302 Pathophysiology of headache Flashcards
What are the pain sensitive cranial structures?
-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
What are the pain insensitive structures of the cranium?
Brain parenchyma
Ependyma
Choroid plexus
Pia
Arachnoid
Dura over convexity
Skull
What is the definition of a migraine?
Brain disorder caused by altered regulation (neurotransmitters) due to dysfunction of central brainstem functions, and therefore control of sensory afferents (pain sensitive structures)
Name some predisposing factors for migraines
Genetics
- Each of these mutations increases glutamate release, enhanced neuronal activation and lowering of threshold for cortical spreading depression
What are the symptoms of a prodrome phase of a migraine?
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
Activation of which areas during a migraine cause the different symptoms?
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
What are the symptoms of an aura for a migraine?
Visual
-Zig-zag lines, visual fortification
Speech
-Dysphasia
Sensory disturbance
-negative and positive symptoms
What is the diagnostic criteria for a migraine?
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
What things do you ask in a history for headaches?
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
Low levels of which neurotransmitter are
associated with headaches?
Serotonin
High levels of the metabolite 5H1AA seen in CSF and urine suggesting a higher turnover of Serotonin
What is the role of dopamine in migraines?
Dopamine hypersensitivity leads to symptom:
Nausea, vomiting
Yawning
What is CGRP and how does it link to headaches?
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
What is triptan?
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
What is cortical spreading depression (CSD)?
A wave of sustained depolarization (neuronal inactivation) moving through intact brain tissue and associated with brain ischemia, migraine aura, and seizures
What causes the photosensitivity in migraines
The thalamocortical pathways is modulated by the inputs including from the retina
What is the role of the trigeminal nerve in migrains?
It overreacts to stimuli causing a wave of brain activity that leads to a headache and other symptoms
What are the cervical nerve inputs to migraines?
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
What is included in the postdrome phase of a migraine?
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
Which structures are involved in the prodrome, aura, and postdrome of a migraine?
Prodrome:
Hypothalamus, Thalamus
Aura:
Cortical spreading depression
Migraine attack:
Release of CGRP
Trigeminocervical complex
Upper cervical nerves
How are migraines linked to hormones?
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
What are the lifestyle changes that help treat migraines?
Avoidance of triggers
Hydrate, reduce caffeine, alcohol
Regular meals
Good sleep hygiene
Exercise
What pharmacological treatments are there for migraines?
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
Name some novel drugs for migraines?
-Ditans (Lasmiditan)
5HT-1F receptor agonist
Inhibits peptide release
-Gepants (Umbrogepant, Rimgepant)
CGRP receptor antagonist (small molecule)
What are the different types of headaches?
-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
What are some causes of tension headaches?
Stress, Anxiety, Depression, Lack of sleep
Poor posture
Accumulative reaching a threshold for triggering a headache
What are some clinical assessment red flags of headaches?
-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
What are the common types of secondary headaches?
-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
