Cluster headache: pupillometric patterns as a function of the degree of anisocoria

Fifty-three patients with cluster headache, mean age 42.6 years, were examined by means of pupillometry. Pharmacological stimulation was carried out by the instillation of eye drops; the sympathomimetic agents hydroxyamphetamine (a norepinephrine releaser) and phenylephrine (an agent acting directly on the postsynaptic receptors) were applied. Pupillary dilatation was measured at set time intervals, comparing the responses of the symptomatic and non-symptomatic sides. The material was divided into groups according to the degree of basal anisocoria. The subgroup with the most pronounced basal miosis of the symptomatic side demonstrated a uniform pattern of deficient symptomatic side dilatation after OH-amphetamine and supersensitivity to phenylephrine. The other groups demonstrated the same general pattern, but to a far lesser degree. In cluster headache, the extent of nonresponsiveness to OH-amphetamine and of phenylephrine supersensitivity on the symptomatic side thus, at least partly, seems to be a function of the degree of anisocoria. The response pattern in cluster headache seems to differ from that of 3rd neuron Horner's syndrome with an anisocoria of the same extent.     

Cluster headache: Further observations on the dissociation of pain and autonomic findings

A 51-year-old male cluster headache patient had during five bouts in the course of 11 years always had the headache attacks on the left side. Autonomic abnormalities were, however, present on the right side. Pupillometrically, there was thus a Horner-like syndrome on the right (non-symptomatic) side, with miosis and a relatively more marked dilatation of that eye subsequent to topical application of a directly working sympathomimetic agent (phenylephrine) than after an indirectly working one (hydroxyamphetamine), whereas this was not the case on the symptomatic side. The findings on evaporimetry were not as clear-cut as the pupillometric findings; however, even facial sweating was consistent with a pathologic condition on the right (non-symptomatic) side. A primary dichotomy of pain and autonomic signs (that is, not due to change of side of pain localization) thus seems to be present in this case.     

Pupil responsiveness in cluster headache: A dynamic TV pupillometric evaluation

In this study the variations in pupil diameter induced by different stimuli (dark-light adaptation, light reflex, electric stimulation of the sural nerve) were investigated in episodic (in the active or remission phases) and in chronic cluster headache (CH) patients. Pupil size monitoring was performed with a monocular, infrared TV pupillometer, and sural nerve stimuli were applied after the pain threshold had been measured as the flexion reflex threshold of the biceps femoris muscle (RIII reflex). The results were compared with those obtained in patients with "peripheral" (third neuron) Horner's syndrome and in healthy sex- and age-matched controls. On the symptomatic side we found an impairment of pupil response to light flashes and nociceptive stimuli; similar findings were sometimes evident on the pain-free side, too. These results substantiate previous observations that in cluster headache a dysfunction of the integrative central nervous system pathways also exists intercritically and mostly bilaterally, involving both autonomic regulation and pain perception mechanisms.     

Cluster headache: Combined assessment with pupillometry and evaporimetry

Twenty-nine patients with cluster headache have been examined with the pupillometer and the evaporimeter. Pupils were dilated by sympathicomimetic drugs instilled into the conjunctival sacs, and responses of the two sides were compared. Forehead sweating was stimulated by body heating and by pilocarpine injection, and sweat evaporation on the two sides was compared. Most patients demonstrated the known patterns of hyposecretion on heating, of pilocarpine supersensitivity, and of deficient pupillary dilatation on OH-amphetamine stimulation on the symptomatic side and a supersensitivity of this pupil to phenylephrine. There were deviations from the rule for all methods of testing. Sixteen patients demonstrated a typical supersensitivity response of the pupil and of the sweat glands on the symptomatic side. Six patients had no such response, and seven patients had a discrepancy between the pupillary and the sweat gland response to stimulation, supersensitivity being present in one system only. There was a high degree of concordance between the results of the various methods of examination.     

Cluster headache: On the significance of so-called minibouts

Cluster headache periods (bouts) have, at the lower end of the scale, been supposed to last for periods as short as 1-2 weeks. Patients who usually have bouts of ordinary duration occasionally have brief attacks in the remission phase ("abortive attacks"). The group described here had a temporal pattern, clearly at variance with both these patterns: The six patients had mostly or entirely bouts of less than 1 week's duration. We have termed such short-lasting bouts minibouts, on the supposition that such cases belong within the cluster headache cycle. All the patients were men and had a history of unilateral headache without side shift, and usually the solitary attacks had some autonomic accompaniments, although of a moderate degree. In four cases only mild attacks occurred, whereas in two cases the attacks were rather severe and not consistent with full working ability. The group as such may not be homogeneous. The nosologic status of patients with bouts lasting only 1-2 days is somewhat uncertain. As long as the substrate of cluster headache is not outlined, the lower end of duration of minibouts cannot be accurately identified. The fact that three patients recently have experienced bouts of ordinary length strengthens the view that such cases really belong to the cluster headache cycle.     

Cluster headache and SUNCT: similarities and differences

SUNCT is probably a distinct syndrome, although it shares some common features with cluster headache (CH): male sex preponderance, clustering of attacks, unilaterality of headache without sideshift, pain of non-pulsating type with its maximum in the periocular area, ipsilateral autonomic phenomena (e.g. conjunctival injection, lacrimation, rhinorrhea, increased forehead sweating), systemic blood pressure increment with heart rate decrement, blood flow velocity decrement in the middle cerebral artery, and hyperventilation. In spite of these similarities, SUNCT syndrome differs clearly from CH as regards a number of clinical variables, such as duration, intensity, frequency, and nocturnal preponderance of attacks. The two syndromes also differ markedly as regards precipitation of attacks, the usual age at onset, and efficacy of various treatment alternatives. Laboratory investigations have disclosed differences as regards presence or absence of Horner-like picture and possibily also the respiratory sinus arrhythmia pattern. All in all, these differences seem sufficiently ponderous to make it likely that SUNCT syndrome and CH differ essentially. SUNCT seems to be a “neuralgiform” headache, but different from trigeminal neuralgia. Received: 2 April 2001 / Accepted: 23 July 2001     

Sweat gland and pupillary responsiveness in Horner''s syndrome

Eight patients with Horner's syndrome (five with a 1st neuron lesion and three with a 2nd neuron lesion) were examined for their pupillary responses to pharmacologic stimulation with tyramine (2%) and with phenylephrine (1%) eye drops. The same patients were also evaluated for their forehead sweating pattern on stimulation with body heating and pilocarpine injection, using the Evaporimeter. Five patients had a brain stem (1st sympathetic neuron) lesion, while three patients had had a traumatic C8-Th1 root avulsion and hence had a preganglionic neuron lesion. The average response with the phenylephrine eye test and the pilocarpine sweat test differed markedly between the two groups; only the central neuron lesion group had a supersensitivity reaction to both drugs. These procedures may be of diagnostic value in localizing the lesion in patients with a Horner's syndrome of unknown etiology. Patients with 3rd neuron lesion have not been examined with this combination of techniques.     

Cluster headache-like headache, Hageman trait deficiency, retrobulbar neuritis, and giant aneurysm

A 56-year-old, previously reported woman with cluster headache-like headache with bouts of unilateral (the side of predominance changing through the years) severe headache had a familial history (three generations) of partial Hageman factor deficiency and bleeding episodes. A giant aneurysm was found to be lodged in the anterior communicating artery on the left side. Clinically, the features were atypical for cluster headache: onset at a young age (14 years), episodes of retrobulbar neuritis appearing at the side of pain, etc. Studies of forehead sweating indicated that the right side was the pathologic one, from an autonomic point of view, as did pupillometric studies. However, during attacks, which were left-sided at the time, forehead sweating was marked laterally on the left side and on the upper eyelid, but not on the right. The "signal" usually reaching the autonomically stigmatized side during attacks of cluster headache, therefore, did not seem to reach the sweat glands on that (the right) side during the attack in the present case. This headache may, therefore, be distinct from cluster headache, both from a clinical and from an autonomic function point of view.     

Cluster headache after orbital exenteration

A 37-year old man developed an ipsilateral headache which fulfilled the criteria for cluster headache after orbital exenteration because of traumatic lesion of the bulb. The headache could be treated successfully by drugs usually applied in the therapy of cluster headache. Six similar cases of cluster headache after orbital exenteration could be identified in the literature suggesting that the eye itself is not necessarily part of the pathogenesis of cluster headache. We hypothesize that orbital exenteration can cause cluster headache by lesions of sympathetic structures. Possibly, these mechanisms are similar to those of sympathetic reflex dystrophy (Sudeck-Leriche syndrome) causing pain of the limbs.     

Cluster headache and vertigo

The term "cluster vertigo" was originally used by Gilbert to describe episodes of vertigo in patients with Ménière's syndrome. Since these patients also had co-existing cluster headache, he suggested that both disorders could have had a common pathophysiology. There is no evidence in the literature for an increased incidence of Ménière's syndrome in cluster headache patients, so the argument that cluster headache and Ménière's syndrome may have a common pathogenesis cannot be supported. Subsequent authors have used the term "cluster vertigo" to denote a variant form of cluster headache and have confused the matter further. This was not the intention of the original author. The terminology is misleading and should not be used to describe a sub-type of cluster headache. A case of cluster headache with accompanying vertigo is described as a contrast to the patients described by Gilbert in whom headache and episodes of vertigo occurred independently.     

Cluster headache associated with moyamoya

A 34-year-old man with right-sided cluster headache presented with a stroke from right-sided moyamoya. Following surgery on the right, both moyamoya and cluster headache remitted, but eighteen months later a cluster attack and symptoms of cerebral ischemia from moyamoya recurred on the left. Again, following surgery on the left, both moyamoya symptoms and cluster attacks disappeared. Cluster headache secondary to moyamoya has not previously been described. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

Cluster headache with aura

The objective of our study is to report the frequency and characteristics of cluster headache with aura among the population of patients with cluster headache treated in our outpatient neurology clinic. 254 patients were submitted to semi-structured interviews to identify the presence of symptoms similar to the migraine aura. 5 patients who suffered from a cluster headache with aura filled a diary with the characteristics of the pain attacks and the aura. All the patients with either episodic or chronic cluster headache were studied. The pain attacks were associated with symptoms similar to the migraine aura in five patients (2%). These disorders were usually ipsilateral to the pain and consisted of paresthesias of the trigeminal territory, clumsiness of the limbs or visual disturbances. Neither paresis nor hypoesthesia could be proved by clinical examination during the attack. We propose to reserve the name of cluster headache with aura to these cases that show similar symptomatology to the migraine aura. These manifestations suggest the participation of the central nervous system in this type of cluster headache. Received: 16 July 2001, Accepted in revised form: 4 December 2001 Correspondence to E. Martínez-Fernández     

Cluster headache in the Republic of San Marino

The prevalence of cluster headache (CH) in the Republic of San Marino (21,792 inhabitants; 10,893 men and 10,899 women) was studied, reviewing the past 15 years' medical records of neurological, ophthalmological, and otorhinolaryngological services. Further cases were searched for by means of a letter sent to each inhabitant. Control of the case collection method was performed on a random sample of 1314 inhabitants over 7 years, interviewed for possible past or present cluster headache. We found 15 cases of CH (14 men, 1 woman), for an estimated prevalence ratio of 69 cases per 100,000 population. No previous reports have been published on the prevalence of CH in the general population.     

Cluster headache — clinical findings in 180 patients

Anamnestic data and clinical features were accurately investigated in 180 patients with cluster headache; 161 were episodic sufferers and 19 were chronic. A significantly high familial incidence of coronary heart disease was found. The patients' medical history revealed a significantly high incidence of peptic ulcer disease and head injury with brain concussion. It is stressed that the side on which head injury took place is very frequently the same side on which cluster headache is located, although the latency between the two events appears to be a long one. The study of timing of cluster periods suggests, for some patients, a constant, typical temporal pattern not necessarily related to seasons or the months of the year. Cluster attacks frequently occur during certain periods of the day (onset being most frequent between 1 and 3 p.m.). Cluster headache cannot be considered as a nocturnal headache.     

Cluster headache in the Taiwanese -- a clinic-based study

Cluster headache has not been fully investigated in Asians. One hundred and four patients (90M/14F; mean age 39.2 +/- 12.2 years) with cluster headache were recruited from two major headache clinics in Taiwan. They filled out a structured cluster headache questionnaire. All participants were diagnosed to have episodic cluster headache. Mean age of onset was 26.9 years; mean latency of diagnosis was 8.1 years. A trend of decrease in male/female ratio with time was noted. Seventy-three percent were ex- or current smokers (M: 79%, F: 36%). Restlessness was reported by 51% patients. Only 1 patient (1%) reported visual aura. Patients responded well to standard acute and prophylactic treatment. The monthly incidence of cluster period was inversely related to sunshine duration. Compared to Western series, our patients were different in several aspects including the absence of chronic cluster headaches and a low prevalence of restlessness and aura. Racial and geographical factors might contribute to these discrepancies.     

Cluster headache associated with sleep apnoea

This study of sleep changes in patients with cluster headache (CH) was conducted in view of the nocturnal predominance of this condition, the efficacy of oxygen and the fact that the attacks follow oxygen desaturation. Proposed mechanisms include impairment of carotid body activity secondary to hypothalamic vasomotor regulatory dysfunction. Sixteen patients with episodic CH and 29 healthy volunteers underwent nocturnal polysomnography. Five (31.3%) patients with episodic CH were found to have sleep apnoea (SA). Two patients with SA experienced two attacks during the study period. The attacks followed episodes of oxygen desaturation and were associated with REM sleep. In two patients with SA and CH, treatment with continuous positive airway pressure abolished their oxygen desaturation, sleep apnoeas and headaches. Our study confirmed the high percentage of CH associated with SA. We suggest that oxygen desaturation may be a trigger factor in some patients and play a role in the pathogenesis of CH.     

Cluster headache in women: Clinical findings and relationship with reproductive life

Cluster headache (CH) occurs rarely among women; for this reason only a limited number of studies have been reported on the characteristics of the disease in the female population. In this study, 82 females (age range, 14-72 years) with episodic (69 cases) or chronic (13 cases) CH were investigated. The clinical features of headache and the physiologic events related to reproductive life were compared with those of various control groups. We did not find any remarkable differences in clinical features between men and women. Unlike other forms of primary headache, the course of CH does not seem to be modified by menstruation, pregnancy, or puerperium. Finally, our data seem to confirm a hypofertility trend, mostly after onset of CH, which had previously been noticed by other authors.     

Cluster headache: Forehead sweating pattern during heating and pilocarpine tests

Thirty-one patients with cluster headache were examined with regard to their forehead sweating pattern, by means of the Evaporimeter. Sweating was stimulated in two different ways: by body heating and by parenterally administered pilocarpine. The resulting increase in evaporation was frequently measured at different positions on both sides of the forehead, and the possibility of variations in the pattern related to the passage of time was specifically scrutinized. Some typical patterns emerged. The previously reported, marked asymmetries of response (deficient heat-induced sweating and pilocarpine supersensitivity of the symptomatic side) at the medial positions in the forehead were confirmed. However, the asymmetries invariably faded to some extent with the passage of time. Patients with cluster headache show gross similarities with, but also some minor differences from, the sweat pattern of patients with brain stem lesions causing a Horner's syndrome. A subdivision of the material into groups in accordance with the pupillometric pattern after sympathomimetic stimulation made it clear that the cases of definite evaporimetric asymmetries ("typical reactions") belonged to the group with a typical pupillometric pattern. These results suggest that from an "autonomic" point of view, subpopulations may exist within the clinical entity of cluster headache.     

Latent dysautonomic pupillary lateralization in cluster headache. A pupillometric study

Forty-five patients with cluster headache in the asymptomatic phase were studied by electronic pupillography, testing autonomic function of both pupils pharmacologically. Topical sympathetically-acting mydriatics, tyramine and cocaine and the cholinoceptor blocker, homatropine, induced defective mydriatic responses on the symptomatic side, indicating latent impairment of sympathetic function. The abnormality was found in interattack intervals of the cluster period or during intercluster phases. The tyramine test can be proposed for objective diagnosis of cluster headache. We postulate that cluster attacks are triggered and lateralized by a permanent latent unilateral sympathetic dysfunction. Lithium reduced the mydriatic response to tyramine of the pupil contralateral to the pain, thus restoring the equilibrium between both pupils; this therapy may correct the asymmetric sympathetic function by attenuating the activity in the asymptomatic side.