Migraine mimicking stroke: What to do?

This month in the journal, Alberto et al. present data from the first systematic review (1), that we are aware of, regarding migraine with aura as a stroke mimic (SM) both in patients with and without systemic thrombolysis with rt-PA. Their review encompasses literature from 1995 until 2017; 32 papers were chosen to review, and 18 works analyzed the number of SMs treated with i.v. rt-PA. They conclude that migraine with aura is the third most common stroke mimic, following seizures and psychiatric disorders. It is responsible for about 18% of all improper thrombolytic treatments. Despite the absence of strong supporting data, thrombolysis in migraine with aura seems to be a procedure with an extremely low risk of adverse events such as major bleeding. The reported rate of adverse events was 0.01%. Importantly, no case of intracerebral hemorrhage (ICH) following rt-PA has been published in stroke mimics.

Other clinical implications of this study (1) indicate that more than 6% of rt-PA administrations are performed in patients without an acute ischemic stroke (stroke-mimics). Migraine with aura is the final diagnosis in more than 1% of patients evaluated in the emergency setting for the suspicion of acute ischemic stroke, and it is responsible for about 1.8% of thrombolytic treatments. Diagnosis of migraine with aura remains a challenge.

Interestingly, young women appear to be a cohort of patients (1) that arrive early in the ER for stroke assessment. In this cohort the presence of neurological aura, particularly if it involves speech or vision without hemiplegia, for example, could be a flag that this is a stroke mimic.

So, what have we learned from this work (1)? The authors state: “Even if literature does not report ICH after rt-PA administration in a patient with MA, there is a non-ignorable burden of potentially harmful consequence: The bleeding risk rises up in absence of a careful check of the main well-known contraindications” (1). Further, they suggest: “MR imaging protocol including perfusion weighted imaging (PWI) may help in recognizing MA as the cause of an acute neurological symptom, especially in the acute phase, while T2*- weighted gradient recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) sequences may help ruling out amyloid angiopathy” (1).

This current publication becomes more interesting because of the recent publication of the 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals (2) from the American Heart Society and American Stroke Association in Stroke. This document lays out precise guidelines regarding intravenous rt-PA therapy and mechanical evacuation of clot material (thrombectomy). The processes regarding the clinical assessments of patients are detailed in a tabular form: For each scenario, there is a determination of whether the benefits of the treatments or procedures outweigh the risks. Stroke mimics are mentioned in the tables, along with an evidence level and recommendation on their management. The paper concludes that the benefits outweigh the risks of treating SMs based on literature quoted (2,3). Given that the current study in this journal shows extremely low risks associated with rt-PA, this judgment would seem reasonable.

In fact, the AHA/ASA publication (2) would advise proceeding with the stroke care even if there is any doubt about the possibility that the patient’s presentation could represent an acute ischemic stroke (AIS). In Table 6 of the Stroke paper (2) they say: “The risk of symptomatic intracranial hemorrhage in the stroke mimic population is quite low; thus, starting IV alteplase is probably recommended in preference over delaying treatment to pursue additional diagnostic studies. (Class IIa; LOE B-NR).” Here, the consensus is that the benefits outweigh the risks. These guidelines are based on the best evidence currently available. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of AIS.

Migraine with aura can easily mimic AIS and present to an emergency department as an SM. Alternatively, the opposite of an SM could occur and present as a “stroke chameleon” (4). In this setting, the presentation would look like a migraine but subsequently be found to represent an acute stroke.

Confounding all of this is that migraine with aura itself can be a risk factor for stroke, particularly in young women who smoke and take estrogen containing compounds; stroke and migraine can occur independently in the same person, and some diseases present with migraine and stroke, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL (5). Further, it must be remembered that headache often accompanies acute stroke, and observational studies show that 15% to 40% of patients with AIS report headache in close temporal relation to the event (5). This means it is probably not the headache that is the mimic, but the aura of migraine. Thus, the real secret to distinguishing migraine from stroke may be in cases where the slow march of a migraine aura over 20 minutes is contrasted with the abrupt onset of aura symptoms in strokes (5). Migraine sensory paresthesia, as an aura, can typically involve one side of the tongue (6) unlike stroke, in our experience.

In neurological diagnosis, is important to have a differential diagnosis to allow time, thoughtful contemplation and reflection upon various disorders to be sure what the accurate diagnosis in each case is thought to be, to avoid misdiagnoses. In an age when knowledge and technology may well lead to better, earlier and accurate diagnosis of stroke, it would seem wise to avoid prematurely attributing neurological symptomology to stroke in the presence of other benign disorders. Therapy is not without risks in the SM group of patients, in that “erroneous administration of intravenous alteplase to a patient without acute ischemic stroke is not without potential risks and harm, including intracranial and extracranial hemorrhage, minor and major, allergic phenomena such as angioedema, and associated wasted resources of drug and the obligatory post-thrombolysis care in an intensive care unit associated with its administration” (3). It is a difficult area for neurologists, one suspects it will become more problematic in the future.

It thus seems prudent, given the increasing length of time to treat and team involvement in a stroke assessment and care, to continue to document these cases of stroke mimics and to pursue diagnostic alternatives through possible algorithms (7) for clinical assessment. In the end, maybe it is the discussion between the caring physicians, patient, and family that is most important. Some day, somewhere, harm may occur in an SM, and this area of neurological practice will require increasing certainty to prevent serious untoward events, despite what is currently known about SMs in practice.

In a review of acute stroke care (8) in the neurological educational series Continuum, offered by the American Academy of Neurology, Dr Andrew M Southerland states: “The clinical evaluation of the patient with acute stroke is clearly a dynamic process, requiring mastery in the focused stroke history, neurologic examination, and diagnostic assessment, all while working through a time-sensitive and team-based environment. Arriving at a correct and timely treatment decision not only warrants proficiency with acute stroke protocol but also requires knowledge of neurovascular anatomy, clinical stroke syndromes, and common mimics (i.e. does the case make neuroanatomic and cerebrovascular sense?). With the rapid evolution of acute stroke therapies and advanced diagnostics, the fundamentals of the bedside assessment must continue to be promoted as the foundation of acute stroke care. “Be quick, but don’t hurry” (7). This appears to be as good a recommendation as can be found on this subject under review.