non-epileptic psychogenic, non-epileptic organic and epileptic attack disorders, especially nocturnal frontal lobe epilepsy.

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“…A number of studies have reported the coexistence of epilepsy and movement disorders in the same individuals or in different individuals within a family (Guerrini et al, 1999(Guerrini et al, , 2002Guerrini, 2001). In a recent report, a mutation was identified in a calcium-sensitive potassium channel in childhood-onset paroxysmal nonkinesigenic dyskinesia with absence epilepsy associated with rare tonicclonic seizures and generalized spike-wave complexes on electroencephalogram (Du et al, 2005).…”

Section: Epilepsy or Movement Disorder?mentioning

confidence: 99%

Nicotine-Induced Dystonic Arousal Complex in a Mouse Line Harboring a Human Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy Mutation

Teper¹,

Whyte²,

Cahir³

et al. 2007

J. Neurosci.

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We generated a mouse line harboring an autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) mutation: the ␣4 nicotinic receptor S248F knock-in strain. In this mouse, modest nicotine doses (1-2 mg/kg) elicit a novel behavior termed the dystonic arousal complex (DAC). The DAC includes stereotypical head movements, body jerking, and forelimb dystonia; these behaviors resemble some core features of ADNFLE. A marked Straub tail is an additional component of the DAC. Similar to attacks in ADNFLE, the DAC can be partially suppressed by the sodium channel blocker carbamazepine or by pre-exposure to a very low dose of nicotine (0.1 mg/kg). The DAC is centrally mediated, genetically highly penetrant, and, surprisingly, not associated with overt ictal electrical activity as assessed by (1) epidural or frontal lobe depth-electrode electroencephalography or (2) hippocampal c-fos-regulated gene expression. Heterozygous knock-in mice are partially protected from nicotine-induced seizures. The noncompetitive antagonist mecamylamine does not suppress the DAC, although it suppresses high-dose nicotine-induced wild-type-like seizures. Experiments on agonist-induced 86 Rb ϩ and neurotransmitter efflux from synaptosomes and on ␣4S248F␤2 receptors expressed in oocytes confirm that the S248F mutation confers resistance to mecamylamine blockade. Genetic background, gender, and mutant gene expression levels modulate expression of the DAC phenotype in mice. The S248F mouse thus appears to provide a model for the paroxysmal dystonic element of ADNFLE semiology. Our model complements what is seen in other ADNFLE animal models. Together, these mice cover the spectrum of behavioral and electrographic events seen in the human condition.Key words: nicotine; epilepsy; ADNFLE; dystonia; mecamylamine; synaptosome IntroductionNocturnal frontal lobe epilepsy (NFLE) is characterized by clusters of stereotypic episodes of arousal from sleep associated with dystonic neck, limb, and trunk movements that occur during stages 2-4 of non-rapid eye movement (REM) sleep (Montagna, 1992;Plazzi et al., 1995;Provini et al., 1999;Provini et al., 2000).Less commonly, there are prolonged ballistic limb and trunk movements, resulting in injury Combi et al., 2004). Autosomal-dominant NFLE (ADNFLE) , a familial subtype of NFLE, was initially associated with a missense (S248F) mutation in the ␣4 nicotinic acetylcholine receptor subunit (␣4-nAChR) gene (Steinlein et al., 1995) at position 6Ј in the M2 transmembrane region. Subsequently, in other ADNFLE pedigrees, additional mutations were discovered at the ␣4 M2-10Ј (Steinlein et al., 1997;Hirose et al., 1999), M2-17Ј (Steinlein et al., 1997;Hirose et al., 1999), and ␤2 subunit M2-22Ј positions and one at the ␤2 M3 position that contacts M2 in most structural models (De Fusco et al., 2000;Phillips et al., 2001;Bertrand et al., 2005). A mutation in ␣2 (Aridon et al., 2006) was identified in a pedigree with atypical nocturnal epilepsy.Electrophysiological analyses of heterologously expressed ADNFLE alleles sugge...

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Early‐onset Absence Epilepsy and Paroxysmal Dyskinesia

Cited by 70 publications

References 28 publications

Ca2+-activated K+ channels of the BK-type in the mouse brain

Ca2+-activated K+ channels of the BK-type in the mouse brain

Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Nicotine-Induced Dystonic Arousal Complex in a Mouse Line Harboring a Human Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy Mutation

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