Severe Attacks of Familial Hemiplegic Migraine, Childhood Epilepsy and <i>ATP1A2</i> Mutation

Lebas, Axel; Guyant‐Maréchal, Lucie; Hannequin, Didier; Riant, Florence; Tournier‐Lasserve, Elisabeth; Parain, D.

doi:10.1111/j.1468-2982.2008.01603.x

Cited by 39 publications

(17 citation statements)

References 9 publications

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“…Although the precise protein/protein interaction remains unexplored, these results provide a unifying synaptic mechanism for migraine relevant phenotypes across different models. Interestingly, this glutamatergic gain of function is larger in FHM 1 and 2 than in CK1d T44A , potentially consistent with the differences in severity between hemiplegic and non-hemiplegic forms of migraine 84 . The cellular and synaptic gain of function found in CK1d T44A in response to higher stimulus intensity recapitulates the intensity dependent hypersensitivity phenotype found in most migraineurs.…”

Section: Discussionsupporting

confidence: 63%

Increased presynaptic excitability in a migraine with aura mutation

Suryavanshi

Sawant-Pokam

Brennan

2019

Preprint

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6 Migraine is a very common and disabling neurological disorder that remains poorly understood at 7 the cellular and circuit level. Transgenic mice harboring a mutation in casein kinase 1 delta 8 (CK1dT44A) represent the first animal model of non-hemiplegic migraine. These mice have 9decreased sensory thresholds to mechanical and thermal pain after treatment with the migraine 10 trigger nitroglycerin; and an increased susceptibility to cortical spreading depression (CSD), which 11 models the migraine aura. In this study, we investigated cellular and synaptic mechanisms within 12 sensory cortical circuits that might underlie the migraine relevant phenotypes of CK1dT44A mice, 13using in vitro and in vivo whole cell electrophysiology. Surprisingly we found that at resting state, 14CK1dT44A neurons exhibited hyperpolarized membrane potentials, due to increased tonic 15inhibition. Despite this reduction in baseline excitability, CK1dT44A neurons fired action potentials 16 more frequently in response to current injection. And despite similar synaptic and dendritic 17 characteristics to wild type neurons, excitatory but not inhibitory CK1dT44A synapses failed to adapt 18to high frequency short-stimulus trains, resulting in elevated steady state excitatory currents. The 19increased steady state currents were attributable to an increased replenishment rate of the readily 20 releasable pool, providing a presynaptic mechanism for the CK1dT44A phenotype. Finally, during 21in vivo experiments, CK1dT44A animals showed increased duration and membrane potential 22 variance at 'cortical up states', showing that the intrinsic and synaptic changes we observed have 23 excitatory consequences at the local network level. In conclusion excitatory sensory cortical 24 neurons and networks in CK1dT44A animals appear to exhibit decreased adaptation and increased 25 gain that may inform the migraine phenotype. 26 27

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Section: Discussionsupporting

confidence: 63%

Increased presynaptic excitability in a migraine with aura mutation

Suryavanshi

Sawant-Pokam

Brennan

2019

Preprint

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“…Other researches showed diffusely slow and polymorphic theta activity with some epileptiform discharges over the cerebral hemisphere contralateral to the symptomatic hemiparesis 5,6. Recent report revealed the temporospatial dynamics of EEG during the full duration of a sporadic hemiplegic migraine attack.…”

Section: Discussionmentioning

confidence: 95%

“…During attacks of basilar migraine, unilateral or bilateral delta waves are recorded frequently 3. As in cases with HM, there have been a few findings of EEG reported as slow sharp waves and diffuse slowing with epileptiform discharges during hemiplegic migraine attack 4–6. However, these EEG of hemiplegic migraine were performed without sleep deprivation (SD).…”

Section: Introductionmentioning

confidence: 99%

Intermittent Theta Slowings in Contralateral Side of Weakness after Sleep Deprivation on Spot EEG in Sporadic Hemiplegic Migraine

et al. 2016

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Hemiplegic migraine (HM) is an uncommon type of migraine which is classified into sporadic and familial subtype. The noticed electroencephalogram (EEG) findings during HM attack are diffuse slowing contralateral to the weakened limb, but are usually normal in asymptomatic states.A 52-year-old woman who suffered from headache accompanying right arm weakness and aphasic symptoms admitted to our hospital. She underwent total five times of EEG including 2 times before admission. Only the last EEG exam after 24 hours of sleep deprivation (SD) showed intermittent slowing and higher amplitude of positive occipital sharp transients (POSTs) on the left parieto-occipital area. Here, we report a case with HM who revealed abnormal EEG findings after SD, which was not observed in the routine EEG study without SD.

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“…Interestingly, no patients experienced some of the previously reported FHM-related syndromes such as basilar migraine, 2,11 cognitive impairment, 2 or epilepsy. 9,10 Screening for FHM based on relatives' testimonials was specific but not sensitive. The diagnosis of FHM type 1 based on the first-degree relatives' information seems reliable because all of the patients who were described as symptomatic were confirmed to have the disorder; however, exclusion of the diagnosis on the same grounds cannot be considered because some subjects described as asymptomatic were found to be affected after our examination.…”

Section: Commentmentioning

confidence: 93%

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

Barros¹,

Damásio²,

Tuna³

et al. 2013

JAMA Neurol

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To document and discuss the broad phenotypic variability in a Portuguese family with cerebellar ataxia, hemiplegic migraine, and related syndromes caused by missense mutation c.1748 (p.R583Q) in the CACNA1A gene. Design: Observational 12-year follow-up study. Setting: Community and hospital care. Patients: Sixteen patients in a 4-generation family were identified in 1998 in a population-based survey. The follow-up revealed 28 patients (25 of whom were observed) and 32 unaffected relatives with an a priori risk of 50%. Results: Four major phenotypes (migraine with multiple auras, transient focal neurological deficits without headache, coma triggered by minor head trauma, and slowly progressive cerebellar ataxia) were present in various combinations. The initial manifestation was ataxia in 16 patients and a transient episode in 12 patients. Eighteen patients did not have migraine, and 11 showed only ataxia. The c.1748 (p.R583Q) mutation in CACNA1A was confirmed in all 23 of the patients who were tested but was not found in any of the 27 adult relatives. The CACNA1A CAG repeat expansion was excluded. Conclusions: A unique missense mutation in the CACNA1A gene, which exhibits a very high penetrance and expressivity, may present a phenotypic spectrum that is broader than current descriptions. Single-gene disorders can behave as complex traits, which reinforces the importance of genetic modifiers in the tightly regulated function of P/Q-type calcium channels. The clinical spectrum of missense mutation CACNA1A-related disorders is much broader than strictly familial hemiplegic migraine.

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Severe Attacks of Familial Hemiplegic Migraine, Childhood Epilepsy and ATP1A2 Mutation

Cited by 39 publications

References 9 publications

Increased presynaptic excitability in a migraine with aura mutation

Increased presynaptic excitability in a migraine with aura mutation

Intermittent Theta Slowings in Contralateral Side of Weakness after Sleep Deprivation on Spot EEG in Sporadic Hemiplegic Migraine

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

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