ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2007
Familial hemiplegic migraine.
Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Understanding the nature of psychiatric comorbidity in migraine: a systematic review focused on interactions and treatment implications.The journal of headache and pain · 2019Pooled it
- Reduced cerebellar inhibition in migraine with aura: a TMS study.Cerebellum (London, England) · 2009Trial
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- Whole brain fluorescence imaging iniScience · 2026Article
- Mechanisms underlying the increased susceptibility to initiation of cortical spreading depression in a genetic mouse model of migraine.The journal of headache and pain · 2025Article
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- Article
- CACNA1A loss-of-function affects neurogenesis in human iPSC-derived neural models.Cellular and molecular life sciences : CMLS · 2025Article
- Migraine with and without aura-two distinct entities? A narrative review.The journal of headache and pain · 2025Review
- Mechanisms underlying CSD initiation implicated by genetic mouse models of migraine.The journal of headache and pain · 2025Review
- Familial Hemiplegic Migraine (FHM) with Transient Psychotic Symptoms: A Case Report and Literature Review.Turk psikiyatri dergisi = Turkish journal of psychiatry · 2025Review
- Calcium Ions in the Physiology and Pathology of the Central Nervous System.International journal of molecular sciences · 2024Review
- A Review of theDiseases (Basel, Switzerland) · 2024Review
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.European journal of human genetics : EJHG · 2024Article
- Increased presynaptic excitability in a migraine with aura mutation.Brain : a journal of neurology · 2024Article
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- Article
- Astrocytic Glutamate Transporters and Migraine.Neurochemical research · 2023Review
- Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the NaBiomedicines · 2023Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
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 alpha(1) subunits of the neuronal voltage-gated Ca2+ channels Ca(V)2.1 and Na+ channels Na(V)1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the alpha2 subunit of the Na+, K+ 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 alpha2 Na+,K+-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+ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K+ (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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.