Migraine

• prevalence peaks between the ages of 35 and 39 years
• 75% of affected persons report the onset of migraine before the age of 35 years
• female-to-male ratio of 3:1
• an onset of migraine after the age of 50 years should arouse suspicion of a secondary headache disorder
• Triggers:
  • Food
    • tyramine (found in cheese)
    • phenyl ethylamine (found in chocolate)
    • tyrosine / aspartame
    • monosodium glutamate (MSG)
    • caffeine – withdrawal and caffeine
    • nitrates (found in processed meats)
    • histamine (found in wine and beer)
  • Daily use of pain meds – rebound headache.
  • Hormonal changes/menstrual periods
  • Lights
    • Flashing lights, fluorescent lights, light from the TV or computer and sunlight can trigger you
  • Changing weather conditions such as storm fronts, barometric pressure changes, strong winds or changes in altitude.
  • Being overly tired. Overexertion.
  • Dieting, or not drinking enough water.
  • Changes in your normal sleep pattern.
  • Loud noises.
  • Exposure to smoke, perfumes or other odors.
• the frequency of attacks is variable:
  • as high as several per week
  • as low as several per lifetime
• attacks often begin in the morning, possibly waking the person from sleep, but may begin at any time of day or night

classification

1. Migraine without aura
2. Migraine with aura (classical)
   1. Migraine with typical aura
      1. Typical aura with headache
      2. Typical aura without headache
   2. Migraine with brainstem aura(dysarthria, vertigo, or ataxia)
   3. Hemiplegic migraine
   4. Familial hemiplegic migraine (FHM)
   5. Sporadic hemiplegic migraine (SHM)
3. Retinal migraine
4. Chronic migraine
5. Complications of migraine – Status migrainosus, Persistent aura without infarction, Migrainous infarction
6. Migraine aura-triggered seizure
7. Episodic syndromes that may be associated with migraine
   1. Recurrent gastrointestinal disturbance
      1. Cyclical vomiting syndrome
      2. Abdominal migraine
   2. Benign paroxysmal vertigo
   3. Benign paroxysmal torticollis

Defined as: At least five attacks  with

• Headache attacks
  • lasting 4–72 hours (untreated or unsuccessfully treated)
• Character (2 of)
  • unilateral location
    •     Unilateral in 50%
    •     Often frontal in location
  • throbbing/pulsating quality
  • moderate or severe pain intensity
  • aggravation by or causing avoidance of routine physical activity (eg walking or climbing stairs) 
• Associated (1 of)
  • nausea and/or vomiting
  • photophobia and phonophobia
• +/- AURA
  • fully reversible aura symptoms:
    • Visual/ sensory/speech/language/motor/retinal 
  • characteristics:
    • at least one aura symptom spreads gradually over ≥5 minutes
    • two or more aura symptoms occur in succession
    • each individual aura symptom lasts 5–60 minutes
    • at least one aura symptom is unilateral
    • at least one aura symptom is positive
    • the aura is accompanied or followed within 60 minutes by headache

four phases

Prodrome /  aura  /  headache  / postdrome

• 20% experience prodromal changes of hypothalamic involvement before the actual aura or pain commences. 
  • craving for food
  • thirst
  • fatigue/yawning
  • irritability
  • altered emotional states
• 33%  experience an aura
  • Visual auras
    • central loss of vision (central scotoma)
    • hemianopia  
    • flickering lines  
    • zig-zag formation

• Sensory
  • ‘pins and needles’/paraesthesiae
  • Numbness usually starts in the hand, migrates up the arm, then involves the face, lips, and tongue
• motor
• speech aura
• isolated typical aura without the headache– indicates a migraine.
  • This is particularly important in the elderly where the headache of migraine is often absent, causing diagnostic confusion with transient ischaemic attacks. The aura of migraine is distinct, and quite different from vascular phenomena such as amaurosis fugax
• 60–94% have postdrome phase

Tips and traps in diagnosis

• the three-question ID Migraine questionnaire 

1. felt nauseated or sick in the stomach
2. were bothered by light (or a lot more than when they do not have headaches)
3. had limited ability to work, study or do what they needed to do for at least one day.

• sensitivity of 84%
• specificity of 76%
• “yes” to 2/3  effectively identifies migraine sufferers

SNNOOP10 list of red and orange flags
Red flag	Related secondary headache
Systemic symptom/fever	Intracranial infection, carcinoid or phaeochromocytoma
History of neoplasm	Metastatic disease
Focal neurological deficit	Stroke, brain abscess or infection
Worse with eye movement and impaired vision	retrobulbar neuritis
Abrupt onset headache	Subarachnoid haemorrhage(thunderclap headache), pituitary apoplexy, reversible cerebral vasoconstriction syndrome, haemorrhage, cranial or cervical vascular pathology
Onset after the age of 50 years	Giant cell arteritis, neoplasm, mass lesion, vascular disorder, stroke
Change in pattern or recent onset	Neoplasm, headaches from vascular or non-vascular disorders
Positional headache	Intracranial hypertension or hypotension
Precipitated by sneeze/cough/exercise	Posterior fossa malformation, Chiari malformation
Papilloedema	Intracranial hypertension, mass lesions, venous sinus thrombosis
Progressive or atypical presentation	Neoplasm, non-vascular disorder
Pregnancy or puerperium	Postdural headache, pre-eclampsia, venous sinus thrombosis, hypothyroidism, diabetes, pituitary apoplexy, cranial or cervical vascular disorder
Painful eye/autonomic features	Pathology in posterior fossa, pituitary or cavernous sinus, Tolosa–Hunt syndrome or ophthalmic cause
Post-traumatic	Subdural haematoma or other vascular disorder
Pathology of immune system	Opportunistic infection or metastasis
Painkiller overuse or new medication	Medication-overuse headache or medication incompatibility

Neuroimaging Indications

• First or worst severe Migraine Headache
• New onset Migraine Headache in age over 50-55 years old
• Sudden onset Headache
• Abnormal Neurologic Examination
• Not indicated in nonacute Migraine with normal exam

Treatment

• Remove and avoid precipitants
  • avoid triggers (stress, fatigues, hunger, chocolate, red wine, cheese)
  • Avoid OCP (incr stroke risk in pt with migraine with aura, higher risk if >45, smoker)
  • rest in dark, quiet room
• Treatment of migraine is most effective if instigated at the onset of symptoms

Acute treatment 

Mild/Moderate (<2 hours)

NSAID	Oral antiemetics
Aspalgin 900mg	metoclopramide 10mg orally
Panadeine/Aspirin  combo	Prochlorperazine (Stemetil) (5–10 mg)
Naproxen 500–7500 mg	Domperidone (Motilium) (10 mg)
Ibuprofen 400–600 mg
diclofenac potassium 50mg

• Note: 10% Caucasians/ 1-2% Asians are codeine ‘non-responders’, as they cannot metabolise codeine to morphine 
• Avoid NSAIDs in volume depletion, CCF, any impairment of renal function + with concomitant ACEI and or diuretics.

Moderate Migraine refractory to above

• Consider administering at 1 hour for failed improvement with initial meds listed above
• Triptan agents
  • best given early when headache is mild, though not during the aura. 
  • 20-50% can relapse within 48 hr
  • only triptans that have been shown to be effective in children are nasal sumatriptan and oral zolmitriptan
  • All triptans are contraindicated in
    • known/possible CAD
    • within 24 hours of ergot-containing preparations
    • should be used with caution in patients on lithium, MAO inhibitors or SSRIs to avoid serotonin syndrome. 
    • The symptoms of serotonin syndrome:
      • Autonomic: abdominal cramps, diarrhoea, hypotension or hypertension, tachycardia, profuse sweating, hyperpyrexia.
      • Cognitive: agitation, coma, confusion, disorientation.
      • Musculoskeletal: myoclonus, tremors
  • Some patients respond better to a combination of a triptan and a nonopioid analgesic (eg aspirin, ibuprofen, naproxen)

eletriptan	40 to 80 mg orally	If symptoms recur, wait at least 2 hrs before repeat dose	max160 mg/24 hours
naratriptan	2.5 mg orally	If symptoms recur, wait at least 4 hrs before repeat dose	5mg/24 hours
rizatriptan	10 mg orally wafer	If symptoms recur, wait at least 2 hrs before repeat dose	max 30 mg/24 hours
sumatriptan	20 mg intranasally	If symptoms recur, wait at least 2 hrs before repeat dose	max 40 mg/24 hours
	50 to 100 mg orally	If symptoms recur, wait at least 2 hrs before repeat dose	max 300 mg/24 hours
	6mg SC	If symptoms recur, wait at least 1 hr before repeat dose	max12 mg/24 hours
zolmitriptan	2.5 mg orally	If symptoms recur, wait at least 2 hrs before repeat doseIf 2.5 mg tolerated but not effective in previous migraine, give 5 mg at onset of next migraine	max10 m/24 hours

• Consider coadministration with NSAIDs (Indomethacin is available as a suppository)

Severe Migraine Headache (2-6 hours) – Intractable migraine (status migrainosus)

sumatriptan 6 mg	6mg SC	only if a triptan has not been given in the last 2 hours and a parenteral triptan has not been tried
ketorolac	30 mg IM	only if an oral NSAID has not been given in the last 4 to 6 hours
Chlorpromazine(Largactil)	12.5 mg in  NS 0.9% 100 mL IV 30 min	exclude a prolonged QTc intervalfluid bolus to avoid hypotensionmax dose 37.5 mg (2x repeat infusion in needed)if acute dystonic reaction: benzatropine 1-2mg IV
dexamethasone	12 – 20 mg IV	Repeat after 12 hours if needed

Other

• Ergotamine
  • No longer available in Australia
  • 1-2 mg: Oral, rectal, intranasal, parenteral
  • Cheap and long-lasting
  • is used together with caffeine.
    • Caffeine may result in tremors, insomnia and anxiety.
  • Ergotamine is not recommended in children.
  • should not be used in conjunction with macrolides antibiotics
  • severe side effects
    • PUD
    • Rebound headache
    • more risk with CAD.
    • Do not use ergotamine if sumitriptan used in last 6 hours
• Opioid analgesics
  • should be considered as a last resort for acute headache management and if required should provoke a red flag consideration

Rebound/overuse  headache

• Medication overuse will result in a refractoriness of headache frequency , development of chronic daily headache and severity that is very difficult to break
• if the patient is using rescue ergot preparations, analgesics (especially codeine), or triptans on more than 2 days per week, there is the real potential for rebound headache to develop
• Overuse of acute antimigraine drugs frequently negates the effectiveness of prophylactic medication
• Rx
  • 3-week course of naproxen 250-500mg bd, taken regularly, may break the cycle of frequently recurring or unremitting headaches and the habit of responding to pain with analgesics. 
  • If it fails, it should not be repeated

Prophylaxis 

• (if >1/12 depending on function of ADLs)
• all these agents is to ‘start low and go slow 
• Where headaches occur more frequently than once per fortnight, prophylaxis should be offered and the choice determined by the headache type

Medication	Dosage	50% responder rate*	Regulatory status	Authors’ notes
Level A evidence – oral medications (EFNS or AAN)
Propranolol	40 mg (increase at intervals of one week or greater [ie ≥1 weekly] by 40 mg to maximum 40–160 mg total daily dose [BD or TDS])	30–40%	PBS: GB-M, TGA: Yes	Useful in anxiety, perimenopause; caution regarding mood and vivid dreams
Topiramate	25 mg (increase ≥1 weekly by 25 mg to maximum 50–100 mg BD)	46.3%	PBS: Auth-M, TGA: Yes	Useful for weight loss
Sodium valproate	200 mg (increase ≥1 weekly by 200 mg to maximum 200–600 mg BD)	42%	PBS: GB-O, TGA: No	Avoid in women of childbearing age
Flunarizine	5 mg (5–10 mg daily)	58.6%	PBS: No, TGA: SAS	Use with caution in individuals with depression
Level A evidence – injectable medications
OnabotulinumtoxinA	155 units, three times per month	47.1% in CM	PBS: Auth-M, TGA: Yes
Erenumab	140 mg, once per month	41% in CM	PBS: No, TGA: Yes
Fremanezumab	225 mg, once per month	47.7% in CM	PBS: Yes, TGA: Yes
Galcanezumab	240 mg, once per month	27.6% in CM	PBS: Yes, TGA: Yes
Level B evidence (EFNS or AAN)
Amitriptyline	10 mg (increase ≥1 weekly by 10 mg to 25–75 mg daily)	58.6%	PBS: GB-O, TGA: No	Useful for sleep/mood
Pizotifen	0.5 mg TID (1.5–3 mg/d)		PBS: Yes, TGA: Yes	Weight gain (21%–41%), sedation (37%–50%)
Venlafaxine	37.5 mg (increase ≥1 weekly by 37.5 mg to 75–150 mg daily)	28%	PBS: RB-O, TGA: No
Level C evidence (EFNS or AAN)
Candesartan	4 mg (increase ≥1 weekly by 4 mg to 8–32 mg daily)	40.4%	PBS: GB-O, TGA: No	Well tolerated
Gabapentin	300 mg (increase ≥3 days by 300 mg, 900–3600 mg total daily [BD or TDS])	46.4%	PBS: GB-O, TGA: No	Can be useful during perimenopausal
Magnesium	400 mg (400–600 mg daily elemental dose)	–	PBS: No, TGA: No	Well tolerated
Coenzyme Q10	150 mg (150–300 mg daily)	–	PBS: No, TGA: No	Well tolerated
Riboflavin	400 mg (400 mg daily)	–	PBS: No, TGA: No	Well tolerated
Other medications
Cyproheptadine	4 mg (4–12 mg daily)	–	PBS: No, TGA: Yes	Well tolerated
Melatonin	2 mg (4–8 mg daily)	54.4%	PBS: No, TGA: No
Lamotrigine	Pending interactions	46%	PBS: No, TGA: No	Useful with prominent aura symptoms/mood
Nortriptyline	10 mg (increase ≥1 weekly by 10 mg to 25–75 mg nocte)	28.6%	PBS: RB-O, TGA: No	Useful where amitriptyline is not tolerated

EFNS, European Federation of Neurological Societies

AAN, American Academy of Neurology;

Guide to choosing migraine prophylactic drugs

First-line agents	Second-line agents	Third-line agents
AmitriptylinePropranololNadolol	TopiramateGabapentinVenlafaxineCandesartanLisinoprilMagnesiumButterburCoenzyme Q10Riboflavin	FlunarizinePizotifenDivalproex sodium
Special considerations	Appropriate agents
Hypertension or cardiovascular disease	Propranolol, nadolol, lisinopril, candesartan
Initial insomnia	Amitriptyline
Mood disorder	Amitriptyline, venlafaxine
Seizure disorder	Topiramate, divalproex sodium, gabapentin
Pregnant or trying to conceive	Magnesium
Obese	Topiramate
Poor tolerance of medication side effects	Riboflavin, coenzyme Q10, butterbur, propranolol, lisinopril, candesartan

General Measures

• Avoid Stress bursts
  • Spread home or work load out evenly
  • Maintain good Posture
  • Avoid craning neck forward
  • Stay relaxed
• Keep a Headache diary
  • Record date, day of week, and time of day
  • Record precipitating and relieving factors
• Sleep Changes
  • Avoid excessive Fatigue (get adequate sleep)
  • Do not sleep later than normal on weekends
  • Risk of let-down Headache
• Habits
  • Eat at regular times and do not miss meals
  • Eliminate foods thought to provoke Headache
    • Alcohol
    • Red wines
  • Limit foods associated with Rebound Headache
    • Caffeine sources (Tea, Coffee, Soda)
    • Analgesics
  • Consider stopping provocative medications
    • Oral Contraceptives
• Environmental
  • Restrict physical exertion on hot days
  • Avoid glare or exposure to flickering lights
  • Avoid noise or strong smells

Migraine in children

• Common causes of headaches
  • febrile illnesses, with or without ear, nose and throat involvement
  • migraines
  • tension headaches
  • meningitis
  • space-occupying lesions
  • subarachnoid haemorrhage
• Red flags
  • Acute and severe headache
  • Progressive chronic headaches
  • Focal neurology
  • Age <3 years
  • Headache/vomiting on waking
  • Consistent location of recurrent headaches
  • Presence of ventriculo-peritoneal shunt
  • Hypertension
• Migraines often short lived, resolve in 2-3 hours with sleep
• Use ibuprofen first line, avoid aspirin – risk Reye syndrome
• If nausea – ondansetron
• Can use triptans in children > 6 years