The cluster phenomenon: an unspecific feature?
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Biomedical subjects
Publications and source records attributed to O Sjaastad.
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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.
Three cases of what could be considered "mild" cluster headache have been described. All three patients were generally able to carry out their work during attacks; all three were men and had unilateral headache with the predominant pain in the ocular region. Relatively few symptoms and signs indicated autonomic system involvement, but at least tearing was invariably present on the symptomatic side. The bouts were generally short-lasting in two of the patients (and partly in the third one), fitting the pattern of "mini-bouts". Thus, in one of the cases four of the five major criteria (male sex, excruciating severity, cluster phenomenon, autonomic involvement, and unilaterality) were present. In the two other patients the full-blown cluster phenomenon was lacking. Such cases may represent the left-side slope of a "Gaussian severity distribution scale" with regard to cluster headache.
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.
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Prostaglandins and leukotrienes have been implicated in the pathogenesis of various types of headache, mainly because some, but not all, cyclo-oxygenase inhibitors are effective in their treatment. We have therefore investigated whether a pathologically changed turnover of arachidonic acid (AA)-containing phospholipids can be seen in headache patients, using isolated polymorphonuclear cells (PMNs) from healthy controls and patients with chronic paroxysmal hemicrania (CPH) and cluster headache. PMNs from healthy controls incorporated 55% of the added (1-14C)AA into total lipids, and 0.5% +/- 0.14% of this radioactivity was found in the phosphatidylserine (PS) fraction. PMNs from a cluster headache and a CPH patient showed 300% and 900% increase in PS labeling from AA, respectively. No other phospholipids showed any difference between controls and patients. The results are discussed in connection with membrane signal transduction via the PS-dependent protein kinase C.
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.
Pupillometric studies were carried out in eight patients with chronic paroxysmal hemicrania (CPH) and in age- and sex-matched controls in the basal condition and after instillation of 2% tyramine (CPH, n = 5; controls, n = 17), 1% OH-amphetamine (CPH, n = 6; controls, n = 12), and 1% phenylephrine (CPH, n = 6; controls, n = 17). The pupil on the symptomatic and non-symptomatic sides in CPH patients was significantly smaller in the basal condition than in controls, particularly on the symptomatic side. The mydriatic responses to pharmacologic stimulation were essentially similar on the symptomatic and non-symptomatic sides. An evaporimetric study of the forehead sweat glands, using the body heating and pilocarpine tests, was also carried out in these patients and in age- and sex-matched controls. "Early", "intermediate", and "late" measurements demonstrated symmetry of forehead sweating. The findings for both methods of examination thus contrast with those in cluster headache patients. Pupillometric and forehead sweating patterns therefore suggest differences in the pathogenesis of the two headache entities. These tests may be used to distinguish CPH and cluster headache clinically.
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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.
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.
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Tension headache (TH) and control subjects (n = 22, 11 in each group) were evaluated within a habituation experimental design, in which psychophysiologic responses to auditory stimulation were measured. Auditory stimuli were 20 80-dB, 1000-Hz tones, each lasting 2 sec and sounded at irregular intervals. Subjects were evaluated twice, with a 6-month interval. At the time of the first session TH subjects were being treated with tricyclic antidepressant, yielding a positive clinical effect. Medication was withdrawn 3 weeks before the second session. Phasic responses in heart rate and temporal artery pulse amplitudes and averaged EMG levels from the frontal muscles were measured. Significantly lower heart rate reactivity and significantly less pronounced left temporal artery pulse amplitude responses were found in non-medicated TH subjects than in controls. TH patients showed a pulse amplitude increase in response to stimulation, whereas control subjects showed a decrease. The pulse amplitude response pattern was normalized in medicated TH patients. EMG levels were similar in TH patients and controls when patients were receiving medication, whereas TH patients showed significantly higher frontal EMG levels than control when medication had been withdrawn.
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 greater than 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.
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.
The main criteria of "cervicogenic headache" are considered to be as follows: relatively rare and long-lasting unilateral attacks of severe headache, although seemingly of a non-excruciating character, signs of neck involvement, and lack of "cluster pattern". In the present communication, the clinical manifestations in 11 patients fulfilling these criteria are described. All 11 patients selected in accordance with these criteria proved to be females, the age at onset ranging from 6 to 40 years (mean, 30 years). The mean duration of symptoms was 13 years. Six patients had had previous head/neck injuries. All patients had pain periorbitally, in the temporal region, and in the low occipital region (nape of the neck); less frequent were frontal, parietal, and facial pain and pain in the upper part of the occipital region. The duration of attacks was from 3 h to 3 weeks, and the interval between attacks lasted from 2 days to 2 months. The commonest accompanying phenomena were phonophobia, dizziness, ipsilateral eyelid edema, ipsilaterally blurred vision, and irritability. Some of the patients also had nausea (n = 7) and vomiting (n = 6). On physical examination, slight to moderate reduction of movements in the neck was noted, and five patients had ipsilaterally reduced sensation for touch in the trigeminal area. All the patients except one were severely afflicted. Attacks could, in addition to occurring spontaneously, be precipitated in all patients by head movements or by pressure at specific points in the neck.
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