title: New insights into migraine pathophysiology.
abstract: OBJECTIVE
  This article will review new and exciting developments in migraine research, with particular emphasis on mutations associated with familial hemiplegic migraine and the role of cortical spreading depression in its pathophysiology and treatment.
  
  
  RESULTS
  The recent discovery of multiple point mutations in familial hemiplegic migraine has led to the suggestion that migraine and its variants may be due to a paroxysmal disturbance in ion-translocating mechanisms. Mutations associated with familial hemiplegic migraine render the brain more susceptible to prolonged cortical spreading depression caused by either excessive synaptic glutamate release or decreased removal of glutamate and potassium from the synaptic cleft, or persistent sodium influx. Suppression of cortical spreading depression has become an interesting target for preventive migraine treatment. Prolonged treatment with beta-blockers, valproate, topiramate, methysergide or amitriptyline reduced the number of potassium-evoked cortical spreading depressions and elevated the electrical stimulation threshold for the induction of cortical spreading depression in rats. Recent imaging studies in patients suffering from migraine without aura also point to the presence of silent cortical spreading depression as an underlying mechanism. Repeated waves of cortical spreading depression may have deleterious effects on brain function, and perhaps cause silent ischaemic lesions in vulnerable brain regions such as the cerebellum in susceptible individuals.
  
  
  CONCLUSIONS
  This review emphasizes several neurobiological aspects of migraine that reveal paroxysmal disturbances in neuronal and vascular function, that in turn reflect disturbances in the maintenance of ionic gradients.
authors.affiliation: Department of Neurology, Hospital Ruber Internacional, Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Sanchez-Del-Rio
authors.forename: Uwe
authors.initials: U
authors.lastname: Reuter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
mesh_terms: D000818:Animals; D013181:Cortical Spreading Depression / Q000502:physiology; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D017354:Point Mutation; D011110:Polymorphism, Genetic