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Complicated Migraines Alyssa E Complicated Migraines Alyssa E. Blumenfeld, MS,* M. Cristina Victorio, MD,† and Frank R. Berenson, MD‡ Migraines are a common paroxysmal disorder that may present with a multitude of neurologic symptoms. Migraines have been re-categorized in the most recent edition of the International Classification of Headache Disorders. In this article, we review the literature on hemiplegic migraines, alternating hemiplegia of childhood, migraine with brainstem aura, retinal migraine, ophthalmoplegic migraine, Alice in Wonderland syndrome, and acute confusional migraine. We also discuss the principal clinical features, diagnostic criteria, and treatment options for these disorders. Semin Pediatr Neurol 23:18-22 C 2016 Elsevier Inc. All rights reserved. Introduction Hemiplegic Migraine The International Classification of Headache Disorders ICHD 3β defines hemiplegic migraine as a form of (ICHD) is the progressively changing classification system migraine with aura that includes motor weakness. This of headache disorders, which physicians use to properly diagnosis is made when the aura consists of fully diagnose headache conditions. Complicated migraine, reversible motor weakness and visual, sensory, and now classified by ICHD third edition (beta version) speech or language symptoms.2 Hemiplegic migraine is (ICHD 3β) as migraine with aura, is an imprecise term classified as its own migraine sub form because patients used to define types of migraine, which present with with this condition present with differences in genetic and significant neurologic deficits that may persist beyond the pathophysiological mechanisms than those with migraine conclusion of the head pain.1 The International Headache with typical aura.2 In these cases, the migraine aura has a Society defines migraine with aura as recurrent attacks of “stroke-like” quality, which results in some degree of fully reversible, unilateral, and central nervous system hemiparesis and is often accompanied by disturbances in (CNS) symptoms, which in most cases are followed by a speech and communication.2,3 In most patients, the onset migrainous-type headache.2 These symptoms develop of attacks is in the teen years and early 20s, beginning gradually and may include visual, sensory, or motor with a hemiparesis or motor deficit that precedes the components of the CNS.2 Migraine aura is reported in headache and may persist throughout the duration of the approximately 14%-30% of children and adolescents and episode.1 These neurologic disturbances may occasionally is causally attributed to and often distinguished by persist for days or weeks after the conclusion of the cortical spreading depression of Leão.1,2 In this article, headache phase. we will analyze the cardinal features of complicated migraines and commonly recognized headache variants including hemiplegic migraine, alternating hemiplegia of Familial Hemiplegic Migraine childhood, migraine with brainstem aura, retinal Familial hemiplegic migraine (FHM) is an autosomal dom- migraine, ophthalmoplegic migraine, Alice in Wonder- inant form of migraine in which at least 1 of the patient’s land syndrome (AWS), and acute confusional migraine first-degree or second-degree relatives has migraine aura (ACM). with motor weakness.2 ICHD 3β now designates 3 different genetically defined subtypes, which account for 50%-70% of published FHM families.4 FHM type 1 (FHM1) is due to a mutation of the CACNA1A gene in the chromosome 19p32 region and n From the Medical College of Georgia, Augusta University, Augusta, GA. accounts for approximately 50% of all FHM cases.2 This † ’ Division of Pediatric Neurology, Akron Children s Hospital, Akron, OH. missense mutation creates defective neuronal-gated calcium ‡Atlanta Headache Specialists, Atlanta, GA. channels, leading to the belief that this form of FHM Address reprint requests to Frank Berenson, MD, Atlanta Headache 3 Specialists, 5887 Glenridge Dr, Suite 140, Atlanta, GA 30328. E-mail: represents a channelopathy. Studies have shown that [email protected] this mutation causes calcium-channel opening at a more 18 1071-9091/16/$-see front matter & 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2016.01.007 Complicated migraines 19 negative membrane potential, lowering the channel activa- Environmental stress such as temperature extremes and tion threshold, and delaying its inactivation, therefore, odors, water exposure, physical activity, lighting and food creating cortical and subcortical hyper excitability.4 Patients may be triggering factors, and neurologic deficits can with FHM1 have a 90% chance of experiencing the trade- improve or resolve with sleep.9-11 In a study conducted mark loss of motor function during an attack.4 by Sweney et al,9 50% of the patients with AHC examined FHM type 2 (FHM2) is secondary to a mutation on the reported a family history of headache. Recent genetic studies ATP1A2 gene in the chromosome 1q23 region, which codes have identified ATP1A3 mutation as a major genetic cause of for a Na/K-ATPase. FHM type 3 (FHM3) presents with a AHC.9 sodium channel defect secondary to mutation on the SCN1A AHC is strongly associated with epilepsy. About 41% of gene. FHM2 and FHM3 are often associated with recurrent patients report distinctive convulsive episodes perceived to seizures and are much less common than FHM1.2 be epileptic in nature.9 Patients have cognitive impairment, A distinct diagnosis of sporadic hemiplegic migraine although progressive cognitive decline is not universally exists, which is clinically the same as FHM, but lacks a found.9,12,13 Diagnostic evaluation of AHC should include family history. Sporadic hemiplegic migraine cases often metabolic screening to exclude mitochondrial disorders, require neuroimaging, lumbar puncture, and additional tests neuroimaging to rule out stroke and vasculopathy, and to rule out other potential causes.1 cerebrospinal fluid analysis for neurotransmitters, pterin metabolites, and methyltetrahydrofolate to exclude dopa- mine biosynthesis disorders. EEG may be needed to Diagnosis and Treatment diagnose epilepsy.9 Initially, it is difficult to make a diagnosis of hemiplegic AHC attacks are treated supportively by removing inciting migraine because of its multiple similarities with CNS triggers and facilitating sleep early on.10 Flunarizine is lesions resulting from vascular anomalies, demyelinating considered the mainstay of prophylactic treatment, and disease, neoplasm, occlusive cerebral vascular disease, etc.1 benzodiazepines are thought to improve attacks.9,10 In some cases, neuroimaging (magnetic resonance imaging [MRI] and magnetic resonance angiography) and electro- encephalogram (EEG) may be necessary. Migraine With Brainstem Aura Treatment of hemiplegic migraine is complicated and Basilar migraine, Bickerstaff migraine, and basilar artery highly debated. Nonsteroidal anti-inflammatory drugs are migraine, is now referred to as migraine with brainstem considered the mainstay in abortive treatment because of aura. According to the ICHD 3β, aura symptoms for this their proven efficacy and tolerability.5 Although there is a disorder are specifically referable to the brainstem and are black box warning, scientific data suggest that Triptans are a not ischemic in etiology. This disorder is characterized by safe and effective treatment for patients suffering from fully reversible speech or language, sensory or visual auras hemiplegic migraine.6 Calcium-channel blockers, such as that are not accompanied by retinal or motor symptoms Verapamil, have also proven to be effective as preventative and, by definition, spread over 5 or more minutes, last from and abortive treatment.7,8 Other treatments that may be 5-60 minutes, and may be followed by a headache within 1 effective but have not been verified include acetazolamide in hour. In addition, there must be at least 2 of the following patients with cerebellar ataxia and intranasal ketamine, “brainstem” features present: dysarthria, vertigo, tinnitus, which has been shown to reduce the duration and intensity hypoacusis, diplopia, ataxia, and decreased level of of attacks in some patients.8 Ergotamines can also be used as consciousness.2 monotherapy though the efficacy and tolerability data are This disorder typically involves both the left and right inconsistent.5 visual fields and may begin with unilateral or bilateral visual symptoms.14,15 Visual symptoms are typically followed by bilateral paresthesias of arms and legs and are frequently Alternating Hemiplegia of Childhood associated with a combination of the aforementioned Alternating hemiplegia of childhood (AHC) is a rare, “brainstem” symptoms. The most common clinical mani- sporadic neurodevelopmental syndrome with an incidence festations include vertigo (73%), nausea and vomiting of 1 in 1,000,000 children.9 ICHD 3β classifies AHC as an (30%-50%), ataxia (43%-50%), and visual field deficits episodic syndrome that may be associated with migraine. (43%).15-19 In a small number of patients, consciousness This disorder is characterized by recurrent bouts of inter- may be impaired, ranging from drowsiness to confusion, mittent, often migratory, alternating hemiplegic episodes amnesia, and coma.20-23 Both focal and generalized seizures associated with other neurological features such as dystonia, have been reported, especially in the pediatric population.24 choreoathetosis, and developmental delay.9,10 The onset of Migraine with brainstem aura typically presents in adoles- hemi- or quadric-plegic or dystonic episodes
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