Timothy C. Hain, MD Page last modified: December 18, 2016
Timothy C. Hain, MD Page last modified: December 18, 2016 See also -- many pages on migraine on this site
FHM is an autosomal dominant condition characterized by migraine, hemiparesis, and in some families, progressive cerebellar atrophy. FHM1 is associated with a mutation in the a-1a subunit gene for calcium channels (CACN1A). Four different missense mutations have been identified. Two other genes (AT-P1A2 and SCN1A) have also been associated with hemiplegic migraine, a potential gene (PRRT2). There are undoubtedly more. There are both familial and sporadic hemiplegic migraines, termed "FHM#", and "HM".
Mutations in this subunit of CACN1A have also been identified in one of the episodic ataxias, and in one of the spinocerebellar atrophies (SCA-6).
FHM2 is associated with a mutation in the ATPase gene. It has recently been suggested that both of these mutations render the brain more susceptible to glutamate release (Moskowitz et al, 2004).
FHM1 and FHM2 are characterized by enhanced susceptibility and sustained attacks of visual, somatosensory and aphasic auras as well as by prolonged motor weakness or paralysis. Photophobia, phonophobia, nausea and vomiting are also common symptoms. Motor weakness is uncommon in classic migraine (migraine with aura).
There are also sporadic hemiplegic migraine patients -- presumably without the same underlying genetic abnormality. These are remarkable patients who develop recurrent paralysis on one side of the body, generally in combination with severe headaches. All of the patients that we have seen to date are women. Typically these patients are disabled. Depression is common as well (Louter et al, 2016).
Although little has been published about this, we think that some patients with HM respond to carbonic anhydrase inhibitors (examples: acetazolamide, topiramate -- see references below), and also that some respond to verapamil (Yu et al, 2003). While valproate and lamotrigine are reportedly effective, so far we have not been impressed. We also think that haloperidol drops are sometimes very useful in aborting attacks. We are reluctant to use triptans in hemiplegic migraine, although evidence that they are dangerous (see below) is not present. All of these medications of course have their risks.
One would think that given that the mechanism may be glutamate excitotoxicity (Moscowitz et al, 2004), memantine would be another candidate drug.