302 Pathophysiology of headache

Question 1

What are the pain sensitive cranial structures?

Answer 1

-Cranial venous sinuses with afferent veins
-Arteries at the base of their brain and their major branches
-Arteries of the dura
-Dura near the base of the brain and large arteries
-Dural Cranial and Extracranial nerves
-All extracranial structures

Question 2

What are the pain insensitive structures of the cranium?

Answer 2

Brain parenchyma
Ependyma
Choroid plexus
Pia
Arachnoid
Dura over convexity
Skull

Question 3

What is the definition of a migraine?

Answer 3

Brain disorder caused by altered regulation (neurotransmitters) due to dysfunction of central brainstem functions, and therefore control of sensory afferents (pain sensitive structures)

Question 4

Name some predisposing factors for migraines

Answer 4

Genetics
- Each of these mutations increases glutamate release, enhanced neuronal activation and lowering of threshold for cortical spreading depression

Question 5

What are the symptoms of a prodrome phase of a migraine?

Answer 5

Fatigue/cognitive change:
-Concentration difficulty, fatigue, memory impairment, depression, elation, irritability

Homeostatic alterations:
-Food cravings, thirst, frequency of urination, yawning, sleep disturbance

Sensorysensitivites/nonpainfulmigrainoussymptoms:
-Neck stiffness, photophobia, phonophobia,osmophobia, nausea

Question 6

Activation of which areas during a migraine cause the different symptoms?

Answer 6

Increased ADH secretion – thirst/urination

Increase sensitivity of TCC – Neck stiffness

PET and functional MRI :
show changes in the connectivity within the hypothalamus. The hypothalamus can often be viewed as the “generator”of migraine – homestatic alterations

changes in connectivity with other regions of the brain – fatigue/cognitive change

Increased activity in the occipital lobe – visual sensitivities

Activation of brainstem – nausea

Differences in thalamic and thalamo-cortical activity – allodynia, aberrant sensory processing

Question 7

What are the symptoms of an aura for a migraine?

Answer 7

Visual
-Zig-zag lines, visual fortification

Speech
-Dysphasia

Sensory disturbance
-negative and positive symptoms

Question 8

What is the diagnostic criteria for a migraine?

Answer 8

A: At least five attacks fulfilling criteria B-D

B: Headache attacks lasting 4-72 hr (untreated or unsuccessfully treated)

C: Headache has at least two of the following four characteristics:
-unilateral location
-pulsating quality
-moderate or severe pain intensity
-aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)

D: During headache at least one of the following:
-nausea and/or vomiting
-photophobia and phonophobia

E: Not better accounted for by another ICHD-3 diagnosis

Question 9

What things do you ask in a history for headaches?

Answer 9

Presenting headache
-Constant or episodic?
-Site: Unilateral or bilateral/holocranic
-Headache load: -Frequency/duration/severity

Character of pain: Throbbing, stabbing etc
Precipitating factor

Previous history of headaches

Question 10

Low levels of which neurotransmitter are
associated with headaches?

Answer 10

Serotonin

High levels of the metabolite 5H1AA seen in CSF and urine suggesting a higher turnover of Serotonin

Question 11

What is the role of dopamine in migraines?

Answer 11

Dopamine hypersensitivity leads to symptom:

Nausea, vomiting
Yawning

Question 12

What is CGRP and how does it link to headaches?

Answer 12

CGRP causing dilation of cerebral and dural blood vessels, release of inflammatory mediators from mast cells, and transmission of nociceptive information from intracranial blood vessels to the nervous system

Question 13

What is triptan?

Answer 13

Groups of medications used to treat migraines

Triptans are able to block the pain signals from the peripheral (1st order neuron) through preventing release of neuropeptides including CGRP

Triptans do not have any effect in preventing activation of the central (2nd order neuron) as the latter is sensitised through prolonged activation.
Leads to chronic pain and allodynia

C-fibres:
Release CGRP
5-HT 1F receptor to Seretonin agonist e.g triptan

Adelta fibres
Contain CGRP receptors
5-HT1F receptor to Seretonin agonist e.g triptan

Blood vessels
CGRP receptors
5-HT1B receptor to Seretonin agonist e.g triptan

Question 14

What is cortical spreading depression (CSD)?

Answer 14

A wave of sustained depolarization (neuronal inactivation) moving through intact brain tissue and associated with brain ischemia, migraine aura, and seizures

Question 15

What causes the photosensitivity in migraines

Answer 15

The thalamocortical pathways is modulated by the inputs including from the retina

Question 16

What is the role of the trigeminal nerve in migrains?

Answer 16

It overreacts to stimuli causing a wave of brain activity that leads to a headache and other symptoms

Question 17

What are the cervical nerve inputs to migraines?

Answer 17

Cervical nerves supply the posterior part of the scalp

A GON injection (local anaesthetic and steroids) can help block the pain arising from these nerves and modulate the trigeminocervical complex in the brainstem further reducing pain sensitivity from the trigeminal nerves supplying the anterior part of the scalp and face)

Blocking these nerves at the back to the neck can stop a headache

Question 18

What is included in the postdrome phase of a migraine?

Answer 18

Neuropsychiatric
-Mood changes, impaired concentration, sleep disturbance

Sensory symptoms
-Head soreness, photophobia, phonophobia, speech disturbance

GI symptoms
-Flatulence, N&V, Constipaiton, food craving, abdominal pain, diarrhoea

General systemic symptoms
-Tiredness, urinary retention, fluid retention

Question 19

Which structures are involved in the prodrome, aura, and postdrome of a migraine?

Answer 19

Prodrome:
Hypothalamus, Thalamus

Aura:
Cortical spreading depression

Migraine attack:
Release of CGRP
Trigeminocervical complex
Upper cervical nerves

Question 20

How are migraines linked to hormones?

Answer 20

Migraines are more common in females

More prevalent around menstruation and menopause due to a decrease in Oestrogen

Reduced during pregnancy due to an increase in Oestrogen

Net effect of Oestrogen is to increases Seretonin levels
Therefore migraines are more likely when Oestrogen levels decrease causing Seretonin levels to decrease

Oestrogen facilitates the glutaminergic system
-Glutaminergic pathways are involved in the induction of Cortical spreading depression
-Prostaglandin secretion is highest during menstruation which is involved in signalling pain. This contributes to menstrual migraines

Question 21

What are the lifestyle changes that help treat migraines?

Answer 21

Avoidance of triggers
Hydrate, reduce caffeine, alcohol
Regular meals
Good sleep hygiene
Exercise

Question 22

What pharmacological treatments are there for migraines?

Answer 22

Abortive treatments:
Triptans – Decrease CGRP release
NSAIDs – Decrease prostaglandin secretion
Paracetamol
Antiemetics – Decrease Dopamine centrally
Preventatives:
Oral drugs
Anti-hypertensives
Anti-epileptics
Antidepressants
Injectables
Botox – blocks release of neurotransmitters
CGRP antagonists – blocks CGRP pathway

Question 23

Name some novel drugs for migraines?

Answer 23

-Ditans (Lasmiditan)
5HT-1F receptor agonist
Inhibits peptide release

-Gepants (Umbrogepant, Rimgepant)
CGRP receptor antagonist (small molecule)

Question 24

What are the different types of headaches?

Answer 24

-Tension (a mild migraine)
Pain > 4 hours
No migrainous features
Often bilateral
Prefers to be still

-Migraine
Pain > 4 hours
+++ migrainous features
Unilateral or bilateral
Prefers to be still

-Cluster
Pain < 4 hours
Prominent autonomic symptoms
Side-locked
Agitated

Question 25

What are some causes of tension headaches?

Answer 25

Stress, Anxiety, Depression, Lack of sleep
Poor posture

Accumulative reaching a threshold for triggering a headache

Question 26

What are some clinical assessment red flags of headaches?

Answer 26

-Age: Greater than 50 yrs
-Onset: Thunderclap < 5mins, NDPH
-Severity: “worst headache of their life”
-Progression: Rapid or developing associated features.
-Triggers: Provoked by valsalva, exercise, sex, postural change.
-Systemic symptoms: Rash, weight loss, fever, neck stiffness.
-Risk factors: HIV, Suspected malignancy, surgery, shunt in situ, inflammatory disorders, recent head injury.
-Neurological signs: optic nerve swelling, hemiparesis, altered consciousness, visual field defect, cranial nerve palsies, seizures.
-Raised ICP features: N&V, Position dependent, Visual obscurations, pusalatile tinnitus, worse with Valsalva maneouvres

Question 27

What are the common types of secondary headaches?

Answer 27

-Brain tumours
-Vascular disorders
-Brain haemorrhage
-Giant cells arteritis
-Reversible cerebral vasoconstriction syndrome (RCVS)
-Non-vascular intracranial disorder
-Idiopathic intracranial hypertension
-Low pressure headache
-Disorders of homeostasis
-Hypertensive encephalopathy
-Facial pain
-Trigeminal neuralgia