Headaches and Migraines essay plan

Question 1

1. Introduction

Answer 1

Headaches are extremely common neurological conditions.

Migraine is the most studied — affects ~15% of population and is the second leading cause of disability worldwide in women <50 (GBD 2016).

Primary headaches: migraine, tension-type headache (TTH), cluster.

Secondary headaches: e.g. medication overuse, infection.

Essay focus: Migraine, with reference to others (TTH, cluster, MOH) — pathophysiology, current treatments, limitations, future directions.

Question 2

2. Pathophysiology of Migraine

Answer 2

Now considered a neurovascular + central sensitisation disorder

Key processes:
Cortical spreading depression (CSD): wave of neuronal + glial depolarisation → aura

Trigeminovascular activation → release of CGRP, substance P → neurogenic inflammation

Central sensitisation: amplifies pain → allodynia

Serotonin: ↓ 5-HT between attacks; ↑ during attacks

Key regions: trigeminal nucleus caudalis, thalamus, hypothalamus, brainstem

Question 3

Other Headaches

Answer 3

Tension-Type (TTH): Most common, bilateral, mild/moderate, no nausea; muscle tension + central pain modulation

Cluster (TAC): Severe, unilateral, orbital pain + autonomic signs (tearing, ptosis); rare but disabling

Medication Overuse (MOH): >15 days/month; due to overuse of triptans or NSAIDs

Question 4

4.1 Current Treatments (acute)

Answer 4

NSAIDs (e.g. ibuprofen): first-line for mild attacks

Triptans (e.g. sumatriptan): 5-HT1B/1D agonists → block CGRP release, vasoconstriction

Effective in 30–50% but contraindicated in cardiovascular disease

Limits: Must be taken early; low efficacy in some; side effects

Question 5

4.2 Current Treatments (preventative)

Answer 5

Indicated if >4 attacks/month

Beta-blockers (propranolol), TCAs (amitriptyline), antiepileptics (topiramate)

Also treat comorbid anxiety/depression

CGRP monoclonal antibodies (e.g. fremanezumab): monthly injection, well-tolerated

Question 6

5. Limitations of Current Therapies

Answer 6

Triptans: low response rate, side effects

Preventatives: poor adherence, delayed onset

MOH risk: 60% improve if drug stopped, but high relapse

Question 7

6. Future / Novel Therapies

Answer 7

Gepants (e.g. rimegepant): oral CGRP receptor antagonists — non-vasoconstrictive, effective in triptan-ineligible patients

Ditans (e.g. lasmiditan): 5-HT1F agonist — also non-vasoconstrictive

Neuromodulation: vagus nerve stimulation, TMS — non-drug option

Botox: approved for chronic migraine (>15 days/month)

Question 8

7. Conclusion

Answer 8

Migraine is a complex neurological disorder involving CGRP, serotonin, and central sensitisation.

While treatments like triptans and preventatives are moderately effective, novel drugs like gepants and anti-CGRP antibodies offer better safety and precision.

A personalised, multimodal approach (drugs + neuromodulation + behaviour) is likely to improve outcomes.