Trigeminal cephalgias and facial pain syndromes associated with autonomic dysfunction

Trigeminal autonomic cephalgias (TACs) include a spectrum of primary headache syndromes associated with cranial autonomic dysfunction. Other types of headache and facial pain syndromes can be associated with marked localized facial or ear autonomic changes. We report on a group of patients suffering from episodic migraine with cranial autonomic features, patients with different presentations of the 'red ear syndrome' (RES), cluster headache with prominent lower facial involvement and crossover cases. In our experience crossover between TACs and migraine, RES and cluster headache is not uncommon. We propose that all these conditions belong to the same group and a unifying causative mechanism is proposed.     

Dissociation between Pain and Autonomic Disturbances in Cluster Headache

The relationship between pain and autonomic disturbances in cluster headache was studied in 54 patients whose attack always recurred on the same side, and in 7 others whose attack had affected either side on different occasions. In one of these seven patients, facial flushing and ocular sympathetic deficit was observed on the original side of headaches. In most patients, the orbital region was warmer on the painful side but in three cases this region was cooler during and between attacks. Lacrimation and rhinorrhoea were more common in severe attacks, and the temperature difference between the orbits increased with increasing severity of pain. These findings support the view that certain autonomic disturbances in cluster headache are provoked by pain. Residual autonomic dysfunction could influence autonomic activity during cluster headache. If so, residual dysfunction on the pain-free side could explain the dissociation between autonomic disturbances and pain observed in a few cases.     

Recognition and treatment of cluster headache in the emergency department

Cluster headache has a dramatic presentation marked by rapidly escalating intensity of pain and prominent signs of autonomic dysfunction. Despite its distinctive features, diagnostic delay and misdiagnosis are common. Prompt recognition of this headache disorder provides an opportunity for effective treatment. This article provides a practical approach to the diagnosis and management of patients with cluster headache in the emergency room setting.     

Sympathetic skin response in migraineurs and patients with medication overuse headache

BACKGROUND: Autonomic dysfunction has been reported in patients with migraine, and it may play a role in promoting attacks. OBJECTIVE: To investigate changes in the autonomic function of migraineurs and patients with medication overuse headache via sympathetic skin response, and to determine whether psychiatric comorbidity is related to any changes recorded. METHODS: A consecutive series of patients with migraine (n = 45) and medication overuse headache (n = 53) were studied. Patients with other chronic diseases requiring medication were excluded. Sympathetic skin response latencies and amplitudes from the patients with headache (N = 98) and 40 healthy controls were compared statistically. RESULTS: Sympathetic skin response latencies in patients with medication overuse headache and in migraineurs were significantly longer than in controls. To analyze the effect of psychiatric comorbidity, patients with medication overuse headache and migraineurs were each divided into 2 groups: those with psychiatric comorbidity and those without comorbidity. When the sympathetic skin response results of these 4 groups were compared with controls, the only statistically significant difference was between the sympathetic skin response latencies of controls and the latencies of patients with psychiatric comorbidity. We could not find any difference between the results from patients without psychiatric comorbidity and those of controls. CONCLUSION: Psychiatric disease may affect the results of autonomic function testing in migraineurs and patients with medication overuse headache. Consideration should be given to excluding patients with psychiatric comorbidity from studies investigating autonomic dysfunction in patients with headache.     

Miscellaneous primary headache

There are many types of miscellaneous primary headache, but two groups have been selected for discussion: trigeminal autonomic cephalalgias (TAC) and cephalalgias without autonomic dysfunction(CWAD). TAC are strictly unilateral and CWAD are usually bilateral.Sudden onset and relatively short duration characterize most,but some are frightening to patient and doctor alike. One, thunderclap headache, is symptomatic until proven otherwise. Although the others are rarely symptomatic, therapy can be difficult until it is recognized that diagnosis often predicts treatment.     

Neuroimaging in cluster headache and other trigeminal autonomic cephalalgias

The central nervous system mechanisms involved in trigeminal autonomic cephalalgias, a group of primary headaches characterized by strictly unilateral head pain that occurs in association with ipsilateral craniofacial autonomic features, are still not comprehensively understood. However, functional imaging methods have revolutionized our understanding of mechanisms involved in these primary headache syndromes. The present review provides a brief overview of the major modern functional neuroimaging techniques used to examine brain structure, biochemistry, metabolic state, and functional capacity. The available functional neuroimaging data in cluster headache and other TACs will thus be summarized. Although the precise brain structures responsible for these primary headache syndromes still remain to be determined, neuroimaging data suggest a major role for posterior hypothalamus activation in initiating and maintaining attacks. Furthermore, pathophysiological involvement of the pain neuromatrix and of the central descending opiatergic pain control system was observed. Given the rapid advances in functional and structural neuroimaging methodologies, it can be expected that these non-invasive techniques will continue to improve our understanding into the nature of the brain dysfunction in cluster headache and other trigeminal autonomic cephalalgias.     

The sweating anomaly in cluster headache

We describe a patient with a typical history of cluster headache for more than 18 years. During the first approximately 10 years of his disease, the pain was right-sided, and pupillometric and evaporimetric measurements indicated a sympathetic deficiency on this same side. However, for the next >6 years, his pain was consistently left-sided, although the signs of sympathetic dysfunction still were more marked on the right side. This was also true for the findings obtained during the interictal period and for the heating test performed within an attack. The implications of this interesting case are discussed. The view that two separate lines of symptom production lead to the pain and the autonomic phenomena seems to be supported by this case history. The cluster headache syndrome may also be a bilateral disorder, with only the weight of balance pointing one way or the other. Finally, the autonomic test results of this patient could reflect an autonomic "scar" in the previous headache side.     

The Phenomenon of Dysautonomia and Mitral Valve Prolapse

In recent years research has shown that subsets of patients with mitral valve prolapse also have associated autonomic or neuroendocrine dysfunction that can result in a number of related symptoms, including fatigue, palpitations, chest pain, exercise intolerance, dyspnea, dizziness, headache, sleep disorders, gastrointestinal disturbances, cold extremities, and panic attacks. These patients have been classified as having mitral valve prolapse syndrome. This article discusses the pathogenesis and management of mitral valve prolapse syndrome and serves to make clinicians aware of newer developments in the study of autonomic function and dysfunction.     

Spontaneous oscillations in cerebral blood flow velocity give evidence of different autonomic dysfunctions in various types of headache

OBJECTIVES: Our objectives were to determine if: (1) patients with migraine have B wave abnormalities in comparison to normal controls and patients with chronic tension headache and (2) patients with chronic tension headache have an imbalance in autonomic activity that is reflected in differences in Mayer wave activity in comparison to normal controls. BACKGROUND: B waves and Mayer waves are spontaneous oscillations in cerebral blood flow velocity with a frequency of 0.5 to 3 or 4 to 7 cycles per minute, respectively, and can be measured by transcranial Doppler sonography. There is experimental evidence that B waves are generated by certain brain stem nuclei which modulate the lumen of the small intracerebral vessels via monoaminergic nerve endings. In contrast, Mayer waves in cerebral blood flow velocity have no central generator but mirror the Mayer waves in arterial blood pressure which represent peripheral autonomic activity. Migraine may be attributed to a neurotransmitter imbalance in brain stem nuclei. Dysfunctions of the peripheral autonomic nervous system are known in patients with chronic tension headache. METHODS: Using bilateral transcranial Doppler monitoring of the middle cerebral artery B waves and Mayer waves were studied in 30 patients with migraine without aura, 28 subjects with tension-type headache, and 30 normal controls. Coefficient of variation as a quantitative parameter for amplitude of waves and the mean frequency were calculated from the envelope curves of the Doppler spectra. RESULTS: The coefficient of variation of B waves was higher in migrainous patients compared with patients with tension-type headache and normal controls (P<.05), indicating an increase in activity of brain stem nuclei in migraine only. Patients with chronic tension headaches had lower values for Mayer wave activity in comparison with normal controls (P<.05), a sign of an impairment of sympathetic activity. CONCLUSIONS: Our data support the dysfunction of the brain stem monoaminergic/serotonergic system in migraine. In contrast, patients with chronic tension headache have an autonomic dysfunction of peripheral origin presenting as a decrease of sympathetic activity.     

Nerves and Vessels in the Pterygopalatine Fossa and Symptoms of Cluster Headache

SYNOPSIS
The study evaluates the contribution of activated parasympathetic and sensory nerve fibres in the sphenopalatine ganglion area, and of vasodilation in surrounding vessels in this narrow region (pterygopalatine fossa), to the pain and signs of autonomic dysfunction seen during attacks of cluster headache. Agents with anesthetic and vasoconstrictor effects were applied nasally to reach this area. It was found that the anesthetic effect is the most important, both regarding pain and autonomic symptoms. The effectiveness was also evaluated: this treatment is useful to stop attacks of cluster headache, but the beneficial effect is less than that reported in previous studies.     

Migraine Headache Following Stellate Ganglion Block for Reflex Sympathetic Dystrophy

The alteration of extracranial blood flow in conjunction with clinical signs of autonomic nervous system dysfunction have led to various explanations concerning the pathophysiology of migraine headache.
Reflex sympathetic dystrophy, a painful disorder of the sympathetic nervous system, can be treated by blocking the sympathetic nerves located in the stellate ganglion, resulting in vasodilation, ptosis, miosis, and anhydrosis. In theory, these changes could trigger a migraine headache attack secondary to autonomic dysfunction reflecting an imbalance between sympathetic and parasympathetic nervous systems. This may be especially true in a patient with a previous history of meningitis that may have resulted in a disorder of cerebrovescular regulation. We report a 56-year-old man with no previous history of migraine who developed migraine with aura after a stellate ganglion block. Those episodic headaches occurred with decreasing frequency end severity for over 6 months, with eventual complete resolution. This interesting phenomenon has not been reported in the English literature and may help to better understand the pathophysiology of migraine.     

Endocrinology of cluster headache: Potential for therapeutic manipulation

Cluster headaches have always been among the most intriguing of the commonly recognized primary headache syndromes. This clinical interest is related to a number of factors, including the intense but short-lived nature of the pain, its sexual predilection, associated trigeminal autonomic dysfunction, and the remarkable circadian and circannual periodicity of cluster periods. Recent advances in neuroimaging and neuroendocrinology have shed light on the pivotal role of the hypothalamus in the biology of cluster headache. We discuss these revelations, along with current clinical observations in headache and sleep medicine.     

A review of hormonal findings in cluster headache. Evidence for hypothalamic involvement

The cause of cluster headache remains to be determined. The involvement of peripheral neurovascular structures can explain the pain and autonomic signs of a cluster attack, but not its rhythmicity. The central theory of cluster headache attributes the cyclic recurrence to involvement of the hypothalamus. To evaluate hypothalamic dysfunction a number of hormone studies have been carried out on cluster headache patients. Alterations in plasma melatonin, cortisol, testosterone, gonadotrophins, prolactin, growth hormone and thyrotropin have been documented, some only in the cluster period but others in the remission phase of the illness. We believe that the hormonal abnormalities in cluster headache support disorders of hypothalamic function.     

Serotonergic Agents in the Management of Cluster Headache

Cluster headache is a highly disabling primary headache disorder, characterized by unilateral headache attacks occurring in association with cranial autonomic symptoms. Serotonergic agents, such as the ergot alkaloids, have traditionally been used for the acute and preventive treatment of cluster headache and other primary headaches. Although it initially was thought that their efficacy was due solely to the vasoconstriction of extracranial cerebral vessels, new mechanisms of action of these drugs have been ascertained as a consequence of advances in elucidation of the pathogenesis of primary headaches and the development of triptans. This article reviews the current knowledge about serotonergic agonists and antagonists used in the management of cluster headache, focusing on their mechanisms of action and on the possible role of serotonin system dysfunction in this complex disorder.     

Chronic headache and pituitary tumors

Pituitary tumors come to clinical attention due to endocrine dysfunction, distortion of local structures surrounding the pituitary fossa, or as an incidental finding during neuroimaging for headache. Explanations for pituitary tumor-associated headache include stretching of the dura mater and invasion of pain-producing structures within the cavernous sinus. However, small functional pituitary lesions may present with severe headache without cavernous sinus invasion or suprasellar extension. Prolactinomas and growth hormone-secreting tumors have a high prevalence of rare headache phenotypes with or without autonomic features, suggesting that biochemical abnormalities within the hypothalamo-pituitary axis may play a role in headache. Somatostatin analogues may be highly effective at aborting headache associated with functionally active pituitary lesions, particularly in the case of acromegaly. A proposed mechanism for this is inhibition of nociceptive peptides. This article summarizes the clinical features, pathophysiology, and potential treatment approaches to pituitary tumor-associated headache.     

LASH: a syndrome of long-lasting autonomic symptoms with hemicrania (A new indomethacin- responsive headache)

A patient presented with a unique, stereotypical, episodic headache disorder marked by long-lasting autonomic symptoms with associated hemicrania (LASH). The autonomic symptoms clearly overshadowed the headache as the major component of the syndrome. Indomethacin controlled both the autonomic symptoms and the headache, suggesting that this is a new type of indomethacin-responsive headache. It may also complete the indomethacin-responsive headache spectrum.     

Autonomic headache with autonomic seizures: a case report

The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a nontrigeminal autonomic headache instead of an epileptic headache.     

Cluster headache syndrome. Ways to abort or ward off attacks.

Cluster headache is a syndrome of severe head and facial pain accompanied by autonomic abnormalities. Men are affected more frequently than women. Headaches occur daily during periods of susceptibility, which may be followed by periods of remission. The etiology of cluster headache is uncertain. Recent work suggests that hypothalamic dysfunction and/or oxyhemoglobin desaturation may be involved in its pathogenesis. Effective medical regimens are available for aborting acute attacks and for preventing attacks. Surgical ablation of the trigeminal ganglion has been effective in some patients when conventional medical therapy has failed.     

Impaired Cardiovascular Reflexes in Cluster Headache and Migraine Patients: Evidence for an Autonomic Dysfunction

SYNOPSIS
To investigate autonomic nervous system involvement in cluster headache (CH) and migraine, we compared the cardiovascular reflex responses of common migraine and CH subjects to a group of controls. A battery of 5 well-codified autonomic tests was applied: (1) deep breathing test (DB); (2) lying to standing test (LS); (3) Valsalva manoeuvre (VAL); (4) postural hypotension test (PH); (5) blood pressure response to sustained handgrip (SHG). Our data confirm an autonomic dysfunction in CH, mainly affecting the parasympathetic system. Evidence for an impairment of sympathetic cardiovascular reflex regulation was obtained in the common migraine group.     

Migraine: a chronic sympathetic nervous system disorder

OBJECTIVES: To determine the degree of diagnostic and clinical similarity between chronic sympathetic nervous system disorders and migraine. BACKGROUND: Migraine is an episodic syndrome consisting of a variety of clinical features that result from dysfunction of the sympathetic nervous system. During headache-free periods, migraineurs have a reduction in sympathetic function compared to nonmigraineurs. Sympathetic nervous system dysfunction is also the major feature of rare neurological disorders such as pure autonomic failure and multiple system atrophy. There are no known reports in the medical literature, however, comparing sympathetic nervous system function in individuals with migraine, pure autonomic failure, and multiple system atrophy. METHODS: A detailed review of the literature was performed to compare the results of a wide variety of diagnostic tests and clinical signs that have been described in these 3 heretofore unrelated disorders. RESULTS: The data indicate that migraine shares significant diagnostic and clinical features with both pure autonomic failure and multiple system atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction. Migraine is most similar to pure autonomic failure in terms of reduced supine plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity, and clinical symptomatology directly related to sympathetic nervous system dysfunction. The peripheral sympathetic nervous system dysfunction is much more severe in pure autonomic failure than in migraine. Migraine differs from both pure autonomic failure and multiple system atrophy in that migraineurs retain the ability, although suboptimal, to increase plasma norepinephrine levels following physiological stressors. CONCLUSIONS: The major finding of the present study is that migraine is a disorder of chronic sympathetic dysfunction, sharing many diagnostic and clinical characteristics with pure autonomic failure and multiple system atrophy. However, the sympathetic nervous system dysfunction in migraine differs from pure autonomic failure and multiple system atrophy in that occurs in an anatomically intact system. It is proposed that the sympathetic dysfunction in migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it is suggested that a migraine attack is characterized by a relative depletion of sympathetic norepinephrine stores in conjunction with an increase in the release of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine triphosphate, and adenosine. An enhanced understanding of the sympathetic dysfunction in migraine may help to more effectively diagnose, prevent, and/or treat migraine and other types of headache.