A Retrospective Analysis of Triptan and DHE Use for Basilar and Hemiplegic Migraine

Paul G. Mathew, MD, FAHS; Regina Krel, MD; Bhuvin Buddhdev, MD; Hossein Ansari, MD; Shivang G. Joshi, MD, MPH, RPh; Warren D. Spinner, DO; Brad C. Klein, MD, MBA

Disclosures

Headache. 2016;56(5):841-848. 

In This Article

Abstract and Introduction

Abstract

Background. Patients with basilar migraine (BM) and hemiplegic migraine (HM) have been excluded from triptan and DHE clinical trials due to a potential risk of ischemic vascular events, and the FDA mandates that package labeling state that they are contraindicated in BM and HM. The objective of this study was to demonstrate that triptans and DHE can be used for the abortive treatment of BM and HM without significant adverse ischemic vascular events.

Methods. A retrospective chart review of patients with BM features or HM who received acute abortive treatment with either triptans or DHE was conducted at 4 headache centers to assess the frequency of ischemic vascular events after administration. The diagnoses of BM or HM were made by headache specialists based on The International Classification of Headache Disorders, 2nd edition (ICHD-II). Searchable terms included BM, vertigo, dysarthria, diplopia, hemiplegia/hemiparesis, facial droop, weakness, confusion, altered consciousness, confusion, ataxia, and aphasia, as well as all triptans or DHE.

Results. The study included 67 patients with BM features and 13 patients with HM. Among those receiving triptans, 40 were in the BM group and 5 were in the HM group. Among those receiving DHE, 27 were included in the BM group and 8 were in the HM group. No side effects of stroke or myocardial infarction were reported. In the triptan group, 5 patients reported adverse effects that included GI upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, 5 patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation.

Conclusion. In this retrospective study, triptans and DHE were used with no reported, subsequent acute/subacute ischemic vascular events for the abortive treatment of migraines with basilar and hemiplegic-type features. Although the small sample sizes generated theoretical statistical event rates of 4.5% for BM and 23% for HM, there has been no clear evidence that BM and HM carry an actual elevated risk for vascular events compared with migraine with aura.

Introduction

Basilar migraine (BM), also known as basilar-type migraine and basilar artery migraine, is a migraine subtype with symptoms that are thought to originate from the brainstem and/or from bilateral simultaneous hemisphere activation. According to The International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria,[1] the diagnosis requires 2 of the following fully reversible symptoms: dysarthria, vertigo, tinnitus hyperacusia, diplopia, visual symptoms simultaneously in both temporal and nasal fields of both eyes, ataxia, decreased level of consciousness, and/or simultaneously bilateral paresthesias. The diagnostic criteria for BM are listed in Table 1. Motor weakness is not compatible with a diagnosis of BM, and suggests hemiplegic migraine (HM). The term BM can be traced back to a paper by Bickerstaff in 1961, which suggested that basilar artery vasoconstriction is part of the pathophysiology of this primary headache disorder.[2] Since the coining of the term BM, and its inclusion in the ICHD-II, there has not been any significant evidence suggesting that posterior circulation vasoconstriction occurs as part of the pathophysiology of BM.

As such in the International Classification of Headache Disorders, 3rd Edition, Beta Version (ICHD-IIIb), the term BM has been replaced with the term migraine with brainstem aura.[3] Despite the lack of evidence for basilar artery vasoconstriction, patients with BM have been excluded from many triptan and DHE clinical trials.

Hemiplegic migraine is another migraine subtype that involves episodes of unilateral reversible motor weakness in the setting of a headache. The diagnostic criteria for HM are listed in Table 2. There are two subtypes of HM. Familial hemiplegic migraine (FHM) requires at least one first- or second-degree relative who carries the diagnosis, while patients with sporadic hemiplegic migraine (SHM) lack any such family history. FHM is an autosomal dominantly inherited migraine subtype, with three known genes.[4] The first gene, located on chromosome 19p13, is the CACNA1A (FHM1) gene, which encodes for the alpha-subunit of a voltage dependent P/Q Ca++. Mutations in the CACNA1A gene causes increased presynaptic calcium and, therefore, which potentially increases susceptibility for cortical spreading depression. The second gene, on chromosome 1q22–23 (FHM2), results in a mutation in the alpha subunit of NA/K+ ATPase pump. This causes a decrease in clearance of synaptic potassium and glutamate. A third gene resides on chromosome 2q24, SCN1A (FHM3). A missence mutation in the gene results in a gain-of-function of a voltage gated Na+ channel. This may result in excess firing of the Na+ channel, which in turn can facilitate cortical spreading depression.[5] It has not been well elucidated whether HM carries an elevated risk of stroke compared with migraine with typical aura. As with BM, patients with HM have been excluded from many triptan and DHE clinical trials.

Triptans are 5-HT1B/D agonists which inhibit the release of vasoactive peptides by trigeminal nerves, and cause vasoconstriction of dilated cerebral arteries. Dihydroergotamine (DHE) interacts with adrenergic and dopaminergic receptors, as well as 5-HT1A/B/D/F, 2A/C, 3, and 4 subtypes resulting in similar effects as triptans, in addition to venoconstriction.[6] Although triptans are a first line therapy for migraine attacks, they have several contraindications. The US Food and Drug Administration (FDA) mandates that package labeling state that triptans and DHE are contraindicated in patients with BM and HM. In addition to BM and HM, both triptans and DHE are also contraindicated in patients with Prinzmetal's angina, pregnancy, ischemic stroke, coronary artery disease, and peripheral vascular disease.[7] In one study involving 63,575 patients with migraine, triptan treatment was not found to increase the risk of stroke, myocardial infarction, cardiovascular death, ischemic heart disease, or mortality.[8] Another retrospective study recently demonstrated the potential safety of DHE use in patients with one posterior fossa symptom, although patients did not strictly meet the criteria for BM.[9] Despite this package label contraindication, in clinical practice some physicians prescribe triptans or DHE for patients who either meet criteria for BM and HM, or have some features consistent with these diagnoses.

A retrospective study from Finland evaluated 76 patients who fulfilled criteria for FHM or SHM, and had used triptans to treat at least one of their attacks. The study demonstrated a positive response to triptans in 47 patients. Minor side effects included fatigue, nausea, and chest pain. There were no cases of stroke or heart attack after triptan administration. One female patient from the cohort with FHM who was treated with 10 mg of rizatriptan was hospitalized because of hemiparesis, ataxia, and dizziness. It is unclear whether this patient's symptoms were her typical FHM symptoms, or new symptoms after rizatriptan administration. Radiographic imaging was normal, including magnetic resonance angiography (MRA). Her symptoms eventually resolved.[10] Another case series in the United States involving 13 patients with BM, familial HM, or migraine with prolonged/prominent typical aura received triptans without any major adverse events.[11]

The objective of this study was to demonstrate that triptans and DHE can be used for the abortive treatment of BM and HM without significant adverse ischemic vascular events.

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