Headache in the elderly

Handbook of Clinical Neurology, Vol. 167 (3rd series) Geriatric Neurology S.T. DeKosky and S. Asthana, Editors https://doi.org/10.1016/B978-0-12-804766-8.00028-5 Copyright © 2019 Elsevier B.V. All rights reserved

Chapter 28

Headache in the elderly ROBERT G. KANIECKI* AND ANDREW D. LEVIN Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States

Abstract Headache is the most common neurologic symptom and affects nearly half the world’s population at any given time. Although the prevalence declines with age, headache remains a common neurologic complaint among elderly populations. Headaches can be divided into primary and secondary causes. Primary headaches comprise about two-thirds of headaches among the elderly. They are defined by clinical criteria and are diagnosed based on symptom pattern and exclusion of secondary causes. Primary headaches include migraine, tension-type, trigeminal autonomic cephalalgias, and hypnic headache. Secondary headaches are defined by their suspected etiology. A higher index of suspicion for a secondary headache disorder is warranted in older patients with new-onset headache. They are roughly 12 times more likely to have serious underlying causes and, frequently, have different symptomatic presentations compared to younger adults. Various imaging and laboratory evaluations are indicated in the presence of any “red flag” signs or symptoms. Head CT is the procedure of choice for acute headache presentations, and brain MRI for those with chronic headache complaints. Management of headache in elderly populations can be challenging due to the presence of multiple medical comorbidities, polypharmacy, and differences in drug metabolism and clearance.

INTRODUCTION Headache is the most common neurologic symptom with approximately 46% of the global population affected at any given time (Stovner et al., 2007). Although it becomes less common with increasing age, the 1-year prevalence of headache in patients older than age 65 is approximately 51% (Prencipe et al., 2001). The International Classification of Headache Disorders, Third edition (ICHD3; beta version) broadly divides headaches into primary and secondary causes. Primary headaches including migraine, tension-type headache, trigeminal autonomic cephalalgias and hypnic headache comprise two-thirds of all headache diagnoses in the elderly (Solomon et al., 1990; Bravo, 2015). A high index of suspicion for secondary headaches in this population is warranted by higher frequency and different symptomatic presentations compared to younger adults (Bravo, 2015). Up to 19.7% of new-onset headaches in

the elderly result from serious secondary causes, compared to 1.6% in younger headache sufferers (Pasqual and Berciano, 1994). Primary headaches are defined by clinical criteria and are diagnosed based on symptom pattern and exclusion of secondary causes. Secondary headaches are defined by suspected etiology (Kaniecki, 2006). Symptomatic overlap may make certain distinctions challenging, but “red flag” characteristics can help differentiate primary from secondary headache disorders (Table 28.1). The presence of any one of these elements should prompt the clinician to pursue diagnostic testing. Symptom pattern and physical examination findings should guide the diagnostic evaluation (Kaniecki, 2006). Most patients will require brain neuroimaging. Head CT is the procedure of choice for acute headache presentations, and brain MRI for those with chronic headache complaints (Loder et al., 2013). Additional testing may be required in specific clinical settings. Those with sudden or

*Correspondence to: Robert G. Kaniecki, MD, Assistant Professor of Neurology, Chief, Headache Division, Assistant Director, Neurology Residency Training Program, University of Pittsburgh Medical Center, Pittsburgh, PA, United States. E-mail: [email protected]

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Table 28.1

Table 28.2

Headache red flags

The International Headache Society diagnostic criteria for migraine without aura

First or worst headache of life Severe headache with sudden onset (thunderclap) New onset headache above age 50 years Change in typical headache pattern or frequency Abnormal neurologic exam Neurologic symptoms persisting longer than 1 h Headache triggered by Valsalva or exertion Headache with seizure or alteration of consciousness New headache with immunocompromised state, HIV infection, malignancy, pregnancy, or systemic illness

“thunderclap” onset should undergo neurovascular studies and possibly lumbar puncture to rule out entities such as subarachnoid hemorrhage and cerebral venous sinus thrombosis (Bravo, 2015). Patients with suspected giant cell arteritis should be screened with serum testing (erythrocyte sedimentation rate, C-reactive protein) and possibly temporal artery biopsy (Bravo, 2015). Other diagnostic evaluations that may help differentiate secondary headaches include thyroid function studies, MRI of the cervical spine, sleep studies, and possibly screening for depression (Kaniecki, 2006).

PRIMARY HEADACHES Migraine EPIDEMIOLOGY Migraine is the second most common primary headache disorder affecting the elderly population, although prevalence and incidence decline with increasing age (Robbins and Lipton, 2010). It is the third most common headache to have its onset after the age of 65, trailing behind tension-type and other primary headache disorders (Song et al., 2016). While migraine prevalence ranges from 26.6% to 37.1% in individuals between the ages of 18 and 59, it affects approximately 8.5% of those above the age of 60 (Lipton et al., 2007). Among women, the 5-year incidence decreases from 8.2 cases per 1000 person-years for ages 20–24 to 0.3 per 1000 person-years for ages 65–69 (Stewart et al., 2008). Women are more than 3 times as likely to suffer from migraines in their child-bearing years, and this disparity persists to a lesser degree following menopause (Victor et al., 2010). There is no clear gender predilection for the development of migraine after the age of 65 (Song et al., 2016).

CHARACTERISTICS Migraines are characterized by severe attacks of headache typically lasting 4 h to 3 days (Table 28.2). Features

A. At least five attacks fulfilling criteria B–D B. Headache attacks lasting 4–72 h without successful treatment C. Headache has two or more of the following features: 1. Unilateral location 2. Pulsating quality 3. Moderate or severe pain intensity 4. Headache worsened by (or causing avoidance of ) routine activity D. At least one of the following during the headache: 1. Nausea and/or vomiting 2. Photophobia and phonophobia E. Not better accounted for by another ICDH-3 diagnosis

may vary between patients or between attacks in the same patient. Pain is often unilateral, pulsating, aggravated by physical activity, and accompanied by nausea, vomiting, or sensitivities to light and noise. These characteristics are most prominent in younger migraineurs, but as one ages these symptoms can change in frequency and expression (Mazzotta et al., 2003). Elderly migraineurs generally experience attacks of lesser severity and duration (Mazzotta et al., 2003). This may be related to an increase in somatosensory pain threshold, decreased vascular reactivity, or in women, possibly due to an estrogen-withdrawal component (Song et al., 2016). Increasing age predisposes to more bilateral pain or a more global pain experience (Martins et al., 2006). Photophobia and phonophobia appear to remain the most frequent accompanying symptoms in the elderly, although they are less common in comparison to younger counterparts (Martins et al., 2006). Vomiting is infrequent, but studies conflict on whether the presence of nausea declines (Mazzotta et al., 2003; Martins et al., 2006). Other distinguishing symptoms in the older population include the presence of dry mouth, and paleness or anorexia during migraine attacks (Martins et al., 2006). Migraines can be episodic or chronic. Episodic migraine involves headache occurring fewer than 15 days per month. Chronic migraine is defined by at least 15 headache days per month, at least 8 of which meet criteria for migraine headaches, for at least 3 months (International Headache Society, 2013). Migraine can be classified further based on the historical presence or absence of aura occurring at least twice over time (Table 28.3). Roughly one-third of migraineurs experience aura preceding the headache or at the onset (Charles and Hansen, 2015). Aura is defined as transient neurologic symptoms lasting 5–60 min that are fully reversible, evolving over time,

HEADACHE IN THE ELDERLY Table 28.3

ACUTE TREATMENT

The International Headache Society diagnostic criteria for migraine with aura

Triptans

A. At least two headache attacks fulfilling criteria B and C B. One or more of the following fully reversible aura symptoms: 1. Visual 2. Sensory 3. Speech and/or language 4. Motor 5. Brainstem 6. Retinal C. At least two of the following characteristics: 1. One or more aura symptoms spreads gradually over 5 min and/or two or more symptoms occur in succession 2. The duration of individual aura symptoms is 5–60 min 3. One or more aura symptoms are unilateral 4. Headache accompanies the aura, or follows within 60 min D. Not better accounted for by another ICDH-3 diagnosis and stroke or transient ischemic attack is excluded

and are most often visual in nature (International Headache Society, 2013). Other aura symptoms can be sensory, motor, speech/language, brainstem, or retinal (International Headache Society, 2013). The proportion of individuals who experience aura increases steadily with advancing age from 13.2% in those aged 18–29 to more than 31.6% in those older than age 60 (Bigal et al., 2006). Even when the pain component decreases or vanishes altogether, aura symptoms may recur in older age and become more frequent. Typically semiology remains the same (Mazzotta et al., 2003; Bigal et al., 2006). One explanation for this dissociation of the migraine symptoms may be that elderly migraineurs retain the physiologic mechanisms responsible for cortical spreading depression (felt to be responsible for aura), while the pain-inducing inflammatory and vasodilatory components of the neurovasculature diminishes (Bigal et al., 2006). This can predispose to challenging diagnostic considerations given the worrisome mimics that become more common in an aging population, such as seizure, TIA or stroke (Ozge, 2013). One distinctive feature of aura that can help differentiate it from neurovascular conditions is the temporal course and anatomic progression, such as an orderly spread and resolution of paresthesias that follows the map of the sensory cortex (Ozge, 2013). It is also common for migraine aura to involve more than one vascular territory. Nevertheless, any clinical suspicion should be pursued with appropriate diagnostic studies such as neuroimaging or EEG (Ozge, 2013).

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These are first-line migraine abortive medications with level A evidence. These agents work primarily via agonism of 5HT1B/1D receptors (Marmura et al., 2015). Effects are exerted at meningeal blood vessels (5HT1B) and trigeminal nerve endings (5HT1D) (Rapoport et al., 2006). Clinical trials generally excluded individuals older than age 65 mainly due to higher cardiovascular disease prevalence and a theoretical risk of vasoconstriction (Haan et al., 2007). For this reason, triptans are contraindicated in individuals with a history of coronary artery disease or ischemic stroke, and should be prescribed to elderly individuals with caution given the greater prevalence of these conditions. Although an epidemiologic study in the United Kingdom suggested that triptans did not increase risk of MI or stroke, patients already at risk for these conditions are less likely to have triptan prescribed for them (Hall et al., 2004). Prior to initiating triptan therapy, it is recommended that individuals with two or more traditional cardiovascular risk factors undergo cardiovascular evaluation, such as a stress test, or, ideally, be referred to a cardiologist (Robbins and Lipton, 2010). Notably, one such risk factor is age >45 years in men and >55 years in women (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001). Multiple triptans with distinctive pharmacodynamic profiles are available and come in a variety of formulations. There is no clear evidence of pharmacokinetic differences in older compared to younger populations (Musson et al., 2001). Common side effects include drowsiness, a sensation of warmth, paresthesias, dizziness, nausea, and a heaviness or tightness in the chest, neck, or jaw (Dodick and Martin, 2004). Ergot alkaloids Ergotamine and dihydroergotamine mesylate (DHE) are examples of ergot alkaloids. These drugs predate the triptans as migraine specific abortive agents, but also have level A evidence supporting their use (Marmura et al., 2015). They have a broader mechanism of action compared to the triptans and bind to multiple serotonin and noradrenergic and dopaminergic receptors (Silberstein and McCrory, 2003). They have the potential to constrict coronary, peripheral, and cerebral vasculature and are contraindicated in patients with coronary, peripheral, and cerebrovascular disease (Robbins and Lipton, 2010). Common side effects include nausea and vomiting, but DHE has lesser propensity for this in comparison to ergotamine (Silberstein and McCrory, 2003). DHE also has greater

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parenteral bioavailability, less potential for vasoconstriction, and stronger a-adrenoceptor antagonism (Silberstein and McCrory, 2003).

syndromes such as akathisia or dystonic reactions may be less common compared to younger populations (Thanvi and Treadwell, 2009).

Nonsteroidal antiinflammatory drugs

Caffeine

Nonsteroidal antiinflammatory drugs (NSAIDs) work mainly by inhibiting COX-1 and COX-2, yielding a decrease in prostaglandin synthesis (Pradalier et al., 1998). Both prescription and nonprescription NSAIDs are available on the market. Ibuprofen, naproxen sodium, aspirin, and diclofenac potassium have level A evidence for the treatment of acute migraine while flurbiprofen and ketorolac have level B evidence (Marmura et al., 2015). There are no comparative data suggesting superiority of any specific NSAID for the treatment of migraine attacks (Silberstein, 2000). Compared to triptans, they may have the added benefit of countering an abnormal skin sensitivity called cutaneous allodynia (Jakubowski et al., 2005). Judicious administration is warranted in the elderly population due to the increased potential for adverse effects, although risk is variable among different NSAIDs due to differences in their ratio of COX-1:COX-2 inhibition (Suleyman et al., 2007). They can not only cause or worsen peptic ulcer disease but also increase the risk of gastrointestinal bleeding, particularly when used in conjunction with anticoagulants (Griffin et al., 1991). Caution is advised in their use in patients with renal disease due to the potential for interstitial nephritis, proteinuria, fluid retention, or acute renal failure (Suleyman et al., 2007). NSAIDs can also increase the risk of cardiovascular complications, and this risk is magnified with concomitant use of aspirin (Farkouh and Greenberg, 2009).

Derived from trimethylxanthine, caffeine has intrinsic analgesic properties, perhaps via vasoconstriction or blocking adenosine receptors on neurons and glia. When combined with certain analgesics it can potentiate their effects by about 40% (Laska et al., 1984; Shapiro, 2008). Despite an acute therapeutic benefit, daily intake should be limited to 100 mg/day because of withdrawal effects and risk of developing chronic headache (Scher et al., 2004). Excessive use may precipitate tachyarrhythmia, palpitations, polyuria, and gastrointestinal upset (Shapiro, 2008).

Antidopaminergic antiemetics Prochlorperazine and metoclopramide have level B evidence for acute migraine management and can be taken alone or in combination with NSAIDs or triptans (Marmura et al., 2015). Their main mode of action is via dopaminergic antagonism that can subsequently reduce nausea and increase gastric motility and medication absorption (Robbins and Lipton, 2010). They also may have independent antiheadache effects. Prochlorperazine and promethazine come in rectal formulations that can be useful in the setting of vomiting or severe nausea (Silberstein, 2000; Kelley and Tepper, 2012). Metoclopramide was found to be more effective than NSAIDs or triptans when combined with intravenous diphenhydramine (Kelley and Tepper, 2012). The side effects are mainly because of dopaminergic blockade and include sedation, akathisia, dystonia, and orthostatic hypotension (Sarchielli et al., 2006). The elderly may be at increased risk for parkinsonism, but acute pyramidal

Opioids and barbiturates Although opioid and barbiturate-containing medications are effective in relieving pain in acute migraine attacks, these agents should be reserved for use only when all other medications are ineffective or contraindicated (Silberstein, 2000). In addition to risk of tolerance and abuse, they may contribute to central sensitization and diminished response to NSAIDs and triptans (Jakubowski et al., 2005). Data suggests they are the most likely medications to contribute to migraine chronification (Bigal et al., 2008a,b). Additional caution is warranted in the elderly due to increased risk of sedation, impaired cognition, and falls (Fick et al., 2003).

PREVENTIVE TREATMENT Antiepileptics Certain antiepileptic agents can decrease the frequency and severity of headaches through multiple actions including modulation of sodium and calcium channels, raising GABAergic transmission, reducing glutamatemediated excitation in the trigeminal nucleus caudalis and periaqueductal gray area, raising the threshold for cortical spreading depression, and disrupting central sensitization (Calabresi et al., 2007). Valproic acid. Multiple placebo-controlled trials have demonstrated excellent efficacy, with level A evidence for migraine prophylaxis. However, its utility in an elderly population is limited by an unfavorable side effect profile (Silberstein, 1996; Silberstein et al., 2012). Common adverse effects among elderly patients include ataxia, sedation, and tremor (Silberstein, 1996). Other side effects include gastrointestinal disturbances, hepatic dysfunction, and weight gain. Rare but more severe consequences include fulminant hepatitis

HEADACHE IN THE ELDERLY and pancreatitis (Silberstein, 1996). Initial dosing should be low for these patients, such as a nightly dose of 250 mg, and the dose should be increased slowly over weeks to a target dose of 500–750 mg (Silberstein, 1996). Topiramate. Topiramate also has level A evidence supporting its effectiveness in migraine prophylaxis (Diener et al., 2009; Silberstein et al., 2012). Adverse effects to consider when prescribing topiramate to an elderly population include dizziness, sedation, and dose-related and reversible cognitive impairments in language, attention, and short-term memory (Kaniecki, 2008). Other common side effects include paresthesias and taste alteration (Kaniecki, 2008). Rare but serious adverse events include acute angle closure glaucoma, nephrolithiasis, and metabolic acidosis (Kaniecki, 2008). Benefits include its potential to cause weight loss and improve essential tremor (Sarchielli et al., 2006). To lessen the burden of these effects in older individuals it may be prudent to start at a dose of 12.5 mg at bedtime and increase the dose every other week to the typical target dose of 100 mg/day (Robbins and Lipton, 2010). Gabapentin. Although gabapentin has level U evidence behind its utility in migraine prevention, it may be particularly useful in elderly individuals with polypharmacy given its low potential for medication interactions (Silberstein, 2006; Silberstein et al., 2012). It may also benefit those with coexisting essential tremor, restless leg syndrome, or neuropathy (Silberstein, 2000; Robbins and Lipton, 2010). Common side effects include dizziness and sedation, and care must be taken to limit the dose strength and frequency in patients with renal impairment (Robbins and Lipton, 2010). Maximum dosing in elderly patients with normal renal function should be limited to 600 mg BID (Hanlon et al., 2009). It should be limited to 300 mg BID if creatinine clearance is between 15 mL/min and 29 mL/min, and 300 mg daily if <15 mL/min (Hanlon et al., 2009). Antidepressants Tricyclic antidepressants. These medications may prevent headaches by modulating brainstem pain pathways and blocking reuptake of multiple neurotransmitters including serotonin and norepinephrine (Galletti et al., 2009). Although amitriptyline is the most wellstudied, with level B evidence in support of its use, it has substantial anticholinergic effects. Other effective Tricyclic antidepressants (TCAs) that may be better tolerated include nortriptyline, protriptyline, and doxepin (Robbins and Lipton, 2010; Silberstein et al., 2012; Goldberg et al., 2014). The anticholinergic properties are the most salient features to be considered in the treatment of elderly patients as they can cause sedation, dry

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mouth, constipation, tachycardia, orthostatic hypotension, and increased risk of falls (Robbins and Lipton, 2010). ECG changes such as PR prolongation and widening of the QRS complex may also be seen (Harrigan and Brady, 1999). These medications should be used very cautiously in men with prostatic hypertrophy due to increased risk of urinary retention (Robbins and Lipton, 2010). Patients taking SSRIs may have decreased TCA metabolism and increased risk of serotonin syndrome (Baumann, 1996). Most TCAs are typically administered at bedtime due to their sedative effects and may even promote sleep (Robbins and Lipton, 2010). The exception is protriptyline, which should be given in the morning due to its activating properties (Robbins and Lipton, 2010). Venlafaxine. This agent selectively inhibits reuptake of serotonin and norepinephrine (SNRI) at the synapse and has level B evidence for use in migraine prophylaxis (Silberstein et al., 2012). It is considered safe in elderly patients, and as a weak cytochrome P450 inhibitor it carries low potential for pharmacokinetic drug interactions (Goldberg, 1997; Ibor et al., 2008). The typical target daily dose is 150 mg, titrated by 25 mg or 37.5 mg increments every 1–2 weeks. Doses should be lower in elderly patients with renal impairment (Goldberg, 1997). Common side effects in the elderly include dry mouth, constipation, nausea, and dizziness (Mukai and Tampa, 2009). Care must be taken to wean off venlafaxine slowly to avoid discontinuation syndrome symptoms, which include potentially serious mood changes, cranial electric shock sensations, sleep disturbance, and delirium (Petit and Sansone, 2011). Beta-blockers These medications probably exert antimigraine effects through multiple actions, although the precise mechanism remains unknown (Robbins and Lipton, 2010). They may reduce the firing rate of the locus coeruleus and periaqueductal gray neurons by blocking B1-adrenergic receptors, thereby inhibiting norepinephrine release and reducing serotonin synthesis (Galletti et al., 2009). Propranolol, timolol, and metoprolol have level A evidence for migraine prophylaxis while atenolol and nadolol have level B evidence (Silberstein et al., 2012). Patients with hypertension, congestive heart failure, or essential tremor might receive dual benefits from these drugs (Robbins and Lipton, 2010). Drowsiness, fatigue, hypotension, impotence, and depression are potential side effects (Silberstein, 2006). Nonselective beta-blockers (timolol, propranolol, and nadolol) should be avoided in patients with chronic obstructive pulmonary disease and asthma since they can exacerbate reactive airway disease (Buchanan and Ramadan, 2006).

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Calcium channel blockers These agents are considered third-line migraine preventive medications with level U evidence. Effectiveness may be related to action on multiple calcium channel subtypes, which can decrease neuronal excitability, serotonin release, and prostaglandin synthesis (Tfelt-Hansen and Tfelt-Hansen, 2009; Silberstein et al., 2012). Verapamil is the best studied and often requires doses higher than those used in hypertension (Tfelt-Hansen and Tfelt-Hansen, 2009). Side effects include constipation, peripheral edema, dizziness, and impotence (TfeltHansen and Tfelt-Hansen, 2009). Since it can also cause hypotension and bradycardia it should be increased no faster than 80 mg per week in elderly individuals, especially if they are taking other antihypertensive agents, and ECG studies should be performed during titration (Tfelt-Hansen and Tfelt-Hansen, 2009; Robbins and Lipton, 2010). Angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor antagonists Although these medications possess only level C evidence for migraine prevention, they are well-tolerated and therefore good for use in older individuals with concomitant hypertension (Robbins and Lipton, 2010; Silberstein et al., 2012). Among the best studied are candesartan and lisinopril; the latter, however, carries risks of cough and angioedema (Goldberg et al., 2014). Memantine Approved for the management of moderate to severe Alzheimer’s disease, this medication may benefit those with migraine and memory impairment. Currently there is level C evidence supporting its use in migraine prophylaxis (Huang et al., 2014). Memantine blocks N-methyl-D-aspartate (NMDA) receptors, which likely contribute to initiation and maintenance of central sensitization (Lindelof and Bendtsen, 2009). It is generally well-tolerated; in the pivotal trials of memantine, there were no side effects reported in the treated group that were significantly more frequent than in the placebo group. However, postmarketing reports indicate that in some cases it may cause agitation, dizziness, flu-like symptoms, diarrhea, and increased risk of falling (Farlow et al., 2008). Nutraceuticals These agents are good for use in an elderly population given limited drug interactions and side effects (Robbins and Lipton, 2010). Butterbur, an extract of the Petasites hybridus root dosed at 50–75 mg/day, has

shown efficacy with level A evidence from multiple studies. It may regulate calcium channels and reduce inflammation (Sun-Edelstein and Mauskop, 2009). Burping is the most commonly reported side effect (Sun-Edelstein and Mauskop, 2009; Loder et al., 2012). A trusted brand should be recommended due to the potential presence of toxic alkaloids that must be safely extracted (Robbins and Lipton, 2010). Vitamin B2 (riboflavin) and Coenzyme Q10 are hypothesized to prevent migraines by lowering mitochondrial energy consumption (Sun-Edelstein and Mauskop, 2009). Riboflavin is dosed at 400 mg/day and patients should be warned that it may change their urine color to bright or neon yellow hues (SunEdelstein and Mauskop, 2009; Loder et al., 2012). Coenzyme Q10 was dosed 100 mg TID in migraine studies, with itching the most common side effect (Loder et al., 2012). Magnesium has level B evidence and is thought to work via NMDA receptor antagonism (SunEdelstein and Mauskop, 2009; Loder et al., 2012). At least 300 mg should be administered daily, but it carries a dose-limiting side effect of diarrhea and should be avoided in patients with renal failure and diarrheapredominant irritable bowel syndrome (Teigen and Boss, 2015). Botulinum toxin A These injections have demonstrated efficacy for chronic migraine prevention with level A evidence. It is especially attractive for use in elderly patients given the minimal potential for systemic side effects or drug interactions (Aurora et al., 2009; Robbins and Lipton, 2010; Loder et al., 2012). The most common side effects are transient neck pain and ptosis. It should be avoided in patients with neuromuscular disorders such as myasthenia gravis (Robbins and Lipton, 2010). CGRP antagonists For decades pharmacologic migraine prevention incorporated medications designed for other therapeutic purposes. More recently migraine specific biologic therapies have been developed and proven effective in the prevention of both episodic and chronic migraine (Tepper, 2019). The monoclonal antibodies erenumab, fremanezumab, and galcanezumab target CGRP (calcitonin gene-related peptide) or its receptor. CGRP is a neuropeptide that contributes to the pathophysiology of migraine by helping to mediate cerebral vasodilation, neurogenic inflammation, and pain sensitization (Urits et al., 2019). These medications may be ideal for use in the elderly due to their low side effect profile (infrequent injection site reactions and constipation) and ease of use (subcutaneous injections once monthly or every 3 months) (Tepper, 2019; Urits et al., 2019).

HEADACHE IN THE ELDERLY

Tension-type headache EPIDEMIOLOGY Tension-type headache (TTH) is the most common primary headache disorder with lifetime and annual prevalence rates of 78% and 16%–44%, respectively (Crystal and Robbins, 2010; Song et al., 2016). Prevalence peaks in the 4th decade of life but decreases steadily beyond the age of 65 (Schwartz et al., 1998; Prencipe et al., 2001; Crystal and Robbins, 2010). Female-to-male ratios among young adults are approximately 3:1, while in elderly adults this falls to 1.8:1 (Crystal and Grosberg, 2009). TTH is the most common diagnosis in older patients with new headache complaints. Between 5.4% and 16.9% of individuals develop a headache for the first time after age 65, with 55.6%–80.6% diagnosed with TTH (Crystal and Grosberg, 2009; Song et al., 2016).

CHARACTERISTICS In contrast to migraine, which is defined in part by the presence of certain symptoms, TTH is characterized by a relative lack of distinctive features [refer to table of ICDH3 criteria of TTH] (Kaniecki, 2006). Qualities typical of TTH include mild or moderate intensity and a bilateral or “band-like” distribution. It is typically steady and nonpulsatile in nature, not worsened by routine activities, and not disabling. Aura is generally absent (Crystal and Grosberg, 2009). Accompanying features may include scalp tenderness and pericranial or cervical muscle soreness or tension. Diagnostic criteria for episodic TTH permit either mild photo- or phonophobia but not nausea (Kaniecki, 2006). TTH attacks can last from 30 min to a week and are subclassified as infrequent episodic (less than 1 day per month), frequent episodic (1–14 days per month for 3 months) or chronic (more than 15 days per month for 3 months).

DIFFERENTIAL DIAGNOSIS Given the paucity of uniquely defining features, there is significant symptomatic overlap with secondary headaches with etiologies ranging from benign to potentially deadly (Kaniecki, 2006). A careful history and examination must be performed to search for “red flag” symptoms or findings signaling underlying organic disease (Table 28.1). Primary or metastatic neoplasms, hemorrhagic or ischemic stroke, subdural hematoma, hydrocephalus, and meningitis may all present with patterns suggestive of TTH (Kaniecki, 2006; Crystal and Grosberg, 2009). Additional diagnostic possibilities include cervical spine disease, sleep apnea, giant cell arteritis, dental or sinus infection, malignant

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hypertension, and metabolic abnormalities such as hypothyroidism and hypoglycemia (Kaniecki, 2006; Crystal and Grosberg, 2009).

ACUTE TREATMENT Simple analgesics such as aspirin, acetaminophen and NSAIDs, whether alone or in combination, all have level A evidence supporting their efficacy in treating TTH (Bendtsen et al., 2010; Goldberg et al., 2014). Acetaminophen and aspirin were demonstrated to be superior to placebo at doses of 1000 mg and 500–1000 mg, respectively (Steiner et al., 2003). While some studies suggest NSAIDs are superior to acetaminophen, there are no comparative efficacy data to support superiority of any specific NSAID. Ibuprofen may be a good initial choice due to a favorable side effect profile (Bendtsen et al., 2010; Goldberg et al., 2014). Caffeine carries level B evidence when used in combination with other analgesics. Excessive use may lead to caffeine withdrawal headache and transformation to chronic TTH (Bendtsen et al., 2010). Opioids should be avoided due to high potential for medication-overuse headache and other deleterious effects such as dependence, somnolence, and increased risk of falls (Fick et al., 2003, Bendtsen et al., 2010). Occipital nerve blockade is a safe option in elderly individuals if pharmacologic treatments are intolerable or contraindicated, but data supporting effectiveness in TTH is mixed (Tobin and Flitman, 2009).

PREVENTIVE TREATMENT Patients with frequent episodic or chronic TTH should be considered candidates for prophylactic therapy (Bendtsen et al., 2010). Amitriptyline is the only medication to receive a level A recommendation and is first-line for prevention (Bendtsen et al., 2010), although its significant anticholinergic effects may limit its use in the elderly. Its metabolite, nortriptyline, has relatively more selective noradrenergic reuptake inhibition. It may be as effective and more tolerable, with less potential for weight gain and sedation (Goldberg et al., 2014). Mirtazapine and venlafaxine have both received level B recommendations and are considered second-line preventive treatment options (Bendtsen et al., 2010). Other agents that could be considered but have scant or mixed data in support of their use include tizanidine, topiramate, gabapentin, and clonazepam (Kaniecki, 2006). Nonpharmacologic treatment measures are attractive for use in elderly patients given typically favorable safety and tolerability profiles. EMG biofeedback has received a level A recommendation for the prevention of TTH (Bendtsen et al., 2010). The goal is to teach patients to control the tension in their musculature via continuous

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feedback (Nestoriuc et al., 2008). Level C recommendations have been given to acupuncture, cognitive behavioral therapy, relaxation training, and physical therapy (Bendtsen et al., 2010).

Trigeminal autonomic cephalalgias The trigeminal autonomic cephalalgias (TACs) are a group of disorders characterized by relatively short attacks of unilateral pain, usually in the distribution of the ophthalmic branch of the trigeminal nerve, associated with ipsilateral autonomic symptoms (International Headache Society, 2013). Most TACs can be divided into two categories, episodic (lasting between 7 days and 1 year with pain-free intervals of at least 1 month) or chronic (persisting longer than 1 year, or with remissions lasting less than 1 month) (International Headache Society, 2013). Elderly patients presenting with these complaints should undergo structural and neurovascular imaging and ESR/CRP measurement to rule out secondary pathology (Prakash et al., 2009; Prakash and Patel, 2014; Pomeroy and Nahas, 2015). Potential structural pathologies include pituitary or cerebellopontine angle tumors, cortical venous thrombosis, a vascular loop compressing the trigeminal nerve, posterior fossa stroke, sinusitis, glaucoma, and nasopharyngeal carcinoma (Pomeroy and Nahas, 2015; Prakash and Patel, 2017).

CLUSTER HEADACHE

Differential diagnosis Features suggestive of a secondary cause of a cluster headache include an abnormal neurologic exam, attack duration greater than 4 h, lack of periodicity, interictal pain, and poor response to treatment (Dodick and Capobianco, 2001). Potential mimics include carotid artery dissection, glaucoma, sinusitis, vascular malformations, and neoplasms involving the pituitary, hypothalamus, or ipsilateral cavernous sinus (Leroux and Ducros, 2008). Diagnostic evaluation should include a brain MRI with special attention to the pituitary and cavernous sinus. Some cases may require cerebral angiography (Leroux and Ducros, 2008; Robbins and Lipton, 2010). Acute treatment Given the particularly excruciating nature and rapid escalation of cluster headache pain, nonoral routes are preferred for abortive treatment (Leroux and Ducros, 2008). Triptans. Subcutaneous sumatriptan 6 mg and intranasal zolmitriptan 5 and 10 mg are supported by level A evidence for the treatment of episodic and chronic cluster headache attacks. Intranasal sumatriptan 20 mg and oral zolmitriptan 5 and 10 mg have received level B ratings (Robbins et al., 2016).

The 1-year prevalence of cluster headache is about 0.05% with a lifetime prevalence of 0.1%. Typical age of onset is 26–30 years (Russell, 2004; Fischera et al., 2008). Although it becomes less prevalent with increasing age, the incidence of cluster headaches can continue into the 10th decade of life. Up to 4% of headaches in the elderly may result from cluster headaches (Tonini and Bussone, 2010).

Oxygen. 100% oxygen via a nonrebreather facemask at a rate of 10–15 L/min is the only other therapy with level A evidence for the acute treatment of episodic and chronic cluster headache (Robbins et al., 2016). It is an ideal agent for use in the elderly, among whom triptans are frequently contraindicated. While generally safe for use in the geriatric population, it should be avoided in patients with chronic obstructive pulmonary disease because of the potential for hypercarbia (Robbins and Lipton, 2010).

Characteristics

Transitional prophylaxis

Cluster headaches are characterized by bouts of severe unilateral periorbital or temporal pain. They are distinguished from other TACs by the presence of up to eight attacks daily, lasting from 15 to 180 min (International Headache Society, 2013). In addition, a sense of agitation or restlessness can satisfy the diagnostic requirement for at least one ipsilateral autonomic feature (International Headache Society, 2013). The diagnosis of episodic cluster headache requires at least two cluster periods lasting between 1 week and 1 year, with headache-free periods of at least 1 month (International Headache Society, 2013). Chronic cluster headaches persist for at least 1 year without remission, or have headache-free periods lasting less than 1 month (International Headache Society, 2013).

Bridging agents can be used during the first 1–2 weeks of a cluster cycle to offer respite from attacks, and can be discontinued once the maintenance medication becomes therapeutic (Ashkenazi and Schwedt, 2011).

Epidemiology

Peripheral nerve blocks. This local therapy consists of a combination anesthetic and steroid injected into the region of the greater occipital nerve ipsilateral to the headache. Many clinicians also add injections to the lesser occipital, auriculotemporal, supratrochlear, and supraorbital nerves (Robbins and Lipton, 2010). This is considered a safe and reasonable choice in elderly patients and has garnered a level A recommendation for use in episodic and chronic cluster headaches (Robbins et al., 2016).

HEADACHE IN THE ELDERLY Corticosteroids. Although a variety of oral steroid taper regimens exist and are commonly used as transitional measures, there is insufficient evidence for the American Headache Society to render a recommendation level for use in either episodic or chronic cluster headache (Robbins and Lipton, 2010; Robbins et al., 2016). Use in elderly individuals should be minimized or avoided due to risk of osteoporosis and aseptic osteonecrosis of the femoral head (Robbins and Lipton, 2010). Caution is also warranted for patients with hypertension, diabetes and underlying affective disorders due to risk of exacerbation (Robbins and Lipton, 2010). Maintenance prophylaxis When used for episodic cluster headache, these medications are maintained for the duration of a typical cycle and can be tapered off shortly thereafter. Chronic cluster may require long-term management (Francis et al., 2010). Verapamil. This calcium channel blocker is widely used and considered the treatment of choice in episodic and chronic cluster headache prophylaxis. Evidence is assessed as level C by the American Headache Society but level A by the European Federation of Neurological Societies (Ashkenazi and Schwedt, 2011; Robbins et al., 2016). Typical management requires 180–360 mg in divided doses, but as much as 960 mg may be needed for benefit (Leroux and Ducros, 2008). Electrocardiographic monitoring is recommended at times of dose escalation. Verapamil is thought to be effective due to the abundance of calcium receptors on the hypothalamus, a key anatomic component in cluster headache (Tfelt-Hansen and Tfelt-Hansen, 2009). Lithium. This mineral salt has proven efficacious for the prevention of episodic and chronic cluster headache, although its use is supported by a level C recommendation from the American Headache Society (Robbins and Lipton, 2010; Robbins et al., 2016). It is considered second-line prophylactic therapy due to high potential for drug interaction, adverse effects, and need for blood level monitoring (Ashkenazi and Schwedt, 2011). It is commonly dosed between 600 mg and 900 mg per day, but should be titrated to a range of 0.4–0.8 mEq/L (Ashkenazi and Schwedt, 2011). Lithium serum levels require monitoring, especially because its concentration can be increased by common medications used in the elderly such as NSAIDs and diuretics (Robbins and Lipton, 2010). Renal and thyroid function should be also tested routinely due to risk of diabetes insipidus and hypothyroidism (Ashkenazi and Schwedt, 2011). Common adverse effects include tremor, nausea, thirst, and polyuria while signs of

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toxicity may include ataxia, nystagmus, confusion, extrapyramidal signs, and seizures (Robbins and Lipton, 2010; Ashkenazi and Schwedt, 2011). Melatonin. Melatonin 10 mg at bedtime may be effective for episodic and chronic cluster headache and has received a level C recommendation (Robbins et al., 2016). It is safe and tolerated well by elderly individuals, but the dose should be titrated slowly as it carries the potential for sedation (Robbins and Lipton, 2010; Robbins et al., 2016). Hemicrania continua. The incidence of hemicrania continua is not truly known, partially due to a tendency for diagnostic error, but it appears to account for 1.3%– 2.3% of headaches in headache clinics (Prakash and Patel, 2017). The mean age of onset is in the 4th decade of life but it may first manifest at any stage of life (Cittadini and Goadsby, 2011). It is the fourth most common cause of side-locked headache, behind cluster headache, migraine and cervicogenic headache (Prakash and Patel, 2017). It is characterized by a strictly unilateral and continuous headache of moderate intensity punctuated with more severe attacks exhibiting migrainous features. Diagnosis also requires the presence of at least one ipsilateral autonomic feature (Prakash and Patel, 2017). An additional diagnostic prerequisite is absolute responsiveness to indomethacin, which can pose a diagnostic challenge in elderly individuals in whom NSAIDs are often avoided or contraindicated (Robbins and Lipton, 2010). Typically, indomethacin is initially dosed at 25 mg 3 times daily and titrated to an effective dose over days to weeks, sometimes up to total daily doses as high as 500 mg (Prakash and Patel, 2017). Comorbid disorders that are frequent in the elderly and can preclude its titration include renal dysfunction, cardiovascular disease and peptic ulcer disease (Robbins and Lipton, 2010). The effectiveness of alternative treatments is less clear, but some case reports and open-label studies have shown success with topiramate, celecoxib, lamotrigine, gabapentin, and melatonin (Robbins and Lipton, 2010; Prakash and Patel, 2017). Paroxysmal hemicrania. This is a very rare disorder with an estimated prevalence of 1 in 50,000; however, this may be falsely low as it is likely underreported and underdiagnosed (Prakash and Patel, 2014). The mean age of onset is between 37 and 42 years but cases have been reported in individuals as young as 1 year and as old as 81 years (Prakash and Patel, 2014). Attacks are multiple in a day, lasting between 2 and 30 min, and are associated with at least one ipsilateral autonomic symptom. Response to indomethacin is a final diagnostic requirement (International Headache Society, 2013).

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The treatment approach and differential considerations are essentially the same as for hemicrania continua (Prakash and Patel, 2014). SUNCT/SUNA. These two entities are, respectively, Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing (SUNCT), and Short-lasting Unilateral Neuralgiform headache with cranial Autonomic features (SUNA). There is debate whether they are separate or singular disorders, but together have an estimated incidence of 1.2 per 100,000 and prevalence of 6.6 per 100,000 (Pomeroy and Nahas, 2015). These disorders are distinguished from the other TACs by their high frequency and short duration of attacks. SUNCT is further characterized by the presence of both conjunctival injection and tearing, whereas SUNA has only one or neither of these features (International Headache Society, 2013). Patients may experience up to one hundred attacks per day, each lasting between 1 s and 600 s (International Headache Society, 2013). Lamotrigine is considered first-line treatment for SUNCT/SUNA with typical therapeutic doses ranging from 100 mg to 400 mg daily (Pomeroy and Nahas, 2015). Rash is the most common adverse reaction, and it should be titrated slowly to avoid StevensJohnson syndrome, especially with concomitant use of valproic acid (Robbins and Lipton, 2010). Some success has also been reported with topiramate, gabapentin, and carbamazepine (Pomeroy and Nahas, 2015).

Hypnic headache EPIDEMIOLOGY Although it affects younger individuals as well, hypnic headaches become much more common after age 50 with an average onset of age 60 (Holle et al., 2013). True prevalence is unknown, but it appears to be twice as common among women and may comprise up to 0.35% of total patients and up to 1.7% of elderly patients seen at tertiary headache centers (Liang and Wang, 2014).

CHARACTERISTICS Often referred to as an “alarm clock headache,” hypnic headache occurs only during sleep, and typically strikes between 2 a.m. and 4 a.m. (Holle et al., 2013; Bravo, 2015). Attack duration is 15 min to 4 h and patients can have up to six attacks per night, each of which are preceded by a return to sleep (Holle et al., 2013; International Headache Society, 2013). There must be at least 10 attacks per month for 3 months. Although lack of cranial autonomic features and restlessness are part of the diagnostic criteria in the ICDH-3 beta, these symptoms can occur and may be more common than recognized previously (Holle et al., 2013). Variations may

include pain of dull and moderate intensity, bilateral distribution and lack of migrainous features such as pulsatile quality, photo/phonophobia, and nausea (Holle et al., 2013; Bravo, 2015).

DIFFERENTIAL DIAGNOSIS Hypnic headache always warrants investigation as numerous structural mimics have been described (Holle et al., 2013). Examples include cerebellar hemangioblastoma, pituitary neoplasms, and lesions of the posterior fossa (Holle et al., 2013). Nonstructural considerations include nocturnal hypertension, obstructive sleep apnea, and medications such as angiotensin converting enzyme (ACE) inhibitors and withdrawal from lithium (Holle et al., 2013; Bravo, 2015).

TREATMENT There is limited evidence on which to base treatment. Many clinicians begin with nocturnal caffeine 60 mg for the treatment of acute attacks as well as prophylaxis (Holle et al., 2013; Bravo, 2015). Success has also been reported with lithium in the range of 150–600 mg/day, but side effects and other toxicities may limit its use in the elderly population (Holle et al., 2013).

Primary cough headache Primary cough headache is a rare disorder with a lifetime prevalence of 1% and a mean age of onset above 60 years (Cordenier et al., 2013; Bravo, 2015). It is precipitated only by cough or Valsalva, but not sustained exertion, and lasts between 1 s and 2 h (International Headache Society, 2013). It most often begins abruptly, peaks immediately, and subsides over seconds to minutes (Cordenier et al., 2013). There is some correlation between the frequency of cough and the severity of the headache. Chiari I malformation is the most common secondary cause in younger patients, but posterior fossa pathology, cervical artery disease and intracranial aneurysms are worrisome considerations in the elderly population (Cordenier et al., 2013). Suppression of cough is often valuable. The treatment of choice for headache prevention is indomethacin (Cordenier et al., 2013).

SECONDARY HEADACHES Giant cell arteritis Also referred to as temporal arteritis, giant cell arteritis (GCA) is a medium- and large-vessel vasculitis that almost exclusively affects the elderly. It has an incidence of 18–30/100,000 in individuals above age 50 and is 3

HEADACHE IN THE ELDERLY times more common among women (Smith and Swanson, 2014; Nesher and Breuer, 2016).

CLINICAL FEATURES Headache is the most common symptom of GCA and occurs in 72% of patients, but it is the presenting symptom in only 33% (Caselli et al., 1988). The nature of the headache is variable. Persistent temporal headache is seen in the minority, and most present with symptoms suggestive of tension-type headache (Smith and Swanson, 2014). Scalp tenderness and jaw claudication may be present, and tongue necrosis is a rare but highly specific finding (Nesher and Breuer, 2016). Up to 20% of patients develop arteritic anterior ischemic optic neuropathy due to involvement of the posterior ciliary arteries, potentially leading to blindness (Smith and Swanson, 2014). Early warning signs include amaurosis fugax, diplopia, blurred vision, and other visual phenomena such as scintillating scotoma (Nesher and Breuer, 2016). Strokes occur in 3%–7%, mainly involving the vertebrobasilar system, resulting occasionally in multiinfarct dementia or even death (Smith and Swanson, 2014). Other less common neurologic consequences include cranial neuropathies, cervical myelopathy or radiculopathy, and peripheral neuropathy (Smith and Swanson, 2014). Up to half of patients develop polymyalgia rheumatica characterized by weight loss, fever, malaise, and myalgias (Smith and Swanson, 2014; Nesher and Breuer, 2016). Examination may reveal prominent or tender temporal arteries but the absence of these features should not alter suspicion (Smith and Swanson, 2014). Other vascular findings suggestive of GCA include diminished temporal artery pulsation, carotid or brachial bruits and aortic regurgitation (Smith and Swanson, 2014). Fundoscopic examination may reveal signs of ischemic optic neuropathy such as optic disc swelling, optic disc pallor or afferent pupillary defect (Smith and Swanson, 2014).

DIAGNOSIS The American College of Rheumatology requires that three of five features be present: Age 50 years or above, new onset of headaches, temporal artery abnormality on clinical exam, an erythrocyte sedimentation rate (ESR) >50 mm/h, or abnormal temporal artery biopsy demonstrating vasculitis with predominantly mononuclear cell or granulomatous inflammation (Hunder et al., 1990). The latter is considered the gold standard and should be considered in all suspected cases even after treatment is initiated (Nesher and Breuer, 2016). Although there is no consensus on whether a unilateral or bilateral biopsy should be obtained, the length of the sample should be at minimum 5 mm to increase yield

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(Smith and Swanson, 2014; Nesher and Breuer, 2016). Jaw claudication and diplopia carry the highest likelihood of a positive biopsy (Smith and Swanson, 2014).

TREATMENT Once GCA is suspected, treatment should be initiated without delay due to the potentially devastating consequence of irreversible vision loss (Bravo, 2015). Initial treatment is with corticosteroids, commonly 40–60 mg of prednisone (0.75 mg/kg at a minimum) unless vision disturbance is present, in which case intravenous methylprednisolone 500–1000 mg is administered for 3 days (Smith and Swanson, 2014). The initial dosing is continued for 2–4 weeks followed by a very slow taper over at least 6 months. Dose-adjustments should be guided by the reemergence of clinical features (Smith and Swanson, 2014). Since patients may be maintained on steroids for years, consideration should be given to steroid-sparing agents such as methotrexate to avoid steroid-related complications such as infection, diabetes, hip fractures, and cataracts (Smith and Swanson, 2014).

Trigeminal neuralgia The annual incidence of trigeminal neuralgia (TN) is up to 27/100,000 and increases with advancing age, peaking between the 5th and 7th decades (Bravo, 2015; Oomens and Forouzanfar, 2015). It consists of multiple brief and paroxysmal attacks of severe lancinating pain in the region of the trigeminal nerve. Approximately 95% are strictly unilateral, and 95% are isolated to the maxillary and mandibular divisions. Pains may be spontaneous or triggered by otherwise innocuous cutaneous stimulation such as light touch, talking, chewing, or even a light breeze (Bravo, 2015). It can be caused by compression and/or demyelination of the trigeminal root fibers. In “classic” trigeminal neuralgia the etiology is neurovascular compression, most commonly involving the superior cerebellar artery. Those with other structural origins to TN, such as multiple sclerosis, neoplasms or herpes zoster, are given the diagnosis of “painful” trigeminal neuralgia (Oomens and Forouzanfar, 2015).

TREATMENT First-line therapy for trigeminal neuralgia is medical management. Carbamazepine and oxcarbazepine are considered first-line therapies. Although the former is less expensive, the latter is often better tolerated (Oomens and Forouzanfar, 2015). The recommended starting doses for carbamazepine and oxcarbazepine in the elderly are 100 mg and 150 mg, respectively, titrated to clinical effect (Oomens and Forouzanfar, 2015).

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Adverse effects are common in the elderly, and may include dizziness, somnolence, ataxia, hyponatremia, elevated liver enzymes, thrombocytopenia, osteoporosis, and folate deficiency. Monitoring of liver enzymes, complete blood count, electrolytes, calcium, and serum drug levels is recommended (Oomens and Forouzanfar, 2015). Drug interactions with anticoagulants, tricyclic antidepressant and antipsychotic agents, calcium channel blockers, macrolide antibiotics, metronidazole, and assorted chemotherapeutic and cardiovascular medications must be monitored (Spina et al., 1996). Add-on or second-line therapies have weaker evidence and include baclofen, lamotrigine and gabapentin (Oomens and Forouzanfar, 2015). In those patients with classic trigeminal neuralgia failing two medication trials, procedural options are then recommended. Posterior fossa microvascular decompression is the most effective surgical procedure and should be offered to all reasonable surgical candidates (Phan et al., 2015). A recent systematic literature review showed similar outcomes among young and elderly populations (Phan et al., 2015). Despite lower recurrence rates among the elderly, there is a slightly higher rate of complications such as stroke, thromboembolism, and even death (Phan et al., 2015). Safer alternatives for poor surgical candidates include radiofrequency ablation, chemical destruction, and stereotactic radiosurgery (Oomens and Forouzanfar, 2015).

Headache due to cerebrovascular disease ACUTE ISCHEMIC STROKE Approximately 27% of patients experience a headache at the onset of TIA or acute ischemic stroke. Factors that increase the likelihood of headache include female sex, migraine history, cerebellar stroke and blood pressure <120/70 mm Hg at presentation (Tentschert et al., 2005). Headache is more common in posterior circulation and cortical strokes and is rarely present with lacunar infarcts (Jamieson et al., 2014). Patients younger than 40 years of age are more than 4 times as likely to experience headache as patients aged 80 years and above (Tentschert et al., 2005). The pain tends to be a continuous pressure sensation located in the bilateral occipital and frontal regions and can worsen with Valsalva maneuvers such as coughing or sneezing. It is rarely incapacitating and the severity does not necessarily correlate with infarct size or location (Goddeau and Alhazzani, 2013; Jamieson et al., 2014).

INTRACEREBRAL HEMORRHAGE Headache is present at the onset of 34%–58% of patients with intracerebral hemorrhage (ICH), but is less common

among the elderly (Jamieson et al., 2014). Headache at onset may signal a more severe ICH such as intraventricular hemorrhage (IVH), severe hydrocephalus, midline shift or herniation, as well as increased 30-day mortality (Melo et al., 1996). The nature of the pain is variable. Unilateral headache may indicate an ipsilateral supratentorial hemorrhage, whereas headaches associated with infratentorial bleeds may be more diffuse and include migrainous features (Kumral et al., 1995). Headaches due to ICH often precede the development of focal neurologic signs and are more likely to cause nausea and vomiting compared to headaches resulting from other stroke subtypes (Verdelho et al., 2008).

SUBARACHNOID HEMORRHAGE Headaches due to subarachnoid hemorrhage (SAH) are classically described as “the worst headache of my life” with a thunderclap onset (sudden severe onset and reaching peak intensity within 5 min or less). This description is neither sensitive nor specific and encompasses less than half of cases (Jamieson et al., 2014). The headache is often accompanied by nausea, vomiting, and neck stiffness. Localizing signs such as oculomotor nerve palsy or hemiparesis may be present if the SAH is secondary to aneurysmal rupture (Goddeau and Alhazzani, 2013). The Ottawa SAH Rule (Table 28.4) is capable of ruling-out SAH with 100% sensitivity, but it is only about 14% specific (Perry et al., 2013).

CERVICAL ARTERY DISSECTION Between 60% and 95% of carotid artery dissections may cause pain in the ipsilateral head, face, and neck. An associated ipsilateral Horner syndrome occurs in nearly Table 28.4 The Ottawa SAH rule For alert patients older than 15 years with new severe nontraumatic headache reaching maximum intensity within 1 h Not for patients with new neurologic deficits, previous aneurysms, SAH, brain tumors, or history of recurrent headaches (three episodes over the course of 6 months) Investigate if one high-risk variables present: 1. 2. 3. 4. 5. 6.

Age 40 years Neck pain or stiffness Witnessed loss of consciousness Onset during exertion Thunderclap headache (instantly peaking pain) Limited neck flexion on examination

(Permissions obtained)

HEADACHE IN THE ELDERLY half of patients (Biousse et al., 1994; Silbert et al., 1995). Roughly 70% of vertebral artery dissections are associated with headache that typically presents as a steady or throbbing pain in the neck or occipital region (Silbert et al., 1995). Both extra- and intracranial dissections are typically managed with antiplatelet agents or anticoagulation for a duration of 3–6 months, although anticoagulation for intracranial dissection may increase the risk of intracranial hemorrhage (Kernan et al., 2014).

CEREBRAL VENOUS SINUS THROMBOSIS Headache is the most common presenting symptom of cerebral venous sinus thrombosis. It may be seen in up to 90% of cases, and may be the only feature in up to 40% (Jamieson et al., 2014). The headache may exhibit migraine or tension-type qualities. Thunderclap onset is common. Pain is often persistent and may worsen with exertion, lying down, or Valsalva maneuvers (Jamieson et al., 2014). Anticoagulation is the treatment of choice, even in select patients with associated intracranial hemorrhage. There is no consensus on the ideal duration, but it is typically 3–12 months (Kernan et al., 2014).

Spontaneous intracranial hypotension Spontaneous intracranial hypotension (SIH) has an annual incidence of about 5/100,000 that peaks in middle age (Lin et al., 2017). It results from CSF leakage, most commonly from the nerve root sleeves in the cervical or thoracic region (Kranz et al., 2017). The ICHD-3 diagnostic criteria include a CSF pressure <6 mmHg, but this is insensitive and most patients have pressures in the normal range. It may be more appropriately framed as a disorder of low CSF volume (Kranz et al., 2017). The classic sign of positional or orthostatic headache (present or aggravated with upright positioning and relieved shortly after lying down) is not universal and may disappear over time (Kranz et al., 2017). Common associated symptoms include neck pain or stiffness,

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nausea, vomiting, blurred vision, facial pain or numbness, tinnitus, and limb paresthesias (Lin et al., 2017). Diagnostic evaluation. Brain MRI with and without contrast is the first-line diagnostic test and may show diffuse pachymeningeal thickening and enhancement (Fig. 28.1). Venous engorgement, pituitary hyperemia and enlargement, effacement of the perichiasmatic or prepontine cisterns, and descent of the cerebellar tonsils below their usual anatomic position are other common findings (Lin et al., 2017). Subdural fluid collections or hematomas are less commonly seen. Identifying the site of leakage is often challenging. Spinal MRI sometimes shows epidural fluid collections, but the actual leak site may remain elusive. CT myelography more readily identifies fast leaks and can reveal CSF-venous fistulas but it is more invasive (Kranz et al., 2017). Radioisotope cisternography also is invasive and insensitive in localizing leaks. Treatment. Conservative treatment consists of bed rest, caffeine, and hydration, but the mainstay of therapy is an autologous epidural blood patch (Kranz et al., 2017). Nontargeted lumbar epidural blood patches are up to 70% successful on first attempt but may need to be repeated (Kranz et al., 2017). Targeted blood patches are more effective and can be performed when the site of leakage is identified (Kranz et al., 2017). Surgery is an option for recalcitrant cases and may include ligation of meningeal diverticula, duroplasty, packing of fibrin glue, or direct dural repair (Lin et al., 2017).

Cervicogenic headache Cervicogenic headache has an estimated prevalence of 4.1% and affects about half of individuals with headache following whiplash injuries (Bogduk and Govind, 2009). The diagnosis requires either clinical or imaging evidence of a disorder of any component of the cervical spine known to cause headache (Table 28.5) (International Headache Society, 2013). Supportive

Fig. 28.1. Intracranial hypotension with diffuse pachymeningeal enhancement. (A) Coronal section. (B) Axial section.

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Table 28.5

Medication overuse headache

The International Headache Society diagnostic criteria for cervicogenic headache A. Clinical, laboratory, and/or imaging evidence demonstrating a lesion or disorder of the cervical spine or soft tissue known to be able to cause headache B. Evidence for causation by at least two of the following: 1. Temporal relationship of the headache and appearance or development of the cervical disorder or lesion 2. Improvement or resolution of the headache parallels the improvement or resolution of the cervical disorder or lesion 3. Reduced cervical range of motion and worsening of the headache by provocative maneuvers 4. Blockade of a cervical structure or its nerve supply results in resolution of the headache C. Not better accounted for by another ICDH-3 diagnosis

features include a unilateral side-locked location, neck pain that precedes the headache, and pain triggered by neck movement or cervical manipulation (Bogduk and Govind, 2009). Stretching and physical therapy may be helpful in some cases. Simple analgesics and muscle relaxants are often used symptomatically. Patients with frequent or persistent headache are often treated with amitriptyline or gabapentin, with variable success, and with amitriptyline attention must be paid to anticholinergic side effects, including somnolence, bladder problems, or memory impairment. For persistent cervicogenic headache, occipital nerve blocks may be diagnostic and therapeutic (Bravo, 2015).

Intracranial neoplasms The notion that a brain tumor may underlie a new-onset headache is a source of significant anxiety for patients and often motivates them to seek medical care (Kahn and Finkel, 2014). The 1-year risk of developing an intracranial neoplasm among patients with new-onset headache is between 0.045% and 0.15% but has a prevalence of 0.28% in patients above age 50 years (Kernick et al., 2008; Kahn and Finkel, 2014). Up to 29% of patients with brain tumors report headache as their initial symptom, but as many as 64% report headache at the time of diagnosis (Kahn and Finkel, 2014). The classic presentation of a severe headache upon wakening with nausea and vomiting is present in only 17% of patients, and the headache can mimic any of the primary headaches (Bravo, 2015). NSAIDs or opioids are commonly used to treat the pain, and steroids can help with edema or hydrocephalus (Kahn and Finkel, 2014). Neurosurgery, radiotherapy, and chemotherapy are definitive treatments but the headache may persist in nearly 10% of patients (Kahn and Finkel, 2014).

Medication overuse headache (MOH) occurs with equal frequency in young and older groups with a population prevalence between 1.0% and 1.7% (Diener et al., 2016). It is defined as a headache occurring at least 15 days per month in patients with a preexisting headache disorder and overuse of acute or symptomatic headache drugs (International Headache Society, 2013). “Overuse” refers to treatment on more than 15 days per month with simple analgesics such as NSAIDs; more than 10 days per month with triptans, ergotamines, and/or combination analgesics; or more than 5–10 days per month with opioids or barbiturate-containing compounds (Diener et al., 2016). Risk factors include preexisting pain disorders, smoking, physical inactivity, and female gender (Diener et al., 2016). Counseling patients on MOH is sufficient to eliminate overuse in greater than 70% of patients, and withdrawal of the overused medication can result in significant headache improvement in half of patients after 2 months (Bravo, 2015; Diener et al., 2016). If education alone is unsuccessful, preventive management with topiramate or onabotulinumtoxinA is an option if migraine is the underlying headache disorder (Diener et al., 2016).

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