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Headache

Paul G. Mathew, M.D.,1,2 and Ivan Garza, M.D.3

ABSTRACT

KEYWORDS: Primary headache, migraine, trigeminal autonomic cephalgias, cluster headache, tension-type headache

EVALUATION The rst major step that a neurologist must take when evaluating a headache patient in an outpatient neurology practice is to establish whether the headache is a primary or secondary type of headache. Primary headaches are those that cannot be attributed to an underlying disorder, whereas secondary headaches are due to a specic underlying cause or disorder. In the case of secondary headaches, addressing the underlying disorder can often, but not always, lead to resolution of the headaches. Some of the common causes of secondary headaches are listed in Table 1.

History The most fundamental and essential component in the evaluation of headaches is a thorough history. Table 2 summarizes the important elements of a headache hisDepartment of Neurology, Brigham and Womens Faulkner Hospital, John R. Graham Headache Center, Jamaica Plain, Massachusetts; 2 Division of Neurology, Cambridge Health Alliance, Cambridge, Massachusetts; 3Department of Neurology, Mayo Clinic, Rochester, Minnesota. Address for correspondence and reprint requests: Paul G. Mathew, M.D., John R. Graham Headache Center, 1153 Centre Street, Suite 4970, Jamaica Plain, MA 02130 (e-mail: PMATHEW@partners.org).
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tory. The history should be chronological, and should document the evolution of all associated symptoms. It is vital to have the patient recall when the headaches began, and whether there were any triggering events around the time of onset. Events such as head trauma, the presence of infectious diseases or inammatory processes, and other neurologic disorders can all be associated with the development of headaches. Other details that should be elicited include the location, radiation, quality, frequency, and duration of pain. For female patients with headaches, seeking any prior or current association with menstruation, pregnancy, and/ or hormone therapy can be useful. In addition, assessing the presence of photophobia, phonophobia, osmophobia, nausea, vomiting, cutaneous allodynia, unilateral runny/stuffy nose, monocular tearing, monocular eye redness, and unilateral eyelid ptosis can be helpful in classifying headaches. Patients
Ofce-Based Neurology; Guest Editor, Devon I. Rubin, M.D. Semin Neurol 2011;31:517. Copyright # 2011 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. DOI: http://dx.doi.org/10.1055/s-0031-1271313. ISSN 0271-8235.

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Headache is one of the most common complaints among patients presenting to an outpatient neurology practice. The evaluation, diagnosis, and treatment of headache can be rather cumbersome and at times quite challenging for even the most seasoned neurologist. Many complex issues that although not causative, can play an exacerbating role in the genesis of headaches. In this article, the authors review some of the essential elements that are part of headache evaluation including headache-specic history, physical examination, warning signs of secondary headache disorders, and when to consider further studies. They then provide a brief review on the diagnosis of primary headache disorders according to the International Headache Societys International Classication of Headache Disorders, 2nd Edition (ICHD-2), and treatment strategies of the more common primary headache disorders with a focus on migraine, trigeminal autonomic cephalalgias, tension-type headache, and chronic daily headache.

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Table 1 Causes of Secondary Headache


Cause Cerebrovascular diseases Altered CSF dynamics Intracranial space-occupying lesion Infection Trauma Musculoskeletal Medications
CSF, cerebrospinal fluid.

Examples Carotid or vertebral artery dissension, cerebral venous sinus thrombosis, arteriovenous malformations, subdural hematoma, giant cell arteritis Idiopathic intracranial hypertension, hydrocephalus, spontaneous CSF leak Neoplasm, abscess Meningitis, encephalitis, abscess, sinusitis Cervical spine disorders, temporomandibular joint disorders Medication overuse headache

Table 2 Essential Elements of a Headache History


Age of onset Frequency Duration Time of onset Time to maximum intensity Characteristics location, quality, severity Associated symptoms and signs before, during, and after headache Precipitating factors Aggravating factors Relieving factors Previous treatments Review of systems Past medical history Family history Social history occupation, habits, etc. Emotional state

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often deny many of these features, but the presence of these features can be assessed by asking about typical pain behaviors during more severe headaches. For example, migraine patients often deny photo- or phonophobia, but will admit to the preference of a dark, quiet room. Establishing the presence of a visual, sensory, language, or motor aura can be useful in migraine headache classication, but determining whether a symptom is a true aura or secondary to another cause can often be challenging. Common aura pretenders include blurred vision secondary to an ophthalmologic cause, tingling due to a peripheral nerve disorder such as carpal tunnel, and concentration issues rather than true aphasia due to chronic pain or sleep issues. Several factors can help delineate true aura from symptoms from another cause. A true aura typically occurs before or during the early portion of the pain phase of migraine headaches. Auras tend to have a gradual progression over minutes, such as enlarging scotomas, or a marching progression of numbness, weakness, and/or tingling

through an extremity. True language auras will manifest as the inability to name objects, read, write, understand others, and/or carry out simple conversation, rather than vague word-nding difculties. Accompanying family members or friends can help to clarify features of language involvement. Classic visual auras consist of ashing or scintillating lights in the periphery of the vision, rather than just blurry vision, which is a common complaint, but not a true aura. Sleep is another behavior that should be scrutinized routinely during a headache history because poor sleep hygiene can worsen headaches. Total hours of sleep, sleep interruptions and awakenings, the presence of snoring, restlessness, waking up feeling poorly rested, and excessive daytime sleepiness are all aspects of sleep that should be analyzed. Triggering or worsening of headaches with position changes, physical activity, coughing, sneezing, talking, chewing, and/or popping or clicking of the jaw are important details, especially when considering secondary causes of headaches. The clinician should remain vigilant of the red ags that could suggest a secondary headache rather than a primary headache disorder. These include age of headache onset >50 years, a new, rst, or worst headache, a signicant change in the characteristics of prior headaches, a headache always on the same side, increasingly worsened frequency and/or severity of headache, headache not responding to treatment, known systemic illnesses that predispose to secondary headaches (e.g., cancer or human immunodeciency virus [HIV]), signs of systemic illness (e.g., fever, weight loss), posttraumatic headache, neurologic symptoms not consistent with typical aura (e.g., seizures), or an abnormal neurologic examination. Table 3 lists disorders that should be considered when certain red ags are present. Finally, a detailed history should also include past medical history, surgical history, social history, family history (especially of headaches), medication history, and procedural history. Medication history is of particular importance, and this should include the medication dose, length of treatment, outcome, and adverse effects.

HEADACHE/MATHEW, GARZA

Table 3 Headache Red Flags and Diagnostic Considerations


Sign/Symptom Thunderclap headache is a sudden onset severe headache, maximum in intensity immediately, or in less than 60 seconds. Possible Causes Secondary Subarachnoid hemorrhage Other intracerebral hemorrhage Carotid/vertebral dissection CNS angiopathy Intracranial aneurysm CSF leak Pituitary apoplexy Third ventricle colloid cyst Ischemic stroke Cerebral venous sinus thrombosis Hypertensive crisis Reversible cerebral vasoconstrictive syndrome Primary orgasmic headache Migraine Primary thunderclap headache During or after physical exertion Secondary causes (43% had structural lesions in one series) Subarachnoid hemorrhage Intracranial neoplasm Third ventricle colloid cyst Arterial dissection Pheochromocytoma Cardiac ischemia Primary causes Migraine Primary exertional headache Nocturnal, wakening from sleep Secondary Intracranial space-occupying lesions Raised intracranial pressure Idiopathic intracranial hypertension (pseudotumor cerebri) Medication overuse headache (rebound headache) Obstructive sleep apnea Cervicogenic Primary Hypnic headache Cluster headache Migraine Orthostatic (worse while standing) CSF leak Secondary (following lumbar puncture, ENT surgery, neurosurgery, etc.) With papilledema Spontaneous (no clear cause) Secondary Intracranial space-occupying lesions Cerebral venous sinus thrombosis CT brain without contrast (acute setting) MRI and MRV brain Lumbar puncture with opening pressure only if no intracranial space-occupying lesions found MRI head with gadolinium if spontaneous CSF leak suspected ENT or neurosurgery referral MRI brain with contrast Cervical spine X-ray or MRI Possibly overnight oximetry Acute setting or with rst occurrence: CT head Consider CSF MRI brain with gadolinium and MRA head/neck Testing to Consider CT in the acute setting MRI with gadolinium MRA head and neck MRV CSF if imaging normal Pheochromocytoma evaluation

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Table 3 (Continued )
Sign/Symptom Possible Causes Intracranial hemorrhage Primary Idiopathic intracranial hypertension (IIH or pseudotumor cerebri) Tend to be young, obese women Transient visual obscurations During sexual activity and increases with sexual excitement At orgasm, typically an explosive or thunderclap Secondary causes Subarachnoid hemorrhage Arterial dissection CSF leak Primary orgasmic headache if other causes ruled out Brief headache with coughing, sneezing, straining, or Valsalva Secondary causes (50% have structural disease) Posterior fossa lesions (e.g., tumor) Arnold-Chiari malformation CSF leak Intracranial aneurysms Primary cough headache
CNS, central nervous system; CSF, cerebrospinal fluid, CT, computed tomography; ENT, ear, nose, throat; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; MRV, magnetic resonance venography.

Testing to Consider Ophthalmology exam required

Primary preorgasmic headache

Less worrisome for secondary cause when compared with orgasmic headache On rst onset, it is mandatory to exclude a subarachnoid hemorrhage and arterial dissection Nonacute setting: MRI brain with gadolinium and MRA head/neck MRI brain with gadolinium Possibly MRA head

Physical Examination and Diagnostic Testing All patients that present with a chief complaint of headaches should have a thorough physical examination and neurologic examination, which should always include funduscopy to assess for papilledema or signs of increased intracranial pressure. For headache patients, additional examination maneuvers should be considered as a supplement to the neurologic examination to help identify certain etiologies. Palpation of the head and neck can be useful in assessing for cutaneous allodynia, temporal arteritis, and muscular tension. Examination of the temporomandibular joint can be helpful, as pain associated with popping and clicking of this joint can exacerbate headaches. Percussion over the occipital nerves (Tinel sign) may often reproduce a painful neuralgic paroxysm in occipital neuralgia. In addition, assessing neck stiffness on active and passive range of motion can suggest a cervicogenic component or meningismus. Imaging studies, and the type of imaging obtained, should be considered on an individual case basis. In general, imaging studies should be pursued in newonset headaches, worsening headaches with changes in character, headaches with focal neurologic signs, and any time the patient claims to be having the worse headache of his or her life. In patients with typical migraine headaches, imaging is seldom needed, but should be considered when the headache is associated

with a protracted or atypical aura, occurs after trauma, occurs after age 50 years, ts a basilar-type or hemiplegic form (see ICHD-2), is associated with increasing frequency, quality, or severity, or if a patient is in status migrainosus. Additionally, if the patient presents with their rst or most severe migraine, imaging should be considered. Table 3 reviews suggested neuroimaging studies that should be performed in certain circumstances.

PRIMARY HEADACHE DIAGNOSIS Once the clinician has ruled out a secondary headache, making an accurate primary headache diagnosis is critical because each type of primary headache disorder has known treatment options that differ among the different primary headaches. The International Headache Societys International Classication of Headache Disorders 2nd Edition (ICHD-2) is the current guideline that headache specialists use for the accurate classication of primary headache disorders. Since its publication in 2004, it has undergone minor revisions and is expected to continue to evolve through time.1 The diagnostic criteria and classication are available online at the International Headache Societys Web site (http://ihs-classication.org/en). Although a detailed discussion of all primary headache disorders is beyond the scope of this article, here we will review the diagnosis and management of

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HEADACHE/MATHEW, GARZA

several of the more common primary headache disorders presenting to an outpatient neurology practice.

Table 4 The International Classification of Headache Disorders, 2nd Edition (IHCH-2) Migraine Diagnostic Criteria1
Migraine without aura A. At least ve attacks fullling criteria BD B. Headache attacks lasting 472 hours (untreated or unsuccessfully treated) C. Headache has at least two of the following characteristics: Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) D. During headache at least one of the following: Nausea and/or vomiting Photophobia and phonophobia E. Not attributed to another disorder Migraine with aura A. At least two attacks fullling criteria BD B. Aura consisting of at least one of the following, but no motor weakness: Fully reversible visual symptoms including positive features (e.g., ickering lights, spots or lines) and/or negative features (i.e., loss of vision) Fully reversible sensory symptoms including positive features (i.e., pins and needles) and/or negative features (i.e., numbness) Fully reversible dysphasic speech disturbance C. At least two of the following: Homonymous visual symptoms and/or unilateral sensory symptoms At least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes Each symptom lasts 5 and 60 minutes D. Headache fullling criteria BD for migraine without aura begins during the aura or follows aura within 60 minutes E. Not attributed to another disorder

ABORTIVE MIGRAINE TREATMENT

Nonsteroidal anti-inammatory medications (NSAIDs), antiemetics, triptans, and dihydroergotamine are the mainstays of abortive treatment for migraine headaches. Other commonly used nonspecic analgesics include acetaminophen, aspirin, cyclooxygenase 2 inhibitors, opiates, and combination analgesics that vary in content. Of the various medications used for migraine headaches, only triptans and dihydroergotamine are specic for migraines. Several different triptans are available for treatment of migraines (Table 5). All oral triptans can be effective and relatively well tolerated. As a class of medications, the differences between oral triptans are generally relatively small, but the effects can vary among individual patients.6 One of the factors for initial consideration in choosing a triptan is cost and formulary coverage of an individuals insurance plan. Sumatriptan is currently the only generic triptan on the market. If sumatriptan is tolerated, but only somewhat benecial, it can be combined with an NSAID and/or an antiemetic such as promethazine. In cases where sumatriptan is ineffective, switching to a different triptan or formulation would be reasonable. In addition to oral formulations, triptans are available as orally dissolving, intranasal, and injectable preparations. These routes of administration that may be particularly useful for these migraine patients with early and prominent vomiting. It is essential to warn patients that triptans often induce transient side effects including chest or throat

tightness, ushing, a heat sensation, dizziness, nausea, drowsiness, and tingling. Warning patients of these transient side effects can prevent patient anxiety related to the future triptan use and even emergency room visits for what patients confuse to be an anaphylactic reaction. Triptans should be avoided in patients with a history of coronary artery disease, stroke or transient ischemic

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Migraine Migraine is the most common primary headache disorder for which patients present for evaluation and treatment. In U.S. population studies, the prevalence of migraine is 18% in women and 6% in men.24 Migraine is divided into migraine with and migraine without aura. The ICHD-2 criteria for migraine are listed in Table 4. Chronic migraine is diagnosed when the migraine headache frequency is greater than 15 days per month (tension-type and/or migraine) and when 8 of those days involve headaches that satisfy criteria for migraine and that respond to treatment with triptans or ergots for greater than 3 months.5 Medication overuse headache (previously called rebound headache) must be excluded when a diagnosis of chronic migraine is considered (see chronic daily headache section). If a patient is using acute headache treatments more than 2 days a week on average, the clinician should suspect medication overuse headache.

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Table 5 Formulations and Half-Lives of Triptan Medications6


Generic Name Almotriptan Eletriptan Frovatriptan Naratriptan Rizatriptan Sumatriptan Zolmitriptan Brand Name Axert1 Relpax1 Frova1 Amerge1 Maxalt1 Imitrex1 Zomig1 Half-Life (Hours) 34 4 26 6 23 2.5 3 Administration and Dose Oral 6.25, 12.5 mg Oral 20, 40 mg Oral 2.5 mg Oral 1, 2.5 mg Oral 5, 10 mg ODT 5, 10 mg Oral 25, 50, 100 mg Intranasal 5, 20 mg Subcutaneous 4, 6 mg Oral 2.5, 5 mg ODT 2.5, 5 mg Intranasal 5 mg
Adapted from Ferrari MD, Goadsby PJ. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 2002;22(8):633658.

PREVENTATIVE MIGRAINE TREATMENT

Preventative medications should be considered in cases where migraines occur with high frequency or signicantly interfere with the patients daily routines. Preventatives should also be considered when abortive treatments are contraindicated, have failed, have adverse effects, or are being overused. Preventative treatments for migraine span several different classes, including b-blockers (propranolol, atenolol, nadolol, metoprolol, timolol), calcium-channel blockers (verapamil), anticonvulsants (topiramate, divalproex sodium, gabapentin), and tricyclic antidepressants (amitriptyline, nortriptyline, protriptyline) (Table 6). There are several factors to be considered when choosing a preventative medication. A medication should be chosen that has proven efcacy. Propranolol, topiramate, divalproex sodium, and amitriptyline have proven efcacy and are considered rst-line medications. The presence of a comorbid condition, such as hypertension or seizures, may lead to choosing a medication that may treat the condition as well as the migraine headaches. In some cases, a medication may be initiated for the comorbid condition in a patient whose headaches may not have necessarily warranted a preventative medication, such as in a patient with infrequent headaches in whom a b-blocker is initiated for hypertension. As a

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attacks, and peripheral vascular disease. Other relative contraindications include uncontrolled blood pressure, smoking, hormone replacement, pregnancy, and breastfeeding. Concomitant use of selective norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) and triptans carry a very low risk of serotonin syndrome, and should not prevent appropriate patients from receiving treatment with triptans.7 Patients, however, should be warned of the symptoms of serotonin syndrome, and should seek medical attention immediately if those symptoms occur. In patients that fail to respond to over-the-counter analgesics and triptans, dihydroergotamine is a reasonable next option. Dihydroergotamine has similar contraindications to triptans.

general guideline, all preventative medications should be started at low doses and titrated slowly until the minimum effective dose is reached. A reasonable goal of prophylaxis is not to eliminate headaches but to decrease their frequency and intensity. All preventative medication trials should have a duration of at least 3 months at a therapeutic dose before a decision regarding efcacy can be made. It is important to realize that adequate doses and durations of medications may cause some level of mild improvement in headache frequency and intensity that does not meet the expectations of the patient and at times the provider. A preventive medication should be considered successful if it decreases headache frequency by 50%. Although monotherapy is preferred, in clinical practice some patients with refractory headaches may receive additive benet from combinations of preventative treatments.8 Botulinum toxin type A injections may be an effective preventative treatment for certain migraine patients.9 This treatment is usually selected in patients with prophylactic medication failure, medication intolerance, limiting comorbidities, and/or poor compliance. If botulinum toxin type A is found to be effective, the benets of botulinum toxin can be as short as 2 months and as long lasting as 4 months, and repeating injections at 3-month intervals is usually required.10 Figure 1 illustrates common injection sites utilized for botulinum toxin type A injections for migraine treatment. Infrequently, patients can develop neutralizing antibodies to botulinum toxin. This risk can be limited by minimizing the frequency of dosing to no more than every 3 months, and using the lowest effective dose.11,12 Based on negative trials and a recent evidence-based review, episodic migraine does not appear to be a good indication for botulinum toxin type A injections.13 Recent randomized, double-blind, parallel-group, placebo-controlled phase followed by open-label phase trials involving over 1200 subjects have yielded encouraging results for the use of botulinum toxin A in chronic migraine and suggested that botulinum toxin A is an effective, safe, and well tolerated treatment for chronic migraine.14,15

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Table 6 Commonly Used Migraine Prophylactic Medications


Initial Dose (mg) 10 10 25500 4060 25 80160 300 1525 Typical Total Daily Dose Range (mg) 25150 25150 7501500 40240 50100 160480 9002400 75200 Adverse Effects Common Weight gain, constipation, sedation Nortriptyline Divalproex sodium Propranolol Atenolol Verapamil Gabapentin Topiramate Same as above Alopecia, weight gain, nausea, tremor Depression, fatigue Same as above Edema, constipation Edema, sedation, fatigue, dizziness Paresthesias, fatigue, weight loss Acute angle glaucoma, hyperthermia, metabolic acidosis, nephrolithiasis
Reprinted from Garza I, Swanson JW. Prophylaxis of migraine. Neuropsychiatr Dis Treat 2006;3(1):281291. Copyright (2006), with permission from Dove Medical Press Ltd.

Drug Amitriptyline

Serious Cardiac dysrhythmias Same as above Pancreatitis, liver failure, thrombocytopenia Bradyarrhythmia Same as above Hypotension, dysrhythmias

There is a frequent association between migraines and menstrual periods in women with migraine headaches. If migraines occur only during their menstrual period, the label of pure menstrual migraine is applied. If they tend to have increased frequency and/or intensity of their migraines around the time of their menstrual periods, but also have migraines outside of their menstrual periods, the label of menstrually associated migraine is applied. In either case, specic prophylactic strategies can be applied around the time of menstrual periods and used in addition to more continuous preventative treatment. One strategy is the use of longeracting triptans, such as frovatriptan or naratriptan, taken twice a day on a standing basis starting 2 days prior to the onset of menses, and continuing for 3 days into menses.16,17 Another strategy for menstrual migraine is

administration of a nonsteroidal anti-inammatory medication, such as naproxen sodium, twice a day on a standing basis starting 2 days prior to the onset of menses, and continuing for 3 days into menses.18,19

Trigeminal Autonomic Cephalgias Trigeminal autonomic cephalgia (TAC) is a category of headaches that manifests as unilateral head pain associated with ipsilateral autonomic features. By denition, individual attacks can only occur on one side of the head, but infrequently sufferers can have attacks on the other side of the head. However, TACs never present as bilateral pain during an individual attack. Autonomic features include lacrimation, conjunctival injection, ptosis, and/or rhinorrhea that are ipsilateral to the pain.20

Figure 1 Common botulinum toxin type A injection sites for chronic migraine. (From Garza I, Cutrer F. Pain relief and persistence of dysautonomic features in a patient with hemicrania continua responsive to botulinum toxin type A. Cephalalgia 2010; 30(4):500503. Reprinted with permission from Mayo Foundation for Medical Education and Research. All rights reserved.)

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Table 7 Trigeminal Autonomic Cephalgias20


Hemicrania Sex Frequency (per day) Length (min) Circadian/circannual Episodic:Chronic Nausea Photophobia/phonophobia Agitation/restlessness Triggers Alcohol Cutaneous Treatment effects Oxygen Sumatriptan, 6 mg Indomethacin 70% 90% No effect No effect 20% 100% No effect <10% 3 M to 1 F 18 30180 Present 90:10 50% 65% 90% Cluster Headache MF 20 230 Absent 35:65 40% 65% 80% Paroxysmal SUNCT/SUNA 1.5 M to 1 F 100 15 Absent 10:90 25% 25% 65%

SUNCT, short-acting unilateral neuralgiform headache with conjunctival injection and tearing; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. Adapted from Goadsby PJ, Cittadini E, et al. Trigeminal autonomic cephalalgias: diagnostic and therapeutic developments. Curr Opin Neurol 2008;21(3):323330.

The category of TAC includes several types of headaches, such as cluster headache, paroxysmal hemicrania, and short-acting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). The primary differences between these headaches are the duration and frequency of the attacks. Table 7 provides a summary that compares the different TACs. Cluster headache is the most common TAC and will be discussed in greater detail below. Paroxysmal hemicrania, by denition, responds to indomethacin. Whether hemicrania continua is a TAC or not remains a matter of debate.

variable occurring once every other day to as frequently as eight headache attacks a day. After a cluster period, there can be months to years of remission before the next attack in the episodic form of the disorder.1 Cluster periods often follow patterns linked to seasonal variation, and individual headache attacks tend to follow temporal regularity, suggesting hypothalamic regulation.22 Chronic cluster is dened as recurring attacks for greater than one year without remission or remission periods less than 1 month. Among cluster sufferers, 10 to 15% suffer from chronic cluster headaches.1
ABORTIVE CLUSTER HEADACHE TREATMENT

Cluster Headache Cluster headache is the most common of the TACs. Unlike migraine, which has a female predilection, cluster headache has an approximate 3:1 male to female ratio although different ratios have been published in different populations.20 Meta-analysis of recent prevalence studies suggests a lifetime prevalence of cluster headaches of 1 in 1000.21 The criteria for cluster headache are listed in Table 8. It is important to note that symptomatic, secondary, or cluster-like headaches have been reported in the setting of intracranial neoplasms, paranasal sinus disease, and cerebrovascular disease. Therefore, at the time of diagnosis of cluster headaches and other TACs, brain magnetic resonance imaging (MRI) with gadolinium is indicated. Clinical judgment should guide whether additional forms of neuroimaging are needed. Cluster headaches typically occur in series known as a cluster period, which can last for weeks to months. During a cluster period, headache frequency is highly

Subcutaneous sumatriptan and concentrated oxygen are the abortive treatment options of choice for cluster
Table 8 The International Classification of Headache Disorders, 2nd Edition (IHCH-2) Cluster Headache Diagnostic Criteria1
A. At least ve attacks fullling criteria BD B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15180 minutes if untreated C. Headache is accompanied by at least one of the following: Ipsilateral conjunctival injection and/or lacrimation Ipsilateral nasal congestion and/or rhinorrhea Ipsilateral eyelid edema Ipsilateral forehead and facial sweating Ipsilateral miosis and/or ptosis A sense of restlessness or agitation D. Attacks have a frequency from one every other day to eight per day E. Not attributed to another disorder

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No effect

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headache. Intranasal sumatriptan, as well as oral and intranasal zolmitriptan have also demonstrated efcacy in aborting cluster attacks.2326 Pure (100%) oxygen should be administered by a non-rebreathing mask at a rate of at least 7 L/min for 15 minutes.27 For patients that fail to respond to these treatments, dihydroergotamine (DHE) may be an effective alternative.28 DHE is available in intranasal and intramuscular preparations, as well as intravenous formulations.
PREVENTATIVE CLUSTER HEADACHE TREATMENT

Two major categories of preventative treatments are used for cluster headaches transitional preventives and maintenance preventives. Transitional preventives are medications that are used for days to weeks with the primary goal of stopping a cluster period and inducing remission. Maintenance preventatives are used continuously to maintain remission. Steroid tapers and occipital nerve blocks are transitional preventative treatments that can be employed to treat cluster periods. Steroid tapers have proven to be the most effective in helping terminate cluster periods, but are limited by relapses and side effects. There is no standardized corticosteroid treatment strategy, and the type of corticosteroid and taper schedule vary among headache specialists. Oral prednisone tapers can be started at doses of 80 mg and tapered over 18 to 21 days. Alternatively, studies have demonstrated the efcacy of dexamethasone at 4 mg twice a day for one week, followed by 4 mg daily for one week.29 Occipital nerve blocks may be effective in treating cluster periods in some patients, but the parameters of the blocks vary between studies. The total volume of the block can range anywhere from 0.5 to 10 mL. Blocks are typically composed of varying strengths and combinations of lidocaine, bupivacaine, and/or prilocaine with or without a steroid component. The steroids utilized in the blocks may include methylprednisolone, triamcinolone, and dexamethasone.30 Maintenance preventative treatments for cluster headache include verapamil, lithium, divalproex sodium, and topiramate among others less frequently used. Verapamil is the rst-line treatment for cluster headaches in terms of efcacy and side effect prole. It is typically started at doses of 80 to 240 mg daily (with 240 mg total dose per day being a usual goal starting dose), and titrated up by 80 mg per week if needed. Occasionally, doses as high as 960 mg daily are required. The titration should be slow because many patients may nd benet at lower doses. Routine electrocardiograms (ECGs) should be checked while titrating the medication to monitor for atrioventricular block and symptomatic bradycardia, especially when doses of verapamil exceed 240 mg/day.31 Lithium is an effective treatment for chronic cluster headaches, but is limited by its side effect prole

and need for monitoring blood levels. Lithium does not appear to be as effective for episodic cluster as it is for the chronic form. Lithium is typically dosed at 600 to 1200 mg daily with a target serum concentration of 0.4 to 0.8 mEq/L. Side effects include weakness, nausea, thirst, tremor, slurred speech, and blurred vision. Lithium toxicity may manifest as nausea, vomiting, anorexia, diarrhea, confusion, nystagmus, ataxia, extrapyramidal signs, and seizures. Lithium can also affect thyroid and kidney function, and therefore baseline function testing is necessary prior to initiation of the medication. Lithium drug levels, creatinine, sodium, TSH, and ECG should be performed periodically while on lithium.29 In patients refractory to a single medication, combinations of preventative medications are often required, usually administering verapamil with other agents (topiramate, lithium, divalproex sodium, etc.). Although botulinum toxin has not demonstrated the same efcacy as is seen with chronic migraine, there have been some limited cases that suggest its potential benet.32,33 In patients that fail to respond adequately to oral medications for long-term prophylaxis, surgical interventions can be considered. Surgical interventions for cluster headache have historically been performed on the ipsilateral side of the headache. Although some of these destructive procedures have demonstrated efcacy in some refractory cases, they do not always consistently provide relief of symptoms. In addition, they can involve serious side effects including corneal anesthesia, anesthesia dolorosa, and jaw deviation. In responsive cases, surgical treatment may relieve symptoms ipsilateral to the surgery, but cluster attacks may start to occur on the nonsurgical side.34,35 More recently, as an alternative to these destructive procedures in patients with medically refractory cluster headache, neurostimulation has been utilized. Neurostimulation involves central targets such as the posterior hypothalamus with deep brain stimulation (DBS), or peripheral targets, such as in occipital nerve stimulation (ONS). Although DBS has demonstrated efcacy with about two-thirds of patients having complete remission of pain in large studies, it is an invasive procedure that carries a small risk of fatal cerebral hemorrhage.36 Occipital nerve stimulation trials have not demonstrated as high of a responder rate as DBS, but ONS is much less invasive. Complications associated with ONS included battery depletion, lead migration, muscle recruitment, neck stiffness, skin discomfort, supercial infections, occipital paresthesias, and painful overstimulation.37 Some patients have good control of their pain with ONS, but continue to have cranial autonomic features, which can be bothersome.38 As with surgery, neurostimulation is typically a unilateral procedure (although some groups advocate for

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bilateral stimulation in some cases), and therefore cluster sufferers that have had unilateral ONS or DBS run the risk of their symptoms occurring on the contralateral side. Since neurostimulation has been available for medically refractory cluster headache, it has been a favored intervention over trigeminal destructive procedures. Surgery for medically refractory cluster headache should be performed at a center with expertise in these procedures.

ABORTIVE TENSION-TYPE HEADACHE TREATMENT

Aspirin, acetaminophen, and NSAIDs have all demonstrated efcacy as abortive treatments for TTH in clinical trials.4649 Triptans in general have not been found to be effective for the abortive treatment of pure TTH.50
PREVENTATIVE TENSION-TYPE HEADACHE TREATMENT

Table 9 The International Classification of Headache Disorders, 2nd Edition (IHCH-2) Tension Type Headache Diagnostic Criteria1
A. At least 10 episodes occurring on <1 day per month on average (<12 days per year) and fullling criteria BD B. Headache lasting from 30 minutes to 7 days C. Headache has at least two of the following characteristics: Bilateral location Pressing/tightening (non-pulsating) quality Mild or moderate intensity Not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: No nausea or vomiting (anorexia may occur) No more than one of photophobia or phonophobia E. Not attributed to another disorder

Chronic Daily Headache Chronic daily headache (CDH) is a term that encompasses a heterogenous group of headache disorders. It is estimated that 4 to 5% of the population suffers from CDH. Chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache are four primary headaches of long duration (>4 hours) that t under this broad category. Other primary headache disorders of shorter duration (cluster headache, hypnic headache, etc.), however, may also present as CDH. Chronic migraine and chronic tension-type headache compose the largest subsets of CDH.60 The criteria for hemicrania continua and new daily persistent headache are listed in Tables 10 and 11. When considering chronic headache syndromes such as CDH, medication overuse can worsen the frequency and intensity of headaches. Previous names given to medication overuse headaches include rebound headache, drug-induced headache, and medication-misuse headache. The criteria for medication overuse headaches are listed in Table 12. According to ICHD criteria, medication overuse headache is considered to be a secondary headache disorder, and occurs in the setting of a preceding primary headache disorder. It is estimated

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Tension-Type Headache Tension-type headache (TTH) is the most common primary headache disorder with a lifetime prevalence of 88% in women and 68% in men.39 The criteria for TTH are listed in Table 9. In general, the headache is described as a dull pressure pain that often is in a cap or bandlike distribution around the head. Tension-type headache is generally less painful and debilitating than other primary and secondary headache disorders, and thus sufferers are less likely to present to a physician for evaluation.40 Tension-type headache can be divided into three categories based on frequency: (1) episodic infrequent TTH, which involves an average of fewer than one headache day per month for no greater than 10 headaches per year; (2) episodic frequent TTH, which involves 1 to 14 headache days per month; and (3) chronic TTH, which involves greater than 15 headache days per month. Progression from episodic to chronic TTH is usually a gradual process that occurs over years, and increasing frequency tends to be associated with increasing intensity of the headache.41,42 Pericranial tenderness with palpation is a feature that can be seen in patients with TTH, and this tenderness seems to be worse during a headache. In addition, the presence of pericranial tenderness tends to correlate with high frequency and intensity of TTH.4345

Because TTH tends to be a low-intensity headache, high frequency or high levels of disability are two reasons to consider prophylactic treatment. The mainstays of preventative treatment for TTH are tricyclic antidepressants. Among the tricyclic antidepressants, amitriptyline has the most clinical data to support its efcacy in TTH.40,51,52 For patients that benet from amitriptyline, but cannot tolerate side effects, nortriptyline or protriptyline may be reasonable alternatives with better side effect proles. Other options with proven efcacy in TTH include topiramate, divalproex sodium, mirtazapine, and tizanidine.5255 Tricyclic antidepressants are considered to be superior to selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors for the prevention of TTH.56 The use of botulinum toxin injections for chronic TTH has not been well supported in double-blind clinical trials.57,58 Some studies suggest that in TTH involving myofascial trigger points, injecting directly into the trigger points may provide efcacy that was not appreciated in earlier studies.59

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Table 10 The International Classification of Headache Disorders, 2nd Edition (IHCH-2) Hemicrania Continua Diagnostic Criteria1
A. Headache for >3 months fullling criteria BD B. All of the following characteristics: Unilateral pain without side-shift Daily and continuous, without pain-free periods Moderate intensity, but with exacerbations of severe pain C. At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain: Conjunctival injection and/or lacrimation Nasal congestion and/or rhinorrhea Ptosis and/or miosis D. Complete response to therapeutic doses of indomethacin E. Not attributed to another disorder1

In one study, opiates usage of at least 8 days per month and barbiturates usage of at least 5 days per month for migraines were both associated with progression of migraines into medication overuse headaches. For this reason, opiates and barbiturates should be avoided as much as possible as abortive treatments of primary headache disorders, or the frequency of administration should not exceed these limits. To a lesser extent, triptans can cause some progression of headaches in those with high frequency of headaches at baseline; therefore, triptan use should be limited to not more than 9 days per month.62 Given their high risk for medication overuse headache, combination analgesics should also be limited to not more than 8 or 9 days a month.

A. Headache that within 3 days of onset fullls criteria BD B. Headache is present daily, and is unremitting for >3 months C. At least two of the following pain characteristics: Bilateral location Pressing/tightening (nonpulsating) quality Mild or moderate intensity Not aggravated by routine physical activity such as walking or climbing D. Both of the following No more than one of photophobia, phonophobia or mild nausea Neither moderate or severe nausea nor vomiting E. Not attributed to another disorder2

CONCLUSION The management of headaches can be a complex and challenging task for the ofce based neurologist. It cannot be stressed enough that only through a thorough evaluation, and the establishment of the correct primary or secondary headache diagnosis can therapeutic efcacy be achieved. This article provides a basic foundation in the essential elements of ofce based headache management, and hopefully serves as a means to the advancement of headache care in the setting of a highly underserved subspecialty.

REFERENCES
1. Headache Classication Subcommittee of the International Headache Society. The International Classication of Headache Disorders: 2nd edition. Cephalalgia 2004;24(Suppl 1): 9160 2. Lipton RB, Stewart WF, Simon D. Medical consultation for migraine: results from the American Migraine Study. Headache 1998;38(2):8796 3. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001; 41(7):646657 4. Lipton RB, Diamond S, Reed M, Diamond ML, Stewart WF. Migraine diagnosis and treatment: results from the American Migraine Study II. Headache 2001;41(7):638 645 5. Olesen J, Bousser MG, Diener HC, et al; Headache Classication Committee. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006;26(6): 742746 6. Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin, 5HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 2002; 22(8):633658 7. Wenzel RG, Tepper S, Korab WE, Freitag F. Serotonin syndrome risks when combining SSRI/SNRI drugs and triptans: is the FDAs alert warranted?. Ann Pharmacother 2008;42(11):16921696

that medication overuse headache has a prevalence of 1 to 1.4% in the general population, and women in their 50s have the highest subset prevalence of 5%.61 In the setting of medication overuse, both abortive and preventative treatments tend to be less effective.
Table 12 Medication Overuse Headache Diagnostic Criteria5
A. Headache present on 15 days/month fullling criteria B and C B. Regular overuse for 3 months of one or more acute/ symptomatic treatment drugs as dened under sub forms of 8.2 Ergotamine, triptans, opioids, or combination analgesic medications on 10 days/month on a regular basis for >3 months Simple analgesics or any combination of ergotamine, triptans, analgesics, opioids on 15 days/month on a regular basis for >3 months without overuse of any single class alone C. Headache has developed or markedly worsened during medication overuse

Downloaded by: World Health Organization ( WHO). Copyrighted material.

Table 11 The International Classification of Headache Disorders, 2nd Edition (IHCH-2) New Daily Persistent Headache Diagnostic Criteria1

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2011

inez JM. Combined therapy for 8. Pascual J, Leira R, La migraine prevention? Clinical experience with a beta-blocker plus sodium valproate in 52 resistant migraine patients. Cephalalgia 2003;23(10):961962 9. Blumenfeld AM, Schim JD, Chippendale TJ. Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache 2008;48(2):210220 10. Mathew NT, Jaffri SF. A double-blind comparison of onabotulinumtoxinA (BOTOX) and topiramate (TOPAMAX) for the prophylactic treatment of chronic migraine: a pilot study. Headache 2009;49(10):14661478 11. Rollnik JD, Wohlfarth K, Dengler R, Bigalke H. Neutralizing botulinum toxin type a antibodies: clinical observations in patients with cervical dystonia. Neurol Clin Neurophysiol 2001;2001(3):24 12. Herrmann J, Geth K, Mall V, et al. Clinical impact of antibody formation to botulinum toxin A in children. Ann Neurol 2004;55(5):732735 13. Shuhendler AJ, Lee S, Siu M, et al. Efcacy of botulinum toxin type A for the prophylaxis of episodic migraine headaches: a meta-analysis of randomized, double-blind, placebo-controlled trials. Pharmacotherapy 2009;29(7):784791 14. Aurora SK, Dodick DW, Turkel CC, et al; PREEMPT 1 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 2010;30(7):793803 15. Dodick DW, Turkel CC, DeGryse RE, et al; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 2010;50(6):921936 16. Newman L, Mannix LK, Landy S, et al. Naratriptan as shortterm prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study. Headache 2001;41(3):248256 17. MacGregor EA, Brandes JL, Silberstein S, et al. Safety and tolerability of short-term preventive frovatriptan: a combined analysis. Headache 2009;49(9):12981314 18. Rothrock JF. Menstrual migraine. Headache 2009;49(9): 13991400 19. Garza I, Swanson JW. Prophylaxis of migraine. Neuropsychiatr Dis Treat 2006;2(3):281291 20. Goadsby PJ, Cittadini E, Burns B, Cohen AS. Trigeminal autonomic cephalalgias: diagnostic and therapeutic developments. Curr Opin Neurol 2008;21(3):323330 21. Fischera M, Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia 2008;28(6):614618 rderreuther S, Krause P, Eggert T. 22. Ladda J, Straube A, Fo Quantitative sensory testing in cluster headache: increased sensory thresholds. Cephalalgia 2006;26(9):10431050 23. Bahra A, Gawel MJ, Hardebo JE, Millson D, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology 2000;54(9):1832 1839 24. Hedlund C, Rapoport AM, Dodick DW, Goadsby PJ. Zolmitriptan nasal spray in the acute treatment of cluster headache: a meta-analysis of two studies. Headache 2009; 49(9):13151323 f C. Sumatriptan nasal spray (20 mg/dose) 25. Hardebo JE, Dahlo in the acute treatment of cluster headache. Cephalalgia 1998; 18(7):487489

26. Ekbom K; The Sumatriptan Cluster Headache Study Group. Treatment of acute cluster headache with sumatriptan. N Engl J Med 1991;325(5):322326 27. Cohen AS, Burns B, Goadsby PJ. High-ow oxygen for treatment of cluster headache: a randomized trial. JAMA 2009; 302(22):24512457 28. Mathew NT. Dosing and administration of ergotamine tartrate and dihydroergotamine. Headache 1997;37(Suppl 1): S26S32 29. Matharu MS, Goadsby PJ. Trigeminal autonomic cephalalgias: diagnosis and management. In: Silberstein SD, Lipton RB, Dodick DW eds. Wolffs Headache and Other Head Pain. 8th ed. New York: Oxford University Press; 2008: 379402 30. Tobin J, Flitman S. Occipital nerve blocks: when and what to inject?. Headache 2009;49(10):15211533 31. Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology 2007;69(7):668675 rderreuther S, Reinisch V, Straube A. 32. Sostak P, Krause P, Fo Botulinum toxin type-A therapy in cluster headache: an open study. J Headache Pain 2007;8(4):236241 33. Ailani J, Young WB. The role of nerve blocks and botulinum toxin injections in the management of cluster headaches. Curr Pain Headache Rep 2009;13(2):164167 34. Jarrar RG, Black DF, Dodick DW, Davis DH. Outcome of trigeminal nerve section in the treatment of chronic cluster headache. Neurology 2003;60(8):13601362 35. Ford RG, Ford KT, Swaid S, Young P, Jennelle R. Gamma knife treatment of refractory cluster headache. Headache 1998;38(1):39 36. Leone M, Franzini A, Broggi G, Bussone G. Hypothalamic stimulation for intractable cluster headache: long-term experience. Neurology 2006;67(1):150152 37. Burns B, Watkins L, Goadsby PJ. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology 2009;72(4):341345 38. Schwedt TJ, Dodick DW, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic cluster headache and hemicrania continua: pain relief and persistence of autonomic features. Cephalalgia 2006;26(8):10251027 39. Rasmussen BK. Epidemiology of headache. Cephalalgia 1995; 15(1):4568 40. Mathew P, Peterlin B. Tension-type headache. In: Jay GW ed. Clinicians Guide to Chronic Headache and Facial Pain. New York: Informa Healthcare; 2010:1626 41. Lyngberg AC, Rasmussen BK, Jrgensen T, Jensen R. Prognosis of migraine and tension-type headache: a population-based follow-up study. Neurology 2005;65(4):580585 42. Jensen R, Olesen J. Initiating mechanisms of experimentally induced tension-type headache. Cephalalgia 1996;16(3):175 182, discussion 138139 43. Sandrini G, Antonaci F, Pucci E, Bono G, Nappi G. Comparative study with EMG, pressure algometry and manual palpation in tension-type headache and migraine. Cephalalgia 1994;14(6):451457, discussion 394395 44. Jensen R, Fuglsang-Frederiksen A. Quantitative surface EMG of pericranial muscles. Relation to age and sex in a general population. Electroencephalogr Clin Neurophysiol 1994;93(3):175183 f CGH, Jacobs LD. Ketoprofen, paracetamol and 45. Dahlo placebo in the treatment of episodic tension-type headache. Cephalalgia 1996;16(2):117123

Downloaded by: World Health Organization ( WHO). Copyrighted material.

HEADACHE/MATHEW, GARZA

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46. Steiner TJ, Lange R, Voelker M. Aspirin in episodic tensiontype headache: placebo-controlled dose-ranging comparison with paracetamol. Cephalalgia 2003;23(1):5966 47. Prior MJ, Cooper KM, May LG, Bowen DL. Efcacy and safety of acetaminophen and naproxen in the treatment of tension-type headache. A randomized, double-blind, placebo-controlled trial. Cephalalgia 2002;22(9):740748 48. Kubitzek F, Ziegler G, Gold MS, Liu JM, Ionescu E. Lowdose diclofenac potassium in the treatment of episodic tension-type headache. Eur J Pain 2003;7(2):155162 49. Brennum J, Brinck T, Schriver L, et al. Sumatriptan has no clinically relevant effect in the treatment of episodic tensiontype headache. Eur J Neurol 1996;3:2328 50. Cady RK, Gutterman D, Saiers JA, Beach ME. Responsiveness of non-IHS migraine and tension-type headache to sumatriptan. Cephalalgia 1997;17(5):588590 51. Bendtsen L, Jensen R. Amitriptyline reduces myofascial tenderness in patients with chronic tension-type headache. Cephalalgia 2000;20(6):603610 52. Goadsby T, Silberstein S, Dodick D. Chronic Daily Headache for Clinicians. Hamilton: BC Decker Inc; 2005:5764 53. Saper JR, Lake AE III, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a doubleblind, placebo-controlled, multicenter outcome study. Headache 2002;42(6):470482 54. Fogelholm R, Murros K. Tizanidine in chronic tension-type headache: a placebo controlled double-blind cross-over study. Headache 1992;32(10):509513

55. Bendtsen L, Jensen R. Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache. Neurology 2004;62(10):17061711 56. Holroyd KA, Labus JS, ODonnell FJ, Cordingley GE. Treating chronic tension-type headache not responding to amitriptyline hydrochloride with paroxetine hydrochloride: a pilot evaluation. Headache 2003;43(9):9991004 57. Padberg M, de Bruijn SF, de Haan RJ, Tavy DL. Treatment of chronic tension-type headache with botulinum toxin: a doubleblind, placebo-controlled clinical trial. Cephalalgia 2004;24(8): 675680 58. Rozen D, Sharma J. Treatment of tension-type headache with botox: a review of the literature. Mt Sinai J Med 2006;73(1): 493498 59. Harden RN, Cottrill J, Gagnon CM, et al. Botulinum toxin a in the treatment of chronic tension-type headache with cervical myofascial trigger points: a randomized, doubleblind, placebo-controlled pilot study. Headache 2009;49(5): 732743 60. Garza I, Schwedt TJ. Diagnosis and management of chronic daily headache. Semin Neurol 2010;30(2):154166 61. Zidverc-Trajkovic J, Pekmezovic T, Jovanovic Z, et al. Medication overuse headache: clinical features predicting treatment outcome at 1-year follow-up. Cephalalgia 2007; 27(11):12191225 62. Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology 2008;71(22):1821 1828