The Thunderclap Headache

1. The Thunderclap Headache Amy Yu, PGY-3 July 14 2010 McGill University

2. Outline • Subarachnoid hemorrhage • Why do we care? • How do we diagnose it? • Then what? • Migraine • Evaluation • Treatment

3. SAH – Why do we care? • Because it can kill your patient • Average case fatality rate 51% • 10% die before reaching the hospital • 25% die within 24 hours of SAH onset • 45% percent die within 30 days • Because you can do something about it • 30-50% have sentinel bleed or "warning leak“ • Sudden and severe headache preceding SAH by 6-20 days

4. SAH – Etiology • Most SAHs are caused by ruptured saccular aneurysms • 15-20% negative angiography • 24% will have lesion on 2nd angiography • Other etiologies • Trauma, AVM, vasculitides, intracranial arterial dissections, amyloid angiopathy, bleeding diatheses, and illicit drug use (cocaine and amphetamines)

5. SAH – Risk factors • Cigarette smoking • #1 preventable RF for SAH, more prominent in women and aneurysmal SAH • Dose-dependent, risk decline with quitting • Hypertension (RR 2.5) • Alcohol • Moderate to heavy consumption RR 2.1 • Sympathomimetic drugs • Phenylpropanolamine (appetite suppressants, cold remedies), cocaine • Estrogen deficiency • Antithrombotic therapy • Not  risk, but worsens outcome

6. SAH – Risk factors • Genetic risk • AD PCKD, EDS, other CT disease • Worrisome family history • Two affected 1st degree relatives • One affected 1st degree relatives: need to screen ~300 ppl to prevent one fatal SAH • 1-2% Prevalence of intracranial saccular aneurysm (up to 5% radiographic & autopsy) • 3-25 per 100,000 Aneurysmal SAH

7. SAH – Presentation • Aneurysm rupture  rapid release of blood in CSF, rapid increase in ICP • Bleeding last a few seconds • Can recur, usually within 1st 24 hours • Most common symptoms • Onset of sudden, severe headache, “worst headache of my life” • Lateralized in 30% (usually ipsilateral to aneurysm) • May have: brief LOC, seizure, nausea, vomiting, meningismus

8. POP QUIZ 37 y.o. ♂ sudden onset severe h/a while weight-lifting. Examination normal. Now h/a free with maxeran. What is the next step in management? • Reassurance and d/c home with f/u • CT head and if normal d/c home • CT head, Lumbar puncture • Admission for observation

9. POP QUIZ 37 y.o. ♂ sudden onset severe h/a while weight-lifting. Examination normal. Now h/a free with maxeran. What is the next step in management? • Reassurance and d/c home with f/u • CT head and if normal d/c home • CT head, Lumbar puncture • Admission for observation

10. SAH – Presentation • Prospective study of sentinel headache in aneurysmal SAH. Linn FH et al. Lancet 1994;344(8922):590-3 • 148 sudden severe h/a patients for evaluation of SAH • 25% was diagnosed with SAH • 12% with headache as the only symptom • Physical exertion • May be an acute trigger for SAH • Moderate or greater exertion in the two hours prior to SAH (OR 2.7, 95% CI 1.6-4.6)

11. SAH – Physical examination • Retinal hemorrhage • Vitreous hemorrhage (Terson’s syndrome) • Meningismus • Decreased level of consciousness • Focal neuro signs (CN III palsy, CN VI palsy, bilateral leg weakness)

12. POP QUIZ Why are the following signs seen in aneurysmal SAH? • CN III palsy • CN VI palsy • Bilateral leg weakness

13. POP QUIZ Why are the following signs seen in aneurysmal SAH? • CN III palsy – PCoA, SCA • CN VI palsy – Raised ICP • Bilateral leg weakness – ACA involvement

14. SAH – CT head, non-contrast • Sensitivity • 98% in first 12 hours • 93% in first 24 hours • 80% at 72 hours • 70% at 5 days • 50% after 7 days

15. SAH – Lumbar puncture • Classic finding • Elevated opening pressure • Elevated RBC count that does not diminish between Tube #1 to #4 • Xanthochromia post centrifugation

16. POP QUIZ LP done for first thunderclap headache, CT head normal Tube #1 132 RBC, Tube #4 19 RBC • What is your diagnosis? • What further information would you like? • What is the next step?

17. Distinguishing Traumatic Lumbar Puncture From True SAH Kaushal, Edlow J of Emerg Med, Vol 23, No 1, pp. 67–74, 2002 • CSF Red cell count • RBC disappears over days to weeks • No standard criterion for how many RBC’s in the CSF can definitely diagnose a SAH • Three-tube test • No absolute differences associated with diagnosis, unless the count in final tube approaches zero • Cannot assess concurrent SAH and traumatic tap • Consider letting out extra CSF in the 3rd tube

18. SAH vs. Traumatic tap • Xanthochromia • Hemoglobin degradation appears 4-10 hours from bleed, may last for > 2 weeks • Needs immediate centrifugation and analysis • Visual inspection very poor specificity • Need spectrophotometry, but unavailable at most centres • Sensitive, but non-specific

19. SAH vs. Traumatic tap • Differential of xanthochromia • High CSF protein • Jaundice • Carotene addiction • Meningitis • Severe degenerative disc disease

20. SAH vs. Traumatic tap • Opening pressure • Can help R/O other conditions (IIH, CSVT) • Not elevated in traumatic tap, is elevated in 60% of SAH • Abbrescia KL, The effect of lower-extremity position on cerebrospinal fluid pressures, Acad Emerg Med. 2001 Jan;8(1):8-12. • Positioning of the legs lead to 1cmH2O difference • Other tests • CSF D-dimer • CSF Bilirubin • Requires further validation • Repeat LP at higher interspace • Clot formation

21. You diagnose SAH, now what? • Consult neurosurgery and neuroradiology • CTA and MRA • Non-invasive • Useful for screening and surgical planning • Sensitive at identifying aneurysms >3-5mm • CTA 83-98%

22. Pitfalls in SAH evaluation • Be alert and think about SAH when faced with acute, severe headache • Understand the limitations of CT head • If you think about doing an LP, you should probably do it • CTA or MRA are not diagnostic tests for SAH • Remember that 2-5% of the population may have an unruptured aneurysm

23. DDx of thunderclap headache • Other vascular disease (AVM, dissection) • Intracerebral hemorrhage • Migraine headache • Tension headache • CVST • Pituitary apoplexy • CSF hypovolemia syndrome • Syncope

24. Part II:Migraine management

25. Migraine epidemiology • Migraine prevalence • 18% female • 6% male • Highest among 25-55 year olds • International classification of headache disorders (2004)

26. Migraine without aura A. At least 5 attacks fulfilling criteria B-D B. Headache attacks lasting 4-72 h (untreated or unsuccessfully treated) C. Headache has ≥2 of the following characteristics: 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (eg, walking, climbing stairs) D. During headache ≥ 1 of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia E. Not attributed to another disorder

27. Typical aura w/ migraine h/a A. At least 2 attacks fulfilling criteria B–D B. Aura consisting of ≥1 of the following, but no motor weakness 1. Fully reversible visual sxs (positive and/or negative features) 2. Fully reversible sensory sxs (positive and/or negative features) 3. Fully reversible dysphasic speech disturbance C. ≥2 of the following 1. Homonymous visual sxs and/or unilateral sensory sxs 2. At least 1 aura symptom develops gradually over 5 min and/or different aura symptoms occur in succession over 5 min 3. Each symptom lasts ≥5 and ≤60 min D. H/A fulfilling criteria B-D for Migraine without aura begins during the aura or follows aura within 60 min E. Not attributed to another disorder

28. Migraine with aura • Typical aura with migraine headache • Typical aura with non-migraine headache • Typical aura without headache • Familial hemiplegic migraine (FHM) • Sporadic hemiplegic migraine • Basilar-type migraine

29. The rational clinical examination series • Does This Patient With Headache Have a Migraine or Need Neuroimaging? • Michael E. Detsky et al. • JAMA, September 13, 2006, Vol 296, No. 10

30. POUNDing • Pulsatile quality • duration of 4-72 hOurs • Unilateral location • Nausea or vomiting • Disabling intensity • Yes to 4 out of 5, LR 24 of definite migraine versus non-migrainous headache • Yes to 3 out of 5, LR 3.5 • Yes to 1-2 out of 5, LR 0.41

31. Individual variables • 4 most predictive variables distinguishing migraine from tension-type headache • Nausea LR 19 • Photophobia LR 5.8 • Phonophobia LR 5.2 • Exacerbation by physical activity LR 3.7

32. Does this patient need neuroimaging? • Variable prevalence of intracranial pathology • 1% in chronic headache • 43% in thunderclap headache • Rule out red flags • Cancer or HIV • Sudden onset of symptoms • Onset after age 50 years • Accelerating pattern • Systemic illness (fever, stiff neck, rash) • Focal neurologic signs and symptoms

33. Nonspecific treatment • NSAIDs • ASA • Acetaminophen • Baclofen • Antihistamine • Opioids • Combinations • ASA and Acetaminophen • ASA/Amphetamine/Caffeine (Excedrin) • ASA/Butalbital/Caffeine (Fiorinal) • Acetaminophen/Codeine (Empracet)

34. Nonspecific treatment • NSAIDs • Ensure adequate trial, e.g. Advil Gel caps 600mg at onset of headache • May reverse central sensitization in migraine • ASA 1gm IV is used in Europe for acute migraine • 1gm effervescent ASA (Alka-Seltzer) • Avoid Opioids • Significant side effect (nausea, sedation, etc.) • May worsen central sensitization • Avoid Butalbital (Fiorinal) • No benefit shown • High risk of habituation and dependency

35. Aspirin with or w/o antiemetic for acute migraine h/a in adults Kirthi V et al. Cochrane Database Syst Rev. 2010 Apr 14;4:CD008041 • ASA 900mg or 1000mg superior to placebo • NNTs 8.1 (2-hr pain-free), 4.9 (2-hr h/a relief), 6.6 (24-hr h/a relief) • ASA reduces N/V, photo-, phonophobia • Metoclopramide significantly further reduces N/V • Sumatriptan 100 mg was better only for 2-hour pain-free • Adverse events with ASA • Mostly mild and transient • Slightly more often than placebo • Less common than Sumatriptan 100mg

36. Specific Tx – Triptans • 3 main mechanisms of action • Cranial vasoconstriction • Peripheral trigeminal inhibition • Inhibition of transmission through second order neurons of the trigeminocervical complex

37. Oral triptans in acute migrainetreatment: a meta-analysis of 53 trials Michel D Ferrari et al. Lancet 2001; 358: 1668–75 • Collected raw patient data of 53 double-blind, randomised, controlled, clinical trials of oral triptans in migraine (12 unpublished) • Summarized estimates across studies for important efficacy and tolerability parameters • Rizatriptan, Eletriptan, and Almotriptan provide the highest likelihood of consistent success

38. Oral triptans in acute migrainetreatment: a meta-analysis of 53 trials • Rizatriptan 10 mg (Maxalt) • Consistent and rapid freedom from pain is desired • Eletriptan 80mg (Relpax) • High efficacy and low recurrence, lower tolerability • Almotriptan 12.5mg (Axert, Almogran) • High tolerability and good efficacy • Sumatriptan 50mg and 100mg (Imitrex, Imigran) • Good efficacy and tolerability • Longest clinical experience • Zolmitriptan 2.5mg and 5mg (Zomig, AscoTop, Zomigon) • No specific advantages nor flaws • Naratriptan 2.5mg (Amerge, Naramig) • Good tolerability • Slower onset of improvement (useful in mild or moderate migraine) • Frovatriptan (Frova) • Lack of data

40. Triptans • Should be used if >10 days 50% disability in 3 mths • Administered as early as possible after onset of h/a • Safe medications in patients without cardiovascular disease or major vascular RF • No clinically important differences in coronary vasoconstriction effects  No triptan is demonstrably safer than the others • Choice dependent on patient characteristics and preferences • Individual responses to a triptan cannot be predicted

41. Specifc Tx – Ergots • Vasoconstriction by stimulating • Adrenergic receptors • 5-HT receptors • Norepinephrine receptors (venoconstrictors) • Two main Ergots • Ergotamine (ET), more potent vasoconstrictor • Superior to placebo, inferior to PO Sumatriptan 100mg • Dihydroergotamine (DHE) • Also inferior to Sumatriptan, but recurrence rate lower

42. Ergotamine • Oral bioavailability is <1% • 1st pass hepatic metabolism • Rectal suppository: better plasma level, less nausea • Oral ET is appropriate for slowly evolving migraine without early-onset nausea • One 1-mg tablet at the start of an attack • Maximum total dose of 6 mg per attack • Maximum 2 days per week with an interval of at least 4 days • Avoiding habituation, rebound, and daily headache

43. Dihydroergotamine • Worse oral bioavailability than ET • Incomplete passage through GI mucosa • Hepatic 1st pass metabolism • 40% bioavailability intranasally • Peak plasma level • IV 1-2 minutes • IM 24 minutes • IN 30-60 minutes • Advantages • Fewer side-effects • Habituation is rare • Once h/a relief is established, recurrence is low

44. Dihydroergotamine • IN DHE • 1 spray (0.5mg) into each nostril at first sign of migraine, can be repeated in 15 minutes (2mg in 4 sprays) • Relatively low clinical efficacy • High frequency of prolonged nasal stuffiness • SC and IM DHE is equivalent • DHE 1mg SC/IM, can be repeated in 60 minutes • Patients are advised to mix DHE with 0.25-0.50 mL of 1% to 2% lidocaine to reduce injection-site burning • Maximum 4mg per attack, 21mg per week

45. Ergots – summary • Do not mix Ergots or with triptans • Do titrate dose to minimize side effects (nausea) • Recognize ET is highly associated with medication overuse headache • Recognize Ergots are not clearly superior to the triptans (except in the case of IV DHE) and can be less convenient to the patient

46. What to do in the ER? • IV Metoclopramide or prochlorperazine 10 mg • Can be given with Diphenhydramine IV • IV Dexamethasone 10-25mg • Can reduce h/a recurrence • Consider Prednisone for a few days with rapid taper (e.g. Prednisone 50mg x3d, 40mg x3d, etc.) • IV DHE 1 mg + Metoclopramide 10 mg • Do not mix triptan or other ergots on same day • Avoid in patients with vascular disease • SQ 6mg Sumatriptan • Avoid in vascular disease, but can be used as a step-up to oral Triptan

47. Other Tx to consider in the ER • NSAIDs • Advil • Ketorolac 30mg IV, 60mg IM • Magnesium 1gm IV • Good for patients with aura • ASA

48. Medication overuse headache • Abortive agents should be used ≤2 d/week • DHE and Naproxen are less likely to cause MOH • ICHD2 revised criteria for MOH A. Headache present on ≥15 days a month B. Regular overuse for >3 mths of ≥1 acute/symptomatic tx drugs 1. Ergotamine, triptans, opioids, or combination analgesic medications on ≥10 days a month for >3 mths 2. Simple analgesics or any combination of ergotamine, triptans, analgesic opioids on ≥15 days a month for >3 mths without overuse of any single class alone C. Headache has developed or markedly worsened during medication overuse

49. If too much barbiturate or codeine is on board, patient is treated with pheno 15mg tid x 3d, bid x 3d, qd x 3d During these first 3 weeks nortryptiline is begun and patient is allowed to continue with usual symptomatic RX FU at 8-10 weeks from Day 1 35 mg W-3 1) DHE 0.5mg bid x 2 weeks, 0.5mg qd x 2 weeks + DHE as rescue Rx OR 2) Pred. 60 mg qd x3d, 50mg qd x 3d,… OR 3) Naproxen 500mg bid for 2 weeks. Rescue medications as per patient specifics 25 mg W-2 10 mg W-1 Day 1 Pre-detoxification Detoxification STOP all symptomatic Rx Michel Aubé md

50. Thank you for your attention!