Headache /

Migraine
Dr Jason Ray
Neurologist, headache sub-specialist
Deputy lead, headache unit
Outline

Classification of headache disorders

Approach to a headache history

Migraine
Cluster headache
Key illustrative headache disorders Medication overuse headache
Trigeminal neuralgia
Classification
of headache
disorders
Classification of headache disorders

Headache Disorders

Primary Secondary Neuralgia

headache disorder headache disorder

Tension type Migraine Meningitis Medication Trigeminal

headache Cluster overuse neuralgia
headache headache
Classification • Episodic
• <15 days /month of headache
of headache • Chronic
disorders • ≥15 days / month of headache
Approach to a
headache
history
Taking a headache history 1 – key aspects of
history
The ‘SOCRATES’ method The ‘Red flags’
• Site
• Onset S Systemic symptoms (including fever)
Secondary risk factors (neoplasm,
• Character immunosuppression or HIV)
• Radiation N Neurological deficit (including mental state)

• Associated features O Onset (abrupt/thunderclap)

O Older (new onset after age 50)
• Time
P1 Positional headache, papilloedema
• Exacerbating or alleviating factors
P2 Pattern change, progressive or new onset
• Severity
P3 Precipitated by Valsalva (cough, sneeze, bend,
strain)
P4 Pregnancy, post-partum or post-trauma
Key details in the history

• Site
• Is it strictly on one side of the
head? ‘side-locked’
• Onset
• Has it come on suddenly?
• Character
• Is it neuralgiform
(burning/electric) or throbbing?
• Consider cervical disease or a
trigeminal autonomic cephalalgia
• Thunderclap headache
• Is it more likely to be a neuralgia,
or migraine
Key details in the history
• Radiation
• Where else does the pain go?
• Associated features
• Are their ’migrainous’ features
• Are their ‘autonomic’ features
• Time
• How long does it last for?
• Does it always come on at the same
time of day?
• Does it come on with the season?
• Is it respecting the territory of a nerve
• Photophobia, phonophobia, nausea
• Conjunctival injection/lacrimation,
nasal congestion/rhinorrhoea, eyelid
oedema, sweating, miosis/ptosis
• seconds, hours or continuous?
• Evening (cluster headache), or on
waking (pressure or OSA)
• Cluster headache
Associated symptoms: Cranial autonomic
symptoms
• Present in several headache
disorders
• Particularly prominent in TACs –
side locked and ipsilateral to pain
• Conjunctival injection – red eye
• Conjunctival lacrimation - tearing
• nasal congestion
• Rhinorrhoea – runny nose
• eyelid oedema – swollen eye
• Sweating – one side of forehead
• Miosis – pupil shrinks
• Ptosis – eyelid droops
Key details in the history
• Exacerbating or alleviating
factors
• Do ’Valsalva’ manoeuvres make it
worse or bring it on?
• Is it worse with a particular
posture
• Does a particular activity bring it
on?
• Severity
• Consider pressure or posterior
fossa
• Intracranial pressure (either high
or low)
• Task specific headaches or
secondary headaches
Putting it together – primary headache
disorders
Location Associated features
Migrainous features Migraine (Migraine)

Autonomic features SUNCT Cluster Hemicrania continua

Side locked
(unilateral) SUNA Paroxysmal hemicrania
Neither, respects Trigeminal
distribution of CN V neuralgia
Second-
Duration of pain: ±15-180 minutes 4-72 hours Continuous
minutes
Migrainous features Migraine NDPH

Autonomic features (Migraine)

Not side locked

Neither Tension-type headache NDPH

Secondary headaches: the red flags
• Presence of a red flag overrides
the other features of the history
• In patients with brain tumours
77% phenotypically had TTH, 9%
migraine
• How we work a patient up
depends on what our differential
is (which red flag is present)
SNOOP-4 list
S Systemic symptoms (including fever)
Secondary risk factors (neoplasm,
immunosuppression or HIV)
N Neurological deficit (including mental state)
O Onset (abrupt/thunderclap)
O Older (new onset after age 50)
P1 Positional headache, papilloedema
P2 Pattern change, progressive or new onset
P3 Precipitated by Valsalva (cough, sneeze, bend,
strain)
P4 Pregnancy, post-partum or post-trauma
Evaluation of red flags
Red flag
S Systemic symptom
S Secondary risk factors
N Neurological deficit
O Onset (abrupt)
O Older (new >50)
P Positional headache,
papilloedema
P Pattern change,
progressive or new onset
P Precipitated by Valsalva
P Pregnancy, post-partum
or post-trauma
Example differential Consider investigating with…
Intracranial infection CT, MRI, LP
Metastatic disease MRI
Stroke Urgent stroke CT imaging
*see next slide
Giant cell arteritis, cancer, stroke CT, MRI, ESR, biopsy
Intracranial hypertension or MRI, venogram, LP
hypotension
Cancer MRI
Posterior fossa, chiari malformation, MRI, LP
intracranial pressure
Postdural headache, VST, pituitary varies
apoplexy
Thunderclap headaches
Investigation for thunderclap Differentials for a thunderclap
headaches headache
• CT Brain Common:
• Accessible in ED • Subarachnoid haemorrhage
• >95% sensitivity within 6 hours of onset for • Reversible cerebral vasoconstriction
SAH syndrome
• LP Less common:
• In delayed presentation of suspected SAH - • Infection
xanthochromia • Venous thrombosis, arterial dissection
• PRES, ICH, stroke
Consider: • SIH
• Angiogram and venogram (MR or CT) Uncommon/rare:
• RCVS second most common presentation • Pituitary apoplexy
• Imaging may be normal in first week of • GCA, pheochromocytoma, VZV
symptoms (30%) vasculopathy, third ventricular cysts
Imaging findings of thunderclap headaches

Axial c- SAH Sagittal c+ - RCVS

Migraine
Migraine: diagnostic criteria

ICHD-3
A. At least 5 attacks fulfilling criteria B-D Location Associated features
B. Headache attacks last 4-72 hours Migrainous features Migraine
C. At least 2 of the 4 characteristics:
• Unilateral location Side locked Autonomic features
• Pulsating quality (unilateral)
• Moderate to severe pain Neither
• Aggravation by routine physical activity
Duration of pain: 4-72 hours
D. During the headache at least one of:
• Nausea/vomiting Migrainous features Migraine
• Photophobia/phonophobia
E. Not better accounted for by another Autonomic features (Migraine)
Not side locked
ICHD-3 diagnosis
Neither
Epidemiology
• 1:5 to 1:7 people suffer from migraine
• More common then diabetes and asthma
• 4:1 female preponderance

• Second leading cause of years-lived with disability worldwide

Phases of a migraine attack
• Four phases to a migraine attack
• Prodrome: yawning, irritable, food
cravings
• Aura
• Headache phase
• Postdrome: ‘migraine hangover’

• Pain is preceded in prodromal phase

by hypothalamic activation, precedes
a migraine by hours to days
• Aura is caused by a spreading ‘wave’
of depolarisation across the cortex
Migraine aura
• 30% of patients with migraine
• Caused by CSD
• Fully reversible, recurrent, visual,
sensory or other CNS (brain)
symptom
• Usually unilateral, occurs gradually, in
association with migraine
• 90 % of the time visual Fortification spectra
• 15-30 min prior to headache onset
(can occur after headache)
• Need to differentiate from focal
seizure and TIA

Scotoma
Key aspects of migraine pathophysiology
• Cause of activation unknown
(central vs peripheral)
• Activation of trigeminal afferents
that innervate dura and trigeminal
ganglion (TG) releases vasoactive
peptides
• CGRP, substance P, PACAP
• TG rich in serotonin and CGRP
receptors, sits out of the BBB
• Causes vasodilation, nociceptive
signalling through brainstem and
onto second/third order neurons in
other areas of the brain
Management of migraine
Patient presenting
with migraine
Three pillars: Address lifestyle
• Lifestyle management factors

• In everyone Assess monthly

frequency
<2 days/month >4 days/month

• Acute treatment Optimise acute

treatment
Preventative
treatment
• In everyone NSAID/triptan/anti-
emetic
4-14 days/month >15 days/month

Oral preventative Three oral

• Preventative treatment treatment preventative trials

• If having >4 attacks per month, or Assess tolerance

and efficacy 8-12
Highly efficacious
therapies
difficult to control otherwise weeks - BotoxTM
- CGRP
therapies
Lifestyle management

SEEDS
• Sleep
• Routine, quality and quantity
• Exercise
• Gradate aerobic exercise
• Eating
• Balanced diet, avoiding triggers
• Diary
• Keep a headache diary
• Stress
• Management as possible, relaxation, CBT
therapy
Acute treatment

The principles
• Analgesics work better early in an
attack
• Combination of analgesics (if
needed) works better then mono-
therapy
• Aim for pain freedom within 2 hours

• Need to avoid medication overuse

headache
Acute treatment

Simple analgesia (<15 days/month)

• Paracetamol and NSAIDS
• Care in elderly, gastric disease,
Inflammatory Bowel Disease

• Higher dose often required in

migraine
• Aspirin 900mg
• Ibuprofen 600mg
Acute treatment

Triptans (<10 days/month)

• 5HT receptor agonist
• Vasoconstriction, block release
of several neuropeptides and
interfere with pain signalling in
TCC
• Avoid in IHD/vascular disease, or
within 24 hours of ergotamine
• 42-76% pain relief within two
hours
Medication
overuse
headache
Medication overuse headache
• Significantly increases the disability of • Prevention is easier then the cure
migraine • Maximum
• 1% of the general population • 15 days/month: NSAID/paracetamol
• 70% of patients with chronic daily
headaches • 10 days/month: triptans
• 10 days/month: opiates (but don’t use
• Repeated expose to acute analgesia them)
• Reduces endogenous pain inhibition in
the brain
• Increases neurogenic inflammation
(making it easier to trigger attacks)
• Increases sensitisation of central pain
networks
• Net result:
• More frequent headaches
• Less responsive to treatment
Principles of acute treatment of migraine
Assess efficacy of treatment:
• Headache freedom at 2 hours
• Headache freedom at 24 hours
• Adverse effects

Overarching principles:
• Treating the pain earlier is more likely to be effective
• Combination of NSAID with triptan +/- anti-emetic is more effective then
single agent
• Limit the number of migraine days per month to allow effective treatment
and limit disability without concern of mediation overuse headache
Preventative treatment: oral therapies

• Statistically each is as likely to be Medication Benefits Caution

helpful – can’t predict which Topiramate Weight loss Kidney stones,

glaucoma, mood
though Amitriptyline Sedation Weight gain,
• Choose therefore on basis of constipation, sedation

comorbidity and side-effect Candesartan Few side

effects
BP

profile Pizotifen Sedation Sedation, weight gain

(5kg average)
Propranolol Anxiety Depression, vivid
dreams, fatigue, BP,
asthma
Advanced therapies: botulinum toxin

• PBS: chronic migraine, failed 3

oral meds
• 31 injections totalling 155 units
of onaB given at 12-weekly
intervals
• 47.1% of patients have a halving
in their headaches or better
Advanced therapies: Inhibit CGRP

CGRP mAbs
• PBS: chronic migraine, failed 3
oral meds
• One injection into thigh, given
once a month
• 30-40% of patients have a
halving or better in the
frequency of their headaches

…(Coming soon – gepants)

Specific scenarios: stroke & migraine

• Increase in absolute risk of

stroke in migraine with aura
• Absolute risk remains low in
young healthy patients
• Benefit/risk of further factors
need to be considered
• OCP, smoking
Specific scenarios: Menstrual related migraine
• 18-25% of women with migraine also have a menstrual relationship
with migraine
• Reduction in oestrogen in late luteal phase (also impact with
progesterone)
• Interacts with CNS, involved in synthesis of 5-HT, dopamine, galanin,
neuropeptide Y
• Increases sensitivity of 5HT1 receptors and sensitivity of opioid receptors
• Reduces the efficacy of acute treatments
• Perimenstrual attacks more disabling and more difficult to treat
• Short term bridging therapies
Cluster
headache
(& the TACs)
The TACs
Characteristics
Trigeminal Autonomic Cephalgias
short-lasting unilateral neuralgiform paroxysmal hemicrania Cluster hemicrania continua
headache attacks with conjunctival
injection and tearing (SUNCT)

sex distribution females and males approximately females same as males females less than females more than males
equal males

Pain burning, stabbing, sharp throbbing, stabbing, stabbing, boring strictly unilateral, may vary in
boring intensity

frequency of 3 to 200 daily 1 to 40 daily 0.5 to 8 daily persist for more than 3 months
attacks
duration of 5 to 240 seconds 2 to 30 minutes 15 to 180 minutes –
attack
cutaneous yes no No no
trigger
alcohol trigger no no Yes no

indomethacin – absolute response to – absolute response to therapeutic

effect therapeutic trial trial
Epidemiology
• Pooled lifetime prevalence 0.12%
• Accounts for 20% of side-locked headaches
• Male predominance 4:1
• Genetic component (18x for first degree relative)

• The ‘suicide-headache’ - responsible for 1% of all-cause suicide

Key aspects of TAC pathophysiology
• Unilateral activation of the trigeminal
cervical complex (brainstem)
• Releases CGRP
• Unilateral activation of trigeminal nerve
(CNV) – anterior side-locked pain
• CNV connects through superior
salivatory nucleus to parasympathetic
fibres of facial nerve (CNVII)
• Unilateral autonomic symptoms
• Hypothalamus activation
• Circadian and seasonal rhythm to the
pain
Cluster headache: diagnostic criteria

ICHD-3 Anterior, agitated, autonomic

A. At least five attacks fulfilling criteria B-D Location Associated features
B. Severe or very severe unilateral orbital, supraorbital
and/or temporal pain lasting 15-180 minutes (when Migrainous features
untreated)
C. Either or both of the following:
• at least one of the following symptoms or signs, Side locked Autonomic features Cluster
ipsilateral to the headache: (unilateral) Paroxysmal hemicrania
• conjunctival injection and/or lacrimation Neither
• nasal congestion and/or rhinorrhoea
• eyelid oedema
• forehead and facial sweating Duration of pain: ±15-180 minutes
• miosis and/or ptosis
• a sense of restlessness or agitation Migrainous features
D. Occurring with a frequency between one every other day
and 8 per day Autonomic features
Not side locked
E. Not better accounted for by another ICHD-3 diagnosis.
Neither Tension-type headache
Principles of management
• Stop the pain – quickly
• Bridge to a long term strategy –
don’t want it to recur
• Start a long term preventer
Acute treatment
• Triptan: quick onset
• Subcutaneous sumatriptan ($)
• Intranasal sumatriptan
• (can try oral)
• Oxygen: high-flow
• 12-15 L/min 100% O2 via non-
rebreather mask for 20 min
• Refractory:
• Dihydroergotamine and
Indomethacin may also be
effective
Bridging therapies
• Preventative treatment takes
weeks-months to work
• Bridging therapies provide relief
and limit need for acute
treatment
Options:
• Greater occipital nerve block –
can work for up to 3/12
• Prednisolone: 1mg/kg for 3-5
days then taper over 10-14 days
• Naratriptan 2.5 mg twice a day
for 1 week
Preventative treatments

First line Second line and beyond

• Verapamil • CGRP mAbs
• Typically starting at 80mg TDS • Topiramate
• Need to monitor ECG: heart block,
QTc prolongation • Melatonin
• Increase at two weekly intervals • Gabapentin
by 80mg, checking ECG
• Valproate
• GON blocks
• Deep brain stimulation
Trigeminal
neuralgia
Differentiating trigeminal neuralgia
SUNCT Trigeminal Location Associated features
neuralgia Migrainous features
Ratio (M:F) 2:1 1:2
Age of onset 48 52 Autonomic features SUNCT
Side locked
(unilateral) SUNA
Site of pain V1 67% V1: 10%
Neither Trigeminal
V2 33% V2: 35% neuralgia
V3 0% V3: 30%
Second-
Duration (sec) 1-600 <1-120 Duration of pain:
minutes
Frequency/day 1-600 Triggerable Migrainous features
Autonomic Sy Yes No
Autonomic features
Refractory No Yes Not side locked
period
Neither
Trigeminal neuralgia: diagnostic criteria

ICHD-3
A. Pain has all of the following
characteristics:
• lasting from a fraction of a second to
2 minutes
• severe intensity
• electric shock-like, shooting, stabbing
or sharp in quality
B. Precipitated by innocuous stimuli
within the affected trigeminal
distribution
C. Not better accounted for by
another ICHD-3 diagnosis.
Selected aspects of pathophysiology

Classical TN
• neurovascular compression of the TN
close to root entry zone of pons (most
often by SCA)
• Thinning of myelin sheath at point that it
enters the pons
• Allows transmembrane passage of ions –
axon isn’t made to quickly pump out
sodium
• Becomes hyperexcitable, causes ectopic
impulses and cross-talk between fibres
• Perceived as paroxysmal pain
Management of trigeminal neuralgia

Medical
First line: Peripheral
• Block the sodium channels – • Local – blockade of CN V branches
90% (neurectomy, alcohol injection, RF
ablation, cryolesion)
• Carbamazepine • Destructive – glyceral, mechanical
• Oxcarbazepine compression
Second line: • Central
• Gabapentin, pregabalin, • Microvascular decompression (60-
antidepressants 80%)
• Gamma knife at root entry zone
Questions