Hemiplegic Migraine - Genetic Testing May Be Helpful

Patient Expert

Hemiplegic Migraine (HM) is a rare subtype of Migraine with aura (MWA) that is often misunderstood and misdiagnosed. There are two variations of HM:

  1. Familial Hemiplegic Migraine (FHM) runs in families.
  2. Sporadic Hemiplegic Migraine (SHM) often has Migraine in the family history, but not HM.

The symptom that differentiates HM from other types of Migraine is hemiparesis, which is temporary, one-sided paralysis or motor weakness. Otherwise, HM symptoms are the same as those of Migraine with aura. Most Migraineurs who have HM also have Migraine with or without aura.

Findings of a study performed in the Netherlands suggest that genetic testing could be helpful in properly diagnosing and appropriately treating hemiplegic Migraine.

"Since many people with this type of Migraine are initially misdiagnosed and not given the proper treatment, understanding the genetic basis of this type of Migraine may help clinicians in diagnosing and treating the problem. Most patients are initially diagnosed with epilepsy, stroke or other disorders and are treated accordingly with non-effective medications that are associated with a high risk of side effects rather than with effective agents to treat Migraine... Our findings reinforce the growing evidence that familial and sporadic hemiplegic Migraine along with normal Migraine have some shared gene pathways. Unraveling these pathways may help to identify new treatment options"

study author Michel D. Ferrari, MD, PhD, Leiden University Medical Centre, the Netherlands

To date, three genes for FHM have been identified - the CACNA1A gene (FHM1), the ATP1A2 gene (FHM2), and the SCN1A gene (FHM3). Even though FHM and SHM are clinically identical, it's still not known whether and to what extent SHM and FHM are pathophysiologically related. It's also still unknown whether and to what extent FHM genes are also involved in SHM. Previous studies have identified mutations in the FHM1 gene in SHM patients.

The authors of the study state:

"Investigating the involvement of FHM genes in sporadic patients with hemiplegic migraine is important because it may further the insight into the pathophysiology of SHM and the relationship with other types of migraine. Moreover, understanding and establishing the genetic basis of SHM may help clinicians in diagnostic and therapeutic decision making. Many patients are initially misdiagnosed and mistreated. We therefore set out to search systematically for mutations in the known FHM genes in a large set of 39 clinically well-characterized patients with "pure" SHM, who had no interictal (between Migraine attacks) neurologic symptoms."

Study methods: Thirty-nine patients with SHM as defined by the criteria of the International Headache Society (IHS), without associated neurologic features, were scanned for mutations in the three FHM genes. Available family members were interviewed and diagnosed according to IHS criteria.

Study results:

  • Some study participants exhibited basilar-type Migraine symptoms during attacks
  • All were free of interictal (between attacks) signs or symptoms.
  • Age at which hemiplegic attacks began ranged from 4 to 42 years of age.
  • The number of attacks ranged from 2 per lifetime to more than 200 per year.
  • Duration of hemiparesis was variable, from several minutes to 1 week.
  • Four patients reported loss of consciousness during attacks
  • Two patients reported triggering of attacks by minor head trauma.
  • Migraine with aura (one-third), without aura (one-third), or both (one-third) were present in one or more first-degree relatives in approximately 70% of the families.

Sequence variants of the FHM genes were identified in seven SHM patients:

  • one CACNA1A (FHM1) mutation
  • five ATP1A2 (FHM2) mutations
  • one SCN1A (FHM3) polymorphism

Study conclusions: The authors state:

"We show that FHM genes are involved in at least a proportion of SHM patients without associated neurologic symptoms. Screening of ATP1A2 offers the highest likelihood of success. Because FHM gene mutations were also found in family members with "nonhemiplegic" typical migraine with and without aura, our findings reinforce the hypothesis that FHM, SHM, and "normal" migraine are part of a disease spectrum with shared pathogenetic mechanisms."

Summary and Comments: Regarding this study, Migraine and headache specialist, Dr. Fred Sheftell, founder and director of the New England Center for Headache, commented,

"Michel Ferrari and his group in the Netherlands are amongst the foremost leaders in genetic research as pertains to migraine. All we have now to diagnose is the patient's "phenotype" which is the way the gene manifests not the "genotype" or the gene itself. While the International Classification of Headache Disorders provides us with diagnostic criteria for the recognition of headache disorders, most doctors are not familiar with them. Genetic testing such as this is just the beginning to aid in our ability to more accurately diagnose subtypes of migraine such as sporadic and hemiplegic migraine and eventually others as well."

Especially in light of research indicating that Migraine may be a progressive brain disease, proper diagnosis and appropriate treatment are essential to Migraineurs. Hemiplegic Migraine in particular is often misunderstood and misdiagnosed. Many physicians never encounter a single case in their careers. Identifying the common genes opens the doorway to genetic testing that can aid in diagnosis and, perhaps, to the development of more effective treatments.

For more information about hemiplegic Migraine, see Hemiplegic Migraine - the Basics.


B. de Vries, MSc; T. Freilinger, MD; K.R.J. Vanmolkot, MSc; J.B. Koenderink, PhD; A.H. Stam, MD; G.M. Terwindt, MD, PhD; E. Babini, PhD; E.H. van den Boogerd, BSc; J.J.M.W. van den Heuvel, BSc; R.R. Frants, PhD; J. Haan, MD, PhD; M. Pusch, PhD; A.M.J.M. van den Maagdenberg, PhD; M.D. Ferrari, MD, PhD; M. Dichgans, MD, PhD. "Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic migraine." Neurology® 2007;69:2170-2176.

Press Release. "Study Finds Genetic Testing May Help People with Severe Type of Migraine." St. Paul. American Academy of Neurology. December 3, 2007.

Interview with Dr. Fred Sheftell. December 3, 2007.