Advertisement

Syncope and Headache

  • Ramesh K. Khurana
Secondary Headache (M Robbins, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Secondary Headache

Abstract

Purpose of Review

We review the literature on co-occurrence of syncope and headache and share clinical experience.

Recent Findings

Headache in relation to syncope has been the subject of recent interest.

Summary

Orthostatic intolerance has an expanding spectrum with three well-defined entities: orthostatic hypotension (OH), neurally mediated hypotension (NMH), and postural tachycardia syndrome (PoTS). Syncope occurs in patients with OH as well as in patients with episodically occurring NMH. Headache of OH is called coat-hanger ache (CHA) because it affects the neck and shoulders in a coat-hanger pattern. It can serve as a warning symptom of OH as well as a parameter to gauge the benefit of treatment. Awareness of CHA avoids inappropriate tests. Headache type occurring in NMH has not been fully delineated. A questionnaire-based study describes migraine leading to syncope and treatment of migraine to reduce syncope. Laboratory studies in NMH patients provide evidence for only short-duration headache. The author’s approach to such patients is presented.

Keywords

Baroreflex Orthostatic hypotension Reflex syncope Neurally mediated hypotension Coat-hanger ache 

Introduction

This is a focused review with the following objectives:
  • To provide an abbreviated view of orthostatic tolerance

  • To give a brief conceptual overview of syncope-related syndromes of orthostatic intolerance

  • To discuss data on the co-occurrence of syncope and headache

  • To describe clinical and laboratory evaluation

  • To suggest an approach to management of patients with syncope and headache

Orthostatic Tolerance

Standing from supine position is an innate human act. To maintain upright posture and to supply blood to the brain about 25 to 30 cm above heart level requires rapid cardiovascular adjustments—a complexly integrated function involving the cardiovascular, neural, renal, and endocrine systems. Upright posture results in gravity-mediated translocation of 500 to 1000 ml of blood in the lower limbs and splanchnic circulation with consequent reduction in cardiac preload and blood pressure. The baroreflex, a physiological reflex, is the most critical component of this cascade. The afferent pathway of this reflex originates from the mechanosensitive terminals located in the adventitia of the carotid sinuses via the glossopharyngeal nerves and from the aortic arch via the vagus nerves. The pathway terminates in the nucleus of the solitary tract (NTS). From the NTS, the sympathetic pathway projects to the peripheral vessels and the heart via the rostroventrolateral nucleus of the medulla, the intermediolateral column cells of the thoracic cord, and the sympathetic ganglia. The cardiovagal output travels from the NTS to the nucleus ambiguus, vagus nerve, and sinoatrial node. The baroreceptor reflex provides a continuous modulation of blood pressure and heart rate to facilitate orthostatic tolerance. For example, a decline in blood pressure reduces baroreceptor activity, which results in increased sympathetic outflow and decreased cardiovagal outflow. Sympathoexcitation promotes vasoconstriction via alpha-1 adrenoceptors on vascular smooth muscle cells and cardiac acceleration via post-synaptic beta-1 adrenoceptors. Cardiovagal inhibition allows an increase in heart rate. Conversely, an increase in blood pressure is mitigated by sympathoinhibition and cardivagal excitation [1].

Orthostatic Intolerance

Orthostatic intolerance is defined as the inability to tolerate upright posture because of symptoms of dizziness, lightheadedness, or unsteadiness, which are relieved when recumbent. Simply put, orthostatic intolerance signals that orthostatic stress has overwhelmed the circulatory adjustment capability of the individual [1].

Orthostatic intolerance is a heterogeneous disorder comprising at least three well-defined entities: orthostatic hypotension (OH), reflex syncope or neurally mediated hypotension (NMH), and postural tachycardia syndrome (PoTS) [2].

Orthostatic Hypotension

By consensus, OH is defined as a sustained reduction of systolic blood pressure of at least 20 mmHg and diastolic blood pressure of 10 mmHg within 3 min of standing or head-up tilt to at least 60° on a tilt table. In patients with supine hypertension, a sustained reduction in systolic blood pressure of 30 mmHg is considered a more appropriate criterion [2].

This consensus definition has served its purpose, but it has limitations. It limits the duration of testing to 3 min, but a study of 230 patients with OH on standing or on the tilt table found that 46% developed OH in less than 3 min, 15% between 3 and 10 min, and 39% in more than 10 min [3]. The consensus definition does not take into account the rapidity of blood pressure decline, the rate of blood pressure recovery, or the chronicity of OH. Furthermore, it does not address the change in heart rate [4] or the autoregulatory ability of the patient’s cerebral vasculature—important factors in orthostatic tolerance/intolerance [5].

OH is common in elderly subjects. Prevalence ranges from 5 to 30% and increases with age [6]. In a multicenter study of 5201 community-dwelling elderly subjects age 65 years or older, the incidence of OH was 16.2% for asymptomatic patients and 18.2% when OH symptoms were included [7]. Patients may have OH with symptoms, OH without symptoms, or symptoms without OH. The latter two groups may become symptomatic or display OH when exposed to stress such as carbohydrate-rich meals, exercise, or hot surroundings. The most commonly reported symptoms of OH are lightheadedness (88%), weakness (72%), impaired cognition (47%), blurred vision (47%), and vertigo (37%). Only 14% report occurrence of syncope more than once a month, and 28% report syncope less than once a month [8]. As many as a third of patients with profound OH (BP ↓ > 60 mmHg) may be asymptomatic or manifest atypical symptoms such as backache or headache [9]. To quantitatively assess the severity of symptoms, Kaufmann and colleagues designed a ten-item questionnaire [10]. The questionnaire includes six items pertaining to symptoms: dizziness/lightheadedness, vision disturbance, weakness, fatigue, trouble concentrating, and head/neck discomfort. Four items evaluate activities of daily living: standing short time, standing long time, walking short time, and walking long time.

The main causes of OH are volume depletion, drugs, cardiac pump failure, and autonomic failure [11]. Use of diuretics, subclinical blood loss, diarrhea, and vomiting may precipitate OH. Drugs are perhaps the most common cause of OH [12]. Drugs that reduce systemic vascular resistance (alpha-antagonists), vasodilators (nitrates), and norepinephrine depleters (MAO inhibitors) can produce OH. In the author’s experience, tricyclics antidepressants, trazodone, tizanidine, and tamsulosin are frequent offenders. Cardiac disorders such as aortic stenosis, cardiomyopathies, and bradyarrhythmias afflict elderly subjects. Sympathetic efferent activity is deficient in primary or secondary autonomic failure. Primary autonomic failure occurs in central autonomic degenerative disorders with abnormal accumulation of alpha-synuclein. These synucleopathies are multiple system atrophy, Lewy body dementia, Parkinson’s disease, and pure autonomic failure. Spinal cord injury, diabetes mellitus, and amyloidosis are the common causes of secondary autonomic failure [5].

Reflex Syncope

By consensus, reflex syncope or NMH is defined as transient loss of consciousness and postural tone resulting from global cerebral hypoperfusion with spontaneous and complete recovery and no neurological sequelae [2]. The pathophysiological term global cerebral hypoperfusion, incorporated in the definition, differentiates NMH from other causes of transient loss of consciousness.

Reflex syncope is common. The vasovagal type of NMH is predominant in young adults. A chart review of 7814 participants in the Framingham Heart Study, followed for an average of 17 years, found the incidence of a first syncope of 6.2 per 1000 person-years [13]. Vasovagal syncope was the most frequently identified cause (21.2%). This study seems to have included individuals with other causes of transient loss of consciousness. A cross-sectional study of 394 medical students in Amsterdam revealed that 39% had fainted at least once by the median age of 21 years. Women had fainted almost twice as often as men (47 vs. 24%) [14].

Patients present with a stereotyped sequence of symptoms and signs ending in loss of consciousness. Prodromal symptoms of autonomic activation appearing 30–60 s before the actual faint are sweating, pallor of face, nausea, palpitations, salivation, yawning, pupillary dilation, hyperventilation, abdominal cramps, and even urge to defecate. It is followed by symptoms of cerebral and retinal hypoperfusion, such as lightheadedness, difficulty thinking, blurred vision, loss of color vision, graying out of vision, blackout of vision, or tunnel vision. Duration of loss of consciousness is usually 10 to 20 s [15]. Although loss of postural tone is a component of NMH, myoclonic activity may be common. Lempert and colleagues performed a videometric analysis of 42 episodes of self-induced (fainting lark) syncope. They found myoclonic activity in 90%. Head turns, oral automatisms, and righting movements occurred in 79% [16]. Tongue bite and fecal incontinence were rare. The subjects may display retrograde amnesia of 3 to 4 s and post-ictal disorientation of 20 to 30 s [15]. Cognition and diaphoresis improve quickly, but fatigue and nausea may be slow to recover.

Reflex syncope includes three types of syncope: vasovagal, situational, and carotid sinus supersensitivities [11]. Pathophysiologically, reflex syncope is quite different from OH because reflex syncope requires intact afferent, central, and efferent autonomic pathways. Reflex syncope is caused by acute reversible baroreceptor dysfunction with a sudden withdrawal of sympathetic activity. The trigger for vasovagal syncope may be central (emotions, pain, or blood phobia) or peripheral (prolonged orthostasis). Until recently, vasovagal syncope was thought to be caused by relatively empty hypercontractile left ventricle triggering Bezold Jarisch reflex by stimulating C-fiber vagal afferents. However, its occurrence in transplanted hearts with denervated ventricles which are neither empty nor contracting vigorously casts serious doubt on this hypothesis [17]. The pathophysiology of vasovagal syncope remains elusive, but it is likely to be of central origin [18]. Situational syncope is a form of reflex syncope that has well-defined situational triggers ranging from usual, such as micturition, defecation, and cough, to unusual, such as eye examination [19]. Carotid sinus syncope results from a supersensitive carotid sinus that causes severe hypotension (systolic blood pressure decrease of > 50 mmHg) and/or asystole (> 3 s) [11].

Postural Tachycardia Syndrome

Postural tachycardia syndrome (PoTS) is defined as a sustained heart rate increase of 30 bpm or more within 10 min of standing or head-up tilt in the absence of OH. The criteria of PoTS for individuals with low or high supine heart rates are not well defined. For younger individuals age 12 to 19 years, the required heart rate increase is at least 40 bpm [2]. An overlap of symptoms and co-occurrence of orthostatic-triggered NMH may pose a challenge. However, PoTS is a heterogeneous disorder with sustained heart rate increase and abnormal autonomic function tests [20]. Patients with this disorder may present with orthostatic headache [21]. PoTS patients do not have hypotension and will not be discussed further here.

Syncope and Headache

Syncope, defined broadly as loss of consciousness secondary to cerebral hypoperfusion, has multiple etiologies including OH and NMH. Headache may co-exist with syncope in these disorders. Postural headache of OH, or coat-hanger ache (CHA), and headache in association with NMH have been relatively well studied. Co-occurrence of headache and syncope of other causes has received scant attention. In this paper, we will review the literature on headache of OH and reflex syncope and briefly discuss other conditions where headache and syncope manifest in the same patient.

Orthostatic Hypotension and Headache (Coat-Hanger Ache)

Headache in association with OH had been observed previously [22, 23], but Robertson and colleagues provided the first detailed account of this important symptom that often goes unrecognized, entailing costly workup and delay in appropriate diagnosis. The authors prospectively evaluated 25 patients with severe OH and low norepinephrine levels. The majority (92%) of patients reported almost daily occurrence of throbbing or dull headache of variable severity, provoked by upright posture and relieved by lying flat. The headache affected the entire cranium (92%), occipital region (64%), nape (56%), and shoulders (28%) in a coat-hanger configuration [24]. In a subsequent study, Bleasdale-Barr and Mathias evaluated 27 patients with pure autonomic failure (PAF) and 35 patients with multiple system atrophy (MSA). Orthostatic neck pain was reported by 93% of patients with PAF and 51% with MSA. A higher incidence in PAF patients was attributed to a greater fall in blood pressure [25]. We studied 22 patients with severe adrenergic failure and OH (SBP↓ at 1 min, 54.8 ± 24.9 mmHg). CHA was reported by 59% of patients during activities of daily living but by only 18% during 90° head-up tilt for up to 10 min. During daily activities, CHA developed within 3–5 min of standing or after 10 min to 2 h of sitting. When recumbent, patients felt relief within 5 to 20 min. It was described as a dull ache of mild to severe intensity varying in frequency from 2 per month to several per day. It usually affected the posterolateral neck and suprascapular regions, but sometimes only neck, shoulders, or interscapular regions were affected [26]. Kaufmann et al. observed only a mild improvement in CHA in a multicenter study of droxidopa for the treatment of neurogenic OH [27].

CHA has been attributed to ischemia in tonically active neck muscles [25]. Humm and colleagues assessed muscle membrane potential in the trapezius muscle of patients with OH by measuring velocity recovery cycles of muscle action potentials [28]. During head-up tilt, early supernormality decreased and relative refractory period increased favoring membrane depolarization as a result of muscle ischemia. We have observed this complaint without cognitive dysfunction, visual symptoms, lightheadedness, or leg weakness, militating against symptomatic muscle ischemia as the sole manifestation without involvement of more vulnerable structures located cephalad to the heart. One can, therefore, postulate several factors contributing to this symptom in various combinations including nociceptive input from the infratentorial arteries and dura mater of the posterior fossa, epidural hypotension, altered headache threshold due to vagal dysfunction, and altered cerebral pain perception [26].

CHA has unique characteristics, a temporal and postural association with OH, and amelioration with recumbency. CHA is useful as a prodromal symptom of syncope as well as a parameter to tailor management. The Headache Classification Committee of the International Headache Society should consider including CHA as a secondary form of headache attributed to other disorders of homeostasis [29].

Reflex Syncope (NMH) and Headaches

Both syncope and migraine are highly prevalent in the general population with frequent co-occurrence. Co-occurrence of these two disorders has been reported in individuals, families, and epidemiological studies. Smith and Glass reported a case of 14-year-old girl with family history of migraine who suffered from episodes of brief reflex syncope followed by severe occipital headache, photophobia, watery eyes, and slight lethargy that lasted several hours. She had episodes of interictal dull occipital headache without syncope. Pharmacotherapy was not effective, but temperature biofeedback relieved her symptoms [30]. Familial co-occurrence of migraine and syncope has been described in two cases. In the first case, a 47-year-old woman developed “migraines” at age 9 years and syncope at age 27 years. She gave history that her seven children suffered from migraine and syncope [31]. In the second case, 21 family members from three generations of a single family were studied. Eleven of the 14 family members with migraine had syncope, and 11 of the 12 family members with syncope had migraine [32]. Epidemiological study of 396 patients by Selby and Lance revealed loss of consciousness with vascular headache in 42 patients (10.6%). Syncope was not objectively documented [33]. In a population-based study of migraineurs, Thijs and colleagues reported a higher prevalence of syncope than in control subjects (46 versus 31%). There was no correlation between the total number of migraine attacks and syncopal spells [34].

Curfman and colleagues performed a retrospective questionnaire-based study of 248 subjects with recurrent syncope and compared this group with 199 migraineurs [35]. They noted occurrence of headache concurrent with syncope in 127 (52%) patients, and nearly one third of this group had “syncopal migraine.” According to the authors, the following features denoted “syncopal migraine:” orthostatic change as a trigger for migraine, longer duration of syncope (> 1 min), and longer recovery time. Occipital headache preceded syncope in 57%, and antimigraine drugs relieved those episodes in half of these cases.

A few investigators have studied the co-occurrence of two disorders in the laboratory. In a sample of 50 consecutive patients with documented syncope during the head-up tilt test (HUT), Vallejo and colleagues obtained history of migraine in 52% [36]. Ocon and colleagues studied cerebral blood flow in 16 adolescent subjects during HUT-induced syncope. All subjects fainted and developed immediate post-ictal headache upon return to supine position followed by recovery in 2 to 5 min. The data incriminated diminished cerebral autoregulation immediately preceding the faint, a sudden decrease in cerebral blood flow during fainting, and a rapid hyperemic increase in blood flow upon recumbency. The authors attributed post-syncopal headache to a highly pulsatile blood flow stimulating nitric oxide release, which in turn caused release of calcitonin gene-related peptide and stimulation of vascular nociceptors [37]. We investigated the occurrence of headache in 31 patients who manifested presyncope or syncope with concurrent hypotension during HUT [38]. The incidence of preexisting interictal headache (61%) was higher than in the general population. Only 13 of 31 patients (42%) developed headaches; 2 had headache before the start of HUT, 8 developed orthostatic headache 3 to 7 min during HUT, and 3 complained of headache immediately after HUT. No aura was reported. Headache was bifrontal or generalized in location, throbbing or pressure type in character, and mild to severe in intensity. Only 2 individuals experienced photophobia. Seven patients felt nauseated, a likely component of syncope. Two patients who had headache before HUT reported increase in intensity during HUT followed by return to baseline immediately after HUT. Headache resolved in 1 to 15 min after HUT in 10 patients. Two patients had headache for up to 2 h after HUT. None of the 13 patients developed headache that fulfilled established criteria for migraine. In brief, these studies support a higher incidence of migraine in patients with NMH and the occurrence of short-duration headache during and after syncope but fail to support the occurrence of migraine. These studies did not rule out the possibility of migraine-induced syncope. In clinical practice, however, loss of consciousness is rare in migraine [39].

Reflex syncope has been reported in patients with cluster headache. These headaches not only are characterized by cranial and systemic autonomic changes, but they may also be associated with bradycardia, asystole, and syncope [40]. Furthermore, verapamil, a recommended prophylactic treatment, can cause adverse cardiac events including syncope when given in high doses [41]. Neuralgic pain of glossopharyngeal or trigeminal origin, although distinct from headache, may also precipitate syncope [42, 43].

Clinical and Laboratory Evaluation

Evaluation of syncope patients requires a comprehensive history to delineate syncope from seizures, reflex syncope from OH of chronic autonomic failure, acute causes needing emergent care, and rarer causes requiring appropriate tests. History of syncope should be obtained from the patient as well as the witness, if available. History should include precipitating factors such as prolonged standing, hot shower, pain, or medical procedure; prodromal symptoms such as sweating, palpitations, waves of nausea, and yawning; ictal symptoms such as tongue bite and incontinence; and post-ictal symptoms such as disorientation and amnesia for the event. Urinary incontinence, injury other than tongue bite, and motor activity during loss of consciousness may not distinguish between syncope and seizure. Post-ictal confusion exceeding a few seconds is considered more specific for a seizure [44]. A stereotypical recurrence of prodromal symptoms favors the possibility of NMH [11, 15]. Autonomic dysfunction spanning several domains including orthostatic tolerance, sweating, sexual function, bowel habits, and bladder control, if present, indicates OH with autonomic failure [45]. Details of recurrent preexisting headaches, headache preceding or following a syncopal episode, and duration of syncope-provoked headache are important components of history. History of aura with brainstem symptoms, including syncope, may guide toward the diagnosis of basilar-type migraine [46]. Location of headache, precipitation upon prolonged sitting or standing, and improvement when lying flat indicate headache of OH [25].

History of red flags that may suggest a serious underlying cause should include systemic symptoms, focal neurologic symptoms, age > 50 years, sudden onset, positional component, progressive worsening, and precipitation by the Valsalva maneuver [47]. Acute onset of headache and syncope should alert the clinician to the possibility of subarachnoid hemorrhage, carbon monoxide poisoning, cocaine abuse, reversible cerebral vasoconstriction syndrome, and side effects of drugs such as nitroglycerin [48, 49, 50, 51, 52]. Arnold-Chiari malformation or colloid cyst of the third ventricle may cause headache and syncope [53, 54]. History of flushing, diarrhea, and abdominal cramps along with headache and syncope should raise suspicion of mast cell disease [55]. Occurrence of headache, syncope, diaphoresis, and palpitations during micturition points toward paraganglioma of the urinary bladder [56]. Additional useful information can be generated by asking the patient about symptoms experienced during a previous HUT or if an episode was recorded by someone on a cell phone. Asking the duration of orthostatic tolerance before the onset of symptoms may provide an estimate of the required duration for HUT in the laboratory.

General physical examination by a keen observer can provide significant relevant information about autonomic functions. Observations that indicate autonomic dysfunction are vasomotor changes affecting skin when supine and standing, abnormal patterns of sweating assessed with a spoon test, bowel distension, diminished rectal tone, distended urinary bladder, and absence of respiratory sinus arrhythmia. Examination of pupils may suggest Adie syndrome or Horner syndrome [45, 57, 58]. The most important part of the examination is blood pressure and heart rate measurements 5 min after supine rest and during 10 min of standing, with arm supported at the heart level. Patients with reflex syncope have normal hemodynamic response except during presyncope/syncope. Patients with OH show a decline in blood pressure. An increase in heart rate with OH may indicate dehydration and volume depletion. Patients with autonomic failure have subnormal or no increase in heart rate despite a significant drop in blood pressure. Neurologic examination may guide toward the diagnosis of synucleinopathies such as multiple system atrophy and Parkinson’s disease [5, 27, 45]. Papilloedema and focal neurological signs indicate the need for further neurodiagnostic evaluation.

Electrocardiogram and head-up tilt test are extremely useful in the laboratory assessment of syncope. An abnormal electrocardiogram displaying long QT interval or complete atrioventricular block indicates a cardiac cause of syncope. The head-up tilt with continuous monitoring of blood pressure and heart rate can distinguish two types of syncope. The angle and duration of tilt vary from one laboratory to another. Duration of tilt is a more important variable for the study of various types of orthostatic intolerance [59]. Short duration may be sufficient, but longer duration helps differentiate different forms of orthostatic intolerance. In OH, a continuous decline of BP is noted in HUT. In reflex syncope, BP remains steady for several minutes, followed by a sudden drop in BP and syncope. A tilt duration of 30 min identifies most cases of early and delayed OH [60]. We perform 45-min upright tilt test to identify patients with delayed OH and NMH. If autonomic failure is suspected, the Valsalva maneuver, heart rate response to deep breathing, and thermoregulatory sweat test are performed. Other physiologic and pharmacologic tests can be used to localize the responsible lesion along the autonomic pathways. Supine and upright norepinephrine blood levels separate central from peripheral autonomic failure. Abnormally low supine norepinephrine levels without a rise upon standing indicate a postganglionic or peripheral type of autonomic failure. Normal supine norepinephrine levels without any increase upon standing are seen in central or preganglionic autonomic failure [5, 45].

Management

There are comprehensive reviews on the management of OH and NMH [11, 61, 62, 63]. OH without symptoms is usually not an indication for therapy. Treatment of OH is indicated when symptoms affect activities of daily living or culminate in falls or syncope [61, 63]. Infrequent occurrence of NMH requires explanation and reassurance. Frequent occurrence can disrupt life and seemingly become self-perpetuating. These patients benefit from active management [11, 62]. Non-pharmacologic measures may benefit patients with OH and NMH. These measures include avoidance of precipitating factors such as hot shower, large meals, alcohol, and offending drugs; exercise to prevent deconditioning and to improve strength of calf muscles; adequate hydration and increased salt intake; head elevation by 6 to 9 in. at night to reduce nocturnal diuresis and use of abdominal binder to compress splanchnic venous bed [64]; and physical counterpressure maneuvers such as lower body tensing with leg crossing.

Patients should be educated about prodromal symptoms during HUT so that they can try to abort the episode and/or prepare for a safer fall. An acute ingestion of 500 ml water over 2 to 3 min during a prodrome will raise systolic blood pressure via the osmosensitive transient receptor potential vanilloid 4 channel and sympathoexcitation [65]. In this situation, water works as a short-acting drug. If patients are unable to abort the episode with water consumption and physical counterpressure maneuvers, they should lie flat, preferably with legs elevated to facilitate cerebral perfusion. Failure of non-pharmacologic measures necessitates the use of medications to improve blood pressure, with the goal to improve quality of life and not normalize to arbitrary blood pressure values [61, 63]. These medications are fludrocortisone, a mineralocorticoid; midodrine, an alpha-1 adrenoceptor agonist; droxidopa, a synthetic precursor of norepinephrine; and pyridostigmine, an enhancer of sympathetic ganglionic transmission.

When patients present with co-occurrence of syncope and headache, it is important to define syncope type and headache type. If both conditions occur independently, they should be treated as individual entities. Based on history and laboratory evaluation, co-occurrence of syncope and headache with a temporal relationship may dictate different management. CHA and OH have a temporal and postural relationship. CHA can be used as a warning symptom to avoid falls/syncope. It may also be used as a parameter of successful treatment of OH. In the author’s practice, for example, a patient suffering from pure autonomic failure, OH, and CHA was prescribed fludrocortisone. He was able to sit or stand for a longer period before the onset of CHA. Also of interest was a72-year-old woman who had long-standing history of migraine without aura responsive to ergotamine therapy. On her recent visit, she provided history of moderate CHA after 5 to 6 min of walking and severe CHA after dancing. Her examination revealed OH. Further questioning revealed that this symptom (CHA) developed after her primary care physician initiated “preventive” treatment with a beta-blocker, atenolol. Discontinuation of atenolol eliminated this symptom, which suggests that CHA occurred in a patient without neurogenic OH. Awareness of this symptom and discontinuation of a drug prevented unnecessary workup.

Compared with the general population, patients with NMH have a higher frequency of migraine [36, 38] requiring acute and/or prophylactic treatment as per the standard indications. Curfman and colleagues [35] reported that migraine may lead to syncope. They recommended migraine treatment to manage syncope. The menagerie of migraine is well known to physicians who evaluate such patients. The author has not seen cases of migraine transitioning into syncope. A migraine episode with severe vomiting may produce dehydration and cardiac arrhythmia. Trial with standard antimigraine drugs may be useful in patients with “syncopal migraine,” pending further studies to elucidate this temporal relationship. The clinician should be aware that treatment of one disorder may produce an iatrogenic association with another disorder. Management of migraine with a beta-blocker or a calcium channel blocker may result in co-occurrence of migraine and syncope. In the author’s experience, treatment of OH with fludrocortisone or midodrine, especially during the initiation phase, may exacerbate migraine.

Conclusions

In conclusion, recent studies show headache to be an important symptom of syncope. Headache induced by OH has unique characteristics that allow its use as a prodromal symptom of OH as well as a parameter to tailor management. It deserves inclusion in the International Classification of Headache Disorders as a secondary form of headache. Headache co-exists frequently with NMH, but its causal relationship is controversial. Future studies should help delineate this entity. The author’s approach to management is reviewed.

Notes

Compliance with Ethical Standards

Conflict of Interest

Ramesh K. Khurana declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

  1. 1.
    Benarroch EE. The arterial baroreflex: functional organization and involvement in neurologic disease. Neurology. 2008;71:1733–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21:69–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Gibbons CH, Freeman R. Delayed orthostatic hypotension: a frequent cause of orthostatic intolerance. Neurology. 2006;67:28–32.CrossRefPubMedGoogle Scholar
  4. 4.
    Convertino VA. Neurohumoral mechanisms associated with orthostasis: reaffirmation of the significant contribution of the heart rate response. Front Physiol. 2014;5:236.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Schroeder C, Jordan J, Kaufmann H. Management of neurogenic orthostatic hypotension in patients with autonomic failure. Drugs. 2013;73:1267–79.CrossRefPubMedGoogle Scholar
  6. 6.
    Low PA. Prevalence of orthostatic hypotension. Clin Auton Res. 2008;18(Suppl 1):8–13.CrossRefPubMedGoogle Scholar
  7. 7.
    Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS. Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension. 1992;19:508–19.CrossRefPubMedGoogle Scholar
  8. 8.
    Low PA, Opfer-Gehrking TL, McPhee BR, et al. Prospective evaluation of clinical characteristics of orthostatic hypotension. Mayo Clin Proc. 1995;70:617–22.CrossRefPubMedGoogle Scholar
  9. 9.
    Arbogast SD, Alshekhlee A, Hussain Z, McNeeley K, Chelimsky TC. Hypotension unawareness in profound orthostatic hypotension. Am J Med. 2009;122:574–80.CrossRefPubMedGoogle Scholar
  10. 10.
    Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R. The orthostatic hypotension questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012;22:79–90.CrossRefPubMedGoogle Scholar
  11. 11.
    Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30:2631–71.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Gugger JJ. Antipsychotic pharmacotherapy and orthostatic hypotension: identification and management. CNS Drugs. 2011;25:659–71.CrossRefPubMedGoogle Scholar
  13. 13.
    Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347:878–85.CrossRefPubMedGoogle Scholar
  14. 14.
    Ganzeboom KS, Colman N, Reitsma JB, Shen WK, Wieling W. Prevalence and triggers of syncope in medical students. Am J Cardiol. 2003;91:1006–8. A8CrossRefPubMedGoogle Scholar
  15. 15.
    Wieling W, Thijs RD, van DN WAA, Benditt DG, van Dijk JG. Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain. 2009;132:2630–42.CrossRefPubMedGoogle Scholar
  16. 16.
    Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol. 1994;36:233–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Stewart JM. Common syndromes of orthostatic intolerance. Pediatrics. 2013;131:968–80.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Khurana RK. Initial orthostatic and non-orthostatic hypotension in wrestler’s syncope. Clin Auton Res. 2017;27:423–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Khurana RK. Eye examination-induced syncope role of trigeminal afferents. Clin Auton Res. 2002;12:399–403.CrossRefPubMedGoogle Scholar
  20. 20.
    Khurana RK. Orthostatic intolerance and orthostatic tachycardia: a heterogeneous disorder. Clin Auton Res. 1995;5:12–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Khurana RK, Eisenberg L. Orthostatic and non-orthostatic headache in postural tachycardia syndrome. Cephalalgia. 2011;31:409–15.CrossRefPubMedGoogle Scholar
  22. 22.
    Chew EM, Allen EV, Barker NW. Orthostatic hypotension: report of six cases and review of the literature. Northwest Med. 1936;35:297–303.Google Scholar
  23. 23.
    Robertson D, Robertson M. Orthostatic hypotension: diagnosis. Mod Concepts Cardiovasc Dis. 1985;54:7–12.Google Scholar
  24. 24.
    Robertson D, Kincaid DW, Haile V, Robertson RM. The head and neck discomfort of autonomic failure: an unrecognized aetiology of headache. Clin Auton Res. 1994;4:99–103.CrossRefPubMedGoogle Scholar
  25. 25.
    Bleasdale-Barr KM, Mathias CJ. Neck and other muscle pains in autonomic failure: their association with orthostatic hypotension. J R Soc Med. 1998;91:355–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Khurana RK. Coat-hanger ache in orthostatic hypotension. Cephalalgia. 2012;32:731–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83:328–35.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Humm AM, Bostock H, Troller R, Z'Graggen WJ. Muscle ischaemia in patients with orthostatic hypotension assessed by velocity recovery cycles. J Neurol Neurosurg Psychiatry. 2011;82:1394–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Headache Classification Committee of the International Headache Society. The international classification of headache disorders; 3rd ed. (beta version). Cephalgia. 2013;33:629–808.CrossRefGoogle Scholar
  30. 30.
    Smith MS, Glass ST. An adolescent girl with headache and syncope. J Adolesc Health Care. 1989;10:54–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Paisley RD, Arora HS, Nazeri A, Massumi A, Razavi M. Migraine and vasodepressor syncope in a large family. Tex Heart Inst J. 2009;36:468–9.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Daas A, Mimouni-Bloch A, Rosenthal S, Shuper A. Familial vasovagal syncope associated with migraine. Pediatr Neurol. 2009;40:27–30.CrossRefPubMedGoogle Scholar
  33. 33.
    Selby G, LANCE JW. Observations on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry. 1960;23:23–32.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG. Syncope in migraine: the population-based CAMERA study. Neurology. 2006;66:1034–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Curfman D, Chilungu M, Daroff RB, Alshekhlee A, Chelimsky G, Chelimsky TC. Syncopal migraine. Clin Auton Res. 2012;22:17–23.CrossRefPubMedGoogle Scholar
  36. 36.
    Vallejo M, Martinez-Martinez LA, Grijalva-Quijada S, et al. Frequency of migraine in patients with vasovagal syncope. Int J Cardiol. 2014;171:e14–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Ocon AJ, Messer Z, Medow MS, Stewart JM. Increased pulsatile cerebral blood flow, cerebral vasodilation, and postsyncopal headache in adolescents. J Pediatr. 2011;159:656–62.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Khurana RK, Van Meerbeke S. Headache of neurally mediated syncope. Cephalalgia. 2016;36:1350–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Blau JN. Syncope, vomiting, and migraine. Lancet. 1988;2:626.CrossRefPubMedGoogle Scholar
  40. 40.
    Manne JR. Cluster syncope. Am J Med. 2016;129:e13–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Alexandre J, Humbert X, Sassier M, Milliez P, Coquerel A, Fedrizzi S. High-dose verapamil in episodic and chronic cluster headaches and cardiac adverse events: is it as safe as we think? Drug Saf Case Rep. 2015;2:13.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    den Hartog AW, Jansen E, Kal JE, Duyndam D, Visser J, van den Munckhof P, et al. Recurrent syncope due to glossopharyngeal neuralgia. HeartRhythm Case Rep. 2017;3:73–7.CrossRefGoogle Scholar
  43. 43.
    Kapoor WN, Jannetta PJ. Trigeminal neuralgia associated with seizure and syncope. Case report. J Neurosurg. 1984;61:594–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Hoefnagels WA, Padberg GW, Overweg J, van der Velde EA, Roos RA. Transient loss of consciousness: the value of the history for distinguishing seizure from syncope. J Neurol. 1991;238:39–43.CrossRefPubMedGoogle Scholar
  45. 45.
    Khurana RK. Dysautonomia. In: Schuster MM, Crowell MD, Koch KL, editors. Schuster atlas of gastrointestinal motility. Hamilton: BC Decker, Inc.; 2002. p. 335–51.Google Scholar
  46. 46.
    Kirchmann M, Thomsen LL, Olesen J. Basilar-type migraine: clinical, epidemiologic, and genetic features. Neurology. 2006;66:880–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Starling AJ. Diagnosis and management of headache in older adults. Mayo Clin Proc. 2018;93:252–62.CrossRefPubMedGoogle Scholar
  48. 48.
    Call GK, Fleming MC, Sealfon S, Levine H, Kistler JP, Fisher CM. Reversible cerebral segmental vasoconstriction. Stroke. 1988;19:1159–70.CrossRefPubMedGoogle Scholar
  49. 49.
    Keles A, Demircan A, Kurtoglu G. Carbon monoxide poisoning: how many patients do we miss? Eur J Emerg Med. 2008;15:154–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Lansen TA, Kasoff SS, Vingiano W. Headache characteristics in aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 1993;3:216–21.CrossRefPubMedGoogle Scholar
  51. 51.
    Lowenstein DH, Massa SM, Rowbotham MC, Collins SD, McKinney HE, Simon RP. Acute neurologic and psychiatric complications associated with cocaine abuse. Am J Med. 1987;83:841–6.CrossRefPubMedGoogle Scholar
  52. 52.
    Thadani U, Rodgers T. Side effects of using nitrates to treat angina. Expert Opin Drug Saf. 2006;5:667–74.CrossRefPubMedGoogle Scholar
  53. 53.
    Two A, Christian E, Mathew A, Giannotta S, Zada G. Giant, calcified colloid cyst of the lateral ventricle. J Clin Neurosci. 2016;24:6–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Williams B. Chronic herniation of the hindbrain. Ann R Coll Surg Engl. 1981;63:9–17.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Smith JH, Butterfield JH, Pardanani A, DeLuca GC, Cutrer FM. Neurologic symptoms and diagnosis in adults with mast cell disease. Clin Neurol Neurosurg. 2011;113:570–4.CrossRefPubMedGoogle Scholar
  56. 56.
    Zhai H, Ma X, Nie W, Li H, Peng C, Li X, et al. Paraganglioma of the urinary bladder: a series of 22 cases in a single center. Clin Genitourin Cancer. 2017;15:e765–71.CrossRefPubMedGoogle Scholar
  57. 57.
    Khurana RK, Russell C. The spoon test: a valid and reliable bedside test to assess sudomotor function. Clin Auton Res. 2017;27:91–5.CrossRefPubMedGoogle Scholar
  58. 58.
    Cheshire WP, Goldstein DS. The physical examination as a window into autonomic disorders. Clin Auton Res. 2018;28:23–33.CrossRefPubMedGoogle Scholar
  59. 59.
    Khurana RK, Nicholas EM. Head-up tilt table test: how far and how long? Clin Auton Res. 1996;6:335–41.CrossRefPubMedGoogle Scholar
  60. 60.
    Gurevich T, Machmid H, Klepikov D, Ezra A, Giladi N, Peretz C. Head-up tilt testing for detecting orthostatic hypotension: how long do we need to wait? Neuroepidemiology. 2014;43:239–43.CrossRefPubMedGoogle Scholar
  61. 61.
    Jones PK, Shaw BH, Raj SR. Orthostatic hypotension: managing a difficult problem. Expert Rev Cardiovasc Ther. 2015;13:1263–76.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Schleifer JW, Shen WK. Vasovagal syncope: an update on the latest pharmacological therapies. Expert Opin Pharmacother. 2015;16:501–13.CrossRefPubMedGoogle Scholar
  63. 63.
    Shibao C, Lipsitz LA, Biaggioni I. ASH position paper: evaluation and treatment of orthostatic hypotension. J Clin Hypertens (Greenwich). 2013;15:147–53.CrossRefGoogle Scholar
  64. 64.
    Smeenk HE, Koster MJ, Faaij RA, de Geer DB, Hamaker ME. Compression therapy in patients with orthostatic hypotension: a systematic review. Neth J Med. 2014;72:80–5.PubMedGoogle Scholar
  65. 65.
    May M, Jordan J. The osmopressor response to water drinking. Am J Phys Regul Integr Comp Phys. 2011;300:R40–6.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineMedStar Union Memorial HospitalBaltimoreUSA

Personalised recommendations