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Michel D. Ferrari - One of the best experts on this subject based on the ideXlab platform.
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RNA expression profiling in brains of Familial Hemiplegic Migraine type 1 knock-in mice
Cephalalgia : an international journal of headache, 2013Co-Authors: Boukje De Vries, Michel D. Ferrari, Rune R. Frants, Else Eising, Ludo A. M. Broos, Stephany C. Koelewijn, Boyan Todorov, Judith M. Boer, Peter A. C. 't Hoen, Arn M J M Van Den MaagdenbergAbstract:BackgroundVarious CACNA1A missense mutations cause Familial Hemiplegic Migraine type 1 (FHM1), a rare monogenic subtype of Migraine with aura. FHM1 mutation R192Q is associated with pure Hemiplegic...
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Enhanced Subcortical Spreading Depression in Familial Hemiplegic Migraine Type 1 Mutant Mice
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Katharina Eikermann-haerter, Izumi Yuzawa, Tao Qin, Yumei Wang, Kwangyeol Baek, Young R. Kim, Ulrike Hoffmann, Ergin Dilekoz, Christian Waeber, Michel D. FerrariAbstract:Familial Hemiplegic Migraine type 1, a monogenic Migraine variant with aura, is linked to gain-of-function mutations in the CACNA1A gene encoding CaV2.1 channels. The S218L mutation causes severe channel dysfunction, and paroxysmal Migraine attacks can be accompanied by seizures, coma, and hemiplegia; patients expressing the R192Q mutation exhibit hemiplegia only. Familial Hemiplegic Migraine knock-in mice expressing the S218L or R192Q mutation are highly susceptible to cortical spreading depression, the electrophysiological surrogate for Migraine aura, and develop severe and prolonged motor deficits after spreading depression. The S218L mutants also develop coma and seizures and sometimes die. To investigate underlying mechanisms for these symptoms, we used multielectrode electrophysiological recordings, diffusion-weighted magnetic resonance imaging, and c-fos immunohistochemistry to trace spreading depression propagation into subcortical structures. We showed that unlike the wild type, cortical spreading depression readily propagated into subcortical structures in both Familial Hemiplegic Migraine type 1 mutants. Whereas the facilitated subcortical spread appeared limited to the striatum in R192Q, hippocampal and thalamic spread was detected in the S218L mutants with an allele-dosage effect. Both strains exhibited increased susceptibility to subcortical spreading depression and reverberating spreading depression waves. Altogether, these data show that spreading depression propagates between cortex, basal ganglia, diencephalon, and hippocampus in genetically susceptible brains, which could explain the prolonged hemiplegia, coma, and seizure phenotype in this variant of Migraine with aura.
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Severe and Progressive Neurotransmitter Release Aberrations in Familial Hemiplegic Migraine Type 1 Cacna1a S218L Knock-in Mice
Journal of neurophysiology, 2010Co-Authors: Simon Kaja, Michel D. Ferrari, Rune R. Frants, Arn M J M Van Den Maagdenberg, Ludo A. M. Broos, Rob C. G. Van De Ven, Jaap J. PlompAbstract:Familial Hemiplegic Migraine type 1 (FHM1) is caused by mutations in the CACNA1A gene, encoding neuronal presynaptic CaV2.1 (P/Q-type) Ca2+ channels. These channels mediate neurotransmitter release...
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Androgenic suppression of spreading depression in Familial Hemiplegic Migraine type 1 mutant mice.
Annals of neurology, 2009Co-Authors: Katharina Eikermann-haerter, Michel D. Ferrari, Arn M J M Van Den Maagdenberg, Michael J. Baum, Michael A. Moskowitz, Cenk AyataAbstract:Familial Hemiplegic Migraine type 1 (FHM1), a severe Migraine with aura variant, is caused by mutations in the CACNA1A gene. Mutant mice carrying the FHM1 R192Q mutation exhibit increased propensity for cortical spreading depression (CSD), a propagating wave of neuroglial depolarization implicated in Migraine aura. The CSD phenotype is stronger in female R192Q mutants and diminishes after ovariectomy. Here, we show that orchiectomy reciprocally increases CSD susceptibility in R192Q mutant mice. Chronic testosterone replacement restores CSD susceptibility by an androgen receptor-dependent mechanism. Hence, androgens modulate genetically-enhanced CSD susceptibility and may provide a novel prophylactic target for Migraine.
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Familial Hemiplegic Migraine.
Advances in genetics, 2008Co-Authors: Curtis F. Barrett, Arn M J M Van Den Maagdenberg, Rune R. Frants, Michel D. FerrariAbstract:Migraine is a severely debilitating episodic disorder affecting up to 12% of the general population. Migraine arises from both genetic and environmental factors, complicating our understanding of what makes the Migraine brain susceptible to attacks. In recent years, powerful genetic screening tools have revealed several single genes linked to Migraine. One example of a monogenic subtype of Migraine is Familial Hemiplegic Migraine (FHM), a rare form of Migraine with aura. The fact that FHM and common multifactorial Migraine have many overlapping clinical features indicates that they likely share underlying pathophysiological pathways. In addition, the identification of monogenic subtypes has made it possible to generate suitable animal models for Migraine. The purpose of this review is to present an overview of the clinical features of Migraine and discuss the continuing highway of Migraine gene discovery. The genes associated with FHM will be discussed, including what we have learned from studying the functional consequences of FHM mutations in cellular and animal models.
Arn M J M Van Den Maagdenberg - One of the best experts on this subject based on the ideXlab platform.
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Basal astrocyte and microglia activation in the central nervous system of Familial Hemiplegic Migraine Type I mice.
Cephalalgia : an international journal of headache, 2019Co-Authors: Giulia Magni, Arn M J M Van Den Maagdenberg, Marta Boccazzi, Antonella Bodini, Maria P. Abbracchio, Stefania CerutiAbstract:BackgroundGain-of-function missense mutations in the α1A subunit of neuronal CaV2.1 channels, which define Familial Hemiplegic Migraine Type 1 (FHM1), result in enhanced cortical glutamatergic tran...
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Familial Hemiplegic Migraine and Recurrent Episodes of Psychosis: A Case Report.
Headache, 2015Co-Authors: Sonja Labianca, Arn M J M Van Den Maagdenberg, Rigmor Jensen, Lone Baandrup, Lars BendtsenAbstract:Familial Hemiplegic Migraine (FHM) is a rare autosomal dominant form of Migraine with motor aura. We present a case report of a father and son with very similar attacks of Hemiplegic Migraine and recurrent episodes of accompanying psychoses. Previously, such episodes led to hospitalization and extended clinical examinations, which further worsened the psychoses. Since the episodes were recognized as related to the Hemiplegic Migraine, a treatment strategy combining sleep and sedation was initiated and progression onto psychosis was almost completely avoided in both father and son. Genetic analyses found no causal gene mutation in the three known FHM genes, suggesting that the phenotype is caused by a yet unidentified mutation.
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RNA expression profiling in brains of Familial Hemiplegic Migraine type 1 knock-in mice
Cephalalgia : an international journal of headache, 2013Co-Authors: Boukje De Vries, Michel D. Ferrari, Rune R. Frants, Else Eising, Ludo A. M. Broos, Stephany C. Koelewijn, Boyan Todorov, Judith M. Boer, Peter A. C. 't Hoen, Arn M J M Van Den MaagdenbergAbstract:BackgroundVarious CACNA1A missense mutations cause Familial Hemiplegic Migraine type 1 (FHM1), a rare monogenic subtype of Migraine with aura. FHM1 mutation R192Q is associated with pure Hemiplegic...
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Novel SCN1A mutation in the IFMT motif of the α1 subunit of the voltage-gated NaV1.1 channel causing Familial Hemiplegic Migraine
Journal of Headache and Pain, 2013Co-Authors: B. B. A. De Vries, Gisela M. Terwindt, Joost Haan, Ferrari, Stephany C. Koelewijn, Claudia M Weller, O De Fàbregues, Anine H. Stam, Arn M J M Van Den MaagdenbergAbstract:Familial Hemiplegic Migraine (FHM) is a monogenic subtype of Migraine with aura. So far three FHM genes are identified; the CACNA1A gene, the ATP1A2 gene and the SCN1A gene.
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Severe and Progressive Neurotransmitter Release Aberrations in Familial Hemiplegic Migraine Type 1 Cacna1a S218L Knock-in Mice
Journal of neurophysiology, 2010Co-Authors: Simon Kaja, Michel D. Ferrari, Rune R. Frants, Arn M J M Van Den Maagdenberg, Ludo A. M. Broos, Rob C. G. Van De Ven, Jaap J. PlompAbstract:Familial Hemiplegic Migraine type 1 (FHM1) is caused by mutations in the CACNA1A gene, encoding neuronal presynaptic CaV2.1 (P/Q-type) Ca2+ channels. These channels mediate neurotransmitter release...
Katharina Eikermann-haerter - One of the best experts on this subject based on the ideXlab platform.
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Abnormal synaptic Ca2+ homeostasis and morphology in cortical neurons of Familial Hemiplegic Migraine type 1 mutant mice
Annals of neurology, 2015Co-Authors: Katharina Eikermann-haerter, Izumi Yuzawa, Michal Arbel-ornath, Nilufer Yalcin, Kishore V. Kuchibhotla, Eloise Hudry, Carli R. Willard, Mihail Climov, Fatmagul KelesAbstract:Objective Migraine is one of the most common and debilitating neurological conditions. Familial Hemiplegic Migraine type 1 (FHM1), a monogenic Migraine subtype, is caused by gain-of-function of voltage-gated CaV2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV2.1 channels and are highly susceptible to cortical spreading depression (CSD), the electrophysiologic event underlying Migraine aura. To date, however, the mechanism underlying increased CSD/Migraine susceptibility remains unclear.
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Enhanced Subcortical Spreading Depression in Familial Hemiplegic Migraine Type 1 Mutant Mice
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Katharina Eikermann-haerter, Izumi Yuzawa, Tao Qin, Yumei Wang, Kwangyeol Baek, Young R. Kim, Ulrike Hoffmann, Ergin Dilekoz, Christian Waeber, Michel D. FerrariAbstract:Familial Hemiplegic Migraine type 1, a monogenic Migraine variant with aura, is linked to gain-of-function mutations in the CACNA1A gene encoding CaV2.1 channels. The S218L mutation causes severe channel dysfunction, and paroxysmal Migraine attacks can be accompanied by seizures, coma, and hemiplegia; patients expressing the R192Q mutation exhibit hemiplegia only. Familial Hemiplegic Migraine knock-in mice expressing the S218L or R192Q mutation are highly susceptible to cortical spreading depression, the electrophysiological surrogate for Migraine aura, and develop severe and prolonged motor deficits after spreading depression. The S218L mutants also develop coma and seizures and sometimes die. To investigate underlying mechanisms for these symptoms, we used multielectrode electrophysiological recordings, diffusion-weighted magnetic resonance imaging, and c-fos immunohistochemistry to trace spreading depression propagation into subcortical structures. We showed that unlike the wild type, cortical spreading depression readily propagated into subcortical structures in both Familial Hemiplegic Migraine type 1 mutants. Whereas the facilitated subcortical spread appeared limited to the striatum in R192Q, hippocampal and thalamic spread was detected in the S218L mutants with an allele-dosage effect. Both strains exhibited increased susceptibility to subcortical spreading depression and reverberating spreading depression waves. Altogether, these data show that spreading depression propagates between cortex, basal ganglia, diencephalon, and hippocampus in genetically susceptible brains, which could explain the prolonged hemiplegia, coma, and seizure phenotype in this variant of Migraine with aura.
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Androgenic suppression of spreading depression in Familial Hemiplegic Migraine type 1 mutant mice.
Annals of neurology, 2009Co-Authors: Katharina Eikermann-haerter, Michel D. Ferrari, Arn M J M Van Den Maagdenberg, Michael J. Baum, Michael A. Moskowitz, Cenk AyataAbstract:Familial Hemiplegic Migraine type 1 (FHM1), a severe Migraine with aura variant, is caused by mutations in the CACNA1A gene. Mutant mice carrying the FHM1 R192Q mutation exhibit increased propensity for cortical spreading depression (CSD), a propagating wave of neuroglial depolarization implicated in Migraine aura. The CSD phenotype is stronger in female R192Q mutants and diminishes after ovariectomy. Here, we show that orchiectomy reciprocally increases CSD susceptibility in R192Q mutant mice. Chronic testosterone replacement restores CSD susceptibility by an androgen receptor-dependent mechanism. Hence, androgens modulate genetically-enhanced CSD susceptibility and may provide a novel prophylactic target for Migraine.
Gisela M. Terwindt - One of the best experts on this subject based on the ideXlab platform.
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Novel SCN1A mutation in the IFMT motif of the α1 subunit of the voltage-gated NaV1.1 channel causing Familial Hemiplegic Migraine
Journal of Headache and Pain, 2013Co-Authors: B. B. A. De Vries, Gisela M. Terwindt, Joost Haan, Ferrari, Stephany C. Koelewijn, Claudia M Weller, O De Fàbregues, Anine H. Stam, Arn M J M Van Den MaagdenbergAbstract:Familial Hemiplegic Migraine (FHM) is a monogenic subtype of Migraine with aura. So far three FHM genes are identified; the CACNA1A gene, the ATP1A2 gene and the SCN1A gene.
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First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in Familial Hemiplegic Migraine.
European journal of human genetics : EJHG, 2007Co-Authors: Kaate R. J. Vanmolkot, Boukje De Vries, Anine H. Stam, Ashok Raman, Jan B. Koenderink, Eelke H Van Den Boogerd, Judith Van Vark, Jeroen J. M. W. Van Den Heuvel, Nin Bajaj, Gisela M. TerwindtAbstract:Familial Hemiplegic Migraine (FHM) is a rare autosomal-dominant subtype of Migraine with aura, associated with hemiparesis during the aura. Here we describe a unique FHM family in which two novel allelic missense mutations in the Na,K-ATPase gene ATP1A2 segregate in the proband with Hemiplegic Migraine. Both mutations show reduced penetrance in family members of the proband. Cellular survival assays revealed Na,K-ATPase dysfunction for both ATP1A2 mutants, indicating that both mutations are disease causative. This is the first case of compound heterozygosity for any of the known FHM genes.
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Single-fiber EMG in Familial Hemiplegic Migraine
Neurology, 2005Co-Authors: Gisela M. Terwindt, M. D. Ferrari, E. E. Kors, Alla A. Vein, J.g. Van DijkAbstract:Twelve Familial Hemiplegic Migraine (FHM) patients (6 with the I1811L mutation in CACNA1A, 3 with M731T mutation in ATP1A2, and 3 without known mutations) and 10 control subjects underwent single-fiber EMG. Mean jitter did not differ significantly between patients and control subjects or among patients. No blocking was found. The results suggest that neuromuscular function is normal in FHM.
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Toward a molecular genetic classification of Familial Hemiplegic Migraine
Current Pain and Headache Reports, 2004Co-Authors: Joost Haan, Gisela M. Terwindt, Rune R. Frants, E. E. Kors, Arn M. J. M. Maagdenberg, Kaate R. J. Vanmolkot, Michel D. FerrariAbstract:The genetics of Migraine is a fascinating and rapidly moving research area. Familial Hemiplegic Migraine, a rare subtype of Migraine with a Mendelian pattern of inheritance, is caused by mutations in the chromosome 19 CACNA1A gene or in the chromosome 1 ATP1A2 gene. Familial Migraine variants are classified on the basis of clinical, descriptive criteria, but this is insufficient. In the future, a diagnostic classification based on mutationanalysis is needed.
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Involvement of a Ca 2+ Channel Gene in Familial Hemiplegic Migraine and Migraine With and Without Aura
Headache, 1997Co-Authors: Roel A. Ophoff, Gisela M. Terwindt, Rune R. Frants, Monique N. Vergouwe, Michel D. FerrariAbstract:A gene for Familial Hemiplegic Migraine, a subtype of Migraine with aura, was assigned to chromosome 19p13. In this region, we identified a brain-specific P/Q-type calcium-channel alpha 1A-subunit gene, CACNA 1A, with 47 exons covering 300 kb. Sequencing of all exons and their flanking surroundings revealed polymorphic variations, including a (CA)n-repeat and a (CAG)n-repeat in the 3' untranslated region. In patients with Familial Hemiplegic Migraine, we found four different missense mutations in conserved functional domains. One of the mutations has occurred on two different haplotypes in unrelated Familial Hemiplegic Migraine families. Moreover, in episodic ataxia type 2, we found two mutations disrupting the reading frame. Thus, Familial Hemiplegic Migraine and episodic ataxia type 2 can be considered as allelic channelopathies. Involvement of this Familial Hemiplegic Migraine locus in Migraine with and without aura was demonstrated by sib-pair analysis. We showed an increase of shared marker alleles of locus D19S394, which is tightly linked to the gene. The association between the alpha 1A calcium channel and Familial Hemiplegic Migraine, and the increase of shared alleles in Migraine-affected sib-pairs, have uncovered a new pathway for the pathophysiology of Migraine. This finding may provide a rationale for the development of specific prophylactic therapy for Migraine and other (paroxysmal) cerebral disorders.
Salvatore Striano - One of the best experts on this subject based on the ideXlab platform.
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Topiramate-associated worsening symptoms in a patient with Familial Hemiplegic Migraine.
Journal of the neurological sciences, 2008Co-Authors: Pasquale Striano, Federico Zara, Filippo Maria Santorelli, Salvatore StrianoAbstract:Topiramate has been shown to be highly effective for preventive treatment of Migraine and its use has been significantly increased in the last few years. However, around 10% of Migraineurs develop a worsening of their symptoms while on topiramate. We report a 33-year-old woman with Familial Hemiplegic Migraine (FHM) who experienced worsening of her symptoms following repeated topiramate intake. Withdrawal of the drug rapidly constantly induced resolution of the symptoms. This is the first report of topiramate-associated worsening symptoms in FHM. It is important to be aware of this phenomenon, as topiramate is worldwide-used drug for Migraine treatment.
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Short communication Topiramate-associated worsening symptoms in a patient with Familial Hemiplegic Migraine
2008Co-Authors: Pasquale Striano, Federico Zara, Filippo Maria Santorelli, Salvatore StrianoAbstract:Topiramate has been shown to be highly effective for preventive treatment of Migraine and its use has been significantly increased in the last few years. However, around 10% of Migraineurs develop a worsening of their symptoms while on topiramate. We report a 33-year-old woman with Familial Hemiplegic Migraine (FHM) who experienced worsening of her symptoms following repeated topiramate intake. Withdrawal of the drug rapidly constantly induced resolution of the symptoms. This is the first report of topiramate-associated worsening symptoms in FHM. It is important to be aware of this phenomenon, as topiramate is worldwide-used drug for Migraine treatment. © 2008 Elsevier B.V. All rights reserved.