16.3 Headache Disorders & Cranial Neuralgias

Headache is one of the most common acute medical presentations encountered in clinical practice and MRCP(UK) examinations. Candidates must distinguish primary headache phenotypes from life-threatening secondary headache disorders, master the pharmacology of acute and preventive headache treatments, and understand the emergency investigation and management of giant cell arteritis, idiopathic intracranial hypertension, and cranial neuralgias.

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1. Primary Headache Disorders: Migraine

Pathophysiology & Mechanisms

• Trigeminovascular System Activation: Primary neurovascular dysfunction initiates activation of unmyelinated perivascular C-fibres of the ophthalmic division of the trigeminal nerve ($V_1$), which innervate meningeal and pial blood vessels. Activated trigeminal nerve endings release potent vasoactive neuropeptides—predominantly Calcitonin Gene-Related Peptide (CGRP), Substance P, and Neurokinin A—precipitating neurogenic inflammation, mast cell degranulation, plasma protein extravasation, and intense meningeal vasodilation.
• Cortical Spreading Depression (CSD): Migraine aura is caused by CSD—a wave of sustained neuronal and glial depolarization propagating slowly across the cerebral cortex (typically occipital to frontal) at $2\text{–}5\text{ mm/min}$, accompanied by a transient phase of cortical hyperaemia followed by prolonged cortical oligemia (hypoperfusion).

Clinical Phenotypes: With vs. Without Aura

• Migraine Without Aura (~75% of patients): Recurrent attacks lasting 4 to 72 hours. Headache has at least two of: unilateral location, pulsating quality, moderate or severe intensity, and aggravation by routine physical activity. Accompanied by at least one of: nausea and/or vomiting, or both photophobia and phonophobia.
• Migraine With Aura (~25% of patients): Reversible focal neurological symptoms that develop gradually over $\ge 5\text{ minutes}$ and last between 5 and 60 minutes, typically followed by headache within 60 minutes. Visual symptoms are most common: scintillating scotomas (flashing lights), fortification spectra (zigzag jagged lines expanding outward), or central scotomas. Sensory aura involves spreading unilateral tingling followed by numbness.

Acute Abortive Pharmacotherapy

• First-line Combination Therapy (NICE Guidelines): Administer simultaneously at the earliest onset of headache:
  1. Oral Triptan: $5\text{-HT}_{1\text{B}/1\text{D}}$ receptor agonist (e.g. oral sumatriptan 50–100 mg, zolmitriptan 2.5 mg, or rizatriptan 10 mg). Triptans promote vasoconstriction of distended meningeal vessels and inhibit trigeminal release of CGRP.
  2. NSAID or Paracetamol: Soluble aspirin 900 mg, ibuprofen 400–600 mg, or naproxen 500 mg (or paracetamol 1 g if NSAIDs are contraindicated).
  3. Prokinetic Antiemetic: Oral metoclopramide 10 mg or prochlorperazine 10 mg to treat nausea and overcome gastric stasis, enhancing analgesic absorption.
• Triptan Contraindications: Ischaemic heart disease, previous myocardial infarction, coronary vasospasm (Prinzmetal angina), prior stroke or TIA, peripheral vascular disease, or uncontrolled severe hypertension.

Prophylactic Pharmacotherapy

• Indications: Indicated when attacks are frequent ($\ge 2\text{ attacks per month}$), severely disabling despite optimal acute therapy, or in patients at risk of medication-overuse headache.
• First-Line Prophylactic Agents:
  • Propranolol: 80–160 mg daily (non-cardioselective beta-blocker; preferred in non-asthmatic, non-depressed hypertensive patients).
  • Topiramate: 50–100 mg daily (modulates voltage-gated sodium/calcium channels and GABA/AMPA receptors). Promotes weight loss. Critical Teratogenicity Warning: Topiramate is teratogenic, causing major congenital malformations (cleft lip/palate, microcephaly) and neurodevelopmental disorders; it is strictly contraindicated in pregnancy and in women of childbearing potential unless enrolled in a Pregnancy Prevention Programme.
• Second-Line Prophylactic Agents: Amitriptyline (10–50 mg at night, tricyclic antidepressant), Candesartan (16 mg daily, angiotensin II receptor blocker).
• CGRP Monoclonal Antibodies: Targeted biologic therapies for refractory chronic or episodic migraine failing $\ge 3$ conventional oral preventatives: Monoclonal antibodies targeting CGRP ligand (fremanezumab, galcanezumab, eptinezumab) or the CGRP receptor (erenumab).

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2. Tension-Type Headache & Medication-Overuse Headache

Tension-Type Headache (TTH)

• Features: The most common primary headache disorder. Bilateral, non-pulsating, dull ache with a feeling of tightness or pressure around the head (classic "band-like" or "vise-like" distribution). Mild-to-moderate intensity; NOT aggravated by routine physical activity (walking, climbing stairs). Lack of severe nausea or vomiting; either photophobia or phonophobia may be present, but not both.
• Management: Reassurance, lifestyle optimization, simple analgesics (aspirin, paracetamol, ibuprofen). Avoid codeine/opioids. Chronic TTH ($> 15\text{ days/month}$) is managed prophylactically with low-dose oral amitriptyline (10–75 mg nocte).

Medication-Overuse Headache (MOH)

• Pathogenesis & Diagnostic Thresholds: Paradoxical transformation of an underlying headache disorder into a daily or near-daily persistent dull headache driven by chronic, frequent intake of acute symptomatic medications:
  • Triptans, opioids, ergots, or combination analgesics: Consumed on $\ge 10\text{ days per month}$ for $> 3\text{ months}$.
  • Simple analgesics (paracetamol, aspirin, NSAIDs): Consumed on $\ge 15\text{ days per month}$ for $> 3\text{ months}$.
• Management: Abrupt, complete cessation of all overused acute abortive medications. Patients must be educated that headaches will temporarily worsen (rebound withdrawal headache, nausea, anxiety, sleep disturbance lasting 1–2 weeks) before significant clinical improvement is observed.

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3. Trigeminal Autonomic Cephalalgias (TACs)

The Trigeminal Autonomic Cephalalgias are a distinct group of primary headaches characterized by severe, strictly unilateral head pain accompanied by prominent ipsilateral cranial parasympathetic autonomic symptoms.

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4. Secondary Headache: Giant Cell Arteritis & Idiopathic Intracranial Hypertension

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5. Cranial Neuralgias: Trigeminal Neuralgia

• Pathophysiology: Neurovascular compression of the trigeminal nerve (CN V) root entry zone in the cerebellopontine angle, most commonly by an aberrant vascular loop of the Superior Cerebellar Artery (SCA). Pulsatile vascular compression induces focal mechanical demyelination and ephaptic axonal cross-talk (ephaptic transmission). In younger patients ($< 40$ years) or bilateral cases, consider a demyelinating plaque of Multiple Sclerosis.
• Clinical Presentation:
  • Paroxysms of intense, excruciating, electric shock-like, stabbing, or lancinating unilateral facial pain lasting milliseconds to 2 seconds.
  • Confined strictly to the distribution of one or more branches of CN V: $V_2$ (maxillary) and $V_3$ (mandibular) are affected in $> 95%$ of cases; isolated $V_1$ involvement is rare ($< 5%$).
  • Triggered by trivial non-noxious mechanical stimulation of cutaneous trigger zones: light touch, washing, shaving, eating, talking, brushing teeth, or a cold wind.
  • Followed by a brief refractory period during which triggers fail to elicit paroxysms.
  • Neurological examination is completely normal; the presence of sensory loss, absent corneal reflex, or motor weakness mandates neuroimaging to exclude a structural mass (e.g. acoustic neuroma, meningioma) or MS plaque.
• Pharmacological Management:
  • First-Line Therapy: Carbamazepine (100–200 mg twice daily, slowly titrated to 600–1200 mg daily). Inhibits voltage-gated sodium channels. Monitoring Requirements: Full blood count (risk of aplastic anaemia and agranulocytosis), electrolytes (risk of hyponatraemia due to SIADH), and liver function tests. In individuals of Southeast Asian descent, screen for the HLA-B*1502 allele prior to prescribing due to extreme risk of Stevens-Johnson syndrome / toxic epidermal necrolysis.
  • Second-Line Pharmacotherapy: Oxcarbazepine, lamotrigine, or baclofen.
• Surgical Interventions (for medically refractory disease):
  • Microvascular Decompression (Jannetta Procedure): Posterior fossa craniotomy with surgical transposition of the compressing vascular loop away from the CN V root entry zone, interposing a synthetic Teflon sponge. Provides the highest rate of long-term cure with preservation of facial sensation.
  • Percutaneous Rhizotomy / Stereotactic Radiosurgery (Gamma Knife): Reserved for patients unfit for open craniotomy; carries risk of sensory loss and corneal anaesthesia.