A man had left-sided atypical clusterlike headache for II years before he developed symptoms and signs consistent with acromegaly. Preoperative evaluation revealed raised levels of somatomedin C and growth hormone. An MR indicated a left-sided intrasellar mass measuring 8 x 7.5 x 10 mm. He underwent surgery and microscopy confirmed the diagnosis of a benign hypophyseal adenoma. Postoperatively, the acromegalic features regressed, and for the last 4 years the patient has been completely free from headache attacks. On pharmacological testing of the pupillary response to 19 and 5% phenylephrine and 2% tyramine solutions, there was no convincing evidence of persistent sympathetic dysfunction on the earlier symptomatic side.Key words: acromegaly, clusterlike headache, phenylephrine pituitary adenoma, pupil, tyramine Abbreviations: GH growth hormone (Headache 1996;36:184-188) The pathophysiology of cluster headache remains unclear. In most instances, every extensive neurological and neuroradiological examinations will be normal. 1 However. symptomatic clusterlike headache has been reported in a variety of pathological conditions with varying locations. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Recently, pathophysiological interest has been focused on basal midline structures and in particular, the cavernous sinus. [17][18][19][20][21][22][23] We report a case of clusterlike headache associated with an intrasellar pituitary adenoma causing acromegaly. The relevance of the tumor location and its possible implications for the symptomatology, particularly with respect to sympathetic dysfunction, are discussed. CASE HISTORYA 37-year-old man had suffered from left-sided headache attacks for 4 years before he sough medical advice at the Department of Neurology Malmö University Hospital in 1985. His previous history was unremarkable. The headache was strictly left-sided and located behind the eye; radiating towards the left ear, the occiput, and the neck. Because the pain also involved the teeth in the left upper jaw, he had undergone dental treatments, including correction of bite, all of which had been in vain.The attacks occurred with varying intervals of weeks or months. The pain was excruciating, with a stinging and pulsating character. It always started at about the same time in the afternoon and lasted for up to 7 or 8 hours. The patient could only get some relief by a high intake of phenacetin and acetylsalicylic acid. However, by pouring hot water over the neck or by massaging the occipital region on the left side, he could also obtain considerable relief. The pain never sub sided completely before he went to bed. Initially, when the headache attacks started, he thought that attacks could be provoked by intense sunlight, shimmering waves, but also by a cold wind blowing in the face. Whenever he suffered an attack, his left eye was reddened with markedly increased lacrimation. The left nostril was blocked and there was rhinorrhea. During an attack, he did not experience nausea, nor did he ever vomit. Som...

The ciliospinal reflex response is mainly mediated by second- and third-order sympathetic nerves to the dilatator muscle of the iris. As the pupillary response to various pharmacological agents indicates a sympathetic dysfunction in patients with cluster headache, the ciliospinal reflex was studied in 25 patients. Five of these patients with cluster headache exhibited a Horner-like syndrome (miosis, ptosis) on the symptomatic side. The pupillary responses to phenylephrine and tyramine showed that the Horner-like syndrome was due to postganglionic sympathetic nerve dysfunction. Their ciliospinal reflex response on the symptomatic side was significantly less than in controls and in other patients with cluster headache, lacking a Horner-like syndrome. This also applied to the nonsymptomatic side compared to the majority of cluster headache patients without any clinical evidence of sympathetic nerve dysfunction. These findings seem to delineate those patients with a Horner-like syndrome as a subgroup, distinctly separated from the majority of cluster headache patients. Furthermore, the findings indicate that the Horner-like syndrome is not a consequence of repeated attacks of headache over many years, but is a manifestation of bilateral cephalic sympathetic dysfunction being more marked on the symptomatic side. In 18 (72%) of our 25 patients, an asymmetric and lower ciliospinal reflex response on the symptomatic side was seen. In 3 (12%) patients, there was no difference in the response. In 4 patients (16%), the incorrect side was indicated by an asymmetric reflex response. Two of these patients (8%) had suffered from cluster headache on alternating sides. In summary, the findings support the concept that dysfunction of the sympathetic nervous system, whether peripheral or central is involved in the pathophysiology of cluster headache.

Two sisters with cluster headache were studied with respect to the pupillary responses to instillation into the conjunctival sac of a single drop of a 1% solution of phenylephrine and a 2% solution of tyramine. The changes in pupillary diameters were documented by photographic pupillometry prior to and at 15, 30, 60, and 90 minutes after the instillations.Of the two sisters, one (case A) was examined during a symptom-free interval, when she had been free from cluster headache attacks for 2 1/2 years. When the cluster headaches recurred, retesting was performed. The other sister (case B) had been free from cluster headaches for 9 years, when she was examined.The findings indicate hypofunction within the postganglionic sympathetic nerve fibers during a cluster headache period. The hypofunction is bilateral, and thus, can not be a consequence of the unilateral cluster headache attacks. During remissions, tyramine induces a marked mydriasis, particularly on the symptomatic side, tentatively indicating an excessive release of stored monoamines.Key words: cluster headache, pupil, phenylephrine, tyramine, sympathetic dysfunction Abbreviations: CH cluster headache (Headache 1996;36:448-451 ) The pathophysiology of cluster headache (CH) is unknown. Its prevalence is low, estimated at about 70 per 100000, 1 with a marked male preponderance. It is usually not considered a familial disorder, 2 though such cases have been reported. 2-6 A positive family history of CH is encountered in approximately 3% of sufferers, 7 the overwhelming majority being males.We recently had the opportunity to examine two sisters who had suffered from typical episodic CH fulfilling the diagnostic criteria of the International Headache Society (IHS). 8 One of the sisters gave a history of more or less regularly recurrent CH periods for more than 20 years. The other had been free from CH attacks for the previous 9 years. As a cephalic sympathetic dysfunction has been implicated in the pathophysiology of CH, 9-13 the two sisters were studied with respect to the pupillary responses to conjunctival instillation of phenylephrine and tyramine. CASE HISTORIESCase A.-A 43-year-old woman sought medical advice because of recurrent periods of left-sided headache, localized around the eye. She had suffered from such a headache for more than 20 years. The periods were said to last for about 4 weeks and occurred annually, or at least every second year. The attacks had a duration of about 1 to 2 hours and used to occur particularly during nighttime. The headache was very intense and of a nonpulsating type. On rare occasions, she felt nauseated and vomited. During an attack, her left eye was red and tearing, and her ipsilateral nostril exhibited rhinorrhea, without being blocked.Between the headache periods, she was free from neurological symptoms. Her somatic and neurological examinations were normal. In particular, there was no anisocoria, nor any other manifestation of a partial Horner's syndrome. She had a gratifying response to prophylactic pizotifen (San...

An amplified ciliospinal reflex response has been documented in patients with cluster headache, lacking a Horner-like syndrome. The mechanism is unknown. Tentatively, it may be due to an increased release of monoamines from post-ganglionic sympathetic nerve endings or an increased density of postsynaptic adrenergic receptors in the dilatator muscle of the iris. The instillation of a 1% phenylephrine solution into the conjunctival sac induces mydriasis by stimulating postsynaptic adrenergic receptors in the dilatator muscle of the iris, while the instillation of a 2% tyramine solution causes mydriasis by releasing noradrenaline from the presynaptic sympathetic nerve terminals in the iris. According to these premises, a positive correlation should be expected between the ciliospinal reflex response and the pupillary response to tyramine, if the enhanced ciliospinal reflex response was due to an increased presynaptic release of monoamines. No such correlation was found. Nor was there any positive correlation between the ciliospinal reflex response and the pupillary response to phenylephrine, contradicting an increased density of postsynaptic monoaminergic receptors in the dilatator muscle of the iris as the explanation. However, there was a significant positive correlation between the pupillary responses to phenylephrine and tyramine, ruling out any functionally caused "denervation" hypersensitivity in the dilatator muscle of the iris. It is concluded that the amplified ciliospinal reflex response in cluster headache patients (lacking a Horner-like syndrome) reflects compensatory pathophysiological mechanisms proximal to the third-order sympathetic neuron.