Headache disorders — migraine, cluster headache, medication overuse headache and red flags

Definition / Overview

Headache disorders represent some of the most common and disabling neurological conditions encountered in internal medicine. The major primary headache syndromes, migraine, tension-type headache, and the trigeminal autonomic cephalalgias (TACs), arise without identifiable structural cause. The diagnostic challenge lies in distinguishing these from secondary headaches driven by serious underlying pathology, and in managing chronic or refractory presentations that commonly arise in the general medicine context.

Key classification framework:

• Primary headache disorders: Migraine (with/without aura), tension-type headache, TACs (cluster headache, paroxysmal hemicrania, SUNCT/SUNA, hemicrania continua), new daily persistent headache
• Secondary headache disorders: Subarachnoid haemorrhage, meningitis, giant cell arteritis, intracranial hypertension, cerebral venous sinus thrombosis, reversible cerebral vasoconstriction syndrome (RCVS), hypertensive emergency
• Chronic daily headache (CDH): Headache occurring $\geq 15$ days/month; encompasses both primary and secondary aetiologies, and frequently complicated by medication overuse

Red Flags, The Consultant Priority

Before any primary headache diagnosis is entertained, secondary causes requiring urgent evaluation must be excluded. The consultant role demands pattern recognition for features that mandate immediate investigation.

SNOOP4 Red Flag Mnemonic

• Thunderclap headache, maximum severity within 60 seconds, mandates urgent non-contrast CT head (sensitivity $\sim$98% within 6 hours of onset) followed by lumbar puncture if CT is negative; the primary concern is subarachnoid haemorrhage
• New headache $>50$ years with jaw claudication, scalp tenderness, or constitutional symptoms, send ESR, CRP, and platelet count urgently; ESR $>50\,\text{mm/h}$ with consistent clinical features warrants empirical high-dose glucocorticoids before biopsy to prevent blindness
• Fever + meningism, treat as bacterial meningitis empirically while investigating

Migraine

Pathophysiology

Migraine is fundamentally a disorder of central sensory processing, not primarily a vascular phenomenon. The underlying mechanism involves:

• Cortical spreading depression (CSD): A slowly propagating wave of neuronal and glial depolarisation followed by sustained suppression, responsible for the aura
• Trigeminovascular activation: CSD activates the trigeminal nerve, releasing neuropeptides including calcitonin gene-related peptide (CGRP), which drives neurogenic inflammation of meningeal vessels and pain signal propagation to the trigeminal nucleus caudalis
• Central sensitisation: Repeated attacks lower the threshold for pain signalling; allodynia during attacks reflects central sensitisation and predicts poor response to triptans if delayed
• Brainstem modulation: The dorsolateral pons (including the locus coeruleus) plays a pivotal role; functional imaging shows ipsilateral brainstem activation correlating with headache lateralisation

Diagnostic Criteria

Migraine without aura, requires $\geq 5$ attacks meeting:

• Duration 4-72 hours (untreated or unsuccessfully treated)
• $\geq 2$ of: unilateral location; pulsating quality; moderate-severe intensity; aggravation by routine physical activity
• $\geq 1$ of: nausea/vomiting; photophobia and phonophobia

Migraine with aura, requires $\geq 2$ attacks with:

• Fully reversible aura (visual, sensory, speech/language, motor, brainstem, or retinal)
• Gradual onset over $\geq 5$ minutes; each symptom lasting 5-60 minutes
• Headache accompanying or following aura within 60 minutes

Chronic migraine: Headache on $\geq 15$ days/month for $>3$ months, with $\geq 8$ days fulfilling migraine criteria

Clinical pearl: Aura lasting $>60$ minutes is a red flag, consider persistent aura without infarction or migrainous infarction; MRI with DWI is required.

Migraine Complications

Acute Treatment of Migraine

Stepwise approach based on severity and prior treatment response:

1. Mild-moderate attacks: Simple analgesia (aspirin $900\,\text{mg}$, ibuprofen $400\,\text{mg}$, or paracetamol $1000\,\text{mg}$) ± antiemetic (metoclopramide $10\,\text{mg}$ oral/IV)
2. Moderate-severe attacks: Triptan (e.g. sumatriptan $50{-}100\,\text{mg}$ oral, $6\,\text{mg}$ SC; or zolmitriptan $2.5\,\text{mg}$ oral), 5-HT$_{1B/1D}$ agonists acting at trigeminovascular terminals and intracranial vessels
3. Triptan non-response or contraindication: CGRP receptor antagonists (gepants, lasmiditan, rimegepant); note lasmiditan is a 5-HT$_{1F}$ agonist without vasoconstrictive properties, preferred where triptans are contraindicated (ischaemic vascular disease)
4. Status migrainosus / ED presentation: IV prochlorperazine $12.5\,\text{mg}$ or metoclopramide $10\,\text{mg}$ IV with IV fluids; IV sodium valproate $400{-}800\,\text{mg}$; IV ketorolac $15{-}30\,\text{mg}$; IV dexamethasone $8{-}10\,\text{mg}$ reduces recurrence risk

Triptan cautions: Contraindicated in basilar or hemiplegic migraine; in uncontrolled hypertension; and in ischaemic vascular or cerebrovascular disease. Avoid concurrent MAOI use.

Opioids: Strongly discouraged for recurrent migraine, they do not address underlying mechanisms, reduce future triptan responsiveness, and carry substantial dependence risk.

Preventive Treatment of Migraine

Indications: $\geq 4$ migraine days/month, significant disability, acute treatment overuse or contraindication, specific subtypes (hemiplegic migraine, frequent aura).

Cluster Headache

Pathophysiology

Cluster headache is the most severe of the TACs. The hypothalamus, particularly the posterior hypothalamic grey matter, is the key driver: functional and structural imaging demonstrates ipsilateral hypothalamic activation during attacks, explaining the circadian and circannual periodicity characteristic of the condition. Trigeminoparasympathetic reflex activation produces the autonomic features.

Clinical Features

• Strictly unilateral orbital, supraorbital, or temporal pain
• Excruciating intensity, often described as the worst pain imaginable ("suicide headache")
• Duration 15-180 minutes; frequency 1-8 per day during cluster period
• Ipsilateral autonomic features: lacrimation, conjunctival injection, nasal congestion/rhinorrhoea, ptosis, miosis, eyelid oedema, facial sweating
• Restlessness/agitation during attacks, patients pace (distinguishes from migraine where patients prefer to lie still)
• Cluster periods last weeks to months, separated by remission periods (episodic type); chronic cluster if no remission $>3$ months

Acute Treatment of Cluster Headache

1. High-flow oxygen, 100% O$_2$ via non-rebreather mask at $12{-}15\,\text{L/min}$ for 15-20 minutes; effective in $\sim$70% of attacks; safe with no contraindications
2. Sumatriptan $6\,\text{mg}$ SC, fastest-acting triptan formulation; also $20\,\text{mg}$ intranasal
3. Zolmitriptan $5{-}10\,\text{mg}$ intranasal, alternative if SC not available
4. Lidocaine intranasal, $1\,\text{mL}$ of 10% solution ipsilateral nare; adjunct option

Transitional treatment (bridging while preventive takes effect):

• Oral prednisolone $1\,\text{mg/kg/day}$ (max $60{-}80\,\text{mg}$) tapered over 2-3 weeks
• Suboccipital steroid injection (ipsilateral greater occipital nerve block)

Preventive Treatment of Cluster Headache

Refractory cluster headache: Noninvasive vagus nerve stimulation (nVNS) has shown benefit; sphenopalatine ganglion stimulation and occipital nerve stimulation are invasive options in specialist centres.

Medication Overuse Headache

Definition and Mechanism

Medication overuse headache (MOH), previously termed analgesic rebound headache, is defined as headache occurring on $\geq 15$ days/month in a patient with a pre-existing primary headache who is overusing acute medications for $>3$ months. It is not a distinct biological entity but rather a pharmacological reaction superimposed on a susceptible (typically migrainous) brain.

At-risk medications and overuse thresholds:

Clinical Features

• Transformation from episodic to daily or near-daily headache
• Headache often present on waking; improves transiently with analgesia then rebounds
• Reduced efficacy of acute and preventive treatments
• Anxiety around medication access; anticipatory dosing
• History of escalating frequency of acute medication use over months to years

Management of Medication Overuse Headache

Withdrawal is the cornerstone of treatment:

1. Identify and educate, explain the mechanism clearly; validate the patient's experience while setting expectations that withdrawal symptoms will occur (typically 7-14 days)
2. Abrupt versus gradual cessation: - Triptans, NSAIDs, paracetamol: abrupt cessation generally preferred and better tolerated - Opioids, barbiturates: graduated reduction (e.g. 10% dose reduction every 1-2 weeks) to avoid severe withdrawal
3. Bridge therapy during withdrawal: - Naproxen $500\,\text{mg}$ twice daily (if not the overused agent) to soften rebound - Short course prednisolone ($60\,\text{mg}$ tapering over 5-7 days) for severe withdrawal headache - Antiemetics as required
4. Initiate or optimise preventive therapy once the overused medication is ceased, preventive agents are substantially less effective in the presence of ongoing overuse
5. Inpatient withdrawal for opioid/barbiturate-overusing patients or those who have failed outpatient attempts

Prognosis: Approximately 50-70% of patients improve significantly after withdrawal. Relapse rates are significant (~30% at 1 year); ongoing monitoring and support are essential. Patients who continue to have headache after withdrawal likely have an underlying primary headache disorder requiring formal preventive management.

Special Populations and Multimorbidity Considerations

Migraine in Women

• Oral contraceptive pill (OCP): Combined OCP is relatively contraindicated in migraine with aura due to amplified ischaemic stroke risk; progestogen-only options are preferred
• Menstrual migraine: Attacks predictably 2 days before to 3 days after menstruation; mini-prophylaxis with frovatriptan or naproxen perimenstrually may be appropriate
• Pregnancy: Avoid triptans, valproate, topiramate; paracetamol is first-line acute treatment; magnesium may be used for prevention; migraine often improves in second/third trimester
• Postmenopausal: New-onset severe headache in this group mandates exclusion of giant cell arteritis and intracranial pathology before attributing to primary headache

Giant Cell Arteritis, The Consultant Must Not Miss This

• Presents in patients $>50$ years (peak 70 years); $\sim$65% female
• Headache (often temporal, dull, unilateral), jaw claudication, scalp tenderness, visual symptoms (amaurosis fugax → irreversible blindness)
• ESR typically $>50\,\text{mm/h}$; CRP elevated; thrombocytosis common
• Treatment: Prednisolone $1\,\text{mg/kg/day}$ (up to $60\,\text{mg}$), do NOT delay for biopsy if visual symptoms present; temporal artery biopsy remains diagnostic standard but may be negative (skip lesions)
• Tocilizumab (IL-6 receptor antagonist) is now approved as a steroid-sparing agent in GCA

Neuromodulation Options

For patients unable to tolerate pharmacotherapy or with medically refractory headache:

• Single-pulse transcranial magnetic stimulation (sTMS): Approved for acute treatment of migraine with aura
• Non-invasive vagus nerve stimulation (nVNS): Approved for both acute migraine and cluster headache; applied to the neck for 120-second cycles

Long-Case Approach: Synthesising the Headache Presentation

In a long case, the candidate must demonstrate structured reasoning across:

1. Characterise the headache: SOCRATES plus autonomic features, timing, triggers, prior episodes, distinguish primary subtype or identify secondary cause
2. Red flag screen: Apply SNOOP4; determine urgency of investigation
3. Medication history in detail: Quantify acute analgesic use; identify MOH; document all preventive trials and their outcomes (dose, duration, reason for cessation)
4. Comorbidity integration: Cardiovascular risk and triptan/ergotamine safety; depression/anxiety (comorbid in migraine); sleep disorders; medication interactions (particularly with anticonvulsants, antidepressants)
5. Functional impact: Disability assessment (MIDAS or HIT-6 scores in practice); impact on work, family, and quality of life, central to shared decision-making around escalating therapy
6. Formulate a management plan: Address acute treatment optimisation, preventive therapy appropriateness, MOH withdrawal if applicable, and non-pharmacological strategies (sleep hygiene, trigger identification, relaxation techniques, psychology referral)
7. Recognise when to escalate: Neurology referral for diagnostic uncertainty, refractory disease, or consideration of CGRP pathway therapies or neuromodulation

Sources

• Therapeutic Guidelines (eTG)
• Australian Medicines Handbook (AMH)