A. Overview

1. Very common presenting symptom to primary care and emergency room physicians
2. Major focus is on ruling out serious (potentially life threatening) causes of HA
3. In addition, HA as a component of systemic disease should be considered
4. The history with careful attention to details is very helpful in focusing further evaluation
5. The physical exam is also very helpful for ruling out serious causes
6. If the assessment of the doctor and the patient differ considerably after the initial evaluations, referral to a HA specialist or radiographic imaging may be beneficial
7. Types of Headaches considered here
   1. Serious Causes of HA
   2. Common Headache
   3. Migraine Headache
   4. Cluster Headache

1. Usually anatomic or Inflammatory in nature
2. Compare with "common" HA, which is usually vascular
3. Must be ruled out in all patients with "new" HA
4. Overview of Serious Causes of HA
   1. Subarachnoid Hemorrhage
   2. Cerebral Vein Thrombosis (cerebral venous sinus thrombosis)
   3. Cavernous Sinus Thrombosis
   4. Cerebral Parenchymal Hemorrhage
   5. Increased Intracranial Pressure
   6. Meningitis / Encephalitis
   7. Vasculitis / Temporal Arteritis
   8. Pseudotumor Cerebri
   9. Cerebral artery dissections
   10. Acute angle closure glaucoma
   11. Hypertensive Emergency
5. Suggestive of Serious Causes of HA (Box 1, Ref [1])
   1. Fundamental change or progression in HA pattern
   2. First and/or worst HA
   3. Abrupt onset attacks, including those awakening
   4. Abnormal physical examination results
   5. Neurological symptoms lasting >1 hour
   6. New HA in individuals <5 years or >50 years
   7. New HA in patients with cancer, immunosuppression, pregnancy
   8. HA associated with alteration in or loss of consciousness
   9. HA triggered by exertion, sexual activity, or Valsalva maneuver
6. Suggestive of Migraine Versus "Serious" HA Cause [28]
   1. Pulsating
   2. Duration 4-72 hours
   3. Unilateral
   4. Nausea
   5. Disabling
   6. Presence of 4 of these 5 gives likelihood ratio (LR) for migraine of 24
   7. Presence of 3 of these 5 gives LR for migraine of 3.5
   8. Presence of 1 or 2 of these 5 gives LR of 0.4
7. Neuroimaging Recommended for [28]:
   1. Cluster-type headache: LR ~11
   2. Abnormal neurological examination: LR ~5
   3. Undefined HA: LR ~4
   4. HA with aura: LR ~3

B. Subarachnoid Hemorrhage (SAH) [2]

1. About 1-2% of headaches in an emergency department are due to SAH
2. Etiology
   1. Most (~80%) caused by rupture of aneurysm
   2. Usually due to berry aneurysm in Circle of Willis
   3. May lead to vasospasm which can cause cerebral infarction
   4. Increased intracranial pressure (ICP, due to obstruction) and attendant symptoms
   5. Non-aneurysmal SAH occurs in ~20% of cases and has better prognosis
   6. Non-aneurysmal SAH includes isolated perimesencephalic SAH
3. Symptoms
   1. Sudden onset HA; worst HA of life (~25% of these patients have SAH)
   2. May be preceded by "warning" HA (~35% of SAH patients)
   3. This "sentinal bleed" may herald second and usually more serious bleed
   4. Nausea, vomiting, fatigue, weakness leading to obtundation
   5. May have spontaneous resolution of symptoms if bleed stops
   6. Cerebral venous sinus thrombosis may also cause worst HA of life [4]
4. Evaluation
   [Figure] "Circle of Willis"
   1. Major concern is increased intracranial pressure (ICP)
   2. Rapid Neurologic Examination including fundoscopy
   3. Radiography: CT or MRI
   4. Lumbar Puncture (LP) - in any patient with posisble SAH and negative CT
   5. Misdiagnosis occurs in 25-50% of cases; these cases have poorer prognosis
5. Computerized Tomography (CT)
   1. ~95% sensitive for SAH
   2. If CT is negative and suspicion continues to be high, then do lumbar puncture
   3. MRI may also be used and better distinguishes clot from bleed [4]
6. Lumbar Pucture (LP)
   1. Blood in CSF from SAH
   2. Lumbar puncture should be done to rule out the10-15% of CT negative SAH
7. If progression occurs, angiogram and emergent surgery may be required
8. Treatment
   1. Neurosurgical Evacuation of bleed
   2. Nimodipine (Nimotop®) may help prevent vasospasm
   3. Lower blood pressure
   4. Reverse antiplatelet agents (with transfusion)
   5. Correct coagulopathies
   6. Treatment of ICP

C. Increased Intracranial Pressure (ICP)

1. Usually slower onset than SAH
2. Causes of Increased ICP
   [Figure] "Intracranial Pressure"
   1. Mass effect (tumor, abscess)
   2. Hydrocephalus
   3. Malignant Hypertension
3. Types of Hydrocephalus
   1. Elevated pressure - increased CSF production and/or decreased removal
   2. "Normal" pressure - slow onset headache, mental status chages, ataxia, incontinance
   3. Pseudotumor cerebri
   4. Supraduchal
   5. Arnold-Chiari Malformation
   6. Cerebral sinus thrombosis [5]
4. Symptoms include papilledema and Cranial Nerve VI palsy
5. CT essential; consider MRI
6. LP, if indicated and safe, should include both opening and closing pressures
7. Treatment aimed at decreasing cerebral blood flow, lowering pressures
   1. Normalize blood pressures
   2. Reduce seizure risk
   3. Reduce vasospasm
8. Early invasive intervention for ruptured aneurysms associated with improved outcomes
   1. Microvacular neurosurgical clipping - slightly reduced risk of bleeing
   2. Endovascular coiling - associated with better outcomes, reduced seizures overall

D. Meningitis

1. Infectious agents (viral, bacterial, fungal, protozoan)
2. Encephalitis - particularly viral
3. Blood (irritation)
4. Carcinomatous meningitis
   1. Inflammatory reaction to metastatic cancer
   2. Usually occurs with breast, lung, renal cancers
5. Medications - NSAIDs, some antibiotics, intravenous globulin (aseptic meningitis)
6. Lumbar Puncture is essential for diagnosis and to guide therapy

E. Vasculitis

1. Giant Cell (Temporal) Arteritis usually occurs in patients >50-60 yrs old
   1. Headache (or scalp pain) is usually unilateral and may occur with jaw claudication
   2. Commonly associated with Polymyalgia Rheumatica (~30% of cases)
   3. Temporal artery tenderness often present
   4. Leukocytosis and high ESR are common
   5. If suspected, must treat immediately with oral steroids (eg prednisone 60mg po)
   6. Failure to treat may result in blindness
   7. Biopsy of Temporal artery is definitive diagnostic method (80-90% sensitive)
2. Other Systemic Vasculitides
   1. Polyarteritis Nodosa
   2. Systemic Lupus with CNS Involvement
   3. Behcet's Syndrome
3. Isolated Vasculitis of the Central Nervous System
   1. Small to medium vessel vasculitis
   2. Headache, meningitis, encephalitis
   3. Abnormal LP and MRI

F. Pseudotumor Cerebri [7]

1. Introduction
   1. Disorder of intracranial pressure (ICP) regulation
   2. Also called Benign Intracranial Hypertension
   3. CSF pressures increase with normal studies: no mass lesion or hydrocephalus
   4. Major threat is to patients vision
   5. Reported association with use of sulfa antibiotics (TMP/SMX)
   6. No known cause
2. Symptoms
   1. Due only to increased ICP
   2. Headache ~95%
   3. Dizziness ~25%
   4. Nausea ~30%
   5. Visual Changes ~50%
   6. Diplopia ~30%
   7. Change in Mental Status ~10%
3. Signs
   1. Papilledema 100%
   2. CN VI Palsey 20%
   3. Blind Spot increased 90%
   4. Visual Acuity decreased 10%
4. Studies
   1. Computed Tomography should always be done to rule out mass lesion, hydrocephalus
   2. Lumbar Puncture: Pressure >20cm required for diagnosis; all other CSF studies normal
5. Contributing Factors
   1. Young > Elderly (peak mid 30s)
   2. Obesity (~75%)
   3. F>M ~3:1
   4. Probably NOT related to abnormal regulation of estrogen itself
   5. May be related to increased estrones, which are produced by adipocytes
   6. No association with infection, endocrine disease, medications
6. Abnormally low CSF resorption most likely plays a role
   1. Normal CSF production is ~0.35mL/min (21mL/hr)
   2. Lumbar puncture (LP) removes ~30mL but this is replaced in ~1.5hrs
   3. However, LP relieves symptoms in >90% of patients
7. Treatment
   1. Repeated LPs as needed
   2. Each LP should decrease ICP to <18cm
   3. Prednisone 40-60mg po qd x 2 weeks then taper
   4. Glucocorticoids only for resistant symptoms, visual changes, LP failure, patient refusal
   5. Acetazolamide (Diamox®) - 1gm of long acting form qd will reduce ICP
   6. Shunt - very unusual for patients to require shunts
8. Prognosis
   1. ~30% completely resolve with single LP
   2. Multiple LP's will cure most other patients
   3. All symptoms usually resolve over 6-12 months, many within 2 weeks

G. Cerebral Veinous Sinus Thrombosis (CVT) [4,8]

1. Also called cerebral vein thrombosis
   1. Most often affects young adults (75% women) and children
   2. Highly variable symptoms and clinical course
   3. Incidence 3-4 cases per 1 million population annually
   4. >80% have good neurologic outcome; mortality <20%
2. Mechanisms
   1. Thrombosis of central veins - local effects caused by venous obstruction
   2. Thrombosis of major sinuses which cause intracranial hypertension
3. Presentation
   1. Wide range of symptoms, nearly always including very severe (global) headache
   2. Focal motor or sensory deficits
   3. Dysphasia
   4. Seizures - may cause post-ictal hemiparesis ("Todd's paresis")
   5. Impaired consciousness
   6. Intracranial mass appearance on CT or MRI
   7. D-dimers are elevated >500ng/mL in most patients with acute CVT [9]
4. Risk Factors [10]
   1. Oral Contraceptives
   2. Factor V Leiden (activated protein C resistance)
   3. Prothrombin G20210A mutation
   4. Anticlotting factor (proteins C or S, antithrombin) deficiency
   5. Malignancy
   6. Trauma
   7. Autoimmune Disease
   8. Cerebral infection
   9. Pregnancy
   10. Prothrombotic risk found in ~85% of cases
   11. Head inury, direct sinus or jugular vein injury, and neurosurgical procedures also causes
   12. Otitis and mastoiditis may be complicated by CVT
5. Treatment [4]
   1. Heparin acutely - overall reduces poor outcome/death ~50%
   2. Overlap with warfarin and maintain for ~6 months for standard risk patients
   3. Endovascular thrombolysis is experimental
   4. Oral acetazolamide (500-1000mg daily) for intracranial hypertension
   5. Lumbar puncture to relieve tension only after evaluation for space-occupying process
   6. Surgical evacuation of clot
   7. Treat underlying disorder
6. Recurrent sinus thrombosis occurs in 2-4% of cases

H. Cavernous Sinus Thrombosis

1. Usually secondary to oculonasal infections
2. Syndrome
   1. Orbital edema with eye pain, tenderness on palpation
   2. Chemosis, cyanosis of upper face present
   3. Venous congestion
   4. Palsy of CN III, IV, V(3), and VI
3. Patient appears acutely ill
   1. High fever
   2. Headache
   3. Nausea and vomiting
4. Additional Ophthalmic Symptoms
   1. Ophthalmoplegia
   2. Pupillary changes
   3. Retinal hemorrhages
   4. Papilledema
   5. Sensory changes in ophthalmic division (3) of CN V
5. CSF usually normal unless associated meningitis or subdural empyema
6. Differentiate from mucormycetes infection, usually in diabetics or immunosuppressed
7. Treatment with potent anti-staphylococcal and anti-anaerobic antibiotics
8. Anticoagulation usually of minimal benefit

1. Tension
2. Cluster
3. Migraine
4. Neuropsychiatric
   1. Tic doloreux
   2. Cranial Neuralgia
   3. Depression
   4. Fibromyalgia
5. Carotidynia
   1. Pain of face, neck, ear and head
   2. Due to distention or dilatation of one or both extracranial arteries
6. Newly Defined HA Types
   1. Drug rebound HA - common with ergotamines, butalbital, NSAID and Tylenol® overuse
   2. Hypnic HA: throbbing pain, age >65, <1 hour, no systemic symptoms; responds to lithium
   3. Paroxysmal hemicrania: F>M, severe, sharp, periorbital pain; responds to indomethacin
   4. Transformed migraine: increased severity and frequency over decades
   5. Posttraumatic HA: may be due to axonal swelling, usually with head and neck pain
   6. Chronic Daily HA: HA >15 days per month for >3 months (new category; see below)

B. Tension HA [12]

1. Most common type of headache, usually intermittant [13]
   1. Episodic tension HA occurs in 30-80% of persons in North America
   2. Slight female predominance
   3. Increased incidence with increasing education levels
   4. Chronic tension-type HA is very uncommon
2. Probably due to abnormal vascular tone within pericranial muscles
3. Types of Tension Headaches
   1. Generalized
   2. Bilateral
   3. Steady and Dull
4. Diagnostic Criteria
   1. HA pain accompanied by at least 2 of the following 3:
   2. Pressing/tightening (nonpulsatile quality), bilateral, no effect of physical activity
   3. Required: no nausea or vomiting
   4. Photophobia or phonophobia absent, or only one present
   5. Greater than 15 days per month with HA
   6. No evidence of organic disease
5. Classification
   1. Episodic tension type HA associated with disorder of pericranial muscles
   2. Chronic tension type HA associated with disorder of pericranial muscles
   3. HA of tension type not fulfilling criteria above
6. Treatment
   1. Aspirin or Acetaminophen - 1000mg po as needed
   2. Other NSAIDs - Naproxen (375-500mg po) appears to very effective
   3. Treat as if typical vascular (such as migraine) HA
   4. Fiorcet® / Fiorinal® - always last line; may be habit forming
   5. Severe headaches may require hospitalization
   6. Spinal manipulation does not improve episodic tension-type HA [14]
   7. Nitric oxide synthetase (NOS) inhibition is effective in early studies [15]
7. Prophylaxis
   1. Non-pharmacologic: behavioral modification, exercise, biofeedback
   2. Tricyclic antidepressant (see below) - minor improvements [16,17]
   3. Serotonin reuptake inhibitor such as fluoxetine [17]
   4. Anti-epileptics - carbamazepine, gabapentin, others
   5. Consider muscle relaxant such as tizanidine 6-18mg in more severe cases
8. Combined stress management therapy and tricyclics more effective than either alone [16]

C. Carotidynia

1. Pain anywhere above shoulders due to extracranial artery abnormalities
2. Extensive differential
   1. Neuralgias - facial, cluster HA's, disc disease and cervical OA
   2. Musculoskeletal - myofascial pain, muscle strain, TMJ syndrome, bruxism
   3. Infection and/or inflammation - temporal arteritis (GCA) main concern, infections
   4. Classic carotidynia
   5. Rule out other causes as described above
      1. Etiology is migrainous (vasodilation/spasm) or arteriosclerosis (insufficiency)
3. Therapy based on cause and/or classification

D. Intracranial Hypotension [18,19]

1. Orthostatic headaches
   1. ~5 per 100,000 per year
   2. Peak age ~40 years
   3. More common in women
2. Diverse Causes
   1. Due to reduced cerebrospinal fluid (CSF) pressure OR
   2. Reduced CSF volume (or both)
   3. Caused by single or multiple CSF leaks
   4. Thought to be related to leakage of CSF from spinal meningeal diverticuli
3. Diagnosis [20]
   1. Lumbar puncture and measurement of CSF pressure is standard
   2. MRI shows subdural fluid collections, enhancement of pachymeninges, engorgement of venous structures, pituitary hyperemia, sagging of brain (mnemonic: SEEPS)
   3. Color doppler imaging of superior ophthalmic vein may be as effective, non-invasive
   4. Myelography required to idenitfy spinal CSF leadk
4. Treatment
   1. Bed rest
   2. Epidural blood patching
   3. Percutaneous placement of fibrin sealant
   4. Surgical CSF leak repair

E. Common Daily HA [3]

1. HA >15 days per month for >3 months
2. Category includes many primary and secondary HA types
   1. Transformed migraine
   2. Medication overuse HA
   3. Other types
3. Risk Factors
   1. Obesity
   2. History of frequent HA
   3. Caffeine consumption
   4. Overuse of acute HA medications (>10 days/month)
4. Transformed Migraine
   1. Head pain >15 dyas per month for >1 month
   2. Average HA lasting >4 hours / day if untreated
   3. History of any form of episodic migraine or HA with migrainous components
5. Medication Overuse HA
   1. HA present >15 days per month with development or marked worsening of pain during medication overuse and resolution of pain within 2 months of discontinuation of medicine
   2. Overuse: HA medicastion >3 months
   3. Use of ergotamine, triptans, opioids or combinations >10 days/month
   4. Use of simple analgesics at least 15 days per month
   5. Total use of HA medications at least 15 days per month
6. Prevention of Transformed Migraine or Medication Overuse HA
   1. Limit or eliminate caffeine consumption
   2. Regular exercise
   3. Regular mealtimes and sleep schedules
   4. Treat coexistant anxiety and/or depression
   5. Pharmacologic agents similar to that for migraine prevention
   6. Initiate pharmacologic therapy and adjust dose to tolerability or >50% HA reduction
7. Pharmacologic Prevention of Common Daily HA
   1. Tricyclic antidepressant such as amitriptyline 10mg po qhs initially, up to 100mg qhs
   2. SSRI such as fluoxetine or paroxetine, initiate 10mg po qd, up to 60mg daily
   3. Gabapentin target dose 300-1200mg tid
   4. Topiramate target dose 50-200mg qd divided
   5. Divalproex target dose 500-2000mg per day, divided
   6. Tizanidine target dose 8-20mg
   7. Botulinum toxin type A: 25-260U q3 months

1. Migraine without aura (common migraine)
   1. Attacks lasting 4-72 hours (untreated)
   2. At least 2 of: unilateral, pulsating, moderate to severe, aggrevated by movement
   3. At least 1 of: nausea or vomiting, photophobia, phonophobia
2. Migraine with aura (classic migraine)
   1. One or more transient focal neurological aura symptoms
   2. Gradual development of aura symptom over >4 minutes, or several symptoms in a row
   3. Aura symptoms last 4-60 minutes (untreated)
   4. Headache follows or accompanies aura within 60 minutes
3. Ophthalmoplegic migraine
4. Retinal migraine
5. Childhood periodic syndromes
6. Complicated migraine

B. Causes

1. Trigger foods
2. Tobacco Smoke
3. Estrogens
4. Fumes and Vapors
5. Dehydration
6. High Altitudes
7. Genetic Causes
8. Currently unclear what percentage of migraine suffers have genetic cause

C. Symptoms

1. Throbbing HA
2. Nausea / vomiting - due to decreased grastric motility
3. Photophobia
4. Feeling of doom occurs more in "Classic Migraine" as an "aura"
5. In common migraine, there is usually not an aura
6. Most commonly affects 20-40 year old females; rarely new onset >45 years old
7. If new onset "migraine" occurs in patient >40 years old, strongly consider CT scan

E. Therapeutic Intervention

1. Control Pain Acutely
   1. NSAIDS are useful for mild migraines
   2. Serotonin receptor (5-HT1B/D) blockers are first line for moderate to severe migraines
   3. Nausea and vomiting usually reponds to prochlorpromazine or metaclopramide
   4. Opiates may be useful for resistant migraines and for patients intolerant of other drugs
2. More dangerous causes of HA must be ruled out (see above)
3. Prevention of Migraines
   1. Initially, try elimination diet: eliminate all implicated foods and add back singly
   2. Discontinue vasoconstrictor (usually sympathomimetic) medications
   3. Add prophylactic agents (see below)

F. Treatment of Acute Exacerbations [23]

1. Non-Steroidal Anti-Inflammatory Drugs (NSAID)
   1. Mainly for mild to moderate HA
   2. Generally poorer control of concurrent migraine symptoms than other agents
   3. GI distress and bleeding is a concern
   4. Renal dysfunction can occur, particularly with concomitant use of other nephrotoxins
2. Serotonin Receptor Type 1B/1D Agonists [24,25]
   1. First line agents for control of moderate to severe migraines
   2. "Triptans": Sumatriptan (Imitrex®), Zolmitriptan (Zomig®), others
   3. Eletriptan 80mg, rizatriptan 10mg, almotriptan 12.5mg provide highest success rates overall [24]
   4. Side effects include chest pain, vasocontstriction, wheezing, flushing
   5. Contraindications: coronary artery disease, previous reaction, ECG changes
   6. Should not be used with other serotonergic agents, or within 2 weeks of MAO inhibitor
   7. Specific agents discussed under migraine
3. Dihydroergotamine (DHE)
   1. Derivative of ergotamine with less vasoconstriction and adverse effects
   2. Can be given sc, im, iv, and newer intranasal therapy
   3. ~70% of patients will have relief within 2 hours of injection
   4. DHE Nasal Spray (Migranal®) - one spray (0.5mg)/nostril x 1, repeat in 15 minutes
   5. Nasal form may be safer, more effective
   6. May cause hypertension or cardiac valvular lesions
   7. Other ergot derivatives are third line therapy
4. Dopamine Antagonists
   1. Primarily improve nausea and vomiting
   2. Metoclopramide (Reglan®) - also improves gastric emptying; 10mg iv usually given
   3. Prochlorperazine (Compazine®) 10mg iv or per rectum
   4. Chlorpromazine 25mg iv
   5. Often given with diphenhydramine (Benadryl®) or hydroxyzine 25mg iv or im
   6. Side effects of dopamine antagonists: dystonia, tardive dyskinesia
5. Opiates - for severe migraines are used for third line therapy
6. Fiorinal®: Caffeine + ASA + Butalbital (not recommended)

G. Prophylaxis [6,25]

1. Usually for >3 months migraine or migraines >1 / week
2. ß-adrenergic blockers first line
3. Amitriptyline or verapamil usually second line
4. Topiramate (preferred), gabapentin (Neurontin®) are reasonable second line alternatives [26]
5. Divalproex (valproate) usually third line
6. Candesartan (an angiotensin II receptor blocker) - particularly in hypertensive persons
7. Methysergide only for recurrent, refractory migraines
8. Each specific agent for prophylaxis should be used for at least 1 month before switching
9. For details

1. Men ~90%, usually older age of onset (~30 years)
2. Prevalence <1%, much less common than migraine
3. Excruciating unilateral pain, centered over eye
   1. Duration 15-180 minutes and occurs 1-8 per 24 hour period
   2. Recur daily for 3-12 weeks then stop for 3-12 months
   3. Hence the name "cluster"
4. Associated unilateral autonomic symptoms
   1. Conjunctival injection or lacrimation
   2. Nasal congestion or rhinorrhea
   3. Forehead and facial sweating
   4. Miosis
   5. Ptosis or Eyelid edema
5. Nausea and vomiting are very uncommon
6. Patients generally cannot remain still
7. ~85% of patients are cigarette smokers

B. Pathophysiology

1. Inheritability
   1. Familial occurrance in 7% of first degree relatives; 14X increased risk
   2. ~2X increased risk in second degree relatives
2. Newer theories of pathophysiology
   1. Now believed to be neurovascular
   2. Severe unilateral pain mediated by first (ophthalmic) division of trigeminal nerve (CN V)
   3. Autonomic symptoms, including lacrimation, due to activation of parasympathetic outflow from cranial nerve (CN) VII
   4. Activation of blood flow in hypothalamus during attacks has been described [27]
   5. Abnormal hypothalamic grey matter function may play a major role in cluster headaches
3. Sympathetic Paralysis
   1. Miosis and ptosis due to neuropraxic injury of postganglionic fibers in most patients
   2. This dysfunction may originate centrally in the hypothalamus as above
   3. Autonomic symptoms may also be secondary to trigeminal discharge
4. Nitroglycerin, a vasodilator, can trigger cluster HA in susceptible individuals
5. Many experts now regard cluster HA as a hypothalamic syndrome

C. Differential Diagnosis

1. Trigeminal neuralgia
2. Migraine
3. Pheochromocytoma
4. Temporal arteritis
5. Tolosa-Hunt syndrome
6. Raeder's Syndrome
7. Brain Tumor
8. Intracranial Vascular Malformation (AVM, Hemangioma, others)
9. Post-traumatic headache
10. Conversion Disorder

D. Acute Therapy

1. Oxygen 7-10 L/min x 10-60 minutes with non-rebreathing facial mask
   1. Treat for 20 minutes
   2. Sitting, upright position
   3. No contraindications for use of oxygen
   4. ~60% response rate within 30 minutes
2. Lidocaine, 4% intranasal - effective in minority of patients, but very safe
3. Serotinin 5HT1B/D Agonists (Triptans)
   1. Sumatriptan (Imitrex®) 6mg sc or 50-100mg po
   2. ~75% efficacy of sc injected sumatriptan within 20 minutes
   3. Contraindications include cardiovascular and cerebrovascular disease
   4. Zolmitriptan (Zomig®) 5mg nasal spray also effective [11]
   5. No benefit of oral sumatriptan 100mg po tid for prevention of cluster HA
4. Ergotamines (nasal 3 puffs or injection 0.5-1mg, sc, im or iv, or po/per rectum)
5. Caffeine / ergotamine combination agents (Cafergot®, Ercaf®, Wigraine®)
6. Narcotics
   1. Standard: meperidine (Demerol®) im
   2. Butorphanol (Stadol®) nasal spray or

E. Prophylaxis

1. Efficacy of prophylaxis for cluster HA is controversial
2. Verapamil
   1. Mainstay of prophylactic therapy
   2. Dose 120mg tid clearly reduced attack frequency and use of abortive agents [21]
   3. Dose is 120-480mg po qd usually divided; full effect in 2-3 weeks
   4. Overall, very safe agent
   5. Main side effects are bradycardia and constipation
   6. Synergistic with lithium
3. Lithium: 300-1200mg per day (monitor serum levels)
4. Prednisone
   1. Usual starting dose is 30-60mg po qd 1-2 weeks
   2. Then tapered over 1-3 weeks
   3. General precautions for glucocorticoid use
5. Valproex Sodium
   1. 750-1500mg/day in divided doses
   2. Monitor for side effects carefully
   3. Hepatic dysfunction, pancreatitis and bone marrow suppression are possible
6. Ergotamine: 1mg po qhs or bid
7. Methysergide (Sansert®)
   1. Maximum of 4-6 month use with 1 month drug holidays
   2. Dose is 2-8mg divided in 3 doses each day
   3. Retroperitoneal fibrosis is major side effect - cumulative dose and time related
   4. Peripheral ischemia, CNS with halucinatory symptoms are rare
   5. May suppress cluster HA, then discontinue
8. Occipital Nerve Stimulation [29]
   1. Suboccipital region electrodes for nerve stimulation for refrectory cluster HA
   2. Of 8 patients, 2 had >90%, 3 moderate (~40%), 1 mild (25%) improvement

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