Recurrent Episodes of Coma: An Unusual Phenotype of Familial Hemiplegic Migraine with Linkage to Chromosome 1

Échenne, B.; Ducros, Anne; Rivier, François; Joutel, Anne; Humbertclaude, Véronique; Roubertie, Agathe; Azais, M.; Bousser, M. G.; Tournier‐Lasserve, Elisabeth

doi:10.1055/s-2007-973493

Cited by 35 publications

(31 citation statements)

References 2 publications

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“…Last but not least, SD can directly precipitate seizure-like electrocorticogram activity, as first demonstrated by Leão (2). Consistent with our findings, epilepsy is more frequent in FHM patients than in the general population, with seizures occurring either during FHM attacks (71)(72)(73)(74) or interictally (75)(76)(77)(78). Epilepsy has been reported in many patients carrying FHM1 mutations (10,71,(79)(80)(81)(82).…”

Section: Figuresupporting

confidence: 91%

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Eikermann-Haerter¹,

Dileköz²,

Kudo³

et al. 2008

J. Clin. Invest.

187

290

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Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the α 1A subunit of Ca v 2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

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Section: Figuresupporting

confidence: 91%

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Eikermann-Haerter¹,

Dileköz²,

Kudo³

et al. 2008

J. Clin. Invest.

187

290

View full text Add to dashboard Cite

show abstract

“…In addition, one family has been described in which FHM was linked to chromosome 1q, and the proband, but not the other affected family members, had hemiplegic migraine attacks associated with coma. 21 In all these families, however, the impairment of consciousness was short-lived and never as dramatic as in our patients with the S218L mutation; there also was no such dramatic delayed association with minor head trauma.…”

Section: Discussioncontrasting

confidence: 42%

Delayed cerebral edema and fatal coma after minor head trauma: Role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine

et al. 2001

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Trivial head trauma may be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval ("delayed cerebral edema"). Attacks of familial hemiplegic migraine (FHM) can be triggered by minor head trauma and are sometimes accompanied by coma. Mutations in the CACNA1A calcium channel subunit gene on chromosome 19 are associated with a wide spectrum of mutation-specific episodic and chronic neurological disorders, including FHM with or without coma. We investigated the role of the CACNA1A gene in three subjects with delayed cerebral edema. Two subjects originated from a family with extreme FHM, and one subject was the previously asymptomatic daughter of a sporadic patient with hemiplegic migraine attacks. In all three subjects with delayed severe edema, we found a C-to-T substitution resulting in the substitution of serine for lysine at codon 218 (S218L) in the CACNA1A gene. The mutation was absent in nonaffected family members and 152 control individuals. Haplotype analysis excluded a common founder for both families. Neuropathological examination in one subject showed Purkinje cell loss with relative preservation of granule cells and sparing of the dentate and inferior olivary nuclei. We conclude that the novel S218L mutation in the CACNA1A calcium channel subunit gene is involved in FHM and delayed fatal cerebral edema and coma after minor head trauma. This finding may have important implications for the understanding and treatment of this dramatic syndrome.

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“…A single familial hemiplegic migraine locus has been previously mapped to chromosome 19p13.1 [3][4][5][6][7][8][9][10][11][12][13]. Studies in different FHM families showed that additional causative genes must reside in other regions of the genome, including the long arm of chromosome 1 [5,8,9,12,14,15].…”

Section: Introductionmentioning

confidence: 99%

“…Hemiplegia, which is associated in hemianesthesia, can involve the hemisome as a whole, or it can be localised in the upper part, involving in particular the face [3,5,[14][15][16]. During the attack, a state of confusion is often present and it can be compared to a psychotic state (visual or acoustic hallucinations) [5,16,17].…”

Section: Introductionmentioning

confidence: 99%

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Neuropsychologic phenotypes in familial hemiplegic migraine

Roccella

2003

J Headache Pain

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The 3 adolescents studied are from a large family in which the mother and 6 of 8 children are affected by FHM. The affected children are 4 males aged 33, 30, 15 and 13 years, and 2 females aged 30 and 10 years. Convulsions with fever were reported by the Michele RoccellaAbstract Familial hemiplegic migraine (FHM) is a rare autosomal dominant-type migraine with aura. Attacks are characterised by hemiparesis in addition to other aura and migraine symptoms. Few studies have examined the influence of FHM on cognitive functions. This study was aimed to investigate neuropsychological functions in 3 adolescent siblings suffering from FHM assessed six months after the last attack. No relevant deficits were found on a battery of multisectorial tests exploring cognitive functions. Sporadic FHM attack therefore seems not to affect cognition in these patients, at least far from the crises.

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Recurrent Episodes of Coma: An Unusual Phenotype of Familial Hemiplegic Migraine with Linkage to Chromosome 1

Cited by 35 publications

References 2 publications

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Delayed cerebral edema and fatal coma after minor head trauma: Role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine

Neuropsychologic phenotypes in familial hemiplegic migraine

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