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INTERNATIONAL CLASSIFICATION of HEADACHE DISORDERS 2nd edition (ICHD-II) ICHD-II. Cephalalgia 2004; 24 (Suppl 1) Headache: a clinical tour for residents (part 1) November 2009 Lucy Vieira MD ©International Headache Society 2003/4 Introduction Headache: 2 major categories – Primary: migraine, TTH, TACs, other – Secondary: all major categories covered Incidence of migraine Peak Incidence males •Migraine with aura: 5yo (6.6/1000) Peak incidence females Migraine with aura: 12-13yo (14/1000 person-years) without aura: 14-17yo (19/1000 person-years) •Migraine without aura: 10-11yo(10/1000) Migraine * After age 10 i girls>boys Stewart et. al. 1993. Amer J Epidemiol 34:1111-20 – the reported age of migraine incidence in a prevalence study Prevalence of Migraine •Prevalence highest from 25-55 yo. •Prevalence is stable over time. •After age 55 prev. starts to decrease – CDH or remission American migraine study-I- info from 15,000 homes in 1989 AMS-II – 1999. AMPP – 2005. prevalence mig: 18%F (12% adults) 6%M Lipton Headache 38:87-96 1998. Lipton Headache 41:646-57. Lipton Headache 45:792 2005 How Migraine Stacks Up Against Other Common Diseases 12% Affected Americans: 7% 5% 6% 1% Rheumatoid arthritis Asthma Diabetes Osteoarthritis Migraine From the Centers for Disease Control and Prevention, the US Census Bureau, and the Arthritis Foundation. Burden of Migraine Individual: 25% of female migraineurs have>4 severe attacks/m (need bed rest) Societal: loss of work productivity (13 billion/y) - healthcare use: 4% of all visits for headache -accounts for 1/3 of all OTC analgesic use. Lipton 2001 Headache 41: 638-45. Hu 1999 Arch Intern Med 159:813-18. Holmes 2001 Neurology 56(s 1):13-19 Diagnosis Patient meeting criteria for migraine – 56% migraine – 39% sinus diagnosis – 31% tension headache – 7.5% sick headache – 10% cluster headache AMPP 2005 TTH Overall prevalence is 38% (F=M) 3-4X more common than migraine Low Burden and don’t consult MD Peak Prevalence: 30-39 Cluster Headache 80% episodic Prevalence: 0.06-0.4% Male>>female (3:1) CDH 4% of the population -in clinic: most are probable chronic migraine with MOH -in general pop may have CTTH (Bahra etal.2002 Neurology,58,354-361 Co-Morbidity of Migraine (greater than co-incident association) Depression (OR 2.5) Anxiety (OR 2.7) Epilepsy, Bipolar disease, Restless leg syndrome MA: White matter lesions – esp post fossa MA: PFO, ASA Scher Ann et al., Curr Opin Neurol 18:305-310 INTERNATIONAL INTERNATIONAL CLASSIFICATION CLASSIFICATION of of HEADACHE DISORDERS HEADACHE DISORDERS 2nd edition (ICHD-II) 2nd edition (ICHD-II) ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Classification Part 1: Primary headache disorders Classification Part 2: Secondary headache disorders Part 3: Cranial neuralgias, central and primary facial pain and other headaches ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Classification Part 1: The primary headaches 1. Migraine Classification 2. Tension-type headache 3. Cluster headache and other trigeminal autonomic cephalalgias 4. Other primary headaches ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Classification Part 2: The secondary headaches 5. Headache attributed to head and/or neck trauma Classification 6. Headache attributed to cranial or cervical vascular disorder 7. Headache attributed to non-vascular intracranial disorder 8. Headache attributed to a substance or its withdrawal 9. Headache attributed to infection ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Classification Part 2: The secondary headaches 10.Headache attributed to disorder of homoeostasis Classification 11. Headache or facial pain attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cranial structures 12. Headache attributed to psychiatric disorder ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Classification Part 3: Cranial neuralgias, central and primary facial pain and other Classification headaches 13. Cranial neuralgias and central causes of facial pain 14. Other headache, cranial neuralgia, central or primary facial pain ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1. Migraine 1.1 Migraine without aura 1.2 Migraine with aura 1. Migraine 1.3 Childhood periodic syndromes that are commonly precursors of migraine 1.4 Retinal migraine 1.5 Complications of migraine 1.6 Probable migraine ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1.1 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 1.1 Migraine without aura ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1.1 Migraine without aura Notes • If <5 attacks but criteria B-E otherwise met, code as 1.6.1 Probable migraine without aura • When attacks occur on 15 d/mo for >3 mo, code as 1.1 Migraine without Notes aura + 1.5.1 Chronic migraine • Pulsating means varying with the heartbeat • In children: – attacks may last 1-72 h – occipital headache requires caution • In young children: – photophobia and/or phonophobia may be inferred from their behaviour 1.1 Migraine without aura ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1.5.1 Chronic migraine New entrant to classification 1.5.1 Chronic migraine A. Headache fulfilling criteria C and D for New entrant classification 1.1 Migraine withoutto aura on 15 d/mo for >3 mo B. Not attributed to another disorder New proposed definition: Headache on>15 days per month and >8days per month meeting criteria for 1.1 or 1.2 or responding to migraine specific treatment ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1.2 Migraine with aura 1.2.1 Typical aura with migraine headache 1.2 Migraine auraheadache 1.2.2 Typical aura with with non-migraine 1.2.3 Typical aura without headache 1.2.4 Familial hemiplegic migraine (FHM) 1.2.5 Sporadic hemiplegic migraine 1.2.6 Basilar-type migraine ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 RARE INHERITED MIGRAINE SYNDROMES - AD GENE PROTEIN RESULT FHM-1 CACNA1A P/Q Ca2+ channels ↑ presynaptic Ca2+ FHM-2 ATP1A2 Na+/K+ATPase ↓ K+ and glutamate clearance FHM-3 SCN1A Na+ channel Persistent Na+ influx 1. Sanchez del-Rio M et al. Curr Opin Neurol. 2006;19:294–298. 2. Pietrobon D. Neurotherapeutics. 2007;4:274–284. 1.2.1 Typical aura with migraine headache 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 symptoms including positive and/or negative features 2. fully reversible sensory symptoms including positive and/or negative features 3. fully reversible dysphasic speech disturbance 1.2.1 Typical aura with migraine headache ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1.2.1 Typical aura with migraine headache C. At least two of the following: 1. homonymous visual symptoms and/or unilateral sensory symptoms 2. at least one 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. Headache fulfilling criteria B-D for 1.1 Migraine without aura begins during the aura or follows aura within 60 min E. Not attributed to another disorder 1.2.1 Typical aura with migraine headache ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 1.2.6 Basilar-type migraine As 1.2.1 except: B. Aura consisting of 2 of the following fully reversible symptoms, but no motor weakness: 1. dysarthria; 2. vertigo; 3. tinnitus; 4. hypacusia; 5. diplopia; 6. visual symptoms simultaneously in both temporal and nasal fields of both eyes; 7. ataxia; 8. decreased level of consciousness; 9. simultaneously bilateral paraesthesias 1.2.6 Basilar-type migraine C. At least one of the following: 1. at least one one aura symptom develops gradually over 5 min and/or different aura symptoms occur in succession over 5 min 2. each aura symptom lasts 5 and 60 min ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Childhood Periodic Syndromes Dx N&V Cyclic vomiting + Abd. migraine +/- BPV childhood + Abd. Pain Vertigo Duration 1h-5d + 1-72h + Mins-hrs 2. Tension-type headache 2.1 Infrequent episodic tension-type headache <1/m Tension-type headache 2.2 2. Frequent episodic tension-type headache 1-15/m 2.3 Chronic tension-type headache >15/m 2.4 Probable tension-type headache No Nausea or vomiting! ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 3. Cluster headache and other trigeminal autonomic 3. Cluster headache cephalalgias and other trigeminal 3.1 Cluster headache autonomic 3.2 Paroxysmal hemicrania cephalalgias 3.3 Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) 3.4 Probable trigeminal autonomic cephalalgia ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 3.1 Cluster headache A. At least 5 attacks fulfilling criteria B-D B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 min if untreated C. Headache is accompanied by 1 of the following: 1. ipsilateral conjunctival injection and/or lacrimation 2. ipsilateral nasal congestion and/or rhinorrhoea 3. ipsilateral eyelid oedema 4. ipsilateral forehead and facial sweating 5. ipsilateral miosis and/or ptosis 6. a sense of restlessness or agitation D. Attacks have a frequency from 1/2 d to 8/d E. Not attributed to another disorder 3.1 Cluster headache ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 Case • 37 yo male with 3 yr hx HA. 6-8/d • Severe stabbing with ipsilateral lacrimation, nasal stuffiness. Lasts 20 min. Normal exam and investigations. • Seen by 3 prior neurologists. • Failed Sumatriptan, O2, DHE, Verapamil, Methysergide, valproic acid, Lithium. • You see him and he is headache-free within 48 h of new treatment! 3.2 Paroxysmal Hemicrania Unilateral attacks lasting 2-30 minutes Accompanied by at least one of the following: – – – – – 1. 2. 3. 4. 5. ipsilateral ipsilateral ipsilateral ipsilateral ipsilateral conjunctival injection and/or lacrimation nasal congestion and/or rhinorrhoea eyelid oedema forehead and facial sweating miosis and/or ptosis Attacks have a frequency > 5/day most of the time Attacks are prevented completely by therapeutic doses of indomethacin Short Lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) Attacks of unilateral periorbital or temporal stabbing or pulsating pain lasting 5sec4min Ipsilateral conjunctival injection and lacrimation Attack frequency from 3-200/day. Differentiating features of SUNCT and trigeminal neuralgia Feature SUNCT Trigeminal neuralgia _______________________________________________________ Sex ratio (M:F) 2:1 1:2 Site of pain V1 V2/3 Severity of pain Mod. to severe Very severe Duration (seconds) 5–250 <1 Autonomic features Prominent Sparse or none Refractory period Absent Present Carbamazepine response Partial Complete ________________________________________________________ Matharu MS, Goadsby PJ. J Neurol Neurosurg Psychiatry 2002;72(suppl 2):ii19–ii26. 4.1 Primary Stabbing Headache A. Head pain occurring as a single stab or a series of stabs and fulfilling criteria B-D B. Exclusively or predominately felt in the distribution of the first division of the trigeminal nerve. C. Stabs last for up to a few seconds and recur with irregular frequency ranging from one to many per day D. No accompanying symptoms E. Not attributed to another disorder. 4.7 Hemicrania continua (new entrant to the classification) All of the Following: 1. Unilateral moderate pain. 2. Daily and continuous, without pain-free periods. 3. Exacerbations of severe pain. During exacerbations ipsilateral >1: 1. Conjunctival injection and/or lacrimation 2. Nasal congestion and/or rhinorrhoea 3. Ptosis and/or miosis Complete response to indomethacin. Hemicrania Continua Not included in the TACs: neuroimaging shows activation of both areas related to migraine and cluster headache. Matharu MS, et al., Posterior hypothalamic and brainstem activation in hemicrania continua. Headache 2004; 44: 747–61. Distinguishing TACs and related headaches Short Duration Headaches I__1sec______1min_____4min__________15min____________30min_______45min_I……....I__24h ↑ Primary Stabbing Headache (sec) ↑ Trigeminal Neuralgia (sec-2min) ↑ SUNCT (5sec-4min) ↑ SUNA (2sec-10min) ↑ Paroxysmal Hemicrania (2min-30min) ↑ Cluster Headache (15min-180min) …………… ↑ Migraine (4 to 72 hr) Short lasting and/or unilateral headache Headache duration frequency autonomic treatment Type attacks features ----------------------------------------------------------------------------------------Cluster 15-180 1-3/d +++ various min. CPH 2-30 5+/d var.++ indomethacin min. SUNCT secfew-50 ++ lamictal? min PSH sec var none indomethacin HC contin./ many jabs + indomethacin TGN jabs sec many none carbamazepine Autonomic Features Manjit S. Matharu, et al.,Drugs 2003; 63 (16): 1637-1677 Primary short-lasting headaches (<4h) Prominent autonomic features Cluster headache Paroxysmal hemicrania SUNCT syndrome Sparse or no autonomic features Trigeminal neuralgia Idiopathic stabbing headache Cough headache Benign exertional headache Benign sex headache Hypnic headache SYMPTOMATIC TACS: You should always consider investigating TACs! Associated pathologies in 40 TAC-like cases Vascular diseases Inflammatory diseases Infectious diseases Intracranial tumours Extracranial tumours Malformations Post-traumatic Miscellaneous Trucco et al., Cephalalgia 24 (3), 173-184. CPH 4 3 1 7 2 1 1 3 HC 0 0 2 1 0 0 5 1 SUNCT 1 0 1 0 0 4 0 1 CONCLUSIONS Consider MRI of the brain in most patients who present with rarer TAC syndromes. Always proceed to imaging if: 1. Abnormal neurological exam 2. Clinical symptoms are atypical – do not fit strict criteria. 3. Older age at onset 4. Insufficient response or need for prolonged high dose therapy with indomethacin in CPH or HC Giraud, et al., Cluster-like Headache: literature review. J. Headache and Pain 2002,3:71-8 4. Other primary headaches 4.1 Primary stabbing headache 4.2 Primary cough headache 4.34.Primary exertional headache Other primary headaches 4.4 Primary headache associated with sexual activity 4.5 Hypnic headache 4.6 Primary thunderclap headache 4.7 Hemicrania continua 4.8 New daily-persistent headache (NDPH) ICHD-II. Cephalalgia 2004; 24 (Suppl 1) ©International Headache Society 2003/4 4.5 Hypnic Headache A. Dull headache fulfilling criteria B-D B. Develops only during sleep and awakens patient C. >2 foll. Present: A. occurs>15/m B. Lasts>15 min after waking C. First occurs after age 50 D. No autonomic S/S and no more than one of nausea, photo/phono E. Not attributed to another disorder 4.6 Primary thunderclap Headache • Sudden onset with max intensity <1min • Lasts 1h-10d • Doesn’t recur regularly over subsequent weeks or months • Not attributed to another disorder Always make sure that there is no underlying cause! DDX TCH: • Aneurysmal subarachnoid hemorrhage or other ICH • Carotid or vertebral artery dissection • CVST • Pituitary apoplexy • Unruptured cerebral aneurysm or AVM • Reversible cerebral vasoconstriction • CSF hypovolemia syndrome Treatment: TACS Treatment of Cluster Headache: the challenge A syndrome of: -very severe, rapid onset, short duration headaches(15-180min) -with fast recovery (ie: resuming work) -several attacks per 24 hours -occurring at particular times and during sleep. Treatment of Cluster Headache: components • 1. Rapid onset transitional treatment • 2. Prophylactic treatment • 3. Abortive treatment 1. Transitional Prophylaxis for Rapid Suppression of Attacks Options: Prednisone 60 mg po daily for 3 days, then decrease by 10 mg every 3 days (18days) Ergotamine tartrate 1-2 mg po/pr daily hs Greater occipital nerve blocks: lidocaine and Kenalog-40 or 6 mg betamethasone or 40 mg depomedrol DHE-45 0.5-1.0mg SC/IM q8-12h ------------------------------------------------------------------------- Methysergide 2 to 4 mg TID Decadron 4 mg BID for 2 weeks then 4mg Qday for 1 week Greater Occipital Nerve Block Lidocaine 1% or 2% with betamethasone 6mg or triamcinolone 40 mg Uses: -as transitional therapy instead of prednisone -to decrease frequency in chronic cluster headache -60% of patients have a moderate to good response after 1 injection. Peres,M et al.,2002 Cephalalgia,22,520-22 2. Preventative Therapy Throughout the anticipated duration of the cluster period: consider stopping when 14 days headache-free) • First Choice: Verapamil 80 mg TID (incr by 80mg q10-14d); up to 720 mg/d. Check PR int. each dose change. watch conduction block: ECG Q6m • Methysergide maleate 2 mg TID; up to 12 mg/d • Lithium Carbonate 150-300 mg tid • Valproic acid 500-2000mg/day • Topiramate 50-150/day • Gabapentin 300 -3600 mg/day • Melatonin 9-10 mg hs Verapamil 240 to 960 mg/day • Verapamil is the drug of choice for preventative therapy • open labeled and controlled trials have demonstrated effectiveness in 80% of cluster headache patients. -In a RCT of 30 patients, 12 of 15 patients had a reduction in frequency of attacks within two weeks. • Side effects: heart block, constipation, dizziness, ankle swelling, fatigue; rarely gum hypertrophy Bussone G, Leone M, Peccarisi C, Micieli G, Granella F, Magri M, et al. Double blind comparison of lithium and verapamil in cluster headache prophylaxis. Headache 1990;30:411-7. Lithium 600 to 1200 mg per day – (serum level: 0.4 to 0.8 mEq/L) many trials with good results in 60 to 80% of pts (esp. chronic cluster headache) – In a double-blind crossover study of 30 patients, 50% of patients responded in 2 weeks Potential for many side effects and has a narrow therapeutic window. Steiner TJ, Double-blind placebo-controlled trial of lithium in episodic cluster headache. Cephalalgia 1997;17:673-5 Methysergide •2 mg TID (max. 12 mg/day) •decreased headache frequency by >50 percent in 19/20 patients in a pilot study. • use discontinued in the USA: -can cause retroperitoneal, cardiac, and pleuropulmonary fibrosis. •Should be restricted to use in refractory cases and should never be used for more than six months continuously; 1 month drug holiday at that time along with regular screening tests. Mueller L, Gallagher RM, Ciervo CA. Headache 1997;37:437-42. Other drugs that can be tried for the estimated 30% chronic cluster patients who fail usual treatment Clonidine Diltiazem Flunarizine Somatostatin Indomethacin Pizotifen Phenelzine Naratriptan Gabapentin Methylphenidate Mirtazapine Tizanidine Baclofen Warfarin Management of Cluster Headache: Abortive Therapy OXYGEN INHALATION Oxygen inhalation with a non-rebreathing facial mask at least 7-12L/min for about 20 minutes in a sitting position About 60 % patients respond with a substantial reduction in pain in 20 to 30 minutes. Mechanism of action unknown but may be related cerebral vasoconstriction. Cephalalgia 1991;11(Suppl.11):238-39 Nilsson et al., Cephalalgia 2002; 22: 730–39. The Sumatriptan Cluster Headache Study Group. Treatment of acute cluster headache with sumatriptan. N Engl J Med 1991;325:322-6 •Randomized, double-blind, placebo-controlled, study: efficacy of 6 mg sumatriptan s/c. •Headache relief was reported within 15 min in 74% of attacks (cf. placebo 26%, p <0.001). Triptans: alternatives to Imitrex injection In placebo controlled trials, Sumatriptan nasal spray 20 mg was effective within 30 min. (Van Vliet et al.,Neurology 2003; 60: 630–33). Zolmitriptan oral and nasal spray is effective within 30 minutes. (Bahra et al.,Neurology 2000; 54: 1832–39). Ergotamines Ergotamine tartrate PO or S/L has been used for years although there are no recent controlled trials. Effective as transitional therapy BID (for 2 to 3 weeks) or at bedtime to prevent nocturnal attacks. Generally too slow to use at the onset of an attack. DHE S/C,IM,orIV :effective abortive therapy within 15 minutes (Lance and Goadsby, 2005.Mecanisms and management of Headache,pg 217) (Dodick et al.,2000 Cephalalgia:20,787-803) Management of Cluster Headache: Abortive Therapy Summary: Most Effective Drugs – Oxygen inhalation by facial mask at 7-14L/min – Sumatriptan 6 mg S/C injection – Dihydroergotamine 0.5-1.0 mg IV,S/C,IM – Zolmitriptan 5 mg IN Abortive drug treatment • • • • • • • • • • • • Oxygen Sumatriptan succinate subcutaneous (SQ) injection Sumatriptan nasal spray Zolmitriptan Dihydroergotamine (DHE) intramuscular (IM), subcutaneous, or intravenous (IV) injection Dihydroergotamine mesylate intranasal spray Ergotamine tartrate sublingual Intranasal lidocaine Topical intranasal cocaine Capsaicin Butorphanol Olanzapine Non-Drug Treatment Patients should avoid the following: •Afternoon naps or significant changes in their sleeping habits •Alcohol, especially during the cluster period •Prolonged exposure to chemical agents such as cleaning solvents,gasoline, and oil-based paint •Excessive bursts of anger or extreme emotion •Prolonged physical exertion •Extreme changes in altitude Biondi D, Mendes P. Treatment of primary headache: cluster headache. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004. p. 59-72. Intractable Cluster Headache • Surgical Interventions – GON nerve stimulation – Deep Brain Stimulation – Ablative procedures Management of other TACs… Paroxysmal Hemicrania Indomethacin 25 mg TID for 10 days then increase to 50 mg TID for 10 days and consider 75 mg TID. Resolution of the headache usually occurs in first 2 days of the effective dose. “Indotest”: 50 to 100mg IM (Antonaci et al.,1998) – complete pain relief occurred for 8 hours with 50 mg and 11 hours for 100mg. Suggests that if there is no response the diagnosis should be reconsidered. Paroxysmal Hemicrania Prophylactic treatment – Indomethacin: Typical maintenance dose: 25-100mg Qday In CPH – attempt drug withdrawal Q6months Consider adjunctive stomach protection. – Patients who can’t tolerate indomethacin -- no other drug has been shown to be consistently effective. The following may be tried: other NSAIDs, celecoxib, verapamil, flunarizine, acetazolamide, steroids. Mathew, 2000; Shabbir &McAbee 1994; Coria et al, 1992; Goadbsy and Lance 2005 Treatment of SUNCT •SUNCT thought to be highly refractory to all treatment. •Recently, lamotrigine 100-300 mg daily has been reported to be highly efficacious in 7 patients •Gabapentin and topiramate may be second-line agents. •Lidocaine IV •Ltd surgical options D’Andrea G,et al., Neurology 1999;53:1609; Leone M, et al Cephalalgia 2000;20:845–7. D’Andrea G et al. Neurology 2001;57:1723–5 .Graff-Radford SB..Cephalalgia 2000;20:515–17. Matharu M. S. Neurology (in press). Treatment of HC Indomethacin (50-300 mg) – Other NSAIDs may be tried Melatonin 6-12 mghs Topiramate, Verapamil, GON stim have been considered. (Silberstein, Lipton, Goadsby. Headache in Clinical Practice, 2nd Edition 2002) Treatment of Tension Type Headache • Acute: ASA, NSAIDs, tylenol < 2d/w • Preventative: Amitriptyline, Tizanidine • Non-pharmacological therapies: massage, osteopathic, trigger point inj., psychophysiological therapies Some aspects of Treatment of Migraine and Variants ACUTE THERAPY Match agent to headache intensity and to the patient’s co-morbidities Use meds properly and have reasonable expectations Treat early, treat aggressively Avoid rebound Avoid opioids or barbiturates How many days in the last 3 months were you at least 50% disabled ? – Patients who have > 10 days of disability in 3 months (at work, home school or recreational activities): should be offered triptans from the outset Lipton et al., 2000 JAMA284: 2599-2605 Migraine Treatment Algorithm Migraine severity assessment First Line Intermittent Mild to Moderate Intermittent Moderate to Severe On lack of efficacy ASA/NSAID (high dose) ASA/acetaminophen ± anti-emetic Oral triptan PRN Oral triptan PRN Nasal spray/ subcutaneous triptan Alternative oral triptan Nasal spray/ subcutaneous triptan Alternative oral triptan Frequent Suspect chronic daily headache Consider Prophylaxis or Refer to specialist ≥4 attacks/month Evaluate headache frequency Consider Prophylaxis + acute treatment <4 attacks/month Adapted from Dowson AJ et al. Curr Med Res Opin. 2002;18:414-39. Treatment of Migraine Phase I Prodrome Phase II Aura Phase III Early Headache Acute Mild-moderate Disability None Moderate-severe Disability None Phase IV Late Headache Phase V Postdrome Rescue OTCs, NSAIDs, Non-narcotic analgesics Triptans (for moderate) None Triptans Analgesics None Dowson AJ et al. Curr Med Res Opin. 2002;18:414-39. Silberstein SD. Neurology. 2000;55:754-62. Chronic Daily Headache • Affects 4% of the population – 3%/year migraineurs transform to chronic daily headache • causes severe functional impairment – Family life and work productivity Scher AI et al Headache 1998;38:497-506; Castillo J et al Headache 1999:38: 497-506 Types of primary CDH • Short-duration types: (<4hours) – Chronic cluster headache – Chronic paroxysmal hemicrania – Hypnic headache • Long-duration types: (>4hours) – – – – – Hemicrania continua Chronic tension type headache Chronic Migraine Medication Overuse Headache New Daily persistent headache Migraine Progression Low frequency episodic migraine <10/m High frequency episodic migraine 10-14/m Chronic migraine >15/m Some factors associated with chronification: Obesity Head injury Low socioeconomic status and education Caffeine overuse Poor sleep quality (snoring) Stressful life events Co-morbid pain Medication overuse Attack Frequency Bigal et al.,Headache 2002;42:575-581, Scher et al.,Curr Pain HeadacheRep.2002;6:486-91 Scher AI et al.,Pain 2003;106:81-9 Clinical features of transformed migraine Daily or almost daily head pain Average headache >4h/d (if untreated) At least one of the following – History of migraine – Increasing frequency with decreasing severity of migrainous features over at least 3months – Has occasional typical migraines Other causes eliminated Silberstein and Lipton Neurology 1996;47:871-5. Medications Implicated High Probability -Opioids -Ergotamine -Butalbital -Caffeine -ASA/ibuprofen -Triptans Possibly -Nasal decongestants Unlikely -DHE -Neuroleptics -Naproxen sodium Use of barbiturates and opiates predicts chronic migraine Risk for the Development of Transformed Migraine by Medication Use Medication Barbiturates Opiates Triptans NSAIDs Odds Ratio 2.06 1.98 1.250 *0.850 Bigal, Lipton:_ AMPP Headache. 2008;48:1157-1168 95% CI 1.3 - 3.1 1.4 - 2.2 .9 - 1.7 .63 -1.17 What is happening with migraine therapy in Canada? Prophylactic Pharmacotherapy Percent of Migraine Patients (N=606) Prophylactic drug use before and after specialist referral 100 90 80 70 70.4% (n=427) 60 Before referral After referral 50 40 30 20 30.9% (n=187) 10 0 Jelinski SE et al. Cephalalgia. 2005;26:578-88. Medication Overuse • 20.8% (125/606)determined to be medication over-users by neurologists after referral Medications No. (%) of total medication over-users Acetaminophen/NSAIDs* 84 (67.2%) Opiates* 53 (42.4%) Triptans* 27 (21.6%) Barbiturate* 10 (8.0%) Ergotamine* 3 (2.4%) Others 7 (5.6%) Jelinski SE et al. Cephalalgia. 2005;26:578-88. Study Conclusions In the primary care setting: – Triptans are being underutilized – Prophylactic medications are being underutilized – Medication overuse is a significant problem Opiate overuse is of particular concern Jelinski SE et al. Cephalalgia. 2005;26:578-88. Elimination of overuse is a necessary requirement of remission • Medication overuse can make headaches refractory to abortive and preventive medication. • Discontinuation results in significant improvement: response to meds and decr freq HA. • With withdrawal many convert to episodic migraine. Zeeberg et. Al., Neurology 2006;66:1894-98; Cephalalgia 26:1192-98. Mathew et al., Neurology 1990;30:634-8 Guidelines • Limit abortive agents to no more than 2 days per week • Patients who feel compelled to use abortives more often should contact their doctor. Recommended substances (drugs of first choice) for the prophylaxis Evidence Substances Daily dose Level Beta blockers Metoprolol Propranolol 50–200 mg 40–240 mg A A Tricyclic antidepressants Amitriptyline Nortriptyline 10-50 mg 10-50 mg A C Antiepileptic drugs Valproic acid Topiramate 500–1800 mg 25–100 mg A A Calcium channel blockers Flunarizine 5–10 mg A US headache consortium guidelines Neurology 2000,54:1253 and http://www.aan.com/professionals/, Silberstein Headache Currents 2006, Tfelt-Hanson Cephalalgia 2006,261265-74. S. Eversa et al., EFNS guideline on the drug treatment of migraine. European Journal of Neurology 2006, 13: 560–572 Drugs of second choice for prophylaxis (less effective or more side effects) Substances Daily dose (mg) Level Gabapentin 1200–1600 mg Candesartan 16 mg Lisinopril 20 mg Bisoprolol,Nadolol,Atenolol,Timolol B C C A-B Methysergide Pizotifen 4–12 mg 1.5-6 mg C A Fluoxetine 20-40 mg B Petasites (Butterbur) Tanacetum (feverfew) Riboflavin Magnesium 2 X 75 3 X 6.25 mg 400 mg 24 mmol (400mg) B C C C US headache consortium guidelines Neurology 2000,54:1253 and http://www.aan.com/professionals/, Silberstein Headache Currents 2006, Tfelt-Hanson Cephalalgia 2006,261265-74. S. Eversa et al., EFNS guideline on the drug treatment of migraine. European Journal of Neurology 2006, 13: 560–572 Prophylactic Medications and co-morbidity in Migraine Co-morbid disease Topa BB TCA Weight issues avoid Sleep poor ++ HTN depression care ++ avoid + + + ++ anxiety Essential tremor FMS Aura + Gabapentin ++ care Valproic, lamictal + ++ + avoid avoid bipolar epilepsy SSRI Other AED + + +(Lyrica) Lamictal Pathophysiology of Chronic Migraine 1. Central sensitization after repeated bouts of migraine 2. Damage to CNS pain modulation system 3. CNS changes due to medication overuse 4. Abnormal focal neurological activity (CNS pain generators) 5. Persistent activity in a peripheral pain generator (cervical pathology) Ramadan, Nabih M. 2007. Current Trends in Migraine Prophylaxis. Headache: The Journal of Head and Face Pain 47 (s1), S52-S57 Figure 4. Correlation of frequency of migraine attacks per month vs allodynia Mathew, N. T. et al. Neurology 2004;63:848-852 Iron deposition in the PAG in chronic migraine Welch M. Headache 2001;41:629-637 Physiological changes in analgesic overuse • Serotonin levels decrease • 5HT-2A receptors (potentiate nociceptive neurotransmission) are up-regulated • Opiate exposure increases response of afferents when stimulated and enhance desc. Pain facilitation (RVM) • Increase central responsiveness via increased release of CGRP Park,JW et al Headache 2005;45:1229-35 Felice and Porreca Cephalalgia 2009,29,1277-84 Persistent activity in a peripheral pain generator • Convergence of cervical and trigeminal inputs – Cervical spine disease may become a generator of pain Bartsch T Current pain and headache reports 2003;7: 371-76 Bogduk N J of Man and Phys Therapeutics 1992;15:67-70 Located neurons in the TNC that received convergent input from dura and facial skin. Chemical stimulation of the dura caused an incr sensitivity of the cutaneous receptive field neurons to mechanical and thermal stimulation. Both the dural and cutaneous receptive fields increased. Burstein et al., J Neurophysiol 1998; 79: 964-982 Both the dural and cutaneous receptive fields increased: -before field was only periorbital then expands to incl. max and mand regions after chemical stimulation Burstein, R. et al. J Neurophysiol 79: 964-982 1998 Abnormal focal neuronal activity (CNS pain generators) • PET Activation in spontaneous migraine contralateral to the headache • The contralateral PAG modulates the trigeminovascular system Secondary chronic migraine MRI demonstrating a left-sided cavernoma (a and b) with an associated developmental venous anomaly (c) in the dorsal midbrain region adjacent to the periaqueductal grey matter P Goadsby. Cephalalgia 2002;22: 107-111 Pain Modulating System cortical PAG Emotional factors and stress analgesics RVM on TNC off C2 TREATMENT GOALS • Reduce headache frequency • Reduce headache impact on ADLs An approach to the treatment of patients with CDH 1. Formulate the diagnosis – Eliminate secondary causes – Establish the primary headache disorder Always consider medication overuse syndrome – Establish other potentially contributory comorbidities. Treatment of transformed migraine 2. Educate the patient about: Migraine - expectations appropriate use of medication lifestyle factors which may be contributory Stress management CBT Diet/exercise Sleep/wake regular meals Treatment of transformed migraine 3. Begin a program of treatment designed to break the cycle of transformation and raise the threshold for migraines. – Begin prophylactic treatment – Stop all overused meds – Replace with long-acting NSAIDS – Use transitional meds as needed 4. Schedule follow up Lipton et al.,Neurology 2003;60:1064-1070 Katsarva et al., Neurology 2003;60: 682 Migraine in kids AAN 2004 – Acetaminophen, ibuprofen, sumatriptan nasal spray (>12yo). Sumatriptan, riza and zomi also effective in adolescents Preventative: Consider nonpharmacological methods first. – flunarizine, elavil, propranolol, cyproheptidine, Topa, valproate (none are FDA) Childhood per. Syn. - symptomatic Pregnancy Consider CSVT, CVA, Pit tumors, eclampsia Avoid drugs–most improve in 2nd trimester Tylenol, NSAIDs to week 28 (DA) Metoclopramide (category B) Opioids (tylenol codeine or hydrocodone rescue) (cat C), Stemetil carefully IV hydration, metoclopramide, Mg GON block Triptan registry. NEVER USE ERGOTS PREGNANCY Avoid prophylactics – biofeedback better Propranolol, verapamil, Topa (cat C) Lactation – can use sumatriptan – Tylenol, advil, naproxen, codeine, ketorolac, Metoprolol, propranolol, prednisone all compatible with breastfeeding. – LactMED: http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?LACT Trigeminovascular Model of Migraine Trigeminal nerve INHIBITION 5-HT1D 5-HT1F INFLAMMATION Trigeminal nerve fibers release the neuropeptide CGRP, and cause sterile inflammation of the dura matter and vasodilation and cerebral blood flow changes of the cerebral arteries CGRP calcitonin gene related peptide NK neurokinin A SP substance P CGRP NK SP triptans VASODILATION CONSTRICTION 5-HT1B Blood vessel Adapted from Goadsby (1997). Mechanism of action of Triptans • 5-HT1B receptors—blood vessels ◦ Constrict dilated intracranial arteries Potential cardiovascular risk • 5-HT1D receptors—peripheral trigeminal sensory nerves ◦ Inhibit perivascular neuropeptide release (CGRP, Sub P, Neurokinin) Break vasodilator cycle—promote normalization • 5-HT1D and 5-HT1F receptors—central TNC ◦ Interrupt pain transmission within brain Reduce nausea? (nuc Solitarius) The distribution of 5-HT1B and 5-HT1D receptors in the ophthalmic branch of the trigeminal Vth nerve, in the brainstem sensory trigeminal nucleus caudalis and in the solitary tract nucleus where they could mediate an antinausea effects. (Richard Hargreaves,Headache 2007;47 [Suppl 1]:S26-S43) Triptans have limitations Contraindicated: – coronary disease vascular risk factors. Var. response rate, consistency and tolerability Are assoc. with medication overuse headache Expensive Cardiovascular Safety of Triptans Incidence of serious cardiovascular events is extremely low. Risk-benefit profile favors use in the absence of vascular risk factors. – Triptan cardiovascular safety expert panel of the American Headache society – consensus statement Headache 44(5):414, 2004 PHARMICOKINETICS OF TRIPTANS Suma Imitrex Almo Axert Ele Relpax Nara Amerge Riza Maxalt Zolmi Zomig T½ hours 2 3.5 5 6 2-3 3 T max hours 2 2.5 1.5 2.5 1 1 %Oral Bioavail. 14 70 50 70 45 40 Metab. MAO P450/ MAO P450 RENAL/ P450 MAO P450/ MAO Log D -1.3 +0.35 +0.5 -0.2 -0.7 -0.7 Relief of Migraine Pain Rizatriptan 10 mg Sumatriptan 100 mg Sumatriptan 50 mg Headache relief at 2 hours* Zolmitriptan 2.5 mg Eletriptan 40 mg (95% CI) Almotriptan 12.5 mg Naratriptan 2.5 mg 0 10 20 30 40 % Patients 50 60 70 80 (N=24,089) Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Systematic reviews of comparable trials . http://www.jr2.ox.ac.uk/bandolier/index.html accessed April 2007 What to do if there is Suboptimal headache relief or recurrence Treat while headache is still mild Combine triptan with NSAID (Naproxen) Switch to another triptan or formulation or another type of acute therapy Add a prophylactic agent Ensure there is no underlying medication overuse (Smith, T et al.,Headache 2005;45:983-991. Foley,K et al.,Headache 2005;45:538-45) Prospective trial: treatment while pain is milder increases the probability of achieving 24 pain free status Freitag,F et al.,Headache 2007;47:519-530 Smith T. et al., Headache 2005;45:983-991 Chance of migraine 2.5X more during days 1-3 of the cycle Figure 217"> MacGregor, E. A. et al. Neurology 2006;67:2154-2158 MacGregor E.A. et al., Neurology 2004;63:351-53 Pooled rel. risks of stroke stratified by migraine type, oral contraceptive use, and age No of studies Relative risk (95% CI) Migraine (any) All studies 14 2.16 (1.89 to 2.48) Etminan, M Case-control studies 11 2.18 (1.86 to 2.56) BMJ 2005;330:63 Cohort studies 3 2.10 (1.61 to 2.75) Migraine with aura Case-control studies 7 2.27 (1.61 to 3.19) Migraine without aura Case-control studies 6 1.83 (1.06 to 3.15) Migraine among oral contraceptive users Case-control studies 3 8.72 (5.05 to 15.05) Migraine among men and women <45 years Case-control studies 9 2.36 (1.92 to 2.90) Migraine among women <45 years Case-control studies 7 2.76 (2.17 to 3.52) Management of Menstrual Migraine Usual Acute therapies: NSAIDS or triptans Mini-prophylaxis starting a few days before expected headache or 10 days after ovulation and continuing up to one week: – Increase dose of usual prophylactic or… Short-term MM prophylaxis Mg Naproxen DHE-45 NS Estradiol gel Estradiol patch Sumatriptan Naratriptan Zolmitriptan 360 mg/d 550 mg BID NS q8h 1.5 mg Qday 100 mg 25 mg TID 1 mg BID 2.5 mg BID * Refers to before expected headache Day 15-menses Day -7 to +6 Day -2* to +4 Day -2* to +5 same day -2 to +3 Day -2 to +3 Day -2 to +4 Extended duration OCPs Sulak Headache 2007;47:27-37 ER US Headache Consortium Vinson Ann Emerg Med 2002 39:3, 215-222 Recommendations for first line therapy in ER American: IV prochlorperazine and DHE or Sumatriptan s/c Canadian: Dopamine Antagonist., then DHE IV or Sumatriptan s/c Evidence regarding opioids 1. Meperidine - not significantly different than IV chlorpromazine, IM Ketorolac, IV DHE, DHE and Metoclopramide. (Lane PL Ann Emerg Med 1989;18:360-65. Larkin Ann Emerg Med 1992;21:919-24. Belgrade Neurology 1989;39:59092. Scherl Headache 1995;35:256-59.) 2. There is insufficient evidence to establish how to select 1 therapy over another. However almost universal agreement by experts that opioids should be the last choice in most cases. (Matcher Neurology 2000) DHE Dose – IV or IM DHE 0.5 to 1.0 mg Pretreat (or cocktail) IV metoclopramide 10 mg OR IV Prochlorperazine (5 to 10 mg) OR IM hydroxyzine 50 mg or IM promethazine 25 mg Caution: vascular disease, triptan use in the previous 24 h Colman, I Annals of Emerg Med 2005 Parenteral DHE for acute migraine. A review of the literature. Dopamine antagonists Dose: – Prochlor 10 mg IV (repeat q30 minX2) – Chlorprom 10 mg IV (repeat q30minX2) – Pretreat: IV NS bolus. +/-Diphenhydramine 25-50mg IV Caution: – Hypotension, Akathisia (Benztropine 1mg IV), sedation (shouldn’t drive home) Slow HC et. Al. Headache 2005;45:358-71 – Neuroleptics in headache Metoclopramide Dose: – 10 mg IV over 15 minutes Evidence: – Open labeled, placebo controlled*, comparator trials (vs Sumatriptan** and opioids) – Meta-analysis Supports it as monotherapy or polytherapy with a 2nd agent***. Tek Ann Emerg med 1990*. Freidman Neurology 2005**. Cicek Emerg j med 2004*** Colman BMJ 2006 NSAIDS Ketorolac 30 to 60 mg IM Evidence: – Open labeled: effective in acute migraine ER* – Comparator trials – similar to meperidine and chlorpromazine. Prochlorpromazine superior to Ketorolac in kids. *Davis Am J Emerg Med 1993. Davis Am J Emerg Med 1995. Duare Ann Emerg Med 1992. Larkin Ann Emerg Med 1992. Brousseau Ann Emerg Med 2004. Triptans Dose: – 6 mg S/C Evidence – Placebo controlled – superior to placebo on primary and secondary endpoints* – Comparator trials – Metoclopramide and Diphenhydramine similar on pain relief at 2 and 24 hours**. Chlorpromazine and Metoclopramide similar to IM sumatriptan and metoclopramide*** *Akpunonu BE Ann Emerg Med 1995 ** Freidman BW Neurology 2005 ***Kelley J Accid Emerg Med 1997 Other options IV Valproic acid (500 to 1000 mg IV in 100 mg NS infused over 5-20 minutes) IV aspirin IV Magnesium (1 gram of magnesium phosphate in 10% NS IV over 15 minutes) IV Steroids (4-20 mg IV dexamethasone or 125 mg IV hydrocortisone) INTERNATIONAL CLASSIFICATION of HEADACHE DISORDERS 2nd edition (ICHD-II) Headache a clinical tour for residents part 2: Secondary headache disorders ICHD-II. Cephalalgia 2004; 24 (Suppl 1) 2010 Lucy Vieira MD ©International Headache Society 2003/4