headache & migraine Flashcards
Headache pathophysiology
Nerves of muscle and blood vessels surround head, neck, face
○ Pain-sensing nerves set off by: stress, muscle tension, enlarged blood vessels, other triggers
○ Once activated, nerves send messages to brain –> sense pain (as if cmg from deep within head)
primary headaches (ICH3)
migraine
tension-type headache
trigeminal autonomic cephalagias (TACs)
other 1* HA disorders
2* headache
trauma/ injury to head/ neck
cranial or cervical vascular disorder
non-vascular IC disoder
infection
homeostasis disorder
psychiatric disorder
HA. facial pain – disorder of cranium, neck, eyes, ear, nose, sinus, teeth, mouth, facial/cervical struc
neuropathies, facial pains, other headaches
painful lesions of cranial neuropathies and other facial pain
other HA disorders
2nd headache red flags
SNNOOP10
systemic sx (fever)
neoplasm hx (cancer)
Neurologic deficit/ dysfunction
onset of headache SUDDEN
older age (>50yo)
pattern change, recent onset
positional headache (at certain posture)
ppt by sneeze, cough, exercise
papilledema (optic disc)
progressive w/ atypical presentation
preg
painful eye with autonomic features (HR, BP, RR)
post-traumatic HA
pathology of immune system – HIV/ immunocompromised
painkiller overuse / new drug at HA onset
** STROKE sx
FAST (Facial drooping, Arm weakness, Speech difficulties and Time)
weakness of face/arm/leg on 1 side of body
sudden, severe headache w/ no apparent cause
difficulty speaking, understand language
dizzy, loss of balance/ coordination
visual loss
sudden onset of HA, seizures, loss of consciousness
TTH features
- bilateral
- pressing/ tightening (non pulsatile)
- mild-mod pain
- not aggravated by routine activities
- no other sx (pericranial/ cervical muscle tenderness)
- no premonitory sx and aura
duration: 30mins- 7d
freq: infreq ~ daily
differential with cluster headache
- unilateral
- variable pain
- severe - VERY SEVERE pain
- restless, agitation
- cranial autonomic sx SAME SIDE as HA (nasal congestion, swollen eye, sweat)
duration: 15-180mins
freq: freq during clusters
migraines features
- unilateral (can be bilateral too)
- pulsatile/ throbbing
- mod-severe pain
- aggravated by routine activities
- NV, photophobia, phonophobia , aura, allodynia
duration: 4-72hrs
freq:recurrent with variable freq
types of TTH
Infrequent episodic
Freq episodic
Chronic TTH
Medication overuse headache
infreq TTH
<1 ep/ mnth
Duration: 30min - 7d
freq TTH
at least 10 eps occuring on 1-14d/mnth, for >3mnths
Duration: 30min - 7d
chronic TTH
> 15d/mnth average for 3mnths
Duration: hrs-days
MOH
Headache =/> 15 days/mnth in pt with pre-existing headache disorder
Regular overuse > 3mnths of =/>1 drug for acute/ sx tx of headache
* Ergotamines, opioids, triptans/ combi =/> 10 d/mnth
* Simple analgesic (paracetamol, NSAID) =/> 15d/mnth
* Any combi of above or one or more meds than above for =/> 10d/mnth
triggers for TTH
Physical/ emotional stress
Activities that cause head to be held at one position for long time (neck muscle locked, pain receptors triggered)
Alcohol - withdrawal
Caffeine - withdrawal
Cold/ flu or sinus infections
Dehydration
Hunger
mechanism of TTH
1) myofascial - incr tender, inflamm, local ischaemia
2) vascular - incr blood flow to cerebral artery.
Abnormal carotid artery blood flow/ extrcranial vascular resp
3) genetic
4) central - sensitisation, dysfunction in descending pain modulation
acute pain management for TTH
- Paracetamol (w/ or w/o caffeine), aspirin
- NSAID: ibuprofen, naproxen, diclofenac, ketoprofen
prophylactic management for TTH
- Amitriptyline (1st line, tricyclic antidep)
- Mirtazapine (antidep tetracyclic)
- venlafaxine (SNRI)
non-pharm for TTH management
- Avoid triggers
- Stress management
- Posture, neck strain
- Cognitive behavioural therapy, biofeedback, relaxation
- Physical, occupational therapy
- Lifestyle and modification
* sleep hygiene - headache diary (identify triggers)
- medication use (prevent MOH)
how does MOH occur
medication to provide short term pain relief
rebound headache
higher med dose needed to provide relief
vicious cycle of med overuse
diagnose MOH
1) duration of acute HA drugs > 3mnths
2) freq (>/= 15days per mnth)
3) headache not other ICHD3 diagnosis
ergotamines, opioids, triptans/ combi =/> 10d
paract/ NSAID =/> 15d
any combi of above =/> 10d
migraine diagnosis ICHD3 criteria
at least 5 attacks that fulfil —-
1) Headache attack last 4-72hrs (when untx/ unsuccessful)
2) Headache characteristic (=/>2 of 4)
3) Non-headache sx (=/>1) if no aura
- NV
- Photophobia/ phonophobia
4) not accounted for another ICHD3 dx
headache characteristics =/>2 out of 4
Unilateral location
Pulsating quality
Mod-severe pain intensity
Aggravation by/ causing avoidance of routine physical activity (walk, climb stairs)
episodic migraine
over a lifetime
=/>5 migraine attacks lasting 4-72hrs
chronic migraine
> 3 mnths
=/>15 MHDs (mnthly headache day)
and
=/> 8MMDs (mnthly migraine day)
MHDS monthly headache day
a day with migraine-type or TTH
MMDs monthly migraine day (accompanying characteristics)
=/>2 migraine characteristics
* Unilateral
* pulsating
* moderate/ severe
* aggravation by, or causing avoidance of, routine physical activity
If no aura =/> 1 of the following migraine sx
* Photophobia/ phonophobia
* NV
migraine w/ aura
at least 2 attacks fulfilling:
=/> 1 of following reversible aura sx:
(visual/ sensory/ speech, lanaguge / motor/ retinal/ brainstem)
=/>3 of the characteristics
*1 aura sx spread gradually over >5mins
* 2 or more aura sx occur in succession
* each indiv aura sx lasts 5-60mins
* =/>1 sx unilateral
* =/>1 sx is positive
* HA follow/ accompanied by aura (within 60mins)
migraine pathophysiology
prodrome
+/- aura
ictal
postdrome
prodrome caused by
Activation of hypothalamus, neuropeptides (involved in homeostasis)
Regulate homeostasis : burdensome non-pain sx (prodrome, other phases): NV,LOA, fatigue (migraine)
Incr blood flow in early premonitory phase > nitroglycerin induced migraine
neuropeptides like…
leptin, neuropeptide Y and Orexin A/B
hypothalamus responsible for
- Nociceptive processing
- Control sleep-wake cycle
- Feeding
- Thirst
- Arousal
- Autonomic and endocrine regulation
prodrome duration and sx
Few hrs - days
- Fatigue
- Cognitive difficulties
- Mood changes
- Food cravings
- Neck pain
- Yawning
aura caused by
Cortical spreading depression in cortex
1) CSD = Large wave of slow spreading depolarisation within grey matter
a. Inhibits cortical activity
b. 2-6mm/min
2) Change in synaptic activity, EC ion conc, blood flow, metabolism
a. Inhibit cortical activity, reduced blood flow
3) CSD activate trigeminovascular system
Drive aura sx
aura duration and sx
5-60mins
- Visual aura
- Sensory disturbances
- Speech disturbances
- Motor sx
ictal (headache) causes
Neuropeptides (eg CGRP calcitonin-gene related peptide) cause sensitisation, inflammation in central and peripheral trigeminovascular system
lead to pain and non-pain sx in ictal phase
CGRP involvement in migraine pain
- Head pain and other, non-pain sx
- its receptor expressed in multiple anatomic regions relevant to migraine
□ Trigeminovascular
□ Cranial parasympathetic systems
evidence:
- When infused, can induce migraine-like attacks
- CGRP lvls incr sig during migraine attack
- CGRP therapeutics effective
sensitisation and sx (allodynia) in ictal phase
- Sensitise 1* nociceptors and central trigeminovascular neurons
- MRI shows struc abnormalities in brainstem
□ Altered sensory processing and brainstem structure contribute to
□ Severity of allodynia, hypersensitivity to migraine pain
photophobia in migraine
- Retinal and trigeminal nociceptive inputs –> converge in thalamus
□ projects to nociceptive areas of cortex S1/S2
□ exacerbate migraine by LIGHT - Hypersensitise visual cortex (V1/V2) can also contribute to the photosensitive effect
headache duration and sx
4-72hrs
- Headache
- N, V
- Photophobia
- Phonophobia
postdrome caused by
- Region of brain remain activated after headache cessation, olfactory regions, midbrain, hypothalamus
postdrome duration and sx
- Fatigue, food cravings, cognitive sx
Continue in attack but overshadowed by HA sx (pain, NV, aura)
Few hrs - days
* Fatigue
* Difficult conc
* Neck stiffness
interictal
periods b. migraine attacks
hrs - days after attack
- regions remain abnormally active (olfactory, midbrain, hypothalamus)
+ light, - pain
○ Activate visual cortex bilaterally in migraine pts
+light,+ pain
○ Concomitant pain stimulation potentiated visual cortex activation in pt with migraine
TRIGEMINOVASCULAR SYSTEM IN MIGRAINE
- peripheral components
- central components
1) sensitisation/ hyperexcitability
periphery TGM
Relays TGM nociceptor input from meningeal vessels and dura mater –> CNS
central TGM component
(inside the BBB)
○ TGM ganglion receives peripheral nociceptive pain signal —> TGM complex (brain stem) –> thalamus –> cortex
- Experience of pain
○ Activation of other central regions (project TO/ FROM the TGM system) contributes to non-pain sx
TGM thus leads to hyperexcitability
Repeated activation of the trigeminovascular system over time results in a state of nervous system hypersensitivity and sustained pain
Feedback from a sensitized brain may:
1) Potentiate pain signaling
2) Contribute to common migraine symptoms
- Photophobia, phonophobia, and cutaneous/mechanical allodynia
CGRP is a ___?
Calcitonin gene-related peptide
37 aa neuropeptide (calcitonin family of peptides)
roles: nociception, sensory modulation, vasodilation
CGRP receptor found on cell mem of:
migraine patho:
- TGM ganglion
- cerebral and meningeal vasculature
- brainstem
- brain (thalamus eg)
other cell types
- vascular smooth muscle cells
-neurons
- glial cells
- mast cells
CGRP- receptor comprises of
CLR (calcitonin receptor-like receptor) + RAMP1 (receptor activity modifying protein) = heterodimer
translocates from ER –> cell mem
activation of GPCR – heterodimer
1) ligand binding leads to transient receptor activation
2) induce cellular resp (2nd messenger signalling)
3) receptors inactivated and internalised – ENDOCYTOSIS
- recycled/ degraded
CGRP–CGRP-R signaling in migraine pathophysiology
1) activate CGRP-R in TGM
2) CGRP released from storage vesicle by Ca2+ dependent exocytosis
3) peripheral release of CGRP from TGM nerve ending, triggers multiple responses induced by CGRP-R binding ==> sensitise nociceptor TGM neurons
4) peripheral TGM neurons relay migraine pain signals (brainstem –> brain) exp pain
5) central CGRP effect: pain transmission through sensitisation and activation of central processes
- feedback
CGRP results in migraine effects of
vasodilation
peripheral nociceptor activation
neurogenic inflammation
CSD
central TGM sensory activation
central sensitisation
hypothalamic dysfunction and descending control of brainstem, structures
CGRP has high affinity for what else?
AMY1-R (has RAMP1 subunit in common)
expressed in vasculature, pancreas and TGM ganglion
physiologic roles: regulate pp glucose, glycemic control, satiation
acute management of migraine
Mild-mod:
NSAID, non-opioid analgesic, combination
Mod-severe/ mild-mod, respond poorly: migraine-specific agents =
triptans > ergotamine
others: opioids (abusable)
Ditans (5HT1F receptor)
Gepants (Block CGRP receptor)
adjunct for aucte tx
metoclopramide
Anti-emetics: Relief of migraine-related NV when combined with analgesic medication
considerations for acute tx
efficacy, safety, comorbidities, concomitant medications
Rapid pain relief & associated sx
Restore ability to function
risk and benefits of acute tx
Benefits:
* Sx relief
Limitations:
* Potential ADR
- PUD, dependency, tolerance, risk of med overuse headache
* Pt specific CI to use of particular med
* DDI
Preventive treatment for which migraine pt?
AHS: based on HDM and degree of disability caused by attacks
EHF: any pt with migraine, not well-controlled w/ acute + willingness
AHS criteria
offered:
=/>6 HDM, no diasbility
=/>4 HDM, some disability
=/> 3 HDM, severe disability
considered:
4-5 HDM, no disability
3 HDM + some
2 HDM + moderate
- attacks sig interfere with pt daily routines despite acute tx
- freq attacks (=/>4MHD)
- CI/ failure/ overuse of acute tx
- ADR to acute tx
- pt preference
EHF criteria
IMPAIRS QOL +
1) attacks cause =/> 2days DISABILITY per mnth & optimised acute tx does not prevent attack
or
2) risk of overuse of acute tx + pt willing to take daily meds
normal is 4-72hrs
risk and benefits of preventive tx
Potential benefits:
- Avoid escalation in use of acute medications
- May reduce overall cost associated with migraine tx
- MOH
Limitations
- Often associated with pt adherence (ROA)
- SE: dep, cognitive dysfunction, somnolence, constipation, weight gain
- cost of drugs (CGRP ~$2000/ mnth)
preventive tx
antiseizure meds
bb (propanolol, metoprolol)
ARB
CGRP
- gepants (CGRP-R)
- MABS (anti-CGRP antibody// anti-CGRP receptor Ab)
Neuromodulation device
Neurotoxins
initiation of CGRP tx
age =/> 18yo and 1
1) 4-7 MMD + inability to tolerate SE/ inadequate 8wk trial of 2 tx clasess + mod disability MIDAS =/>11, HIT >50
or
2) 8-14 MMD + inability to tolerate SE/ inadequate 8wk trial of 2 tx clasess
or
3) chronic migraine +
inability to tolerate SE/ inadequate 8wk trial of 2 tx clasess //
inability to tolerate/ inadequate resp to min. 2 injs (6mnths) onabotulinumtoxinA
MIDAS scoring disability asssessment
Grade 1 (0 to 5): little or no disability.
Grade 2 (6 to 10): mild disability.
Grade 3 (11 to 20): moderate disability **
Grade 4 (>21): severe disability.
- how many days in last 3mnths, miss work/ shool
- how many days in last 3mnths productivity reduced by 50%
- how many days in last 3mnths, not do HH work
- how many days in last 3mnths productivity in HH work reduced by 50%
- how many days in last 3mnths did you miss regular activities (family, social, leisure)
HIT (headache impact test) criteria
little or no impact (49 or less)
some impact (50–55) **
substantial impact (56–59)
severe impact (60–78).
-how often is pain severe
-how often limit daily activities
- how often wish to lie down
- past 4 wks, how often too tired to work/ daily activities
- past 4 wks, how often felt fed up over HD
- past 4 wks, how often is conc limited
assessing tx efficacy (acute, chronic)
- headache diary
- MIDAS (disability assessment)
- ADR of medications (affect compliance)
continuation of CGRP
- reduction in MHD =/> 50%
- improvement in any of the migraine-specific pt reported outcome measures
- MIDAS (=/>5 pt: base 11-20) (reduce >30%: base >20)
- HIT-6 (=/>5 pt)
- MPFID (=/>5 pt)
