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La migraine
- 1. Pediatric Headache and Migraine Current Management and Controversies in the Emergency Department Lawrence Richer MD MSc FRCPC Associate Professor CHU Sainte Justine Oct 29, 2015
- 2. Disclosure • Faculty: Lawrence Richer • Relationships with commercial interests: – Grants/Research Support: CIHR Catalyst Grant, WCHRI – Speakers Bureau/Honoraria: N/A – Consulting Fees: N/A – Other: N/A • All recommendations made without RCT supporting evidence in pediatrics is declared and only offered as a consideration
- 3. Objectives • Consider difference diagnosis of headache in the Pediatric ED • Review basic migraine physiology as it relates to migraine in the ED • Review current evidence for the treatment of migraine in the ED • Consider some controversies, unanswered questions, and ‘best practices’
- 4. Headache in the ED • URTI • Minor head trauma • Primary headaches – 54% of all non‐traumatic neuro in ED • Secondary headaches – Vascular (stroke, RCVS, hemorrhage) – Intracranial hypertension (tumour, IIH) – Orthostatic headache (IC hypotension, POTS) – Metabolic disorders
- 5. Thunderclap Headache • Reaches 7 or more in < 1 min • Etiology – Subarachnoid hemorrhage – Other vascular • Reversible cerebral vasoconstriction syndrome (RCVS) – recurrence over days • Cerebral artery dissection • Pituitary apoplexy • Sinovenous thrombosis • Posterior reversible encephalopathy syndrome (PRES) – Other (infectious, vasculitis, high or low ICP
- 6. Phases of migraine ED Charles A. The Evolution of a Migraine Attack - A Review of Recent Evidence. Headache. 2012 Dec 20. fatigue; euphoria; depression; irritability; food cravings; constipation; neck stiffness; increased yawning; and/or abnormal sensitivity to light, sound, and smell
- 9. CSD may trigger the trigeminovascular system Ferrari, M. D., Klever, R. R., Terwindt, G. M., & Ayata, C. (2015). Migraine pathophysiology: lessons from mouse models and human genetics. The Lancet. http://doi.org/10.1016/S1474- 4422(14)70220-0
- 11. Genetics • Familial Hemiplegic Migraine – Type 1 (CACNA1A) – vg P/Q type Ca++ channel – Type 2 (ATP1A2) – Na+/K+ ATPase pump – Type 3 (SCN1A) – vg Na+ channel – Other ‐ SLC1A3, PRRT2, and SLC4A4 • Susceptibility genes (clinic and population based) – Glumatminergic neurotransmission – Synapse development and plasticity – Pain sensing – Metalloproteinases – Vasculature and metabolism
- 13. Russo A, Tessitore A, Giordano A, et al. Cephalalgia. 2012 Oct;32(14):1041–8. Executive resting-state network connectivity in migraine without aura. Cognitive symptoms (attention deficit, difficulty finding words, transient amnesia, and reduced ability to navigate in familiar environments)
- 14. Silberstein SD. Emerging target-based paradigms to prevent and treat migraine. Clin. Pharmacol. Ther. 2013 Jan;93(1):78–85.
- 16. ACR Appropriateness Criteria for Child with Headache Primary Headache • No imaging is indicated for typical migraine. • In ophthalmologic migraine with focal neurologic symptoms of unilateral ptosis or complete third‐nerve palsy, MRI is recommended. • MRI is also recommended for patients with miscellaneous findings such as vertigo, basilar artery migraine syndrome, persistent confusion migraine syndrome, progressive chronic headache, or hemiplegic migraine. • MRI should be performed for patients with seizures and postictal headaches. Secondary Headache • If neurologic signs or symptoms of increased intracranial pressure are present, MRI is recommended. If MRI is not available or there are problems with sedation, CT should be performed. • CT of the head without intravenous contrast is recommended for sudden severe headaches (thunderclap headaches). • If subarachnoid hemorrhage is detected, CT or conventional angiography should be performed. MRA is also appropriate but is generally considered less sensitive in detecting small aneurysms. • If intracranial hemorrhage is present, MRI of the brain should be performed if possible. Obtaining a concomitant MRA is recommended. Hayes LL, Coley BD, Karmazyn B et al. American College of Radiology. ACR Appropriateness Criteria. Headache—child. Reston (VA): ACR [Internet]. 2012[cited 2015 Jun 25]; 8. Available from: https://acsearch.acr.org/docs/69439/Narrative/
- 17. CATCH rule
- 18. Appropriateness Rating Category N Imaged % Important Abnormalities Incidental Abnormalities Usually not appropriate 72 4 6% 0 1 May be appropriate 13 8 61% 1 1 Usually appropriate 10 8 80% 1 3 Imaging Audit - 95 patient visits sampled - Diagnosis: headache in 35, migraine in 53, meningeal infection in 1, neoplasm with hydrocephalus in 1, metabolic disease in 1 and other non-relevant conditions in 4 - 4 patients imaged did not meet any appropriateness criteria, but each had prior neurosurgery Hayes LL, Coley BD, Karmazyn B et al. American College of Radiology. ACR Appropriateness Criteria. Headache—child. Reston (VA): ACR [Internet]. 2012[cited 2015 Jun 25]; 8. Available from: https://acsearch.acr.org/docs/69439/Narrative/
- 20. Predictors of Abnormal Imaging • “First”, “Worst”, thunderclap, or progressive – Bilateral headache > secondary cause (Masano, 2014) • *Focal motor findings • *Unsteady gait / ataxia • *Altered level of consciousness • *Signs/symptoms of raised ICP • *Hypertension (and tachycardia) • *Young age Massano D, et al. J Pediatr. 2014;165(2):376‐82.
- 24. Approach to abortive therapy • Start with ibuprofen – Ensure right dose, right time – Add metoclopramide 5‐10 mg PO • Consider other NSAID • Consider a triptan – Almotriptan – Sumatriptan + Naproxen sodium – Rizatriptan • Consider infusion
- 25. Drug Tmax (mins) Potency Dose Ibuprofen 45 ++ 10 mg/kg (max 800 mg) Acetaminophen 45-60 ++ 15 mg/kg (max 1000 mg) Naproxen sodium 60 ++ > 12 years: 220 mg or 275 mg (generic); not controlled release Diclofenac potassium (Cambia)* 15-30 +++ > 12 years: 50 mg oral solution (safety and effectiveness not established in pediatrics) Oral analgesics for migraine *Not approved for pediatric patients
- 26. Triptans Drug Approval Dose Almotriptan Y (Can1) 6.25 mg or 12.5 mg PO Sumatriptan/naproxe n Y (US1) 10 mg/60 mg PO Rizatriptan Y (US2) 5 mg PO (<40 kg) 10 mg PO (>40 kg) Sumatriptan Y (US) 25-100 mg PO 5 or 20 mg NS 3 or 6 mg SC Zolmitriptan Y (US) 2.5 or 5 mg PO/NS Eletriptan N 20 or 40 mg PO Naratiptan N 1-2.5 mg PO 112‐17 years 26‐17 years
- 27. Novel therapies • Calcitonin gene‐related peptide (CGRP) receptor antagonist – Better than placebo – Development terminated • Serotonin 5‐HT1F receptor agonist (Lasmiditan, COL‐144) – Better than placebo • Combined serotonin (5‐HT 1B/1D) receptor agonist and neuronal nitric oxide synthase (nNOS) inhibitor – Negative phase 2 • Transient receptor potential vanilloid (TRPV1) receptor modulators – Negative phase 2
- 28. Novel therapies • Glutamatergic targets – Ketamine – In development ‐ Tezampanel (LY293558), BGG492, LY466195, ADX10059 • Propofol
- 29. WHAT NEXT?
- 30. Trigeminal Sensitization Early treatment (when pain is mild) most effective Non-selective COX A/B inhibitor may still be effective
- 31. Practice variation in Canada • Dopamine antagonists (39.5%) • metoclopramide > prochlorperazine • Fluid bolus (24.3%) • Parenteral NSAIDS (9.8%) • Significant variation between sites with all treatments Richer LP, et al. Pediatrics. 2010;126(1):e150‐5.
- 33. • n=62 • All received 10 ml/kg NS bolus over 30 mins • Discharged with naproxen sodium for 24 hours Brousseau DC, Duffy SJ, Anderson AC, Linakis JG. Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac. Ann Emerg Med. 2004 Feb 1;43(2):256–62. Prochlorperazine vs. Ketorolac
- 34. Agency for Health Research and Quality. Acute Migraine Treatment in Emergency Settings. 2012; Comparative Effective Review Number 84. Adult data only
- 35. Phenothiazine vs. metoclopramide Kelly A-M, Walcynski T, Gunn B. The relative efficacy of phenothiazines for the treatment of acute migraine: a meta-analysis. Headache. 2009 Oct 1;49(9):1324–32. Approximately 15 mm mean difference on VAS in favor of phenothiazines
- 36. Diphenhydramin e Akathisia Rating Scale Objective: 2‐minute seated observation • Inability to remain seated (is the patient shifting)? • Any semipurposeful or purposeless leg or foot movements? Subjective: Three questions • Do you feel restless within, or the urge to move, especially in the legs? • Are you unable to keep your legs still? • Are you unable to remain still, standing or sitting? Prochlorperazine‐induced akathisia = Change in objective scale ≥1 point + change in subjective scale ≥2 points (from preprochlorperazine to postprochlor‐ perazine assessment). Vinson DR, Drotts DL. Diphenhydramine for the prevention of akathisia induced by prochlorperazine: a randomized, controlled trial. Ann Emerg Med. 2001 Feb 1;37(2):125– 31.
- 37. ED visits in pediatric health centers • 35 pediatric EDs (2009–2012) ‐ 32 124 children with migraine – 5.5% had a return ED visit within 3 days • Meds ‐ nonopioid analgesics (66%); dopamine antagonists (50%) – metoclopramide or prochlorperazine; diphenhydramine (33%); ondansetron (21%); Triptans and opiate medications (3% each) • Metoclopramide had a 31% increased odds for an ED revisit within 3 days compared with prochlorperazine – Ondansetron had similar revisit rates to those receiving dopamine antagonists. • Diphenhydramine with dopamine antagonists was associated with 27% increased odds of an ED revisit Bachur RG, et al. Pediatrics. 2015.
- 38. Other dopamine antagonists • Droperidol – Butyrophenone – Mean difference in VAS ~ 40 mm – Possible risk of QT prolongation • Chlorpromazine – Associated with increased risk of hospitalization in one retrospective study
- 39. Ketorolac • Survey (n=40) – 78% always or sometimes use ketorolac among Alberta pediatric ED physicians – 84% of those use it in combination with other medications • Ketorolac + metoclopramide / prochlorperazine – Used in 36% of ED presentations in Canada
- 40. RCT metoclopramide +/‐ ketorolac • n=53 (8 to 17 years) – n=26 ketorolac; n=27 placebo – no significant difference • 1/4 mild akathisa • 2/3 had recurrence of headache Richer et al., not yet published
- 42. Dihydroergotamine – side effects • skin reactions (29 percent) and/or local reactions (22 percent) • sedation (20 percent) • digestive issues (12 percent) • nausea or vomiting (11 percent) • chest symptoms (9 percent)
- 43. Best practice – first line therapy? • Prochlorperazine better than metoclopramide • Consider droperidol if prochlorperazine not available and metoclopramide not sufficiently effective – Probable increased risk of side‐effects • Consider combination therapy – Evidence for DHE + neuroleptic/metoclopramide
- 44. Propofol • Rapid onset – GABAA receptor potentiation – Na+ channel blocker – Endocannabinoid system • Propofol > dexamethasone = SC sumatriptan • Risk of addiction • Ongoing pediatric study (NCT02485418) – IV propofol infusion starting at 20 mcg/kg/min for 20 minutes, then 30 then 40 Moshtaghion H, et al. Pain practice 2014; published online July 12. DOI: 10.1111/papr.12230.
- 45. Ketamine • Analgesic and anesthetic properties – antagonist of NMDA glutamate receptor • Possible treatment of prolonged aura – Blocks cortical spreading depression – Ketamine 25 mg IN vs. Midazolam 2 mg IN – Reduced severity but not duration of aura
- 46. Magnesium • Magnesium sulfate 30 mg/kg IV (max 2000 mg) – Infused over 30 min – 1000 mg dose diluted in 50–100 mL of 5% dextrose water or normal saline – Cardiorespiratory monitor
- 47. Dexamethasone Colman I, Friedman BW, Brown MD, Innes GD, Grafstein E, Roberts TE, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008 Jun 14;336(7657):1359–61.
- 48. Best practice ‐ recurrence • Dexamethasone may reduce headache recurrence although no data availalbe in children • Consider dexamethasone 0.5 mg/kg IV (max 25 mg) single dose prior to discharge especially if known to experience recurrence – Adult studies support IV delivery, but PO bioavailability is high as well
- 49. When to admit? • Partial response in ED • Repeated visits to ED • Dehydration, intractable vomiting • Co‐morbidities – Psychological – Other medical (e.g. hypertension) • Further investigation
- 50. Dihydroergotamin e Side Effects Chest pain (more common with sumatriptan), nausea (more common with DHE), drowsiness, flushing, neck stiffness, vertigo, weakness, and injection site reactions • 70% response • repeated dosing may be more effective (IN and IV) • 3 and 6 day protocols • nausea is a limiting SE • sumatriptan SC may be superior initially, but DHE more likely to sustained pain free Kabbouche MA, et al. Headache. 2009;49(1):106‐9.
- 51. Best practice ‐ admission • Admission may be associated with better outcomes when treating chronic daily headache – Consult other disciplines (e.g. psychiatry) – Hydration and carbohydrate replacement • Consider – Repeated dosing of DHE with neuroleptic / metoclopramide Marmura MJ and Goldberg SW. Current neurology and neuroscience reports. 2015;15(4):13.
- 53. ED Treatment of Post‐Traumatic HA • Avoid medication overuse, light activity, hydration • Are there migraine characteristics? – Use migraine therapy per local protocol – Case series of sumatriptan or DHE show benefit • Amitriptyline frequently prescribed symptom reducing treatment Dubrovsky AS, Friedman D, Kocilowicz H. Pediatric post‐traumatic headaches and peripheral nerve blocks of the scalp: a case series and patient satisfaction survey. Headache. 2014;54(5):878–87.
- 54. Dubrovsky AS, Friedman D, Kocilowicz H. Pediatric post‐traumatic headaches and peripheral nerve blocks of the scalp: a case series and patient satisfaction survey. Headache. 2014;54(5):878–87. • Peripheral nerve block – 71 % reporting immediate relief – Decrease mean intensity of 93% – GON + supra‐orbital nerve (SON) in 60% – GON alone in 27% – GON + lesser occipital nerve +/‐ SON in 14%