Benign Intracranial Hypertension Associated with the Withdrawal of a Non-Ergot Dopamine Agonist

J7ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:371-372 371

SHORT REPORT J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.3.371 on 1 March 1994. Downloaded from

Benign intracranial hypertension associated with the withdrawal of a non-ergot dopamine agonist

S L Atkin, E A Masson, L D Blumhardt, M C White

Abstract reduced from two to three each week to one The cases are reported of two patients each month while receiving CV 205 502, but who developed benign intracranial were more intense and of longer duration. hypertension after the withdrawal of the Headache frequency had increased on the novel non-ergot derived dopamine two occasions when she stopped treatment. agonist CV 205 502 (quinagolide). She was a non-smoker, receiving no other drugs, and rarely drank alcohol. General (J Neurol Neurosurg Psychiatry 1994;57:371-372) examination was normal apart from a body mass index of 27. Neurological examination showed bilateral papilloedema with no other Semisynthetic ergot-derived dopamine neurological signs. A CT scan with contrast agonists were introduced in 1971 for the enhancement was normal apart from an treatment of hyperprolactinaemia. Many empty sella and small ventricles consistent studies have documented the efficacy of these with benign intracranial hypertension. A lum- drugs in decreasing serum prolactin levels, bar puncture showed a pressure of 32 cm of reducing pituitary prolactinoma size and the CSF with normal glucose levels, white blood effects of pituitary compression, and in cell count, and total protein. She was treated restoring gonadal function. The side effects of with steroids and diuretics. A repeat lumbar these drugs include nausea and orthostatic puncture two weeks after the start of treat- hypotension and, less commonly, headache, ment showed a pressure of 18 cm of CSF. fatigue, nasal stuffiness, abdominal cramps, and constipation.' CV 205 502 (quinagolide) is a novel non-ergot derived dopamine ago- Case 2 nist (an octahydrobenzyl(q)quinolone com- A 25-year-old woman with hyperprolacti- pound) which has been available on a 'named naemia due to a microprolactinoma was patient' basis for the treatment of hyperpro- intolerant of bromocriptine. She was success- http://jnnp.bmj.com/ lactinaemia in patients intolerant of fully treated with 75 ,ug CV 205 502 for 30 bromocriptine.2 We report the development months. Two weeks after stopping treatment of benign intracranial hypertension in two she developed morning headaches with nau- patients within two weeks of withdrawal from sea and blurred vision, which continued with CV 205 502. increasing severity over the following two weeks. Her past history showed that identical,

though less severe, symptoms had developed on September 30, 2021 by guest. Protected copyright. Case 1 over a similar time course one year previously A 32-year-old woman who had had trans- when she had stopped treatment with CV sphenoidal surgery for a macroprolactinoma 205 502 for one month. The symptoms had continued to have hyperprolactinaemia resolved shortly after restarting treatment. despite a radiological empty sella. She was She also had a history of headaches character- Department of Endocrinology, Royal intolerant of bromocriptine and treatment istic of migraine with photophobia and visual Liverpool Hospital, with 75 ,ug CV 205 502 restored menses and disturbance which had been more severe, but Liverpool, UK stopped galactorrhoea for 24 months. Two reduced in frequency by 50%, while receiving S L Atkin E A Masson weeks after stopping CV 205 502 she devel- CV 205 502. The frequency of the headaches M C White oped morning headaches, visual disturbance, had increased on the two occasions when she Division of Clinical nausea, and vomiting, which continued with stopped treatment. She had also been taking Neurology, University increasing severity over the next four weeks. the phased oral contraceptive BiNovum for Hospital, Queens Identical had developed one year the four She was a non-smoker Medical Centre, symptoms past years. Nottingham, UK previously, over a similar time course, when and drank alcohol only rarely. General and L D Blumhardt she had stopped CV 205 502 for a period of neurological examination was normal (body Correspondence to: one month. The symptoms had resolved mass index 24) apart from early papil- Dr S L Atkin, Department of Medicine, University of shortly after restarting treatment. She had a loedema. A CT scan with contrast enhance- Hull, Kingston General long history of headaches from adolescence, ment was normal apart from apparently small Hospital, Beverley Road, Hull, HU3 1UR, UK. which were characteristic of migraine, includ- ventricles. A lumbar puncture showed a Received 29 June 1993. ing photophobia, blurred vision, and flashing pressure of 22 cm CSF with normal glucose Accepted 28 July 1993 lights. The frequency of the headaches had levels, white blood cell count, and total 372 Atkin, Masson, Blumhardt, White

protein. She was treated with steroids and year earlier. If this is true, it can be J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.3.371 on 1 March 1994. Downloaded from diuretics, with marked symptomatic relief speculated that CV 205 502 was preventing within two weeks. the development of benign intracranial hypertension. It is also notable that the two patients had Discussion vascular headaches characteristic of migraine Benign intracranial hypertension is a rare dis- which were reduced in frequency and order of unknown aetiology and uncertain increased in severity on treatment with CV incidence. It is more common in obese 205 502. In the two patients the headaches women between the ages of 17 and 40 years3 increased in frequency and decreased in and is associated with the menarche and severity on stopping the drug. Migraine is pregnancy. It is unclear if an apparent associ- common and may be a coincidental feature, ation with menstrual irregularity is more than but the temporal relation of CV 205 502 would occur by chance.34 Drugs associated treatment to the alteration in the pattern of with benign intracranial hypertension include the migraine suggests that CV 205 502 was tetracyclines, naladixic acid, nitrofurantoin, responsible for the reported modulation of corticosteroids (oral and topical), ketamine, the frequency and severity of the headaches. nitrous oxide, vitamin A (excess and defi- Bromocriptine may improve migrainous ciency), oral contraceptives, ketoprofen, and attacks in patients with menstrual migraine,8 thyroxine.5 To date there have been no though marked hypotension may complicate reports of any association between benign bromocriptine treatment in patients with intracranial hypertension and dopamine ago- migraine.9 Our observations and the vascular nists. basis of migraine and benign intracranial CV 205 502 is a quinolone compound hypertension suggest that CV 205 502 may with selective D, receptor agonist activity,6 have a direct action on the cerebral vascula- whereas the lysergic acid derivative ture. bromocriptine has D, and D2 agonist activity. The two drugs have been associated with psychiatric complications.7 Our patients described identical symptoms 1 Vance ML, Evans WS, Thorner MO. Drugs five years later. Bromocriptine. Ann Intern Med 1984;100:78-91. occurring two weeks after stopping CV 205 2 Newman CB, Cragun JR, Kleinberg DL. Effect of CV 502, though the symptoms and signs in 205 502 in hyperprolactinaemic patients intolerant of bromocriptine. Clin Endocrinol 1989;31:391-400. patient two were less severe, possibly due to 3 Tessler Z, Marcus M. Idiopathic intracranial hyperten- earlier presentation. The two patients had sion. Comp Ther 1991;17:13-7. 4 Katz VL, Peterson R, Cefalo RC. Pseudotumor cerebri other features of benign intracranial hyper- and pregnancy. AmJ Perinatol 1989;6:442-5. tension. Patient 1 had an empty sella sec- 5 Blain PG, Lane RGM. Neurological disorders. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: ondary to an operation and patient 2 was Oxford University Press, 1991:535-66. taking oral contraceptives. The similar time 6 Gaillard RC, Nordmann R, Petcher TJ, Brownwell J. A novel octahydrobenzyl(q)quinoline, CV 205 502 with interval in the two patients between stopping potent dopamine agonist properties. In: Molinatti GM, CV 205 502 and the development of symp- Martini L, eds. Endocrinology '85. Amsterdam: Elsevier, 1986:305-8. toms, and the history of identical symptoms 7 Barnett PS, Palazidou E, Miell JP, et al. Endocrine func- one year earlier, strongly suggest a relation tion, psychiatric and clinical consequences in patients

with macroprolactinomas after long-term treatment with http://jnnp.bmj.com/ with the drug. The development of symptoms the new non-ergot dopamine agonist CV 205-502. Q J within two weeks of stopping CV 205 502 Med 1991;295:891-906. 8 Hockaday JM, Peet KM, Hockaday TD. Bromocriptine in and the subsequent resolution of all symp- migraine. Headache 1976;16:109-14. toms within one month of restarting treat- 9 Fanciullacci M, Michelacci S, Curradi C, Sicuteri F. Hyper-responsiveness of migraine patients to the ment suggests that benign intracranial hypotensive action of bromocriptine. Headache 1980;20: hypertension may have been precipitated one 99-102. on September 30, 2021 by guest. Protected copyright.