A 30-year-old woman was admitted to the hospital with suspicion of an acute stroke due to left-sided hemiplegia and right-sided headache. In the ambulance on the way to the hospital, the symptoms gradually disappeared. When asked about her symptoms, she told that she initially had visual disturbances in the form of right-sided flickering lights on the right side of her visual field, where after she gradually had lost all strength in the right side of her body. Fifteen minutes after onset of hemiplegia, the patient developed a severe headache in the left side of the frontal part of the head. The headache was reported as pulsating, the patient became increasingly nauseous and started vomiting, and she further developed hypersensitivity towards lights and sounds.

On arrival to the hospital, she reported that her vision and her strength in her right arm and leg had returned to normal. However, she still described a subtle tingling sensation in the right side of her body, in the right side of her face, and in the right side of her tongue. She still had severe, pulsating headache, photophobia, and phonophobia. She rated the headache 9 on a 0–10 visual analogue scale. The patient had no previous history of stroke or family history of stroke. She is otherwise healthy, does not smoke, rarely drinks alcohol, and exercises regularly.

Her father had previously suffered from the same type of attacks. She had experienced similar episodes before since she was 12 years old, but this was the most severe, which is why she called for an ambulance. Sometimes she would not have an attack for more than 6 months, but during the last 8 weeks, since she was fired from her job, she had attacks one to two times per week. Her GP had told her that she might suffer from migraine and had advised her to take sumatriptan as soon as possible when an attack started. She had tried this but did not feel that the medication worked. In between attacks she would have a mild, left-sided headache, which is why she had now started taking paracetamol and ibuprofen on a daily basis.

The most important differential diagnoses of hemiplegic migraine in the acute phase are stroke and transient ischemic attack (TIA). As is the case for hemiplegic migraine, the symptoms of TIA are fully reversible, and neuroimaging often reveals no abnormalities. A characteristic feature of migraine aura symptoms is the gradual spread of symptoms, usually over 5–20 min. In contrast, cerebrovascular ischemic events usually develop within seconds. Migraine aura often involves positive symptoms such as visual perception of flickering lights, colors, and shapes and sensory symptoms with paresthesia, which is rarely the case for vascular events.

It may be difficult to distinguish hemiplegic migraine from migraine with sensory aura, because patients often describe numbness, which may cause inability to grasp or lift objects, as loss of strength. Todd paralysis following an epileptic seizure may also mimic a hemiplegic migraine attack but is often associated with loss of consciousness and postictal confusion.

In some cases hemiplegic migraine patients present with fever and decreased level of consciousness, making differentiation from CNS infections difficult. A rare differential diagnosis is the syndrome of transient headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL). CSF lymphocytosis and often increased protein levels is characteristic of HaNDL but is sometimes seen in hemiplegic migraine as well. Unlike hemiplegic migraine, HaNDL resolves spontaneously within 3 months.

Between attacks, most patients with hemiplegic migraine have a normal neurological examination, while some patients with familiar hemiplegic migraine type 1 have gaze-evoked nystagmus, ataxia, or dysarthria. During attacks, motor and sensory symptoms most often affect the upper rather than the lower limbs. Cerebral MRI should be performed in every new case of hemiplegic migraine and in the case of changes of the patient’s usual symptoms, attack frequency, or attack severity. CT and MRI examinations rarely show abnormalities outside of attacks, but cerebellar atrophy has been described in familiar hemiplegic migraine type 1. Transient neuroimaging abnormalities have been reported in a few cases in the form of perfusion changes and contrast enhancement. Imaging in the ictal phase is rarely possible due to the unpredictable nature and relatively short duration of the attacks. However, detection of cerebral blood flow (CBF) changes could potentially be applied for diagnostic purposes in some cases. CBF is known to decrease during the aura phase. This hypoperfusion persists when the aura symptoms are gone and into the headache phase. After a few hours, hypoperfusion changes into marked hyperperfusion, persisting for more than 10 h from the point of attack. CBF measurements, e.g., using single-photon emission tomography (SPECT) following an attack and again in the interictal phase, could thus aid in verifying the diagnosis.

A thorough family history is important in order to distinguish familial from sporadic hemiplegic migraine. Genetic testing for mutations of the three genes that are known to cause familial hemiplegic migraine can be helpful in diagnosing the condition, but since hemiplegic migraine is a clinical diagnosis, it is not excluded by negative genetic test result.

On neurological examination the patient had normal vision and strength of the limbs, but she had a subtle decrease of sensibility in the right side of the face in first and second trigeminal branch areas on the right side. Her pericranial muscles were sore at the left side. She underwent an acute CT scan, which was normal.

Her sensory symptoms and headache gradually subsided within 6 h. In the emergency room she was treated with metoclopramide 20 mg, paracetamol 1 g, and diazepam 5 mg. The patient was recommended not to take sumatriptan in the event of future attacks. The use of triptans for hemiplegic migraine is controversial and generally discouraged because of a suspected risk of inducing ischemic events (see below).

The family history revealed that her father had experienced very similar episodes since an early age. The patient had four siblings on her father’s side. The youngest who was 12 years old was beginning to develop similar symptoms.

When discharged from the hospital, she received a diagnostic headache diary for prospective description of a subsequent attack. She was seen in the outpatient clinic 3 months later, having described a single attack of hemiplegic migraine with aura in the form of gradually developing visual and sensory symptoms with positive as well as negative features. She described expressive aphasia and gradually developing hemiplegia most pronounced in her arm, causing her to be unable to move the arm. The headache and associated symptoms had all the characteristic features of migraine.

A 30-year-old with a severe case of sequential visual disturbances, sensory disturbances, hemiplegia, and headache was admitted to the ER. Her symptoms subsided, and during neurological examination she had normal vision and strength and only subtle unilateral hypesthesia, and she had a normal cerebral CT. She still complained of severe unilateral headache with accompanying photophobia, phonophobia, and nausea. She had experienced similar episodes before and she had first-degree relatives with the same type of attacks. Based on the features of her headache and prodromes, familial history, examination, and neuroimaging, she was diagnosed with familial hemiplegic migraine.

According to “The International Classification of Headache Disorders, 3rd edition (beta version)” [Cephalalgia 2013; 33(9)629–808], hemiplegic is defined by the same clinical features as migraine with aura but including motor weakness. Motor weakness in fact characterizes most attacks, even though the term “hemiplegic” implies paralysis. The aura consists of gradually developing and fully reversible visual, sensory, or aphasic symptoms as well as decreased strength. These symptoms are usually unilateral.