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Research paper
Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation
  1. Takahiro Iizuka1,
  2. Yuji Takahashi2,
  3. Mayumi Sato1,
  4. Junko Yonekura1,
  5. Saori Miyakawa1,
  6. Motoi Endo1,
  7. Junichi Hamada1,
  8. Shinichi Kan3,
  9. Hideki Mochizuki1,
  10. Yoshio Momose2,
  11. Shoji Tsuji2,
  12. Fumihiko Sakai4
  1. 1Department of Neurology, Kitasato University, School of Medicine, Kanagawa, Japan
  2. 2Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  3. 3Department of Diagnostic Radiology, Kitasato University, School of Medicine, Kanagawa, Japan
  4. 4Department of Neurology, Saitama International Headache Center, Saitama Neuropsychiatric Institute, Saitama, Japan
  1. Correspondence to Dr Takahiro Iizuka, Department of Neurology, Kitasato University, School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan; takahiro{at}


Objectives To report cerebral blood flow changes during attacks of hemiplegic migraine with prolonged aura (HMPA) longer than 24 h in patients with familial hemiplegic migraine (FHM) with a novel gene mutation.

Methods The authors performed serial neuroimaging studies during acute stage and after recovery of aura symptoms in eight HMPA attacks in two affected individuals of the Japanese family of FHM during a 10-year-observational period. The authors also performed a mutational analysis for all exons of the CACNA1A, ATP1A2 and SCN1A genes in three individuals of this family.

Results Each patient had an individual ‘predominantly affected hemisphere,’ that is, susceptible to hemiplegia during an HMPA attack. Migraine aura lasted 4 to 12 days. Neuroimaging studies performed on days 1 to 4 showed hyperperfusion in the affected hemisphere contralateral to hemiplegia in five attacks, hypoperfusion in three, middle cerebral artery vasodilation in five and augmented vasogenic leakage with cortical oedema in one. Hyperperfusion developed more frequently than hypoperfusion in the ‘predominantly affected hemisphere,’ whereas only hypoperfusion developed in the ‘non-predominantly affected hemisphere.’ All changes were fully reversible. The authors identified a novel heterozygous p.H916L mutation in the ATP1A2 gene in all three individuals.

Conclusions Although the perfusion state could be different depending on the time course of migraine or the timing of scans in relation to cortical spreading depression, prolonged aura symptoms in this family were frequently associated with hyperperfusion and middle cerebral artery vasodilation. Hyperperfusion tended to occur in the ‘predominantly affected hemisphere,’ but the mechanism of HMPA awaits further investigations on additional cases of FHM2.

  • Familial hemiplegic migraine
  • prolonged aura
  • cerebrovascular Circulation
  • spect
  • ATP1A2 gene
  • headache
  • mitochondrial disorders
  • migraine

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  • Funding This study was supported in part by a grant from Research on Psychiatric and Neurological Diseases and Mental Health (H20-KOKORO-020).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval for this genetic study was provided by the institutional review board in both Kitasato University and the University of Tokyo.

  • Provenance and peer review Not commissioned; externally peer reviewed.