-A migraine is a moderate to severe headache (one that causes limitation in activity/need to rest), that is focal (one part of the head), usually throbbing, worse with movement, and has light/sound sensitivity or nausea/vomiting. It typically lasts 2 to 72 hours.

-A migraine with aura is a migraine preceded by a temporary neurological symptom like a change in vision (blind spot/cutting out of part of the vision), numbness or tingling of an arm/face/leg, difficulty with speech (knowing what you want to say but not being able to say words correctly/not understanding words). The aura can last for minutes to an hour. Often, the aura symptoms will follow one after the other (vision then sensation change then speech change). Headaches follow the aura.

-A hemiplegic migraine is a migraine with aura where the aura includes weakness of the face, arm, and/or leg. A distinguishing feature of a hemiplegic migraine is one-sided weakness or paralysis. It may also include other aura symptoms (change in vision, sensation, and/or speech). Those with severe CACNA1A variants may not be able to verbalize changes in vision, sensations or speech to their caregivers. However, unlike other aura symptoms, it can last much longer. Typically, the motor symptoms resolve in under 72 hours, but there are reports of it lasting weeks before returning to normal.

There are 2 types of hemiplegic migraine: sporadic and familial. Familial hemiplegic migraine occurs from a genetic change that can be passed down through families. It can also be identified without a family history. There are 3 types of familial hemiplegic migraine that have been linked to different genetic mutations, CACNA1A mutations cause FHM type 1. An identified gene mutation only occurs in about 7-14% of patients with hemiplegic migraine. Sporadic hemiplegic migraine is when there is no identified gene mutation found.

Hemiplegic migraine is triggered by the start of an electrical phenomenon called cortical spreading depression. Cortical spreading depression is a wave that spreads across the surface of the brain that first activates and then briefly inactivates the nerve cells and then leads to an inflammatory response. When the brain is activated you can have “positive” symptoms like seeing extra things like sparkles/waves, or feeling a tingling. When it deactivates the brain, you can have “negative” symptoms like a blind spot or numbness. When the wave hits the part of the brain that controls movement it deactivates those nerve cells so it is hard to move. A few years ago, it was believed indeed that positive aura features might be indicative of the neuronal excitation during cortical spreading depression, whereas negative features might be caused by the prolonged neuronal depolarization after cortical spreading depression. New data on migraine aura, and data coming from stereo-EEG recordings in patients with epilepsy indicate that the positive and negative symptoms of aura may be caused not only by the features of cortical waves, but also the functional anatomy of the cortical region through which this wave is traveling. (Charles, Curr Opin Neurol 2015, 28:255–260)

Usually the first hemiplegic attack occurs during adolescence, although it can start earlier. Overall prevalence of hemiplegic migraine in the general population is 0.01%. The prevalence of hemiplegic migraine in those with CACNA1A mutation is not known. Attacks can occur with variable frequency, more commonly in females than males, and typically improve with age. Typical triggers for attacks include emotional or physical stress, viral infections as well as other migraine triggers like lack of sleep, menstrual period. In CACNA1A it has also been noted that minor head trauma can also be a trigger for an attack.

Generally, with the first attack of hemiplegic migraine doctors recommend going to the ER. Similar symptoms can be seen in other conditions like stroke, seizure, infection, and brain tumors, and it is important to make sure these conditions are evaluated for.

Once a diagnosis of hemiplegic migraine is made and appropriate testing completed, repeated ER trips are not needed and attacks can be managed at home. Of course, if there is something unusual about the attack that is different from previous attacks e.g. no associated headache, decreased level of consciousness, fever, seizure-like symptoms, or if the symptoms are severe and cannot be managed at home you may need to go to the ER. There are also certain variants of CACNA1A that can lead to more severe presentations, mentioned in section 2, that should always go to the ER.

Head imaging should be obtained. Depending on how quickly certain tests are available, you may have a CT scan or an MRI scan. MRI is the preferred test, but it is not always immediately available so in order to ensure timely identification of stroke, CT may be performed first. A MRI, the more detailed study, is recommended after having a CT, even if the CT is normal. In addition, a blood vessel study like a MR angiogram (preferred) or CT angiogram should be done.In addition to imaging, bloodwork will check the basic functioning of the different organs. If there is concern for infection-fever, elevation in white blood cell count/inflammatory markers in the blood, change in level of consciousness, neck pain a spinal tap may be performed. Lastly, an EEG, to look for signs of seizure may be ordered.All of this testing does not need to be completed every time someone has a hemiplegic attack. If there is known history of hemiplegic migraine, especially with a known genetic mutation, typically no testing need be repeated with every attack. Specifically, repeated CT scans are to be avoided if possible given the cumulative radiation exposure. It is helpful to have a letter from your treating physician to help document the diagnosis and avoid unnecessary repeat testing. 

Hemiplegic migraine is a rare condition and so there are no good research studies of what treatments are helpful to treat attacks. The only information we have is from small studies of a few patients. Many ER physicians may not be familiar with or have treated hemiplegic migraine before. If you have had previously had success with certain medications, it may be helpful to have this documented in a letter from your neurologist to help guide treatment in the ER. It is common, and reasonable, to start with standard ER migraine treatments including a non-steroid anti-inflammatory like ketorolac, a nausea medicine and anti-migraine drug like metoclopramide or prochlorperazine, and IV hydration. These medications can help with the migraine pain. The aura (weakness) can be much harder to treat, even though for many this can be more bothersome than the headache itself. Medications that have shown some possible success include intranasal ketamine, intravenous furosemide, magnesium, and verapamil. Treatments like IV steroids and acetazolamide have also been used.

In some patients with CACNA1A mutations there is a condition that has been labeled as hemiplegic migraine but can be progressive and severe, resulting in uncontrolled seizures, and/or potentially life-threatening brain swelling. It appears these are linked with certain variants in the CACNA1A gene including: p.S218L, p.R1349Q, or p.V1396M. In these patients an attack can often be triggered by a minor head trauma (such as a small fall), illness, or even without an identified trigger. Typically, within an hour of the injury a child might develop a headache or vomiting and may develop a fever. Seizures and alteration in consciousness can occur and the weakness on one side of the body becomes evident after seizures are controlled. This weakness can last for days, weeks or even months, often with speech disturbances. These patients may also have symptoms in between attacks including delayed development, balance difficulty, and abnormal eye movements (nystagmus or paroxymal tonic upgaze).

Similar to more traditional hemiplegic migraine, the dysfunction of the calcium channels leads to cortical spreading depression. This can lead to temporary changes in perception including other aura symptoms like visual changes, sensory changes, speech changes, and weakness. It also can trigger a headache. However, in addition to this dysfunction, some patients can also experience changes in the blood vessels of the brain causing narrowing and reducing blood flow to certain regions of the brain as well as swelling that can lead to the longer lasting weakness as well as change in level of awareness along with seizures.

These types of attacks often start in early childhood including as young as the first year of life.

These types of HM are medical emergencies! In a child with history of these types of attacks, it is recommended to go to the ER unless there is very rapid resolution of all symptoms with home treatment plan. It is recommended that observation be considered at least overnight in the hospital because even prior history of mild attacks cannot fully predict severity of current attack. These parameters should be advised by the treating physician.

Initial attacks will need full evaluation including MRI of the brain, imaging of the blood vessels with MRI or CT, spinal tap, and bloodwork. EEG will also be considered upon admission to the hospital. For repeat attacks, if the patient is not returning to baseline, MRI or CT (if MRI is not available) should be considered to look for swelling even if prior scans have been normal. These investigations are also very important to search for a potential underlying cause that could have triggered the severe attack. Thus investigations are important 1) to search for the consequences of a severe attack (brain, swelling, epileptic activity on EEG) and 2) to search for a potential treatable cause of the severe attack (infection or other). Indeed, in patients with a CACNA1A variant causing hemiplegic migraine, any other acute brain disorder might trigger a severe hemiplegic migraine attack. A stroke can manifest as a severe hemiplegic migraine attack when the patient is ageing, or an infectious meningitis may trigger repeated attacks.

In those with seizures and change in level of awareness, or signs of swelling on imaging aggressive treatment is recommended with steroids (methylprednisolone), verapamil, and aggressive management of seizures. Acetazolamide and hypertonic saline can also be considered. In addition, migraine treatment drugs including pain medication like motrin, ketorolac and metoclopramide can be utilized. A pain medication like Motrin should also be given, especially for non-verbal patients who may be unable to express their pain. Once the patient is discharged from the intensive care unit, recovery can be improved by physiotherapy and speech therapy.

For emergency dosing information, please see the Clinician Quick Guide.