Migraine Aura: Updates in Pathophysiology and Management

DOI: https://doi.org/10.1007/s11910- 020- 01037- 3

Abstract-Summary To provide an updated review of the pathophysiology, diagnosis, and management of migraine with aura.

Migraine with brainstem aura may originate cortically. Although cortical spreading depression (CSD) continues to be the predominant theory surrounding the pathophysiology of migraine with aura, the exact mecha- nism of action of CSD and its role in relation of all phases of migraine including features of aura are not fully understood.

Transient ischemia attacks, stroke, and epilepsy should be considered in your

differential diagnosis of migraine with aura.

There are no specific therapies for migraine with aura.

Introduction Visual symptoms, the most common symptom type, occur in over 90% of patients with migraine with aura.

Recent understanding of migraine pathophysiology has moved towards describ- ing migraine as an attack consisting of four phases, including a prodrome, aura, headache, and postdrome.

This model, reviewed elsewhere, more closely describes the patient’s experience of migraine, and offers a deeper understanding of how and where an attack might start and progress [165].

This review will focus on the aura pathophysiology, clinical features of migraine aura and discuss updates on the management of patients suffering from migraine with aura.

Updates in Migraine Aura Pathophysiology Although this process has been demonstrated in humans during acute brain injury, subarachnoid hemorrhage, and ischemic stroke, this “canonical” CSD (spreading depression limited to the cerebral cortex) has not been demonstrated during migraine aura in humans [166] and there is debate as to whether the aura, from the CSD, trig- gers the rest of the migraine attack including the head pain [167].

Spreading depression in other brain regions in addition to the cortex or CSD of the thalamus with disruption of normal thalamocortical oscillations by cortical depression has been recently suggested as an alternative model to canonical CSD that may better explain the occurrence and spread of different aura types [166].

Although there is robust pre-clinical evidence suggesting that CSD may activate the trigeminovascular system mediating migraine pain, most patients still experi- ence migraine without aura [165, 166].

One study of migraine aura patients found increased functional connectivity between the pons (an area shown to be activated in headache phase in migraine without aura patients) and both somatosensory cortex and between the visual cortex during the headache phase following a visual aura [168].

2.2 Biology

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Updates in the Understanding of Migraine Aura Clinical Features According to the ICHD-3 criteria of migraine with aura, a patient requires at least 2 attacks of aura with one or more fully reversible aura symptoms and at least 3 of the 6 following typical features: (1) at least one aura symptom spreading gradually over

5 min, (2) two or more aura symptoms occurs in succession, (3) each individual aura symptom lasts 5–60 min, (4) at least one unilateral aura symptoms, (5) at least one positive aura symptom, and/or (6) the aura accompanied or followed within 60 min by a headache (169).

Migraine with brainstem aura, previously called basilar migraine, is currently defined in the ICHD-3 as (1) at least two of the following: vertigo, dysarthria, tin- nitus, hyperacusis, diplopia, ataxia, or decreased level of consciousness (GCS < 13), (2) the absence of retinal and motor symptoms, and (3) the typical aura characteris- tics noted in the ICHD-3 criteria for migraine with aura [169].

Migraine with retinal aura is defined as repeated reversible monocular positive or negative visual symptoms following an aura time-course, associated with headache.

Updates in Diagnosis of Migraine with Aura The diagnosis of migraine is particularly challenging in patients with vascular risk factors, co-morbid epilepsy, aura without headache, and atypical aura.

Migraine aura also accounted for 18% of patients who were thrombolyzed with-

out a final diagnosis of stroke [170].

The DOUBT study (Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms), a prospective cohort study (n = 1028 patients, age > 40, no prior stroke, 7.8% with migraine with aura) recently evaluated patients with low- risk symptoms (non-motor and non-speech symptoms of any duration, or motor/ speech symptoms ≤ 5 min) with diffusion-weighted MRI within 8 days of onset [171].

A recent study of cryptogenic stroke in young patients (n = 68, age 18–60) dem- onstrated a high prevalence of PFO in migraine (79%; 93% in migraine with fre- quent aura) compared with no migraine (59%).

Headache may occur in patients with seizures so the presence of headache in

patients with an aura is not synonymous with migraine with aura.

Updates in Management of Migraine with Aura A recent large cohort study (n  =  1884) which did not report estrogen doses but might reflect lower available dosages still found an OR of 6.1 for stroke in migraine with aura patients on CHC, compared with OR 1.77 in migraine without aura on CHC [172].

Frequent attacks of brainstem or hemiplegic aura, even if mild in severity, are

also an indication for the use of prophylactic migraine therapy.

The triptan trials excluded brainstem and hemiplegic migraine aura patients. Small retrospective studies have not shown increased stroke risk associated with triptan use in hemiplegic migraine patients, except for one patient with prolonged symptoms for months without associated DWI change [173].

The evidence for these agents is largely based on open-label studies or observa- tional data, as randomized controlled clinical trials in migraine treatment have gen- erally not separated patients based on aura status.

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Conclusion Prospective diary-based studies have described high inter- and intra-patient vari- ability in the clinical features of migraine aura; therefore, more prospective studies are needed to understand the details of aura phenomenology.

For the clinician, knowledge of atypical features of migraine aura is helpful when the differential diagnosis is considered, as data have shown that a small but significant percentage of patients are misdiagnosed.

Management of patients with migraine with aura should consider the increased risk of ischemic stroke, particularly for patients with “higher risk” aura, smoking history, or other co-morbidities.

Acknowledgement A machine generated summary based on the work of Lai, Joshua; Dilli, Esma. 2020 in Current Neurology and Neuroscience Reports.

Mechanisms of migraine as a chronic evolutive condition