Familial Hemiplegic Migraine

Familial hemiplegic migraine (FHM) is a form of hemiplegic migraine (HM) that is unique because it is the only migraine type that has been scientifically confirmed to be genetically inherited. In fact, the most recent version of the International Headache Society’s guidelines, The International Classification of Headache Disorders, 3rd Edition (ICHD-III), has updated and expanded its description of FHM based on new genetic data and research.1

The ICHD-III classifies HM as a type of migraine with aura (the other types being migraine with typical aura, migraine with brainstem aura, and retinal migraine). Researchers have identified two different types of HM, which share the same set of symptoms but are classified differently according to whether or not the patient has a close relative who also has HM. Familial hemiplegic migraine is the form of HM in which this family link can be established, whereas HM that occurs without evidence of this genetic connection is called sporadic hemiplegic migraine.

FHM is a very rare condition: it is estimated to occur in only about 0.01% of the population. According to a 2002 study of FHM in Denmark with 147 participants from 44 affected families, women were more than twice as likely to have FHM than men. People usually experience their first FHM attack at an average age of 17 years and the frequency of attacks tends to decrease as they get older, with few occurrences reported after the age of 50.2,3

Symptoms of familial hemiplegic migraine

While patients with FHM generally report having symptoms consistent with other types of migraine with aura, FHM attacks always include what are known as “motor aura” in addition to those other types of symptoms. These motor aura usually consist of muscle weakness on one side of the body that typically starts in the hand or foot and moves gradually up through the arm or leg. The severity of the weakness can range from what patients describe as “mild clumsiness” up to (very rarely) full paralysis on one side of the body.4 Though motor aura can last for days or even for weeks in some patients, it always fully reversible, which means that it will eventually disappear completely.

Almost all patients report that their FHM attacks usually include so-called “typical aura” – visual, sensory, or speech/language symptoms. Many patients experience all three kinds of typical aura, in addition to motor aura, during a single FHM attack. Visual aura, the most frequently reported type, are temporary disturbances to the field of vision that can include blind or bright spots spreading outward from a central point, crescents or C-shapes with shimmering edges, blurred vision, moving zigzag lines or shapes, seeing spots or stars, or flashing/flickering light. Sensory aura are often described as a pins-and-needles sensation that spreads over one side of the body. Speech/language symptoms can include trouble with word recall, language comprehension, and writing. In the 2002 Danish study, visual and sensory aura were both reported by more than 90% of FHM patients, with speech/language aura reported by more than 70%. The same study also discovered that 68% of participants also experienced brainstem symptoms (eg, vertigo, slurred speech, ringing in the ears, double vision, etc) during all of their FHM attacks.Aura symptoms were either accompanied by or followed by headache during all FHM attacks for almost every patient (99%).2 In rare cases, FHM symptoms can also include confusion, fever, increase in white blood cells in the cerebrospinal fluid, and even loss of consciousness or coma.1

Diagnosing familial hemiplegic migraine

The presence of motor aura is one key requirement for FHM diagnosis, because they do not occur with any other type of migraine. The ICHD-III’s guidelines for diagnosing FHM state that the patient must have experienced at least two migraine attacks with motor aura plus at least one typical aura symptom.

In addition, the two attacks must satisfy at least two of conditions:

  • One or more aura symptom spreads gradually over at least five minutes, and/or two or more symptoms occur one after the other.
  • Each non-motor symptom lasts between 5-60 minutes; motor symptoms last less than 72 hours.
  • At least one aura symptom is limited to one side of the body.
  • Aura is accompanied by headache, or headache follows within an hour.

Finally, a characteristic that distinguishes FHM from sporadic hemiplegic migraine is that the patient has a close family member with hemiplegic migraine – other types of migraine do not count for this diagnosis. This family member must be either a first-degree relative (parent, sibling, or child) or second-degree relative (uncle, aunt, nephew, niece, grandparent, grandchild, or half-sibling).

Types of familial hemiplegic migraine

Advances in the field of genetics have allowed researchers to pinpoint mutations in three specific genes that cause FHM. Genetic testing can show whether a person diagnosed with FHM is a carrier of one of these gene mutations. As a result, the ICHD-III now classifies four different types of FHM. The first three types are determined by which of the three genes runs in the patient’s family:

  • FHM1: mutation in CACNA1A gene
  • FHM2: mutation in ATP1A2 gene
  • FHM3: mutation in SCN1A gene

The fourth type, FHM4, is diagnosed if genetic testing does not reveal a mutation in any of the genes that are known to be linked to FHM, but the patient has a close family member with HM. It is likely that researchers will someday identify other gene mutations that cause FHM in these families.

How is familial hemiplegic migraine inherited?

The condition is passed on when a person inherits the mutated gene responsible for causing FHM from one of their parents. But inheriting this gene mutation does not necessarily guarantee that you will ever have an FHM attack during your lifetime. This also means that you can pass on an FHM-related gene to your own child without ever knowing that you carry it, but that child may later experience FHM attacks.5

Even though three gene mutations that cause FHM have been identified, researchers do not believe that those genes are also involved in causing non-hemiplegic types of migraines. Finding new gene mutations that are linked to the inheritance of non-hemiplegic migraines within families is an important avenue for future study, because up to 50% of migraineurs have first-degree relatives who also have migraine.6

Causes and treatment

Many of the potential triggers for FHM attacks are similar to other types of migraine with aura, such as stress, bright lights, physical exertion, disturbed sleep patterns, and certain foods and drinks. It is also possible for FHM attacks to be triggered by mild head trauma (reported by 9% of participants in one study2), so FHM patients are often advised not to take part in contact sports.3

FHM aura can resemble the symptoms of serious conditions like epilepsy or transient ischemic attack (a brief blockage of blood flow in part of the brain that often occurs before major stroke). Therefore it is important for clinicians to make sure that the symptoms are migraine-related, especially for patients who have not yet been diagnosed with FHM. Cerebrospinal fluid analysis, MRI, or EEG may be used to help with the diagnosis.

During the acute headache phase of an FHM attack, NSAIDs and other pain relievers are usually recommended. Triptans are an option when analgesics do an insufficient job of relieving headache pain, though using them to treat hemiplegic migraine is somewhat controversial. For people who experience more than two FHM attacks per month, preventative treatment with flunarizine, sodium valproate, lamotrigine, verapamil, or acetazolamide can be effective.3

Written by Anna Nicholson | Last reviewed: November 2014.
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