Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation.
OBJECTIVE
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.
Department of Neurology, Kitasato University, School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. takahiro@med.kitasato-u.ac.jp
Takahiro
T
Iizuka
Yuji
Y
Takahashi
Mayumi
M
Sato
Junko
J
Yonekura
Saori
S
Miyakawa
Motoi
M
Endo
Junichi
J
Hamada
Shinichi
S
Kan
Hideki
H
Mochizuki
Yoshio
Y
Momose
Shoji
S
Tsuji
Fumihiko
F
Sakai
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001345:Autoradiography; D002560:Cerebrovascular Circulation / Q000235:genetics* / Q000502:physiology*; D004252:DNA Mutational Analysis; D056324:Diffusion Tensor Imaging; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D020768:Middle Cerebral Artery / Q000473:pathology; D020325:Migraine with Aura / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation; D010375:Pedigree; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon
D000893:Anti-Inflammatory Agents; C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D011241:Prednisone; D008775:Methylprednisolone