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Kenneth A. Fox, M.D.Assistant Clinical Professor - UCSF Department of Medicine

Chief – Department of NeurologyKaiser Permanente San Francisco

A Practical Approach ToHeadache

Overview

Case Presentation

Headache Emergencies

Common Primary Headache Disorders/Treatment

Medication Overuse/Rebound

Occipital Neuralgia

New Frontiers

Case Wrap-Up

Case Presentation

41F Obesity, Hypothyroidism, Depression

Mod-severe, throbbing R frontal retro-orbital headache x 5d

Associated sxs: N/V, photophobia, blurred vision, L hemisensory disturbance

Took Ibuprofen 400mg q6 hours with incomplete relief

Month prior, 3-4x/wk responsive to repeated dosing of Ibuprofen 400mg over a 24 hour period

No triggers but gets “clusters” around menstrual cycle

Headache Emergencies

Generally Concerning SignsThunderclap onset

“Worst headache of my life”

Progressive pain or associated symptoms

Focal neurological signs/symptoms

Narrow Differential

Patients may possess unique qualifiers (eg. HIV, systemic cancer)

Clinical components may overlap with benign syndromes

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Headache Emergencies

Subarachnoid Hemorrhage

Atraumatic Subdural Hematoma

Carotid/Vertebral Dissection

Pituitary Apoplexy

Venous Sinus Thrombosis

Giant Cell Arteritis

Idiopathic Intracranial Hypertension

Subarachnoid Hemorrhage

Common Clinical Features

Thunderclap, severe holocranial headache

Nausea and light sensitivity are common

Nuchal rigidity/meningismus

Focal neurological symptoms (eg. 3rd Nerve Palsy)

Smaller/”sentinel” bleeds may not have neurological signs

Urgent referral to ER for Head CT/CTA and LP

Subarachnoid Hemorrhage Carotid/Vertebral Dissection

Common Clinical Features

Exquisite, pulsating anterior or posterior neck pain with radiation to jaw or occiput

Can occur with trivial trauma, sudden change in intrathoracicpressure (eg. wretching), or spontaneously

May be associated with neurological signs, such as Horner’s syndrome (carotid) or vertigo/dysequilibrium (vertebral).

Delay between pain and neurological signs/symptoms is common

Obtain CT, MR, or Catheter Angiogram of Neck/Head

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Carotid/Vertebral Dissection

wustl

Pituitary Apoplexy

Common Clinical Features

- Thunderclap headache

- Cardiovascular collapse

- Vision loss and diplopia

Generally have pre-existing adenoma sudden change

Precipitating factors: change in pituitary therapy, major surgery, parturition, anticoagulation, head trauma

Head/Pituitary imaging, corticosteroids, neurosurgery

Pituitary Apoplexy Venous Sinus ThrombosisCommon Clinical Features

Thunderclap/Progressive headache

Cognitive Dysfunction

Seizures

Focal/stroke-like symptoms

Predisposing Factors

Hypercoaguable State

Oral Contraceptive Use

Puerpartum

Inflammatory Bowel Disease

Nephrotic Syndrome

Sickle Cell Disease

MRI, MRV

Treatment - Anticoagulation

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Venous Sinus Thrombosis

j. neuroradiology

Giant Cell ArteritisVasculitis of medium/small vessels (beyond just temporal artery)

Clinical FeaturesThrobbing headacheFatigueDepressionJaw claudicationMyofascial pain, including scalp tenderness

Rare before age 50; 3-9/100k; females>males;

Polymalgia Rheumatica present in 25% of cases

CRP more sensitive than ESR (false negatives early in course)

Vision loss most devastating complication (ischemic optic neuropathy)

Diagnose via TA biopsy (may take more than 1);

Tx: Corticosteroids

Giant Cell Arteritis

Rheumatology.org

Idiopathic Intracranial HTN “Pseudotumor Cerebri”

Cause unknown or associated with medications (Vitamin A), systemic disease (eg. SLE)

Predominantly occurs in obese women aged 20s-40s (risk 1/5k/yr)

Visual disturbances (blurring, diplopia), pulsatile tinnutus

Normal neurological examination except for papilledema

Neuroimaging unrevealing

Increased opening pressure on LP (>200mmH20)

Tx – large volume LP, diuretics, permanent shunting

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Primary Headache Disorders

Tension

Migraine

Trigeminal Neuralgia

Trigeminal Autonomic CephalgiasCluster

Hemicranial continua

Paroxysmal Hemicrania

SUNCT

Headache Patterns

Tension Headache

Recurrent bilateral pressing/tightening quality

Not aggravated by physical activity

Not preceded by aura or associated with N/V, sensory sensitivity, focal neurological symptoms

Muscle tenderness is a prominent feature

Most effective meds: Naproxen, Indomethacin, Ketorolac, Aspirin/Acetaminophen/Caffeine (muscle relaxants not validated)

Non-pharmacological measures include heat/ice, stress management, relaxation/meditation, exercise, sleep hygeine, biofeedback (*acupuncture has yet to be validated)

Migraine Headache

Recurrent pulsating head pain which is typically severe, unilateral, and aggravated by physical activity

Pain may be preceded by aura visual, focal neurological signs

Frequently accompanied by autonomic symptomsNausea ± vomiting, Diarrhea

Sensory input sensitivityphotophobia, phonophobia, kinesophobia, osmophobia

Typically lasts for several hours to several days (status migrainosis)

Sleep often curative, but episodes may start during sleep as well

Onset (of some variety) begin in adolescence

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Migraine PathophysiologyMigraine Pathophysiology

Migraine Abortive Treatments Migraine Abortive Treatments

Combination Analgesics – acetaminophen/aspirin/caffeine (Excedrin) is effective and comparable to Sumatriptan 50mg

NSAIDs

Ibuprofen 200-400mg (half life 1-2hrs)

Naproxen sodium 500mg (half life 12-17 hrs)

Ketorolac 30-60mg IM for severe headache

Antiemetics – Metaclopramide IV

Primary treatment of headaches in ER

Antinociceptive effects not proven with oral formulations

Ergots

Nasal DHE, non-oral option which is generally less effective than Sumatriptan;

DHE IV + antiemetics for severe symptoms in ED

Am Fam Phys 2011

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Migraine Abortive TreatmentsTriptans – 5HT1b/1d agonists

First line treatment for migraines unresponsive to conventional analgesicsAgents [half-life]

Sumatriptan (Imitrex) – Tab 25/50/100mg, SC 6mg, Nasal 5/20mg [2.5h]Zolmitriptan (Zomig) – Tab 2.5/5mg, Nasal 5mg [3h]Eletriptan (Relpax) – Tab 20/40mg [4h]Naratriptan (Amerge) – Tab 1/2.5mg [5-8h]

Frovatriptan (Frova) - Tab 2.5mg [26h]Rizatriptan (Maxalt) – Tab 5/10mg [2-3h]Almotriptan (Axert) - 6.25/12.5mg [3-4h]

Cochrane review - similar effectiveness with all 7 optionsMeta-analysis - most effective agents: Almotriptan, Eletriptan, RizatriptanIncreasing doses may be necessarySwitching agents is reasonable before abandoning classAvoid in patients with Hx CAD, stroke, hemiplegic+basilar migraine

Naproxen + Sumatriptan

2 replicate RCTs trials with >1k patients per trial

1:1:1:1 ratio groups (N500/S85, S85, N500, and Placebo)

Relief from mod-severe migraine pain at 2 hours

Combination conferred superior efficacy compared to placebo and either as monotherapy

No significant adverse events, save heart palpitations in a 58 year old woman

Complimentary mechanisms of action are thought to underlytherapeutic advantages

JAMA 2007

Migraine Prophylaxis: When do we start?

“An effective abortive strategy is the best prophylaxis”

Criteria*Occurrence 2-3x/mo or recurring attack affecting function

Duration > 48 hours

Common accompanying complex neurological symptoms

Inadequate relief, intolerance, overuse of abortive agents

Patient preference

*Ann. Int Med 2002

Migraine Prophylaxis: Setting Expectations

Establish “contract” of commitment

Utilize the lowest effective dose, preferably once daily to start

Trial for at least 8 weeks

Reduce or eliminate frequent use of abortive medication

Introduce multiple agents sequentially (side effects)

Consider comorbid conditions (eg. HTN – beta blocker)

Benefits of all such drugs are variable and rarely curative

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Migraine Prophylactic Treatments

Antidepressants: Amitriptyline (B), Nortriptyline (U), Venlafaxine (B)

Antihypertensives:

• B-b - Propranolol (A), Timolol (A), Metoprolol (A) , Atenolol (B)

• CCBs – Verapamil (U), Diltiazem (U), Nimodipine (U)

Antiepileptics: Valproate (A), Topiramate (A), Gabapentin (U)

Abortives*: Naproxen (B), Ibuprofen (B), Frovatriptan (A)

Botulinum Toxin

Supplements: Butterbur (A), Riboflavin (B), Mag (B), CoQ (C)

(A) Established effective (B) probably effective (C) possibly effective (U) insuff eviden

*For short-term use in menstrual cycle associated migraineNeurology 2012

Migraine Prophylactic Treatments:Weighing The Evidence

(A) Requires at least two consistent Class I studies

(B) Requires at least one Class I study or two consistent Class II studies

(C) Requires at least one Class II study or two consistent Class III studies

(U) Studies not meeting criteria for Class I through Class III

Menstrual Migraine

Migraines which occur at or around (+/- 2 days) menstruation during at least 2/3 cycles

90% women report episodic migraine at other points in the cycle

Acute treatments are the same as episodic migraine

Perimenstrual prophylaxis is an effective strategy for more severe cases

Naproxen, Estradiol, Frovatriptan, Naratriptan validated in RCTs

Continuous hormonal therapy (estrogen/progesterone) used but not validated in RCTs

Combined hormonal contraceptives should not be used by women with migraine with aura owing to increase risk of ischemic stroke*

*Br J Fam Plann 2004

Non-Pharmcologic Measures

Should be a part of all prophylactic treatment plans

Trigger avoidance (eg. Missed meals, foods, caffeine, alcohol, odors, elevation change)

Regular sleep and exercise

Grade A Evidence: relaxation, thermal biofeedback with relaxation, EMG biofeedback, cognitive behavioral therapy

Grade B: behavioral therapy + FDA approve prophylactic

Grade C: acupuncture, TENS, chiropractics, hyperbaric O2, hypnosis

Technical Reviews 1999

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Medication Overuse Headache

Results from overuse of conventional analgesics, triptans, or other acute headache compounds

Typically patients have an antecedent history of episodic TTH or migraine

May overlap with or be mistaken for chronic daily headache

Incidence found to be 14% in a 1 year study of episodic migraineurs, women > men

Occurs with higher prevalence in low-socioeconomic, poorly educated people

Lancet Neurology 2010

Medication Overuse Headache

IHS Diagnostic criteria

Headache present >15 days/mo

Regular overuse of a medication for > 3 mos

Simple analgesics (Excedrin, Ibuprofen, Acetaminophen) >15d/m

Ergotamine, triptans, opioids, and combos >10 days/month

Headache developed or worsened during medication overuse

Headache resolves or reverts to previous pattern within 2m following cessation of overused medications

Cephalagia 2004

Medication Overuse HeadacheTreatment/Medication Withdrawal

No available studies or guidelines

Rapid withdrawal has been favored, and short-term worsening is expected

Switch out short acting for longer acting analgesics

Long acting NSAIDs, Prednisone (50-100mg x 5-10 days) may behelpful

Inpatient Valproate or DHE IV treatments in refractory cases

Non pharmacological approaches, including short-term psychotherapy leads to improved outcomes long-term*

Relapse rate is 9-30% when followed > 6 months in outpatient tx

(multiple studies)

*Headache 2002

Cluster Headache

“Periodicity” – attacks occur in series, lasting days-wks-mos

>5 attacks of severe, unilateral, temporo-orbital pain lasting 15m-3hrs (untreated); 1-8 attacks per day

Typically associated with autonomic symptoms ptosis conjunctival injection, lacrimation, rhinorrhea, diaphoresis

Onset generally in 20s-30s years old

ADAM

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Cluster Headache

Abortive treatments100% O2 at 7-10L/mDHE 1.0mg IM or IVsumatriptan 6mg SCnasal lidocaine (4-6%)

Prophylactic treatmentsverapamil 120-480mg/d prednisone 10-20mg/dvalproate 250-1000mg/dlithium

Non parenteral analgesics and narcotics not effective

Cluster Headache

Lancet.com

Trigeminal NeuralgiaBrief jolts of severe unilateral pain/spasm (bilateral in 4%)

Typically in distribution of CN V2

Provoked by stimulation of specific trigger points

washing, shaving, brushing teeth, eating

Asymptomatic between events and without neuro deficit

Most cases are idiopathic

Rarely secondary to vascular anomalies, and structural lesions of brainstem or facial structures

Brain MRI indicated in most cases

Most effective meds include Carbamazepine, Oxcarbazepine, Baclofen, and Phenytoin

Occipital Neuralgia

Unilateral shooting pains which typically originate at occiput and radiate towards the forehead/orbit

Cervical nerve root impingement or greater occipital nerve impingement

Frequently associated with scalp allodynia

May have migraine- or tension-like features leading to futile trials of conventional analgesics

Responds to Occipital Nerve Block (lidocaine ± steroid)

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Occipital Neuralgia BruxismStereotyped movement disorder characterized by grinding or clenching the teeth during sleep

Etiology unknown: neural, psychological, and mechanical factors have been proposed

High prevalence in general population

Becomes pathologic when linked to dental wear and sleep fragmentation

Linked to TMD and migraine1

Treatments: behavioral, bite guards, botulinum toxin2

1 J Orofacial Pain 2013 2 Am J PMR 2010

New Treatment Frontiers

Drugs

Calcitonin Gene Peptide Receptor (CGPR) Antagonists

Nitrous Oxide Antagonists

Serotonin Receptor/5HT1F Receptor Agonists

Cortical Spreading Depression Inhibitors

Procedures

Occipital Nerve Stimulators – FDA approved for refractory “occipital headache syndromes”

Transcranial Magnetic Stimulation – FDA approved for the treatment of migraine with aura

TENS unit (Cefaly®) – FDA approved for the prevention of migraine

Occipital Nerve Stimulator

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Transcranial Magnetic Stimulation Cefaly® – TENS Unit

Case Presentation(Revisited)

41F Obesity, Hypothyroidism, Depression

Mod-severe, throbbing R frontal retro-orbital headache x 5d

Associated sxs: N/V, photophobia, blurred vision, L hemisensory disturbance

Took Ibuprofen 400mg q6 hours with incomplete relief

Month prior, 3-4x/wk responsive to repeated dosing of Ibuprofen 400mg over a 24 hour period

No triggers but gets “clusters” around menstrual cycle

Case Presentation:Diagnosis/Management

Migraine with aura/Medication Overuse/Transformation

Acute TreatmentNaproxen 500mg bid x 7 days, Sumatriptan 100mg prn breakthrough Consider Prednisone 50mg daily x 7 daysIn future, replace Ibuprofen with early Naproxen 500mg ± Sumatriptanprn

Prophylaxis Topiramate 50mg qhsConsider perimenopausal Naproxen or FrovatriptanConsider Butterbur 50mg bid, Riboflavin 200mg bid

Follow-up in 6 wks with headache diary