Headache

Question 1

PAIN SENSITIVITY OF THE CRANIAL STRUCTURES

i) which four structures are pain sensitive?
ii) name five structures that are pain insensitive
iii) name a key neurotransmitter and key neuropeptide implicated in headache
iv) name three brainstem nuclei involved in processing pain

Answer 1

i) pain sensitive - dural cranial/extra cranial nerves, veins, arteries and all extracranial structures
ii) insensitive - brain parenchyma, ependyma, choroid plexus, meningeal layers (dura over convexity) and skull

iii) NT = 5HT
NP = CGRP (calcitonin gene related peptide)

iv) trigeminocervical complex, superior salivatory nuc, locus coruleus, dorsal raphe nic, hypothalamus

Question 2

HEADACHE CLASSIFICATION

i) which two headaches account for 99% of all primary headaches? name another primary headache
ii) what are secondary headaches?

Answer 2

i) migraine and tension type account for 99%
- also have trigeminal autonomic cephalagias (cluster headache)

ii) secondary > due to another cause > account for 1%

Question 3

MIGRAINE

i) what is it? what is altered?
ii) what is usually seen on imaging?
iii) what are the four phases of migraine? how long may each last?

Answer 3

i) brain disorder caused by altered regulation (NTs) due to dysfunc of central brainstem function and therefore control of sensory afferents (pain sensitive structures)
ii) dont usually see anything structurally on imaging

iii) prodrome > few hrs to days
aura > 5-60 mins
attack > 4-72hrs
post drome > 24-48hrs

Question 4

PHASES OF MIGRAINE

i) name two symptoms that may be seen in prodome, aura, migraine attack and postdrome
ii) which area of the brain is involved in activation of the pathway? what does this alter? which area of the brain is then activated?
iii) which key process is involved in aura?

Answer 4

i) prodome - irritable, depress, yawning, food craving, concentration problems
aura - vis disturb, loss of sight, numbness, tingling
attack - throbbing, drilling, nausea, vom, photophobia, neck pain
post drome - low conc, fatigue, depressed, euphoric, lack of comprehension

ii) hypothalamic activation > alters thalamo cortical circuits and brain connectivity > brain stem activation
iii) aura = cortical spreading depolarisation

Question 5

MIGRAINE PRE DISPOSING FACTORS

i) which rare single gene mutations can cause familial hemiplegic migraines? (3)
ii) what NT do all of these mutations act on? what does this lead to?
iii) how is this NT related to cortical spreading depression

Answer 5

i) FHM1 (calcium channel), FHM2 (astrocyte dysfunction), FHM3 (Na channel)
ii) dysfunction in all causes increased Glu in cleft > increased activation
iii) increased Glu = lowers the threshold for cortical spreading depression

Question 6

PRODROME OF MIGRAINE

i) what are the three categories of symptoms?
ii) how may ADH be implicated?
iii) what may be seen on PET and fMRI?
iv) changes in activity of which brain area may be responsible for allodynia, aberrhant sensory processing?

Answer 6

i) fatigue/cognitive change (low conc, memory, depress, elation, irritable)
homeostatic alteration (food crave, thirst, inc urine, yawn, sleep disturb)
sensory sensitivity - neck stiff, photophobia, nausea

ii) increase ADH secretion
iii) may show changes in connectivity within the hypothalamus (generator of migraine)
iv) differences in thalamuc and thalamocortical activity

Question 7

AURA OF MIGRAINE

i) name three things that may be seen? how can it be differentiated from a stroke?
ii) what key event is the cause of the aura phase?

Answer 7

i) visual - zig zag lines
speech - dysphasia
sensory disturbance - both negative and positive (in stroke its only negative)

ii) cortical spread of depression - increased neuronal depol in a strip and decreased depolarisation around the area

Question 8

CORTICAL SPREAD OF DEPRESSION

i) secretion of which two molecules causes it?
ii) what triggers it?
iii) name three drugs that stop the process that can be used for migraine treatment?

Answer 8

i) large amount of extracell potassium and glutamate secretion
ii) interact between hypothal, thalamus and brainstem nuceli trigger it (decrease the threshold for trigger)
iii) topiramate, amitryptiline, propranolol

Question 9

DIAGNOSTIC CRITERIA FOR MIGRAINE

i) which two broad things are needed for dx?
ii) how many attacks are needed to fulfil criteria?
iii) between which time period must headache last?
iv) one of which two assoc symptoms must be present?

Answer 9

i) absence of red flag symptoms and fulfilment of criteria
ii) at least 5
iii) 4-72 hours
iv) nausea/vomiting and photo/phonophobia

Question 10

SEROTONERGIC PATHWAY

i) what levels of serotonin are assoc with migraines?
ii) high levels of which metabolite are seen in CSF/urine?
iii) which drug class can work on 5HT receptors to relive migraine symptoms? name a downstream molecule that is inhibited
iv) hypersensitivity to which NT leads to assoc symptoms of migrame such as nausea, vomiting and yawning

Answer 10

i) low levels
ii) high levels of 5H1AA

iii) triptans can work on 5HT receptors
- downregulates CGRP release

iv) DA hypersens

Question 11

CGRP

i) what does its release trigger? what treatment against it can be used? which ganglion does it work in?
ii) which nerve fibres release it? are these myelinated?
iii) which fibres contain a recptor for it? what do they then do after CGRP binds?
iv) name another place CGRP receptors are found?

Answer 11

i) release shown to trigger migraines
- MAB against it - migraine prevention
- works in trigeminal ganglion / node of ranvier

ii) released by unmyelinated C fibres
iii) release triggers receptors on A delta dibres > transmit message central then peripheral (percieve pain)
iv) also found on blood vessels

Question 12

TRIGEMINOVASC SYSTEM IN THE DURA

i) which fibres are activated that leads to CGRP release?
ii) what does CGRP release cause? how does this lead to neurogenic inflammation?
iii) what fibres does neurogenic inflam activate? where does the signal get transmitted back to?
iv) which process spreads through the cortex and aggreagates afferents leading to perception of pain

Answer 12

i) c fibres activated
ii) CGRP acts on blood vessels > vasodilation > releas eof proteins > neurogenic inflammation
iii) NG inflam activates a delat fibres > signal back to brainstem
iv) cortical spread of depol

Question 13

PERIPHERAL AND CENTRAL SENSITISATION

i) which part of the pain pathway can triptans block? how do they do this?
ii) why are triptants not very effective for chronic migraines?
iii) name two symptoms that may be seen in chronic headaches

Answer 13

i) triptans block pain signals form periph 1st order neurons > prevent rel of NPs eg CGRP
ii) central sensitisation has been established (2nd order neurons) - so blocking first order doesnt have any effect

iii) central sens has occured >chronic pain, allodynia eg touching scalp is painful
- allodynia not seen in periph sens (only in central sens)

Question 14

TRIGEMINO NEUROVASCULAR SYSTEM

i) which nucleus is activated by the trigeminal cervical complex that leads to ANS symptoms?
ii) name three ANS symptoms seen?
iii) how is photophobia in migraine explained in relation to thalamocortical pathways?

Answer 14

i) TCC activates superior salivatory nucleus > sphenopalatine gang > ANS symp
ii) conjunctival injection (red eye), lacrimation (water eye) rhinorrhea (water nose) , stuffy nose
iii) light decreases the threshold of TC pathways > more exciteable when there is more light input into retina

Question 15

CERVICAL NERVE INPUTS

i) which part of the scalp do cervical nerves supply?
ii) which infection can block pain arising from these nerves? what does it fuether modulate and what is the overall outcome

Answer 15

i) posterior scalp

ii) greater occip nerve injection (local anaes + steroids) can block pain from these nerves
- modulates the TCC > further reduces pain sensitivity from trigeminal nerves supplying ant scalp and face

Question 16

POST DROME

i) do most patients get it?
ii) what are the four main groups of symptoms?

Answer 16

i) yes - 81-94% of patients get it

ii) neuropsych - mood change, impaired conc, sleep disturb
Sensory - sore head, photophobia, phonophobia, speech disturb
GI - flatulence, N+V, constipation, food crave
general systemic - tired, urine retention, fluid retention

Question 17

MIGRAINE SUMMARY

i) which two brain area are responsible for prodrome?
ii) which mechanism occurs in aura?
iii) which NP is released in migraine attack? which complex is involved?

Answer 17

i) hypothalamus and thalamus
ii) cortical spreading depression

iii) release of CGRP
- involvement of trigeminocervical complex

Question 18

HORMONES AND MIGRAINES

i) which two times may they be more prevalent? when may they be less prevalent?
ii) how is oestrogen implicated? how does this further impact 5HT?
iii) how is the Glu system affected? how does this affect migraines with aura?
iv) levels of which molecule are highest during menstruation and how does this contrib to menstrual migraines

Answer 18

i) menstruation and menopause due to decreased oestrogen
- less in pregnany due to increase in oestrogen

ii) low oestrogen leads to low 5HT - lowers threshold for a migraine

iii) high oestrogen levels are assoc with high Glu levels
- Glu facilitates cortical spreading depression > aura
- even though low prev of migraine in pregnancy - more of them have aura

iv) prostaglandin secretion is highest during menstruation > pain
- inc PGs > menstrual migraines

Question 19

TREATMENT FOR MIGRAINE

i) name four lifestyle interventions
ii) name three abortive tx and what they do?
iii) name three preventative treatments?
iv) which two injectables may be given?

Answer 19

i) lifestyle > avoid triggers, hydrate, reduce caffiene, ETOH, regular meals, good sleep, exercise
ii) abortive > triptans (decrease CGRP release), NSAIDs (decrease PG secretion), paracetamol, anti emetics (decrease DA centrally)
iii) preventative > anti hypertensive, epilepsy, anti dep > mod NTs

iv) botox > blocks NT release
CGRP antag > blocks CGRP pathway

Question 20

PACAP PATHWAY

i) what do VPAC1 and VPAC2 mediate? how does this lead to inflammation?
ii) what does systemic admin of PAC1 trigger?

Answer 20

i) VPAC1 and 2 mediate vasodilation > leaky bv, inflammation
ii) PAC1 triggers migrane

Question 21

TYPES OF HEADACHE

i) what is the most important question to ask?
ii) which type of headache prefers to be still, bilateral pain, no migraine features and pain over 4hrs?
iii) name three characs of migrane
iv) what is prominent autonomic symptoms, like movement, agitated, pain <4hrs?
v) name three common causes of tension headahce

Answer 21

i) does the pain last more or less than 4 hours?
ii) tension
iii) pain >4hrs, uni or bilateral, prefer to be still
iv) cluster headache
v) stress, anx, depression, lack of sleep, poor posture

Question 22

RED FLAGS IN CLINICAL ASSESS

i) over what age? what onset?
ii) which three triggers are red flag? why?
iii) three systemic systems?
iv) three RF?
v) what does abssence of red flag symptoms indicate?

Answer 22

i) >50 yrs, onset <5mins
ii) provoked by valsalva, exercise, sex, postural change
iii) rash, WL, fever, neck stiff
iv) HIV, suspected malig, surgery, inflam disorders
v) absence > dealing with a primary headache

Question 23

IDIOPATHIC INTRACRANIAL HYPERTENSION

i) what group is this commonly seen in?
ii) which gene is implicated in increased ICP > headache?
iii) what may be seen in the eyes?
iv) what needs to be done to help this
v) what type of headache is worse on standing/sitting and relieved by laying down? can be triggered by LP?

Answer 23

i) obese young females
ii) 11bHSD1 > increases CSF prod, increases ICP > headache
iii) papilledema
iv) patient needs to lose weight
v) low pressure headache

Question 24

SUMMARY

i) what are headaches classified into?
ii) what type os due to dysfunction in pain network?
iii) what type is due to insult?
iv) what cause should be investigated for if there are red flags in the history

Answer 24

i) primary and secondary
ii) primary
iii) secondary
iv) investigate for a secondary cause