Alternating hemiplegia of childhood or familial hemiplegic migraine?: A novel <i>ATP1A2</i> mutation

Swoboda, Kathryn J.; Kanavakis, Emmanuel; Xaidara, Athina; Johnson, Justine E.; Leppert, M.; Schlesinger-Massart, Mylynda; Ptáček, Louis J.; Silver, Kenneth; Youroukos, Sotiris

doi:10.1002/ana.20134

Cited by 156 publications

(109 citation statements)

References 8 publications

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“…2,7 However, the ATP1A2 mutation was never found in sporadic AHC patients as reported here and by others. 2,7,8 The genetic studies are still ongoing and new hypothesis being are tested. 9 A genetic mechanism should not be excluded for AHC.…”

supporting

confidence: 56%

“…[3][4][5][6] Metabolic studies in Aldh5a1 -⁄ -murine embryos have revealed significant increases in both GABA and GHB as early as day 10 of embryo life, which is of interest since GABA is excitatory during development and might predispose neural circuity to a hyperexcitatory state. 7 GHB also has its own receptor systems, and its accumulation may increase GABA secondarily while exacerbating the effects of GABA on different receptors. 8 Recently, GABA(A) and GABA(B) receptor abnormalities have been suggested in SSADH-deficient patients through studies employing [11C]flumazenil binding and transcranial magnetic stimulation.…”

mentioning

confidence: 99%

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‘Absence of T378N mutation of ATP1A2 gene in five patients with alternating hemiplegia of childhood’

Boileau¹,

Vuillaume²,

Sablonnière³

et al. 2008

Develop Med Child Neuro

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supporting

confidence: 56%

mentioning

confidence: 99%

‘Absence of T378N mutation of ATP1A2 gene in five patients with alternating hemiplegia of childhood’

Boileau¹,

Vuillaume²,

Sablonnière³

et al. 2008

Develop Med Child Neuro

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“…families with features that bridge the clinical spectrum between FHM and alternating hemiplegia of childhood (AHC), a rare syndrome characterized by early onset of episodic hemiplegia or quadriplegia with autonomic disturbances, movement disorders, and progressive cognitive impairment. 71,72 The Na ϩ ,K ϩ -ATPase pumps generate the ion gradients that maintain resting membrane potential and cell volume and provide the driving force for nutrient and neurotransmitter uptake. Glial and neuronal Na ϩ ,K ϩ -ATPases play an important role in clearance of K ϩ from the extracellular space during neuronal activity 73,74 and are fundamental also for the clearance of released glutamate from the synaptic cleft, because active transport of glutamate into astrocytes and neurons is driven by both Na ϩ and K ϩ gradients.…”

Section: Figmentioning

confidence: 99%

Familial Hemiplegic Migraine

2007

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Summary: Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming ␣ 1 subunits of the neuronal voltage-gated Ca 2ϩ channels Ca V 2.1 and Na ϩ channels Na V 1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the ␣ 2 subunit of the Na ϩ , K ϩ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca V 2.1 channel and, as a consequence, increased Ca V 2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the ␣ 2 Na ϩ ,K ϩ -ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na V 1.5 (and presumably Na V 1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K ϩ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K ϩ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategies that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.

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“…6,7 La enfermedad se caracteriza por episodios repetidos de hemiplejía que pueden durar desde algunos minutos hasta varios días; pudiendo existir períodos prolongados sin sintomatología antes de un nuevo episodio. 3 Es habitual la existencia de un retraso inespecífico del desarrollo previo al inicio de los síntomas.…”

Section: Discussionunclassified

Hemiplejía alternante de la infancia: presentación de un caso y revisión de la bibliografía

et al. 2012

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Arch Argent Pediatr 2012;110(5):e86-e90 / e86Presentación de casos clínicos RESUMEN La hemiplejía alternante de la infancia es una entidad de etiología desconocida cuya incidencia estimada es de un caso por millón. Esta enfermedad paroxística, de curso progresivo, se caracteriza por episodios repetidos de hemiplejía que alternan su localización y que pueden durar desde algunos minutos hasta varios días. Los episodios generalmente desaparecen durante el sueño. También se pueden apreciar movimientos oculares paroxísticos, deterioro cognitivo y trastornos autonómicos. Al ser una enfermedad progresiva de mal pronóstico, el alerta por parte del médico generalista es crucial, para poder facilitar el diagnóstico precoz y evitar tratamientos farmacológicos ineficaces. Se presenta el caso de una niña de diez años con diagnóstico de hemiplejía alternante de la infancia; se discuten los hallazgos de las neuroimágenes durante los episodios y se efectúa una revisión de la bibliografía. Palabras clave: hemiplejía alternante de la infancia, convulsiones, hemiplejía, movimientos oculares, resonancia magnética nuclear. SUMMARYAlternating hemiplegia of childhood is an entity of uncertain etiology, with an incidence of about one case per million. This paroxysmal disease with progressive course is characterized by repeated episodes of hemiplegia that alternates its location and that may last from a few minutes to several days. These episodes are usually aborted during sleep. Paroxysmal eye movements, cognitive impairment and autonomic disorders, can also be seen. Due to its progressive course and bad prognosis, it turns out to be important for the generalist physician to be aware of this entity, thus facilitating an early diagnosis and avoiding empiric pharmacologic ineffective treatments. We present the case of a ten year-old girl with alternating hemiplegia of childhood, show imaging of this disease and make a brief review of the literature.

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Alternating hemiplegia of childhood or familial hemiplegic migraine?: A novel ATP1A2 mutation

Cited by 156 publications

References 8 publications

‘Absence of T378N mutation of ATP1A2 gene in five patients with alternating hemiplegia of childhood’

‘Absence of T378N mutation of ATP1A2 gene in five patients with alternating hemiplegia of childhood’

Familial Hemiplegic Migraine

Hemiplejía alternante de la infancia: presentación de un caso y revisión de la bibliografía

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