Familial Hemiplegic Migraine (FHM).

Timothy C. Hain, MD • Page last modified: August 22, 2021

Timothy C. Hain, MD • Page last modified: August 22, 2021

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).

Nonfamilial groups.

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. Most of the time, MRI is normal, but some of these patients have strokes. 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).

Not everyone with hemiplegia and headache and a normal MRI has hemiplegic migraine. We have encountered a patient with severe hemiplegic spells accompanied by headache, where the cause was a pannus of tissue intermittently compression the basilar artery. This patient had Ehlers Danlos as well. She responded remarkably to a "hard cervical collar".

Treatment of hemiplegic migraine (HM).

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.

As mentioned above, not all patients with focal neurologic symptoms, headaches and normal MRI's have migraine. One of our own patients stopped having hemiplegic spells after being given a hard cervical collar.

One would think that given that the mechanism may be glutamate excitotoxicity (Moscowitz et al, 2004), memantine would be another candidate drug.