Headache Attributed to a Disorder of Homeostasis
David W. Dodick
Paul T. G. Davies
INTRODUCTION
The headache disorders within this category were previously referred to as headache associated with metabolic or systemic disease. However, headache attributed to disorder of homoeostasis was felt to more fully encompass disorders of homeostatic mechanisms affecting a variety of organ systems, including altered arterial blood gases, systemic arterial pressure, volume disturbances that occur as a result of dialysis, and disorders of endocrine function. Headache attributed to fasting and cardiac ischemia are also included in this category.
HEADACHE ATTRIBUTED TO HYPOXIA AND/OR HYPERCAPNIA
Headache as a result of disturbances in arterial blood gas concentrations is well established, although it is often difficult to distinguish between the effects of hypoxia and hypercapnia.
HIGH ALTITUDE HEADACHE
International Headache Society (IHS) International Classification of Headache Disorders (ICHD) II code and diagnosis:
10.1.1 High altitude headache
World Health Organization (WHO) code and diagnosis:
G44.882 High altitude headache
Short description: the headache occurs within 24 hours after acute onset of hypoxia with PaO2 less than 70 mm Hg or in chronically hypoxic patients with PaO2 persistently at or below this level.
Clinical Features
The ICHD-II diagnostic criteria for HAH are as follows:
A. Headache with at least two of the following characteristics and fulfilling criteria C and D:
1. Bilateral
2. Frontal or frontotemporal
3. Dull or pressing quality
4. Mild or moderate intensity
5. Aggravated by exertion, movement, straining, coughing, or bending
B. Ascent to altitude above 2500 m.
C. Headache develops within 24 hours after ascent.
D. Headache resolves within 8 hours after descent.
Headache is the most common neurologic symptom and complication arising from ascent to altitudes greater than 2500 ms (30,62). Until recently, there were few systematic attempts to define the clinical features of HAH and only a small number of therapeutic trials, which at times yielded conflicting results (8,16). Most descriptions of HAH were originated with clinicians with extensive personal experience at altitude (4).
A recent study prospectively analyzed the incidence, risk factors, and clinical characteristics of HAH in members of an expeditionary unit to the Kanchenjunga base camp in Nepal (5100 m) (65). Participants were interviewed prior to the trip and while trekking, they recorded headaches experienced at greater than 3000 m using a structured questionnaire incorporating original diagnostic criteria for HAH and acute mountain sickness (AMS) from the ICHD-I. In addition, clinical features of headaches in 19 trekkers from other groups above 3000 m were recorded using the same questionnaire. This study demonstrated that 83% (50/60) reported at least one HAH (median 2, range 0 to 10) at a mean altitude of 4723 m. Those who developed HAH were significantly younger, suggesting that age-related cerebral atrophy might allow a greater capacity to accommodate mild cerebral edema. Women and people with headaches in daily life were also more likely to report severe headaches at altitude. In this study, 95% of the
women reported headaches compared to 82% of the men, and headaches were reported more frequently and were described to be of greater severity compared with the men. At normal altitudes, women have a higher rate of migraine and most other headache disorders than men, raising the possibility that they may be more susceptible to headache at altitude. HAH often awakened participants from sleep or occurred upon awakening and was exacerbated by bending, coughing, or sneezing, suggesting the possibility of intracranial hypertension as a contributing factor.
women reported headaches compared to 82% of the men, and headaches were reported more frequently and were described to be of greater severity compared with the men. At normal altitudes, women have a higher rate of migraine and most other headache disorders than men, raising the possibility that they may be more susceptible to headache at altitude. HAH often awakened participants from sleep or occurred upon awakening and was exacerbated by bending, coughing, or sneezing, suggesting the possibility of intracranial hypertension as a contributing factor.
The typical features of HAH are an onset within 24 hours of reaching a particular height, duration of less than a day, and in most cases a bilateral, generalized, dull pressure sensation. HAH is usually not accompanied by hypoxic symptoms such as a desire to overbreathe or exertional dyspnea, perhaps because subjects may consider these to be normal features at altitude.
Persons rapidly ascending to high altitudes are also at risk of developing AMS, the principal symptom of which is moderate or severe headache, combined with one or more other symptoms including nausea, anorexia, fatigue, dizziness, and sleep disturbances (31). In extreme cases, AMS may progress to an acute encephalopathy characterized by ataxia and a depressed level of consciousness termed high-altitude cerebral edema (HACE). Magnetic resonance imaging (MRI) studies of individuals with HACE have shown vasogenic cerebral edema (32). This suggests that a proportion of headaches at altitude, and certainly AMS, may be part of a similar pathogenic process with HACE at the extreme of the continuum.
MANAGEMENT
The management of HAH is empiric in the absence of controlled trials. Preventative strategies include allowing 2 days of acclimatization prior to engaging in strenuous exercise at high altitudes, avoiding alcohol, and liberalizing fluid intake. Acetazolamide (125 mg, two or three times daily) may reduce susceptibility to AMS. Most high-altitude headaches respond to simple analgesics such as acetaminophen (paracetamol) or ibuprofen (65). Triptans have also been shown to be effective for migraine headaches experienced at altitude (8).
DIVING HEADACHE
IHS ICHD-II code and diagnosis: 10.1.2 Diving Headache
WHO code and diagnosis: G44.882 Diving headache
CLINICAL FEATURES
The ICHD-II diagnostic criteria for diving headache are as follows:
A. Headache, no typical characteristics known, fulfilling criteria C and D.
B. Diving to depth below 10 m.
C. Headache develops during diving and is accompanied by at least one of the following symptoms of CO2 intoxication in the absence of decompression illness:
1. Lightheadedness
2. Mental confusion
3. Dyspnea
4. Flushed feeling in the face
5. Motor incoordination
D. Headache resolves within 1 hour after treatment with 100% O2.
The cause of headache in divers is diverse. Primary headache disorders may occur while diving, including migraine, tension-type headache, primary exertional headache, cervicogenic headache, and headache or facial pain attributed to temporomandibular joint (TMJ) disorder. Divers may also experience headache or facial pain as a result of decompression sickness, arterial gas embolism, paranasal sinus, or otic barotrauma, and due to compression from the mask (“mask squeeze”) or goggles (“goggle headache”). Germane to this discussion, however, are the headaches in divers that can occur as a result of hypercapnia and carbon monoxide toxicity.
Hypercapnia (arterial PCO2>50mm Hg) is known to cause relaxation of cerebrovascular smooth muscle and lead to vasodilation and increased intracranial pressure (66). Hypercapnia is a common cause of headache in divers, as well as a provocative trigger for migraine and cluster headache in susceptible divers (17,33,35). Carbon dioxide may accumulate in a diver who intentionally holds his or her breath intermittently (skip breathing) in a mistaken attempt to conserve air, or takes shallow breaths to minimize buoyancy variations in the narrow passages of a wreck or cave (18). Divers may also hypoventilate unintentionally when a tight wetsuit or buoyancy compensator jacket restricts chest wall expansion, or when ventilation is inadequate in response to physical exertion. Strenuous exercise increases the rate of CO2 production more than 10-fold, resulting in a transient elevation of PCO2 to more than 60 mm Hg (18). Diving headache usually intensifies during the decompression phase of the dive or upon resurfacing. A mechanism analogous to AMS has also been hypothesized to explain headaches affecting professional divers.
In a prospective study of Norwegian saturation divers, 4% reported headache during the first day of decompression, 23% on the last day of decompression, and 34% on the first day after reaching the surface (25). The pain was located over the frontal or vertex regions, recorded as mild in severity with a median of 2.5 on a 10-point visual analog scale (range 0.1 to 7.8), and lasted a median duration of 6 hours (range 1 to 84 hours).
Additional symptoms of CO2 intoxication can include lightheadedness, mental confusion, dyspnea, a flushed
feeling in the face, and motor incoordination, progressing, as CO2 tension rises, to central respiratory and cardiac depression followed by unconsciousness and convulsions. Because the exotic underwater milieu can mask these symptoms, and some divers will not develop headache, the affected diver may have little or no warning preceding apnea and loss of consciousness. Some individuals will have a markedly reduced ventilatory response to elevated PaCO2 and are at greater risk of developing toxicity. Retention of CO2 also potentiates O2 toxicity or inert gas narcosis and may render the diver more susceptible to decompression illness (18).
feeling in the face, and motor incoordination, progressing, as CO2 tension rises, to central respiratory and cardiac depression followed by unconsciousness and convulsions. Because the exotic underwater milieu can mask these symptoms, and some divers will not develop headache, the affected diver may have little or no warning preceding apnea and loss of consciousness. Some individuals will have a markedly reduced ventilatory response to elevated PaCO2 and are at greater risk of developing toxicity. Retention of CO2 also potentiates O2 toxicity or inert gas narcosis and may render the diver more susceptible to decompression illness (18).
Headache also is an early symptom of poisoning from carbon monoxide (CO), an odorless gas that rarely has contaminated a diver’s compressed air supply when, during tank preparation, the air intake system is inadvertently positioned toward street traffic and exposed to the combustion engine exhaust of an idling vehicle (20). Binding to hemoglobin with 250-fold greater affinity than oxygen, CO impairs the oxygen-carrying capacity of hemoglobin. The resulting tissue hypoxia and CO-mediated release of nitric oxide dilates cerebral vessels. Frontal headache, dizziness, exertional dyspnea, and nausea result once blood carboxyhemoglobin levels exceed 10 to 15% (20). Treatment of CO poisoning consists of inhaling 100% oxygen or hyperbaric oxygen to hasten carboxyhemoglobin dissociation and should be administered without delay (20).
MANAGEMENT
Prevention is the best treatment. The diver should take slow, deep breaths and avoid skip breathing or prolonged physical exertion underwater. The regulator should be maintained to a satisfactory performance level to minimize breathing resistance. Treatment of hypercapnia consists of ensuring a patent airway, physical rest, and comfortable deep breathing. Nonsteroidal anti-inflammatory drugs (NSIADs) and ergotamine preparations have been reported to be ineffective (17).
Sedating medications, such as opioids, butalbital, or phenothiazines, should be avoided when diving because they can impair alertness and judgment, especially at depths beyond 20 to 30 m where inert gas narcosis may compound the diver’s cognitive impairment. Opioids carry the additional risk of respiratory depression, which can worsen CO2 retention. β-Blockers for migraine prophylaxis in the diver should be prescribed cautiously because of their potential to unmask latent asthma and because they can reduce exercise capacity.
SLEEP APNEA HEADACHE
IHS ICHD-II code: 10.1.3 Sleep apnea headache
WHO code and diagnosis: G44.882 Sleep apnea headache
Short description: although morning headache is significantly more common in patients with sleep apnea than in the general population, headache present upon awakening is a nonspecific symptom that occurs in a variety of primary and secondary headache disorders, in sleep-related respiratory disorders other than sleep apnea (e.g., pickwickian syndrome, chronic obstructive pulmonary disorder), and in other primary sleep disorders such as periodic leg movements of sleep. A definitive diagnosis of 10.1.3 Sleep apnea headache requires overnight polysomnography.
It is unclear whether the mechanism of 10.1.3 Sleep apnea headache is related to hypoxia, hypercapnia, or disturbance in sleep.
CLINICAL FEATURES
The ICHD-II diagnostic criteria for sleep apnea headache are as follows:
A. Recurrent headache with at least one of the following characteristics and fulfilling criteria C and D:
1. Occurs >15 days per month
2. Bilateral, pressing quality and not accompanied by nausea, photophobia, or phonophobia
3. Each headache resolves within 30 minutes.
B. Sleep apnea (respiratory disturbance index ≥5) demonstrated by overnight polysomnography.
C. Headache is present upon awakening.
D. Headache ceases within 72 hours and does not recur after effective treatment of sleep apnea.
The prevalence of obstructive sleep apnea syndrome (OSA) in an adult population is estimated to be 2% in women and 4% in men, applying the minimum diagnostic criteria of the nocturnal apnea/hypopnea index (AHI) of more than five per hour and daytime sleepiness (74). Sleep-associated disturbances of breathing without daytime sleepiness were even more frequent, demonstrating the importance of applying standardized diagnostic criteria (74). Equally if not more frequent in Western societies is the prevalence of chronic daily headache with a prevalence of about 4 to 5% (60). Due to the high prevalence of both disorders, the association between headache and OSA has generated considerable controversy on the basis of conflicting data.
Several studies have addressed the relationship between OSA and headache. Paiva et al. found that about half of the patients with nocturnal or early morning headache suffered from a sleep disorder including OSA (53). When the sleep disorder was treated with success, the headache generally disappeared, supporting a causal role of the sleep disorder for headache. Previous studies have suggested that headaches, particularly morning headaches, are more common in patients with sleep apnea than in normal subjects (53,68). Furthermore, the prevalence of headache is
reported to be higher in patients with OSA than in a control group (68). Headaches claimed to be associated with OSA are brief, and the occurrence and severity correlated with OSA severity in one study (45). Others have reported that while morning headache is common in OSA, it occurred just as frequently in other sleep-related disorders, and the headache characteristics are quite nonspecific (2,50,55). Furthermore, in a study involving tertiary care headache patients who reported heavy snoring and episodes of interrupted nocturnal breathing, only 1.5% who were examined with polysomnography (PSG) had an apnea/hypopnea index of 5 or higher (38).
reported to be higher in patients with OSA than in a control group (68). Headaches claimed to be associated with OSA are brief, and the occurrence and severity correlated with OSA severity in one study (45). Others have reported that while morning headache is common in OSA, it occurred just as frequently in other sleep-related disorders, and the headache characteristics are quite nonspecific (2,50,55). Furthermore, in a study involving tertiary care headache patients who reported heavy snoring and episodes of interrupted nocturnal breathing, only 1.5% who were examined with polysomnography (PSG) had an apnea/hypopnea index of 5 or higher (38).
MANAGEMENT
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a chronic disease that requires consultation and ongoing follow-up with a sleep medicine specialist, patient education, and alleviation of upper airway obstruction. Because many patients with OSAHS are overweight or have comorbid cardiovascular risk factors or diseases, they must be informed of the interaction of OSA and overall health. Prospective data on the cardiovascular and perioperative benefits of OSAHS treatment are emerging, but the current, most widely accepted patient and physician treatment target is hypersomnolence (24,52).
In many patients, lifestyle modifications including weight loss, alcohol/sedative avoidance, smoking cessation, avoidance of sleep deprivation, and, if appropriate, sleep position restriction will decrease both the symptoms of OSA and the comorbid conditions.
Continuous positive airway pressure (CPAP) is the standard treatment for OSA. CPAP involves the use of a device that pneumatically splints the upper airway during inspiration and expiration. A placebo-controlled, randomized trial showed that CPAP decreases sleepiness and increases quality of life (24). During polysomnography, CPAP is titrated to a level that eliminates snoring and apneas/hypopneas and is then most often prescribed at a “fixed” pressure level that will maintain airway patency during conditions of greatest vulnerability (rapid eye movement [REM] sleep while supine). For most patients, the prescribed pressure is in the 7- to 11-cm H2O range.
Compliance with CPAP continues to be a major issue limiting its use. Usage patterns and problems with CPAP vary among patients, and patient characteristics that consistently predict CPAP compliance have not been identified. Only a few comprehensive, long-term compliance studies have been published, and they indicate that continuing CPAP use generally correlates with AHI severity, average nightly use of fewer than 2 hours at 3 months predicts failure, and ongoing use at 5 years is 65 to 90% (39,47).
Alternative treatment options, including oral appliances, have been developed for mechanically enlarging or stabilizing the upper airway by advancing the mandible or tongue. Subjective improvements in snoring are reported in most case series with oral appliances. Approximately 50% of patients achieve an AHI lower than 10 with the use of oral appliances, and long-term compliance rates are 50 to 100% (61). Randomized crossover comparisons reveal that CPAP devices are more effective at lowering the AHI than oral appliances, which are most appropriate for patients with mild to moderate OSA (73).
Uvulopalatopharyngoplasty, an operation that modifies the retropalatal airway by excision of the uvula, a portion of the soft palate, and tonsils (if present), produces mixed results. Although snoring is usually subjectively improved, objective improvements have not been well documented. Furthermore, less than 50% of patients achieve an apnea index lower than 10 and at least a 50% reduction in apneas (64). Laser-assisted uvulopalatoplasty is not currently recommended for the treatment of OSAHS (44). Radiofrequency ablation techniques can be applied focally to reduce the size of the palate and base of tongue, but efficacy data are limited. Other surgical options include tracheostomy (used rarely) and oral maxillofacial procedures.
DIALYSIS HEADACHE
IHS ICHD-II code and diagnosis: 10.2 Dialysis headache
WHO code and diagnosis: G44.882
Short description: Headache that commonly occurs in association with hypotension and dialysis disequilibrium syndrome. The disequilibrium syndrome may begin as headache and then progress to obtundation and finally coma, with or without seizures. This syndrome is relatively rare and may be prevented by changing dialysis parameters.
As caffeine is rapidly removed by dialysis, 8.4.1 Caffeine-withdrawal headache should be considered in patients who consume large quantities of caffeine.
CLINICAL FEATURES
The ICHD-II diagnostic criteria for dialysis headache are as follows:
A. At least three attacks of acute headache fulfilling criteria C and D.
B. Patient is on hemodialysis.
C. Headache develops during at least half of hemodialysis sessions.
D. Headache resolves within 72 hours after each hemodialysis session and/or ceases altogether after successful transplantation.
Approximately 70% of patients receiving dialysis complain of headaches (3,7). Until recently, headaches in this
population of patients were not systematically evaluated. A recent prospective study of 123 patients with chronic renal failure from three Brazilian hemodialysis services reported headache in 87 of 123 patients (70.7%) (3). Before dialysis, 48% had migraine, 19% had episodic tension-type headache, and 8% had both. Headache related to arterial hypertension was the second most frequent headache diagnosis in these patients (25.4%). Fifty patients (57.5%) experienced headache during the session of hemodialysis. Thirty-four were classified as dialysis headache, seven were classified as migraine, seven as episodic tension-type headache, and two were unclassified. Twenty-four patients (27.6%) reported dramatic improvement of their headaches after the beginning of the dialysis program.
population of patients were not systematically evaluated. A recent prospective study of 123 patients with chronic renal failure from three Brazilian hemodialysis services reported headache in 87 of 123 patients (70.7%) (3). Before dialysis, 48% had migraine, 19% had episodic tension-type headache, and 8% had both. Headache related to arterial hypertension was the second most frequent headache diagnosis in these patients (25.4%). Fifty patients (57.5%) experienced headache during the session of hemodialysis. Thirty-four were classified as dialysis headache, seven were classified as migraine, seven as episodic tension-type headache, and two were unclassified. Twenty-four patients (27.6%) reported dramatic improvement of their headaches after the beginning of the dialysis program.
Similar to other studies, there was a male preponderance in this study, and when headache occurred during hemodialysis, a higher incidence was observed between the third and fourth hour. Similarly, another recent study showed that the prevalence of headaches during hemodialysis was directly proportional to the number of hours in session (15). The headaches that occurred during hemodialysis sessions resembled migraine without aura in 19 patients, tension-type headache in 13, migrainous disorder in 1, and tension-type headache disorder not fulfilling all criteria in 1 patient. They also observed a relative increase in the prevalence of tension-type headache after the beginning of the dialysis program.
While it is clear that hemodialysis can be a trigger for antecedent headache disorders (migraine, tension-type headache), it is equally clear that headaches can occur de novo during hemodialysis. However, the clinical features and their pathogenesis remain to be elucidated. A number of mechanisms may be involved including hypoxemia that occurs at the beginning of the sessions, hyponatremia, changes in serotonin levels, alterations in levels of urea, aldosterone, and dialysis disequilibrium syndrome. Because these metabolic derangements do not resolve immediately, the resolution of dialysis headaches has been lengthened in ICHD-II from 24 hours to 72 hours after a hemodialysis session.
