Objectives Headache Pain Generators Extracranial 1. Define the major categories of headache. Musculoskeletal (spine, muscle) 2. Take a history directed at characterizing a headache pattern in an individual patient and identify the cause or triggers of the Oral (dental) headache. 3. Understand the distinguishing features and patterns of migraine Ocular headache. Ear 4. Know first line treatments for tension versus migraine headaches. Vascular: branches of extracranial carotid, e.g. 5. Recognize warning signs for secondary headache syndromes due to intracranial structural lesions or increased intracranial pressure. temporal arteritis Intracranial Dural and pial sensory fibers Trigeminovascular pathways

Intracranial: Dural and pial sensory fibers Primary Headache Disorders

1. Migraine Headache • With or without aura 2. Tension-type Headache 3. Trigeminal Autonomic Cephalgias Secondary Headache Disorders Primary or Secondary Headache

1. Increased Intracranial Pressure headaches

• Mass lesions • Chronic Daily Headache

• Idiopathic Intracranial Hypertension (IIH) • Tension-type Headache

2. Vascular • Medication Overuse Headache

• Inflammation – example: Temporal Arteritis • “Transformed” Migraine

• Thrombosis – example: Cerebral Venous Thrombosis • New Daily Persistent Headache • Sub-arachnoid hemorrhage (“worst headache of life”)

3. Cervicogenic (spine, nerve roots) • Rule out Secondary Headache 4. Temporal Mandibular Joint (TMJ)

5. Medication Overuse Headache

Headache Exam: History Headache Exam: History Headache onset  aura or warning? Triggers: sounds, smells, movements?  sudden (thunderclap) or gradual Aggravating factors

 prior head or neck trauma  posture, cough, exertion, straining, neck or jaw movements  previous attacks (progression of symptoms?) Headache severity  duration of attacks (< 3 hours, > 4 hours, continuous)  effect on work and family activities  frequency: days per month with headache Pain location (unilateral, bilateral, cervical, retro- Acute and preventive medications orbital, face or jaw)  effectiveness, side effects  Radiation of pain? Co-morbid medical or mental health conditions  Headache-associated symptoms  History of heart disease or stroke  nausea, vomiting  Visual disorders  photophobia, phonophobia  conjunctival injection, rhinorrhea, diaphoresis Family history of headache disorders Headache for the first time OR change in pattern? Headache Exam: Physical Headache Exam: Physical

Screening neurologic examination HEENT examination: eyes, ears, jaw movements

 general assessment of mental status  Palpate occiput

 cranial nerve examination  Palpate temple

 fundoscopy, pupils, eye movements, visual fields, face sensory and motor for  Palpate muscles of mastication for tender points asymmetry and/or weakness Listen for bruits: head, eyes, neck  assessment for unilateral limb weakness or dyscoordination, deep tendon reflex asymmetry Blood pressure measurements – check orthostatic BP

 assessment of gait, including heel-toe walking (tandem gait) The majority of patients with primary headache disorders have a Neck examination normal neurological exam

 posture, range of motion, palpation for muscle tender points Tender points in neck, shoulders, and/or occiput can point to cervicogenic headache  Check for cervical paraspinal muscle spasm, trapezius tender points

Red Flags for Secondary Red Flags for Secondary Headache Headache

First or worst headache of life Emergent (immediate attention):  Abrupt-onset headache – “thunderclap headache” Change in pattern, frequency, or severity of headaches  Thunderclap onset (fast, maximal pain) Headaches ALWAYS on the same side  “worst headache of my life” Headaches refractory to treatment New onset headache after age 50  Fever and meningismus New onset headache with cancer, immunosuppression, or pregnancy  Papilledema with focal signs or reduced level of Associated signs/symptoms: fever, stiff neck, papilledema, cognitive impairment consciousness Headache with syncope or seizure  Acute glaucoma Headache triggered by exertion, valsalva maneuver, or sex Neurologic symptoms >1 hour Urgent (attention within hours to days) Abnormal general or neurologic examination  Papilledema without focal signs or reduced level of consciousness  Relevant systemic illness Neuroimaging is warranted  Elderly patient: new headache with cognitive change Red Flags for Secondary General Practice Points Headache Rule out secondary headache when diagnosing a

Less urgent (attention within days to few weeks, usually) primary headache disorder

 Unexplained focal signs Migraine is the most common headache type in

 Atypical headaches (not consistent with migraine or tension-type patients seeking medical care for headache

 Unusual headache precipitants  Migraine is underdiagnosed and undertreated  Consider migraine in patients with recurrent moderate or  Unusual aura symptoms severe headaches and normal neurologic exam  Onset after age 50 y  Headaches that interfere with daily activities are more likely  Aggravation by neck movement; abnormal neck examination to be migraine, less likely tension type (consider cervicogenic headache) Medication overuse is a risk in patients using  Jaw symptoms; abnormal jaw examination (consider temporomandibular joint disease) combination analgesics or frequent NSAID or acetaminophen

General Practice Points General Practice Points

Common headache triggers Headache management may require: Emotional stress Change in work or lifestyle (disability) Hormones (women) Change in method of birth control (women) Skipping meals Consideration of effects of menstrual cycle (women) Weather Change in environment Sleep disturbance  Possible association with environmental factors Odors  Patient may be able to identify headache triggers through careful headache diary Neck pain

Lights

Caffeine, Alcohol, Smoking

Heat

Food

Exercise/sexual activity General Practice Points Diagnosing primary headache syndromes Headache management includes: Consideration of the complexity of the medication plan Patients with recurrent headache attacks and normal Can the patient follow the schedule? neurologic examination findings 1. Migraine with or without aura if at least 2 of: Consideration of the side effects of the medications proposed for  nausea (with or without vomiting) treatment  light sensitivity /sound sensitivity

Sedation, cognitive side effects  some of the attacks interfere with daily activities

Beneficial side effects, e.g mood stabilization, may make some 2. Episodic tension-type headache if attacks are not medications more effective associated with nausea, and at least 2 of:  bilateral headache Consideration of the teratogenic potential of headache medications  nonpulsating pain Always counsel patients and document counseling  mild to moderate intensity Considerations before and during pregnancy  headache is not worsened by activity

Diagnosing primary headache Diagnosing primary headache syndromes syndromes

CHRONIC HEADACHES Cluster headache or another trigeminal autonomic Patients with headache on ≥ 15 d/mo for > 3 months and with normal cephalalgia if all of the following criteria: neurologic examination  Frequent  Chronic migraine if headaches meet migraine diagnostic criteria  Severe (above) or are quickly aborted by migraine-specific medications  Brief (duration < 3 h) (triptans or ergots) on ≥ 8 d/mo  Unilateral  Chronic migraine with medication overuse if the patient uses ergots, triptans, opioids, or combination analgesics on ≥ 10 d/mo or uses plain  Ipsilateral conjunctival injection, tearing, or restlessness acetaminophen or NSAIDs on ≥ 15 d/mo during the attacks (ipsilateral ptosis or miosis on exam).  Chronic migraine without medication overuse if patients do not have  Need Neurologist referral*** medication overuse Diagnosing primary headache Diagnosing primary headache syndromes syndromes

CHRONIC HEADACHES Patients with continuous daily headache for > 3 mo with normal neurologic examination Patients with headache on ≥ 15 d/mo for > 3 months and with normal neurologic examination Hemicrania continua if the headache is strictly unilateral, is always on the same side of the head

 ptosis or miosis might be present on examination Chronic tension-type headache if headaches fit episodic tension-type diagnostic criteria (above), but > 15 d/mo for >3 months  responds dramatically to indomethacin  May refer to neurologist  May have nausea but mild, not moderate or severe New daily persistent headache if the headache is unremitting since  No more than one of photophobia, phonophobia, mild nausea onset  Episodes last 30 min to few days  Evaluate for secondary headache

 Refer to neurologist

Medication Overuse Headache: Diagnosing Medication Overuse Headache Who is at risk?

Patients with headache for > 15 days per month

 Patient with an episodic headache disorder Use of triptans, ergots, combination analgesics, or opioid-containing  usually migraine or tension-type headache medications ≥ 10 days per month  treated with frequent and excessive amounts of acute symptomatic Use of acetaminophen or NSAIDs ≥ 15 days per month medications Patients may have psychiatric co-morbidities  Headache present or develops upon awakening, and commonly  depression and anxiety occurs daily or nearly daily  psychological and physical drug dependence Patients may have pain-related co-morbidities

 Orthopedic, musculoskeletal pain generators

 Taking multiple analgesics for different disorders Diagnosing Medication Overuse Headache

All acute symptomatic medications used to treat headaches have the potential for causing MOH. MIGRAINE Risk for MOH varies with medication Highest with HEADACHES Opioids

butalbital-containing combination analgesics

aspirin/acetaminophen/caffeine combinations Intermediate to high with triptans

Lowest with nonsteroidal anti-inflammatory drugs

Epidemiology of Migraine Migraine Headache

Migraine is a spectrum of illness  Migraine is a common disorder: affects ~12% of the general population Episodic Migraine  Chronic migraine Transformation may occur over months to years  Female > Male

 17 % of women each year Hallmark of Migraine:

 6 % of men each year Severe headache  Most common in those aged 30 to 39 Usually with nausea and/or light and sound sensitivity  Migraine tends to run in families. Four phases of Migraine headaches 1. Premonitory symptoms: affective/vegetative symptoms 24 to  Migraine without aura is the most common type, ~75 % of 48 hours prior cases • yawning, euphoria, depression, irritability, food cravings, constipation, neck stiffness 2. Aura: one or more focal neurological symptoms (25%) 3. Headache 4. Postdrome: may feel drained/exhausted or elation/euphoria Pathophysiology of Migraine Pathophysiology of Migraine Headache Headache

Cortical spreading depression  activation of pain Recurrent stimulation of central pain pathways causes sensitive trigeminal nerve afferents via: neuronal dysfunction The release of pro-inflammatory mediators Brainstem trigeminal neurons become hyperexcitable. Transduction of the inflammatory signal to trigeminal nerve Leads to structural and functional changes which are both fibers in the meninges intracranial and extracranial. Prolonged activation of trigeminal pain fibers  pain of migraine headaches. Cortical spreading depression: A wave of neuronal Migraine Aura: cortical spreading depression in areas and glial depolarization spreads across the cortex of the brain where depolarization is not consciously Causes aura perceived, e.g. cerebellum Activates trigeminal nerve afferents Alters blood brain barrier permeability

Pathophysiology of Migraine Pathophysiology of Migraine Headache Headache

Stimulation of the trigeminal ganglion release of Typical distribution of migraine headache pain = vasoactive neuropeptides  Neurogenic Inflammation anterior and posterior regions of head and upper neck A sterile inflammatory response Can be explained by convergence of the projections from Vasodilation (calcitonin gene-related peptide) the upper cervical nerve roots and the trigeminal nerve Plasma protein extravasation. Causes prolongation/intensification of the pain of migraine Neurogenic inflammation  Sensitization Neurons become increasingly responsive to nociceptive and non- nociceptive stimulation Response thresholds decrease Response magnitude increases Spontaneous neuronal activity develops Pathophysiology of Migraine Migraine Headache Headache

Sensitization causes many clinical symptoms of migraine Throbbing quality of the pain Worsening of pain with coughing, bending, or sudden head movements Hyperalgesia (increased sensitivity to painful stimuli) Allodynia (pain produced by normally non-noxious stimulation). Genetic basis – complex (additive effect of multiple genes), but frequent Familial hemiplegic migraine – channelopathies Hemiplegic migraine more often sporadic

Migraine Headache – Migraine with Aura– Diagnostic Criteria Diagnostic Criteria

Headache with > 2 of: At least two migraine attacks in life time with: Unilateral location 1. One or more fully reversible auras: Pulsating quality • Visual (+/-) flickering light, loss vision • Sensory (+/-) tingling, numbness Moderate or severe intensity • Speech/language Aggravation by or causing avoidance of routine physical activity • Motor (e.g. hemiplegia) • Brainstem (e.g. vertigo, tinnitus, diplopia, ataxia) During the headache at least one of: • Retina (monocular scotoma or blindness) Nausea and/or vomiting 2. At least one of: • At least one aura symptom spreads gradually (≥5 minutes), and/or two or more Photophobia/phonophobia symptoms occur in succession Headache attacks last 4 to 72 hrs (untreated or successfully treated) • Each individual aura symptom lasts 5 to 60 minutes • At least one aura symptom is unilateral At least 5 such attacks • The aura is accompanied, or followed within 60 minutes, by headache

*International Classification of Headache disorders, 3rd edition *International Classification of Headache disorders, 3rd edition “Complicated” Migraine Headache Migraine: Approach to Disorders Treatment

Neurologic symptoms and/or signs with aura  Pay attention to lifestyle and specific migraine triggers Neurologic symptoms and/or signs during headache or afterward  Irregular or skipped meals Basilar migraine: symptoms referable to brainstem  Irregular or too little sleep  Vestibular migraine: prominent vertigo with or without headache  Stressful lifestyle  Cause of episodic vertigo (“migrainous vertigo”)  Excessive caffeine or alcohol consumption Hemiplegic migraine  Lack of exercise  Triptans not used  Obesity  Familial hemiplegic migraine  2 categories of Pharmacologic migraine treatment Migrainous headache with seizure: Migrainous epilepsy 1. Acute drug therapy for individual attacks 2. Prophylactic drug therapy (when indicated) to reduce attack frequency  Evaluate and treat coexistent medical and psychiatric Refer these to a Neurologist!!! disorders

Migraine: Approach to Migraine: Acute Treatment Treatment

 Encourage patients to participate actively in their treatment and to employ self-management principles:  Headache diaries – available for smart phones and tables  Self-monitoring to identify triggers and headache patterns  When identified, manage migraine triggers effectively  Plan daily activity to avoid triggering or exacerbating migraine

 Use non-pharmacologic approaches  Relaxation techniques/stress management skills  Cognitive behavioral therapy  Sleep evaluation  Acupuncture

Adapted from Becker WJ. 2015. Continuum 21: 953-972. Migraine: Acute Treatment Migraine: Acute Treatment

 Moderate to severe attack:  Mild to moderate attack: Not associated with vomiting or severe  Oral migraine-specific agents are first-line nausea  oral triptans or combination of sumatriptan-naproxen  Simple analgesics (NSAIDs, acetaminophen) or combination analgesics  Moderate to severe attack with vomiting or severe nausea: are first choice agents  non oral migraine-specific medications  Mild to moderate attacks associated with severe nausea or vomiting:  subcutaneous sumatriptan  oral or rectal anti-emetic drug in conjunction with simple or combination  nasal sumatriptan and zolmitriptan analgesics  oral disintegrating tablets may be helpful  non oral antiemetic agents  parenteral agents in ER: ketorolac (NSAID), dihydroergotamine (vasoconstrictive)

Migraine: Prophylactic Migraine: Acute Treatment Treatment  Prophylactic medication when:  Recurrent migraine attacks are causing considerable disability  Frequency of acute medication use is approaching levels that place the patient at risk of medication overuse headache  ≥ 10 days per month for triptans, ergots, opioids, and combination analgesics  > 15 days per month for acetaminophen and NSAIDs  Recurrent attacks with prolonged aura are occurring  Complicated migraine (hemiplegic migraine, basilar-type migraine, etc)  Contraindications to acute migraine medications are Adapted from Becker WJ. 2015. Continuum 21: 953-972. making symptomatic treatment of migraine attacks difficult Migraine: Prophylactic Migraine: Prophylactic Treatment Treatment

Adapted from Silberstein SD. 2015. Continuum 21: 973-989. Adapted from Silberstein SD. 2015. Continuum 21: 973-989.

Migraine: Goals of Prophylactic Tension-type Headache Treatment  Ill-defined and heterogeneous headache syndrome

 Reduce attack frequency, severity, and  Phenotype is non-specific duration  Define by what it is NOT, rather than what it IS  Three recognized sub-types  Improve responsiveness to treatment of  Infrequent episodic (<1 per day per month) acute attacks  Frequent episodic (1-14 days per month)  Chronic (>14 days per month)

 Improve function and reduce disability  Pain is NOT localized and generally not severe

 No significant nausea, no vomiting, no photo/phonophobias  Prevent progression or transformation of episodic migraine to chronic migraine  Can be similar to milder episodic migraine or a secondary headache Tension-type Headache Acute Medications for Tension-  Most common primary or secondary headache type type Headache  Estimated mean lifetime prevalence in adults is 46%  Prevalence for Chronic TTH is 2-3%  40% of TTH patients report a family history of headache  Peak prevalence between 40-49 years of age  Acetaminophen  500mg to 1000mg  Socioeconomic impact of TTH greater than that of migraine  Aspirin  500mg to 1000mg

 Co-morbid with major depression, anxiety disorder, TMJ, C-  Ibuprofen  200mg to 800mg spine disc and spondylotic disorders  Naproxen sodium  375 to 550 mg  Generators: pericranial myofascial factors (episodic TTH) and  Diclofenac  12.5mg to 100mg central nociceptive pathways (chronic TTH)  Persistent activation of trigger points  Caffeine  65mg to 200mg  Peripheral nociceptor sensitization  Eventual second-order neurons sensitized in the spinal trigeminal Monitor for medication overuse nucleus (pain thresholds decreased) Guidelines from the European Federation of Neurological Societies. See Kaniecki, RG. 2012. Continuum 18:823-834.

Non-Pharmacologic Prophylactic Medications for Management of Tension-type Tension-type Headache Headache  Amitriptyline  10-100mg per day  Lifestyle and physical approaches  Nortriptyline  10-100mg per day  Regular sleep and meal schedules  Mirtazapine  30mg per day  Exercise and physical therapy  Cervical muscle stretching  Venlafaxine  150 mg per day  Passive physical manipulations For patients with 2‐3 headache days per week  Behavioral therapies  Relaxation techniques  EMG-guided biofeedback Guidelines from the European Federation of Neurological Societies. See Kaniecki, RG. 2012. Continuum 18:823-834 and  Cognitive-behavioral therapy Becker et al. 2015. Can Fam Phys 61: 670-679.  Acupuncture Trigeminal Autonomic Trigeminal Autonomic Cephalgias Cephalgias  Unilateral headaches • Paroxysmal hemicrania • Hemicrania continua  Spectrum from short-lived but recurrent to chronic

 Associated with one or more cranial autonomic symptoms  Ptosis  Conjunctival injection  Lacrimation  Nasal congestion or rhinorrea

 Cluster

 SUNCT: short, unilateral, neuralgiform, conjunctival, tearing

 SUNA: short, unilateral, cranial autonomic

Adapted from Newman LC. 2015. Continuum 21: 1041-1057.

Pathophysiology of the Trigeminal Autonomic Features of the Trigeminal Autonomic Cephalgias Cephalgias

 Common pathophysiology

 Ipsilateral activation of the hypothalamus:  Cluster headache  SUNCT

 Contralateral activation of the hypothalamus:  Paroxysmal hemicrania  Hemicrania continua

 Trigeminovascular pathway: ipsilateral pain  V1 branch (ophthalmic) activated  Elevated levels of calcitonin gene-related peptide (CGRP)

 Cranial autonomic pathways: autonomic features  Descending input from hypothalamus, release of vasoactive intestinal polypeptide (VIP) Adapted from Newman LC. 2015. Continuum 21: 1041-1057. Cluster Headache Features of the Trigeminal Autonomic Cephalgias  Most common TAC, but uncommon overall (0.1%)

 Severe, unilateral orbital, supraorbital, and/or temporal; pain lasts 15-180 minutes (untreated)

 At least one autonomic symptom in face or ear OR a sense of restlessness or agitation with headache

 Attack frequency between one every other day and eight per day more than half the time during a “cluster”

 Episodic: headaches in bouts from 7 days to 1 year TAC headaches can be distinguished by treatment responses separated by pain-free intervals of at least 1 month

 Chronic: attacks for more than 1 year without remission or remission < 1 month Adapted from Newman LC. 2015. Continuum 21: 1041-1057.

Cluster Headache Treatment Options Cluster Headache Treatment Options

Adapted from Newman LC. 2015. Adapted from Newman LC. 2015. Continuum 21: 1041-1057. Continuum 21: 1041-1057. Cluster Headache Treatment Options

Adapted from Newman LC. 2015. Continuum 21: 1041-1057.

Final Points References Available in PubMed  Headache is among the most common medical complaints. • Aurora SK et al. 2016. Chronic Migraine: An Update on Physiology, Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies. Headache  Episodic tension-type headache is the most frequent headache type January 2017: 109-125. in population-based studies  Migraine is the most common diagnosis in patients presenting to • Becker WJ. 2015. Acute migraine treatment. Continuum 21:953-972. primary care physicians with headache • Becker WJ et al. 2015. Guideline for primary care management of headache in  “Sinus” headache is often self-diagnosed by patients, but many adults. Can Fam Physician 61:770-679. patients presenting with sinus headache turn out to have migraine • Bendtsen L et al. 2016. Muscles and their role in episodic tension-type headache: implications for treatment. Eur J Pain 20:166-175.  Hypertension can cause headaches in hypertensive emergencies, but not with typical migraine or tension headaches. • Kaniecki RG. 2012. Tension-type headache . Continuum 18:823-834. • Levin M. 2015. Approach to the workup and management of headache in the emergency department and inpatient settings. Semin Neurol 35:667-674. • Newman LC. 2015. Trigeminal autonomic cephalgias. Continuum 21:1041-1057. • Silberstein SD. 2015. Preventive migraine treatment. Continuum 21:973-989.