Headache Classification

• Primary
  • Tension Type
    • Tension HA: Bilateral over forehead and neck
    • Cervical Osteoarthritis: Neck
    • Chronic Myositis: Inflammation of muscle tissue
  • Vascular Type
    • Migraine
    • Cluster: Severe, usually w/ autonomic SSx
    • Non-Migraine Vascular: Hangovers, HTN, and post-ictal
• Secondary
  • Trauma
  • Aneurysm and Vascular Malformations
  • Tumor
  • Some systemic disorers
  • Medication-induced

Pathophysiology

The pathophysiology is not fully elucidated. The current theory is that the primary underlying physiology is an intial vasospasm followed by prolonged vasodilation, leading to inflammation and edema. The current theory of the cause of the vasospasm is a phenomena known as the Cortical Spreading Depression (CSD). For an unkown reason, areas of high brain activity, often the occipital lobe, can produce a wave-front of decreased cortical function accompanied by increased extracellular K, H+, and NO, leading to activation of nociceptors of the trigeminal nerve (CN-V) innervating the meninges. This promotes the release of CGRP (calcitonin gene-related peptide), Substance-P, and other neuroinflammatory peptides and inflammatory mediators, which results in significant vasodilation and pain. Relevant 5-HT receptors for migraines include the 5-HT_1B, 5-HT_1D, and 5-HT_1F receptors, which mediate vasoconstriction, inhibition of neurotransmitter release, and inhibition of neuroinflammatory peptides and nociceptive signalling respectively.

Comorbidities

• Depression
• Anxiety Disorders
• Epilepsy
• Stroke
• BPD
• IBS
• CV Dx
• Asthma
• Mitral prolapse
• Raynaud’s Phenomenon

Dx

• Migraine w/ Aura
  • Minimum of 2 attacks
  • Gradual onset
  • Aura lasts 5-60min
  • HA follows aura w/i 60min
  • Normal neuro exam w/ no evidence of other condition inducing HA
• Migraine w/o Aura
  • Minimum of 5 attacks lasting 4-72hrs
  • Any 2 of +…
    • Unilateral
    • Pulsating
    • Aggravated by routine physical activity
    • Moderate-Severe
  • … Any 1 of
    • N / V
    • Photophobia and Phonophobia
  • Normal neuro exam w/ no evidence of other condition inducing HA

    Auras

• Visual
  • Photopsias: Light flashes
  • Teichopsias: Bright, shimmering colors
  • Scotomas: Blind spot in otherwise normal vision
  • Hemiaopias: Blindness in 1/2 field of vision
• Sensory
  • Unilateral tingling or numbness
  • Hemiparesis
  • Opthalmoplegia (eye muscle paralysis)
  • Dysphasia
  • Olfactory Hallucinations
  • Vertigo

    Migraine Variants

• Acephalic: Aura w/o HA
• Hemiplegic: One-sided paralysis w/ dysphagia
• Vertebrobasilar: Diplopia, ataxia, vertigo, and incoordination
• Ophthlmoplegic: Eye muscle paralysis lasting days-weeks after HA
• Retinal: Blindness / visual loss returning to baseline after a few hours

Treatment

Treatment Principles

• Mild-moderate disease
  • Initiate NSAIDs or APAP
  • Initiate combination of APAP / ASA / Cafeine if response inadequate
  • Initiate Severe therapy if inadequate response
• Severe
  • Initiate triptans or ergotamines
  • Initiate combination therapy if response inadequate
  • Sumatriptan, rizatriptan, almotriptan, eletriptan, and zolmitriptan 1st line
  • Naratriptan or frovatriptan for better tolerability
  • Ergotamine or DHE for infrequent HAs or to decrease cost (but less effective)
• Avoid acute therapy to ≤ 2d per week
• Add antiemetics if necessary
  • Metoclopramide 10mg
  • Consider chlorpromazine, prochlorperazine, or promethazine

    Drugs

    NSAIDs

• ASA 325-1000mg PO q6h PRN NTE 4g QD
• APAP 1000mg PO then 500mg PO q4-6h PRN NTE 3-4g QD
  • APAP and metoclopramide is a effective as triptans
• Ibuprofen 400-800mg PO NTE 3200mg QD
• Ketoprofen 75mg PO NTE 300mg QD
• Naproxen 750mg PO then 250mg q12h NTE 1250mg QD
• Ketorolac 30-60mg IM/IV NTE 120mg QD

  Ergot Alkaloids

  MOA

  5-HT_{2A, 1B, 1D, 1F} receptor agonists, as well as partial α₁ agonists

  Drugs

• Ergonovine
• Ergotamine / Dihydroergotamine (DHE)
  • Less likely to cause peripheral vasoconstriction
  • Ergotamine 1-2mg PO
  • DHE 2mg Intranasal

    Triptans

    MOA

    5-HT_{1B, 1D, 1F} agonists

    Drugs

• Sumatriptan (Imitrex)
  • t_1/2: 2hr
  • 50-100mg PO
• Zolmitriptan (Zomig)
  • t_1/2: 2.8hr
  • High ADR rate
  • 2.5mg PO
• Naratriptan (Amerge)
  • t_1/2: 5.5hr
  • 2.5mg PO
• Rizatriptan (Maxalt)
  • t_1/2: 2hr
  • Rapid acting
  • 10mg PO
• Almotriptan (Axert)
  • t_1/2: 3.3hr
  • Low ADR rates
  • 12.5mg PO
• Eletriptan (Relpax)
  • t_1/2: 4hr
  • Very effective, but more common ADRs
  • 40mg PO
• Frovitriptan (Frovan, Miguard)
  • t_1/2: 26hr
  • 2.5mg PO

    Misc

• Isometheptene
  • Works better than tryptans in pts which it is effective for, but does not work for all pts

SEs

• Triptans
  • Somnolence
  • Nausea
  • Dizziness
  • Asthenia
  • Pain in chest
  • Rare
    • Coronary vasospasm
    • Angina
    • V-Tach/Fib
    • MI
• Ergotamines
  • Cyanotic extremeties
  • Ischemic bowel disease
  • N/V
  • Peripheral ischemia

    CIs

• Triptans
  • CVD
  • Cerebrovascular disease
  • PVD
  • Uncontrolled HTN
  • Hemiplegic / Basilar Migraines
  • Use w/ SSRIs/SNRIs due to risk of serotonin syndrome
    • Caution w/ other serotinergic agents
• Ergotamines
  • Same as triptans
  • Renal impairment
  • Hepatic disease
  • Glaucoma
  • Pregnancy

    Prophylaxis

• 1st Line
  • β-Blockers (propranolol or timolol)
    • Propranolol LA 90mg PO QD, then BID, then TID if needed
    • Timolol 10mg PO BID then 20mg PO QD after one month, then 15mg PO BID if needed
    • Atenolol, metoprolo, and bisoprolol can be used if pt needs cardioselective β-blocker, or verapamil can be used
    • If HA frequency has not changed in 8wks, taper and D/C
  • Topiramate
    • Initiate 25mg PO QD, then increase by 25mg weekly to 100-200mg QD
    • Some evidence
  • TCAs
    • Amitriptyline 25-300mg QD
    • Doxepin 10-150mg QD
    • Start low and titrate
    • Drug of choice for mixed headache syndrome (2-8 migraines monthly w/ daily tension HA)
  • Valproate
  • Extended-cycle OCs if menstruation related
• Give in order listed above, unless co-morbid illness (such as depression for TCAs) exists
• 2nd Line (Off-Label)
  • CCBs (verapamil)
  • ACEIs/ARBs
  • Valproate
  • Gabapentin
  • ASA
  • α₁ Antagonists
  • Trazodone
  • Botox
  • Quetiapine
  • Memantine

Status Migrainosus

• Critera: > 72hr w/ or w/o tretment
• Sumatriptan 6mg SubQ w/ anti-emetic and IV fluids
• Consider DHE 1mg SubQ, Ketorolac 30mg IV, and/or steroids

Cluster HAs

• 1st Line
  • Sumatriptan 6mg SubQ, 20mg intranasal
  • O2 100% @ 7-10 L/min
  • Meperidine 50-100mg IM or other opioid
  • Cocaine 10% 0.5mL intranasal
  • DHE
• 2nd Line
  • Sumatriptan 25mg NTE 100mg or equivalent
  • Ergotamine 2mg SL
  • DHE 1mg IM or SubQ
• Prevention
  • Trial off drugs q3-4wks w/o HA
  • Capsaicin 0.03% intranasal
  • Divalproex
  • Verapamil
  • Li
  • Nifedipine
  • Baclofen
  • Ergotamine
  • Topiramate
  • GCs
  • Lidocaine 4% intranasal
  • Gabapentin