Proper Diagnosis and Treatment for the Headache Patient Alexander Feoktistov MD, PhD

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Proper Diagnosis and Treatment for the Headache Patient Alexander Feoktistov MD, PhD Director of Clinical Research Diamond Headache Clinic Chicago, IL 2014

Objectives Get familiar with primary headache prevalence Identify practical diagnostic approach to a headache patient Review clinical presentation of migraine and medication overuse headaches Review headache specific treatment options

Epidemiology: Tension Type Headache FEMALES MALES 50% 50% 63% 38% POPULATION

Epidemiology: Migraine FEMALES MALES 18% 5% 82% 95% POPULATION

Epidemiology 15,700,000 Chronic Daily Headache 5% POPULATION

Epidemiology Symptomatic Low Back Pain Symptomatic Headache 62% 38% 53% 47% POPULATION / YEAR PREVALENCE

Diagnostic Approach Questions: Answers: LOCATION SEVERITY QUALITY DURATION A. SYMPTOMS UNILATERAL 8/10 THROBBING 24-48 hours N/V/PHT/PHN LEFT EYE 10/10 STABBING 60 minutes PTOSIS DIAGNOSIS MIGRAINE CLUSTER

Diagnostic Approach Details: Answers: LOCATION SEVERITY QUALITY DURATION A/S UNILATERAL 8/10 THROBBING 24-48 hours N/V/PHT/PHN TEMPORAL ARTERITIS GENDER AGE OF ONSET FEMALE 72 YO

Diagnostic Approach FREQUENCY (less or >15 days/month) FAMILY HISTORY (MIGRAINE) TRIGGERS CYCLICITY OR PATTERN MEDICATION HISTORY (TYPES, FREQUENCY)

Diagnostic Approach RED FLAGS: Systemic: fever, weight loss Abnormal Neuro Signs: confusion, rigidity New onset at older age Headache pattern change Abrupt onset, worst headache Exertional headache pattern

Diagnostic Approach HISTORY! Neuro examination Blood work (anemia, electrolytes, leukocytosis, ESR, LFT) ECG (arrhythmias, QT prolongation) No role for EEG (unless Sz, syncope etc) Imaging (MRI>CT)

Diagnostic Approach WHEN TO SCAN? Abnormal neuro examination Headache pattern change Refractory headache Atypical features (age of onset etc) Prolonged/complicated aura

Diagnostic Approach 6% 4% 20% 90% 80% Primary Other Brain tumor 18% 82 % Brain tumor Headache Brain tumor HA Change

Diagnostic Approach Real case: 44 yo female presented with 2 years history of severe headaches. She described her HA as being initially episodic but progressively worsening, severe, unilateral or bilateral, throbbing pain associated with nausea, vomiting, photo and phonophobia. She was diagnosed with migraine without aura 6 months ago by her PCP. Treated with NSAIDs, triptans, beta-blocker, topiramate, venlafaxine with minimal relief. In the past 2 months she noticed that coughing and sneezing would exasperate her HA. Eventually she developed an episode of severe throbbing headache with intractable vomiting and with the diagnosis of status migraine she was admitted for rehydration and IV pain management. Physical and neuro examinations were unremarkable. MRI-Brain was done.

Diagnostic Criteria: Migraine A. At least five attacks fulfilling criteria B D B. Headache attacks lasting 4-72 hours C. Headache has at least two 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 (e.g. walking or climbing stairs) D. During headache at least one of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia E. Not better accounted for by another ICHD-3 diagnosis. The International Classification of Headache Disorders, 3rd edition (beta version)

Diagnostic Criteria: Aura A.At least two attacks fulfilling criteria B and C B.One or more of the following fully reversible aura symptoms: 1.visual 2.sensory 3.speech and/or language 4.motor 5.brainstem 6.retinal C.At at least least two of the following four characteristics: 1.At least one aura symptom spreads gradually over > 5 minutes, and/or two or more symptoms occur in succession 2.Each individual aura symptom lasts 5-60 minutes 3.At least one aura symptom is unilateral 4.The aura is accompanied, or followed within 60 minutes, by headache D.Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded.

visual aura

Case Presentation 32 yo female presents with ongoing typical, yet intractable headache for 5 days. She has long standing history of unilateral, throbbing headache associated with sensitivity to light and noise, nausea and vomiting. Each headache episode usually lasts 24-48 hours and occurs 2 times per week and she is unable to function on those days. Excedrin and Butalbital/Caffeine/APAP are usually helpful but providing only minimal relief this time She started experiencing headaches in middle school. Has family history of headaches - mother was diagnosed with chronic sinus headaches PMH is unremarkable and Neuro exam is normal. Patient appears to be in distress. What is the Dx? What would you do?

Diagnostic Criteria: Status Migrainosus 1.4.1 Status Migrainosus A. A headache attacks fulfilling criteria for migraine B. Unremitting for > 72 hours C. Pain and/or associated symptoms are debilitating The International Classification of Headache Disorders, 3rd edition (beta version)

Migraine Treatment 77% 77% 23 % 23% 44% 56 % Migraine Population Need prophylaxis Do not need prophylaxis On Prophylaxis Not on Prophylaxis 72,000,000 16,560,000 9,273,600

Acute Treatment Ergotamine - 1928 Migranal Nasal Spray D.H.E.-45 - IV protocol, mainstay of status migraine treatment Triptans - early 1990 s Sumatriptan (Imitrex) - PO, SQ, NS Sumatriptan / Naproxen (Treximet) Zolmitriptan (Zomig) - PO, NS Rizatriptan (Maxalt) - PO, ODT Naratriptan (Amerge) Amotriptan (Axert) Frovatriptan (Frova) Eletriptan (Relpax)

Acute Treatment NAME ROUTE Half-life Onset (50% reduction) Sumatriptan sq, ns, po 2 hrs 30min, 30-60min, 1-2 hr Treximet po 2 hrs 1-2 hrs Zolmitriptan ns, po, odt 3 hrs 30-60 min, 1-2 hr Rizatriptan po, odt 1.5 hrs 1-2 hrs (highest %) Naratriptan po 5-6 hrs 2-4 hrs Almotriptan po 3 hrs 2 hrs Eletriptan po 3-6 hrs 2 hrs Frovatriptan po 26 hrs 4 hrs

Acute Treatment (triptans) Contraindications: poorly controlled HTN Severe hepatic or renal impairment h/o basilar migraine h/o hemiplegic migraine CAD of high risk patients MAO inhibitors use Should be avoided during pregnancy Considerations: Should not be used within 24 hrs post ergotamine-containing medications use Serotonin syndrome when used in combination with SSRI or SNRI (RARE!) Treatment should be limited to 2 doses per day (2 hours apart) and 2 days per week

Prophylactic Treatment Beta-blockers: propranolol (120-240 mg/day) Ca-channel blockers: verapamil (180-360 mg/day) Anticonvulsants: topiramate (100-200 mg) divalproex sodium (500-1000 mg) Antidepressants: TCA - Amitriptyline (25-100 mg) SNRI - Duloxetine (30-60 mg) MAOI - Phenelzine (30-45 mg) Important point: Delayed response (may take up to 4-6 weeks) Botulinum Toxin type A

Non-pharmacological Treatment Diet (low tyramine, low caffeine) Regular meal pattern Regular sleep pattern Biofeedback Stress management and psychotherapy

Non-pharmacologic treatment: Cefaly Transcutaneous Supraorbital Nerve Stimulator Should be used for 20 minutes, daily 54% of satisfied patients Reduced migraine days and medication use (p<0.05) Low SE profile: Paresthesias - 2% Fatigue - 0.9%

Case Presentation 38 yo female, presents with history of daily headaches in the past 15 years. She describes headaches as aching, pressure-like and at times throbbing headaches located globally in her head. She rates the severity of her daily, constant headache as 4-5/10 and states that she can function with these. She states that 2-3 times per week headaches increase in severity for 24-36 hours and her current rescue medications are no longer effective. The headaches are associated with sensitivity to light and noise, occasional nausea. Denies vomiting. She broke up with her boyfriend 2 months ago and her headaches intensified. She has been experiencing headaches since teenage years. They used to occur couple of times per month but gradually, over years they have been getting more frequent. OTC used to provide consistent pain relief but over the past years use of rescue medication has increased. She does notice that currently her medications are not providing consistent pain relief. She is currently using: 1. Excedrin: 2-6 tablets/day, daily x years, 2. Butalbital/Caffeine/APAP - 15-28 tablets/day for 1-2 months (prior to that - 6-8 tabs/day x 2 years) PMH is unremarkable and Neuro exam is normal. What is the Dx? What would you do?

Types of Medication Overuse Headache 8.2.1 Ergotamine-overuse headache 8.2.2 Triptan-overuse headache 8.2.3 Simple analgesic-overuse headache (ASA, NSAIDs, acetaminophen) 8.2.4 Opioid-overuse headache 8.2.5 Combination-analgesic-overuse headache 8.2.6 MOH attributed to multiple drug classes not individually overused The International Classification of Headache Disorders, 3rd edition (beta version)

What is Medication Overuse? OTC - >15 days/month for at least 3 months Rx - >10 days/month for at least 3 months Combination (not individually overused) >10 days/month for at least 3 months May occur in patients with migraines, tension type headaches, cluster headache and NDPH

MOH Epidemiology 95% CDH 5% 7,850,000 50 % MOH 50 % USA POPULATION

MOH Treatment Philosophy Discontinuation of the offending agent! Detoxification Consider inpatient therapy Start aggressive abortive therapy Monitor for withdrawal symptoms Start prophylactic therapy

Admission Criteria Presence of intractable headache Complications and comorbid conditions Treatment that requires close monitoring due to potential adverse reactions or drug interactions Failed outpatient treatment Failed outpatient detoxification protocols Significant disability due to headache

Admission Criteria of the NHF Severe dehydration Diagnostic suspicion of organic etiology: infectious disorder (eg, brain abscess, meningitis), acute vascular compromise (eg, aneurysm, subarachnoid hemorrhage) Prolonged unrelenting headache with associated symptoms, such as nausea and vomiting, which, if allowed to continue, would pose a further threat to the patient's welfare Status migraine or dependence on analgesics, ergots, opiates, barbiturates, or tranquilizers Pain that is accompanied by serious adverse reactions or complications from therapy - continued use of such therapy aggravates or induces further illness Pain that occurs in the presence of significant medical disease, but appropriate treatment of headache symptoms aggravates or induces further illness Failed outpatient detoxification Intractable and chronic cluster headache, for which inpatient administration of histamine or dihydroergotamine (DHE) may be necessary Treatment requiring copharmacy with drugs that may cause a drug interaction, thus necessitating careful observation (eg, monoamine oxidase inhibitors and beta-blockers)

Opioids Detoxification Abstinence syndrome is rarely medically serious Nausea, diarrhea Muscle pain and myoclonus Worsening headache, Anxiety, insomnia Mild withdrawal symptoms up to 6 months

Opioids Detoxification Decrease by 10% of the original dose per week Use adjuvants: Steroids - Methylprednisolone 80 mg IM x 1 NSAIDs - Ketorolac 30 mg IV q 8 Muscle relaxants - Orphenadrine 30 mg IV q 6 Clonidine 0.1-0.2 mg PO q 6-8 hrs Manage behavioral issues

Butalbital Detoxification Expect withdrawal symptoms: Confusion, agitation Seizures Hypertension Insomnia Respiratory depression

Butalbital Detoxification Stop Butalbital containing agent Start Phenobarbital taper: Phenobarbital 30 mg per 100 mg of Butalbital used Taper off by 30 mg every 3 days Use adjuvants

INPATIENT TREATMENT PROGRAM IV DHE-45 protocol Other IV therapies NSAIDs Muscle relaxants Valproic acid, Levetiracetam Detoxification Initiation and/or adjustment of prophylactic medications

IV DHE-45 PROTOCOL 9 doses protocol 1st dose - 0.5 mg IV over 20-30 minutes Doses 2-9 - 1 mg IV Each dose is 8 hrs apart Pre-medicate with antiemetics Adjust the dose or infusion rate as needed.

OTHER IV THERAPIES Valproic acid: 500-1000 mg IV over 7-15 minutes every 8-12 hrs (Max - 2000 mg/day) Monitor LFT, sedation, dizziness Magnesium sulfate: 1000 mg IV over 15-30 minutes every 8-12 hrs Monitor magnesium serum level, neuro exam Droperidol 0.625-2.5 mg IV in combination with diphenhydramine Monitor ECG

OTHER IV THERAPIES NSAIDs Ketorolac 30 mg IV q 6-12 hrs MUSCLERELAXANT S Orphenadrine 30-60 mg IV q 6-12 hrs CORTICOSTEROIDS Methylprednisolon e sodium succinate - 120 mg IV q 12 hrs for 2 doses Methylprednisolon e acetate - 80 mg IM x 1

OTHER IV THERAPIES Non-pharmacological therapy Biofeedback Acupuncture Physical therapy Stress management Behavioral therapy Life style modifications and patients/family education

OTHER Discharge planning (multidisciplinary) Continuity of care and regular follow up Realistic short term and long term goals Patient education!

CONCLUSIONS Headaches are extremely common Early recognition is important to establish specific treatment 50% of CDH patients have MOH Targeted acute and prophylactic therapy Adequacy of therapy (outpatient vs inpatient)

Migraineurs, You Are In A Good Company Vincent van Gogh Claude Monet Julius Caesar Napoleon Sigmund Freud Elvis Presley