J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.7.917 on 1 July 1989. Downloaded from

Letters 917 admission he was noted to have poor Effect of tropatepine, an anticholinergic drug, ings246 that, under our experimental condi- memory, fine horizontal nystagmus, bilateral on regional cerebral blood flow in patients with tions, the total CBF of non-demented Park- restriction ofupward gaze and an inability to Parkinson's disease. insonians (especially regularly treated ones) walk heel to toe. Fundoscopy was normal as does not exhibit major changes in compari- was the rest of his neurological and general examination. A repeat of CT revealed a Sir: Despite the recent discovery of altera- son with normal subjects. We failed to find midline mass lesion obliterating most of the tions in numerous central neurotransmitters any decrease in the frontal pattern, unlike third ventricle and growing into the left and peptides in Parkinson's disease,' only Besetal.' lateral ventricle. The lateral ventricles were dopaminergic or anticholinergic agents have Secondly, our results demonstrate that more prominent than on the previous scan. been found to be active therapeutic agents. acute administration of an anticholinergic Histological examination of a small frag- Previous studies have shown that acute drug, in contract to levodopa23 or ment of the tumour following burr-hole administration of dopaminergic drugs bromocriptine,4 failed to change total or biopsy revealed the features of an (levodopa23 or bromocriptine4) induced a rCBF in Parkinsonians. In fact a physio- astrocytoma. The fragment was considered significant increase in rCBF in Parkinson's logical role for cholinergic mechanisms in the disease. However, as far as we know, no regulation of CBF has been suggested: bind- too small for grading. has The patient initially responded to dexa- study investigated the effects of anti- ing studies showed the presence of mus- methasone and local radiotherapy and in cholinergic drugs on rCBF in Parkinsonians. cannic cholinergic receptor sites in cerebral August 1987 a further CT head scan again In this study, we investigated the influence of blood vessels' and cholinergic agents (like revealed the midline mass lesion but tropatepine, an anticholinergic agent com- acetylcholine or physostigmine) were found monly used in the treatment of Parkinson's to increase CBF.' Soremin et al" suggested indicated some shrinkage. Following this, his that, in rabbits, the cholinergic cerebral condition gradually deteriorated and he died disease. in November 1988. Fifteen patients with idiopathic Parkin- vasodilatation does not depend on cerebral There seems little doubt that this man's son's disease (10 men and five women, mean metabolic activation and involved mus- exercise induced diplopia resulted from his age: 63 5, SD 8-1 years), stage II to IV on the carinic receptors located beyond the blood modified Hoehn and Yahr's staging were brain barrier. Few studies have investigated midline astrocytoma. At presentation this included in this All these were tumour was presumably producing a small study. patients the effects of anticholinergic drugs in man: elevation of the cerebrospinal fluid pressure regularly treated with levodopa (plus dopa using individual detectors and the [133 Xe] as demonstrated by the possible enlargement decarboxylase inhibitor). Tropatepine inhalation technique, Honer et al" recentlyProtected by copyright. hydrochloride was injected acutely by found that high doses of another anticholin- of the ventricular system seen on CT scan, intramuscular route at a dose of 10 ergic drug, scopolamine reduced and the pressure recorded at lumber punc- mg, global CBF ture. As the illness progressed, raised which is the dose commonly used in clinical and especially frontal cortex perfusion in intracranial pressure became more pronoun- practice to counteract the extrapyramidal normal subjects. Although we used a thera- seems efiects of neuroleptic drugs. A first rCBF peutic and effective dose (see the patient with ced. It likely that the onset ofdiplopia measurement was made with SPECT the induced side effect) of tropatepine, we during exercise was due to a futher elevation were unable to find similar results of intracranial pressure exer- (Tomatic 64, Medimatic, Copenhagen) (for in Parkin- produced by description see2) at time 0 (that is, at 11 a.m. sonians. tion. before Exercise induced diplopia is not a well drug injection). The second P CELSIS* recognised presenting feature of measurement was performed at time 90 min, J L MONTASTRUCt midline that is at the mean maximal peak plasma 0 RASCOLt cerebral tumours although disturbances of level of was measured and J M SENARDt gaze are not unusual.' A "Medline" com- tropatepine. PCO2 different regions of interest (ROIs) were J P MARC-VERGNES* puter search back to 1966 using "exercise," determined as previously described.2 The A RASCOLt "sports" and "diplopia" as key words changes were evaluated before and after INSERM U 230,* revealed no publications on the association. t test and the level of The case does provide circumstantial tropatepine by paired Laboratoire de Pharmacologie in significance was p < 0 05. Medical et Clinique INSERM U 317,t http://jnnp.bmj.com/ evidence that, humans, exercise tends to There was no significant difference in and Service de Neurologie, elevate intracranial pressure. It is possible, PCO2 before and after tropatepine (39-2, SD Centre Hospitalier Universitaire Purpan however, that this pressure elevation only 3-1 versus SD 3-1 Under basal et de occurs when abnormalities 39-9, mmHg). Faculte Medecine, pathological conditions in Parkinsonians, mean rCBF Toulouse, France. exist. was 50 6, SD 11-4 ml/100 g/min which is a Thanks are due to Teresa Bryant who for a under helped with the preparation of this letter. normal value such population Referees our experimental conditions." 1 Hirsch et R A SHINTON Acute administration of did Javoy-Agid F, Ruberg M, E, al. D G JAMIESON tropatepine Recent progress in the neurochemistry of not significantly change total CBF (50-7, SD Parkinson's disease. In: Fahn S, Marsden on September 25, 2021 by guest. University Department ofMedicine, 10-7 ml/1OOg/min) or rCBF in any ROI. The CD, Jenner P, Teychenne P, eds. Recent Dudley Road Hospital, effect on extrapyramidal symptoms were not Developments in Parkinson's disease 1986; Birmingham B18 7QH, UK investigated and no side effect was observed New York: Raven Press, 67-83. Reference except in one patient in stage II who 2 Montastruc JL, Celsis P, Agniel A, et al. developed 60 min after tropatepine a con- Levodopa-induced regional cerebral blood I Walton J. Brain's Diseases of the Nervous flow changes in normal volunteers and System. Oxford: Oxford University Press, fusional state wmcnwhich spontaneously alsap-disap- patients with Parkinson's disease. Lack of 1985. pearedpesnared aftertafter4 hours. correlation with clinical and neuropsy- The study allows two conclusions to be chological improvements. Movement Dis- Accepted 7 March 1989 made. First, it confirms our previous find- orders 1987;2:279-89. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.7.917 on 1 July 1989. Downloaded from

918 Letters 3 Leenders KL, Wolfson L, Gibbs JM, et al. The frontal and temporal headache. Sinus remains well. At no stage has there been any effect of L-Dopa on regional cerebral blood radiographs were consistent with sinusitis. renal or respiratory system disorder. flow and oxygen metabolism in patients with She did not improve with antibiotics and This women had a 5 year history of 1985;108:1 71-9 1. Parkinson's disease. Brain ENT opinion was that there was no sig- recurrent cranial and peripheral nerve 4 Celsis P, Rascol 0, Demonet JF, Agniel A, et al. nificant sinus disease. ESR was 100 mm in I lesions including the left optic, left infraor- Effect de la Bromocriptine sur le debit san- guin cerebral dans la maladie de Parkinson. hour, temporal artery biopsy specimen was bital, left phrenic and left recurrent laryngeal Rev Neurol (Paris) 1988;144:367-71. normal; she was referred to the neurology nerves before the diagnosis of Wegener's 5 Fahn S, Elton RL and Members ofthe UPDRS department and treated with prednisolone granulomatosis was made when an oro- Development Committee. Unified Parkin- with resolution of her headache. antral fistula developed. The initial diagnosis son's Rating Scale. In: Fahn S, Marsden CD, Four months later on prednisolone 20 mgs based on the severe headache, high ESR and Calne D, Goldstein M. eds. Recent Develop- per day, she developed double vision due to response to steroids was giant cell arteritis ments in Parkinson's disease vol II. Macmillan an almost complete right external ophthal- and the subsequent external ophthalmo- Healthcare Information, Florham Park, New was mm was to this disorder also. Jersey, 1987;153-63. moplegia without ptosis. ESR 46 in plegia attributed 1 could have 6 Marc Vergnes JP, Celsis P, Montastruc JL, et al. hour; and her signs resolved after 5 days of The correct diagnosis probably Hemodynamique cerebrale et pharmacologie prednisolone 100 mg per day which sub- been made by biopsy of antral mucosa in clinique dans la Maladie de Parkinson. sequently was gradually reduced. March 1986. Any cranial nerve may be Therapie 1988;43:83-88. In November 1983, while on prednisolone affected by Wegener's granulomatosis but 7 Bes A, Guell A, Fabe N, Arne-Bes MC, Geraud 12-5 mg per day, she developed a left vocal ocular involvement is frequent;3 the optic G. Effects ofdopaminergic agonists (piribedil cord paralysis and a chest radiograph neuropathy was unusual in the rapid res- and bromocriptine) on cerebral blood flow in showed elevation of the left hemidiaphragm. ponse to a modest dose of steroids and was parkinsonism. J Cereb Blood Flow Metab 1 due to compression by con- 1983;3:S490-1. ESR was 20 mm in hour: mediastinal presumably 8 Harik SI. Neurotransmitter receptors in tomography, CT thorax and neck, bron- tiguous inflammatory granulomas. The cerebral microvessels. In: Mac Kenzie ET, choscopy, sputum cytology, thyroid and phrenic and recurrent laryngeal nerves were Seylaz J, Bes A. eds. Neurotransmitters and bone isotope scans were all normal. The presumably affected by a vasculitis of the the Cerebral Circulation. LERS vol 2, 1984; gradual reduction in prednisolone dosage vasa nervorum and the external ophthalmo- New York, Raven Press, 1-9. was continued and her voice was much better plegia may be explained by orbital muscle 9 Sercombe R, Lacombe P, Seylaz J. Functional one year later. She remained on 2 5 mg rather than third nerve involvement since significance of the cerebrovascular reactivity prednisolone daily until March 1986 when ptosis and pupillary abnormality wereProtected by copyright. to autonomic neurotransmitters. In: Mac Kenzie ET, Seylaz J, Bes A. eds. Neurotrans- she developed numbness and nagging pain in absent. mitters and the Cerebral Circulation. LERS the left side of her face and forehead. This case report serves to emphasise that vol 2, 1984; New York, Raven Press, 65-89. Sensation over the left infraorbital nerve was Wegener's granulomatosis may be a rather 10 Soremin OU, Sonnenschein RR, Rubinstein impaired, ESR was 40 mm in 1 hour and indolent process and that, in the presence of EH. Cholinergic cerebral vasodilatation in sinus radiographs showed an opaque left cranial or peripheral neuropathy, symptoms the rabbit: absence ofconcomitant metabolic antrum. Left maxillary antral examination of sinus disease should be fully investigated, activation. J Cereb Blood Flow Metab revealed an absent medial wall which was including biopsy. 1982;2:241-7. attributed to previous surgery; antral wash- S KIRKER 11 Honer WG, Pohounik I, Smith G, Lucas LR. ings contained polymorphs only with no M KEANE Scopolamine reduces frontal cortex per- fusion. J Cereb Blood Flow Metab malignant cells. Her symptoms improved M HUTCHINSON 1988;8:635-41. with prednisolone 15 mg per day. CT of her Department ofNeurology, naso-pharynx revealed no other abnor- Adelaide Hospital, Address for correspondence: Dr JL Montastruc, mality. In January 1987 on 7-5 mgs of Dublin 8, Laboratoire de Pharmacologie Medicale et Clin- prednisolone she developed sudden visual Ireland ique, INSERM U 317, Faculte de Medecine, 37 impairment of the left eye with pain around Correspondence to Dr S Kirker. allees Jules Guesde, 31073 Toulouse cedex, France. the orbit. Examination revealed constricted peripheral vision in the left eye with visual References http://jnnp.bmj.com/ acuity of N48, and a left relative afferent I pupillary defect. There was full recovery Drachman DA. Neurological complications of Wegener's granulomatosis. Arch Neurol Benign recurrent multiple mononeuropathy in after one week on 30 mgs prednisolone per 1963;8: 145-54. Wegener's granulomatosis day, and the dose was gradually reduced. 2 Anderson JM, Jameson DG, Jeffersen JM. In June 1987 because of osteoporosis the Non-healing granulomas and the nervous Sir: Neurological involvement in Wegener's steroids were gradually reduced and discon- system. Q J Med 1974;44:309-2 1. granulomatosis is common,' occurring in tinued six months later. In August 1988 she 3 Haynes BF, Fishman ML, Fuci AS, Wolfe SM. 26% of patients in a review of 374 cases.2 In complained of left maxillary pain and an The ocular manifestations of Wegener's the more localised form, midline granuloma, oro-antral fistula with erosion of all the Granulomatosis. Am J Med 1977;63: 131-41. on September 25, 2021 by guest. 12% of 125 patients had neurological surfaces of the maxillary antrum was found. Accepted 28 March 1989 involvement but only one had a peripheral Histology of the fistula lining showed multi- neuropathy. We wish to report a patient with nucleated giant cells and necrosis surroun- a 5 year history of recurrent multiple mono- ded by pallisading ofhistiocytes with necrot- Progressive systemic sclerosis presenting as a neuropathy prior to histological diagnosis of ising vasculitis of small arteries, characteris- case of trigeminal neuropathy Wegener's granulomatosis. tic of Wegener's granulomatosis. She was A 62 year old woman presented in March started on cyclophosphamide 75 mg per day Sir: A 58 year old shipyard welder first 1983 with a two month history ofsevere right and reducing doses of prednisolone, and noticed numbness over the right lower lip in