Migraine Headache Pathophys + Diagnosis
Hey Team,
Let’s talk about migraine. Not treatment yet, we’ll save that for later. This is a refresher on pathophysiology, diagnosis, and clinical definitions, partly for the group and partly for me. Our understanding has evolved, and it’s worth updating our shared mental model.
Pathophysiology
Migraine is best understood as a primary disorder of neuronal dysfunction, driven by abnormal brain excitability and dysregulated pain modulation rather than a purely vascular process.
Cortical events trigger trigeminovascular activation, leading to CGRP-mediated neurogenic inflammation and progressive sensitization.
In migraine with aura, the initiating event is cortical spreading depression, a slow, self-propagating wave of neuronal depolarization followed by transient cortical suppression.
As this wave moves across the cortex, it produces focal neurologic symptoms (eg, visual aura) and activates meningeal trigeminal afferents while altering blood–brain barrier permeability.
Migraine without aura may reflect cortical spreading depression occurring in regions where depolarization is not consciously perceived (eg, cerebellum), still triggering downstream trigeminovascular activation.
Activation of the trigeminovascular system results in release of vasoactive neuropeptides, particularly CGRP, which amplifies nociceptive signaling and sustains headache pain.
Repeated or prolonged activation leads to peripheral and central sensitization, manifesting as throbbing pain, worsening with movement or coughing, photophobia, hyperalgesia, and cutaneous allodynia, and helps explain why delayed ED treatment is often less effective.
This framework explains the broad symptom profile of migraine and underscores why early, mechanism-targeted therapy matters in the emergency department.
Triggers
An evidence-based review concluded that stress, menstruation, visual stimuli, weather changes, nitrates, fasting, and wine are probable migraine triggers. This reinforces that migraine attacks often reflect a lowered neurologic threshold, rather than a single causative exposure.
Clinical Presentation
Migraine is a disorder of recurrent attacks that unfold over hours to days. A typical attack progresses through four phases: prodrome, aura, headache, and postdrome.
Prodrome
Occurs in up to 70% of patients, typically 4 to 48 hours before headache onset. Common symptoms include light or sound sensitivity, fatigue, neck pain, and cognitive or mood changes (eg, irritability or euphoria). Patients may also report food cravings, yawning, and changes in bowel function.
Migraine Aura
About 25% of patients experience one or more focal neurologic symptoms during the aura phase, and most will go on to develop headache. Typical aura features include gradual onset, duration less than one hour, a mix of positive and negative symptoms, and complete reversibility.
Positive symptoms reflect active neuronal discharge and may be visual (bright lines, shapes), auditory (tinnitus, noises), somatosensory (paresthesia, burning), or motor (jerking or rhythmic movements).
Negative symptoms reflect loss of function, such as vision loss, numbness, or weakness.
Migraine Headache
The headache is often, but not always, unilateral and typically throbbing or pulsatile as intensity increases. Over one to several hours, patients commonly develop nausea, sometimes vomiting, and worsening pain with routine physical activity. Photophobia and phonophobia are common, often leading patients to seek a dark, quiet environment.
Postdrome
After headache resolution, patients may experience transient pain with sudden head movement and often feel drained or exhausted, though some report mild euphoria or a sense of clarity.
Diagnosis
Migraine is a clinical diagnosis based on the International Classification of Headache Disorders (ICHD-3). The term “complex migraine” is no longer used and should be avoided, as it is imprecise and often conflates migraine with aura, hemiplegic migraine, or other neurologic syndromes. Current classification relies on specific, reproducible criteria.
Migraine without aura
At least 5 attacks
Headache lasting 4 to 72 hours (untreated or unsuccessfully treated)
At least 2 of the following:
Unilateral location
Pulsating quality
Moderate or severe intensity
Aggravation by or avoidance of routine physical activity
During headache, at least 1 of the following:
Nausea and/or vomiting
Photophobia and phonophobia
Not better accounted for by another diagnosis
Migraine with aura
At least 2 attacks
One or more fully reversible aura symptoms (visual, sensory, speech/language, motor, brainstem, or retinal)
At least 3 of the following:
Gradual spread over ≥5 minutes
Two or more symptoms in succession
Each symptom lasts 5 to 60 minutes
At least one unilateral symptom
At least one positive symptom
Headache accompanies or follows within 60 minutes
Not better accounted for by another diagnosis
More to come on treatment, but having a shared, up-to-date framework will allow us to accurately diagnose our patients.
Sources:
Best,
Dillon
