42 Hemiplegic Migraine
42.1 Case Description
42.1.1 Clinical Presentation
A 36-year-old male patient presented with 3-hour history of neurological deficit. Initial presenting symptoms were diplopia and dizziness, followed by nausea and left hemiparesthesia, with progression of symptoms to include left-sided weakness. Subsequently, during the course of his assessment in the emergency department, a right-sided headache developed with pain behind the right eye. An examination revealed normal vital signs, left facial droop, inability to visually track toward the left, left visual and sensory neglect, impaired proprioception in the left arm, and reduced power in the left upper and lower extremity. On questioning, a past medical history of migraine with aura was revealed. Otherwise there were no relevant comorbidities and cardiovascular risk factors, and family history was noncontributory.
42.1.2 Imaging Workup and Investigations
Noncontrast computed tomography (NCCT) of brain was normal, with no evidence of infarction, hyperdense vessel sign, or hemorrhage (Fig. 42.1). No intracranial proximal large artery occlusion was seen on computed tomography angiography (CTA). Note was, however, made of generalized paucity of distal middle cerebral artery (MCA) branches over the right hemisphere compared to the contralateral left side (Fig. 42.1). Computed tomography perfusion (CTP; Fig. 42.2) demonstrated prolonged time to peak (TTP) within the right cerebral hemisphere compared to the left, indicating delayed flow and hypoperfusion of the right hemisphere; relative cerebral blood volume was preserved.
Magnetic resonance imaging (MRI) was performed to further investigate (Fig. 42.3). No abnormality was seen on T2 fluid-attenuated inversion recovery (FLAIR), or diffusion-weighted imaging (DWI). Contrast-enhanced MR angiography of the extracranial arterial system was normal, with no evidence of proximal disease or stenosis of the right common or internal carotid artery (ICA). MR venogram was also normal.
Sporadic hemiplegic migraine (SHM).
Aspirin 325 mg was administered orally at the time of initial presentation when etiology was unclear. Supportive management was instigated with intravenous fluids (500 mL normal saline), intravenous antiemetic for nausea (10 mg metoclopramide), and simple analgesia (500 mg acetaminophen). The patient’s symptoms gradually improved. He was discharged from hospital 10 hours following initial onset of symptoms, at which time the left weakness and sensory disturbance were fully resolved, with residual mild headache and nausea remaining. Follow-up CTP study performed 2 days later showed reversal of previously noted prolonged right hemispheric TTP with no residual perfusion defect remaining (Fig. 42.4).
Hemiplegic migraine is a rare form of migraine with aura, where aura includes motor weakness. 1 Typical hemiplegic migraine starts in the first or second decade of life. Patients who have an affected first- or second-degree relative are diagnosed as having familial hemiplegic migraine (FHM), whereas patients without an affected relative are considered to have SHM. FHM has an autosomal dominant mode of inheritance. Genetic studies have shown mutations in genes that encode proteins involved in ion transportation, with three genetic subtypes identified: in FHM 1, the mutation is in the CACNA1A gene on chromosome 19 which encodes for calcium channels; in FHM 2, the mutation is in the ATP1A2 gene on chromosome 1 which encodes for a subunit of the sodium–potassium ATPase pump; in FHM 3, the mutation is in the SCN1A gene on chromosome 2 which encodes for a sodium channel. Sporadic cases can be caused by a de novo mutation in a gene that causes the familial form or by inheritance of a gene mutation from an asymptomatic parent. 2 However, at least a quarter of familial and most sporadic cases do not have a mutation in these three genes, suggesting there are other involved genes still to be identified.
Migraine aura pathophysiology is most probably that of cortical spreading depression, where a brief neuronal excitation initiates a depolarization wave that moves across the cortex and is followed by prolonged inhibition of neuronal activity. Dysfunction of the ion transporters coded by the gene mutations in FHM not only results in abnormal glutamate metabolism and neuronal hyperexcitability, but also reduces the threshold for cortical spreading depression. 2
42.2.2 Workup and Diagnosis
Diagnosis of hemiplegic migraine relies on meticulous description of the aura as well as the exclusion of symptomatic causes. The International Classification of Headache Disorders, 3rd edition (ICHD-3) lists the following diagnostic criteria for hemiplegic migraine. There must be at least two attacks which fulfill both of the following criteria: First is an aura which consists of a fully reversible motor weakness as well as fully reversible visual, sensory, and/or speech/language symptoms. Second, there must be at least two of the following four characteristics: (1) at least one aura symptom spreads gradually over 5 minutes or more and/or two or more symptoms that occur in succession; (2) each individual nonmotor aura symptom lasts 5 to 60 minutes and motor symptoms last less than 72 hours; (3) at least one aura symptom is unilateral; and (4) the aura is accompanied or followed within 60 minutes by a headache. Finally, the symptoms should not be better accounted for by another ICHD-3 diagnosis and transient ischemic attack and stroke should have been excluded.
As seen from the diagnostic criteria, motor weakness is always associated with at least one other aura symptom, the most frequent being sensory symptoms (98%), followed by visual aura (89–90%), aphasia (72–81%), and brainstem aura (69–72%). 2 , 3 , 4