524 Maters arising prolong the lives of those suffering, thereby Most of these problems are not taken into 6 Poser C, Paty D, Scheinberg L, et al. New J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.6.524-b on 1 June 1992. Downloaded from providing the necessity for self-action by the consideration in Sibley's article. diagnostic criteria for . Ann patient. It is germane to point out that the "scien- Neurol 1983;13:227-31. Perhaps when we advise patients and tific" evidence of epidemiology and biostatis- families who face difficult decisions, we tics overlooks the fact that such studies can at Sibley et al reply: would be better to heed the available evi- best only be estimates within a cohort and dence about who will do well and who will do cannot be generalised; epidemiological stud- We age- and sex-matched MS patients with badly rather than withholding recommenda- ies are most useful in providing aetiological healthy controls solely to establish the degree tions because unduly cautious statisticians clues but cannot be used to deny possible of accident-proneness of MS patients. It choose to neglect the downside effects of causal relationships.2 As was pointed out by probably needs to be clearly restated that the their theoretical arguments. Neurologists are Schoenberg, "Statistical significance (or lack patients were used as their own controls in an especially favourable position to under- thereof) does not equal biological when they were not "at risk". stand the misery that accompanies chronic, significance". Physical trauma had no positive influence overwhelming brain damage. This knowledge It is difficult to understand, on the basis of on either exacerbation rate or progression of places them in a position to understand the what is already known about the pathogen- MS in our group of MS patients as a whole, humane needs in such cases and advise esis of MS, how trauma such as laceration of or in various subgroups divided according to families accordingly. the hand, contusion of the right finger, a root sex, age, degree of disability, or duration of FRED PLUM canal procedure, or a thorn in the foot can disease-all of these data could not Department ofNeurology, be and Neuroscience, possibly lead to the appearance or recurrence presented in our paper in the interests of The New York Hospital-Cornell Medical Center, of symptoms of MS. Sibley et al dismiss the brevity. We have not analysed separately 525 East 68th Street, alteration of the blood-brain barrier in the based on sites of residence or socioeconomic New York, NY 10021, USA genesis of the MS lesion; in doing so they factors. disregard the numerous recent publications I am sure that Dr Poser is aware that we 1 Bates D. Defining prognosis in medical coma. which have amply confirmed this fact, have no way ofidentifying MS patients whose J Neurol, Neurosurg Psychiatry 1991;54: including statements by such authorities as disease has not 569-7 1. yet been recognised. His 2 Levy DE, Bates D, Caronna JJ, et al. Prognosis McDonald and Barnes' who commented statement that some of them will not have in non-traumatic coma. Ann Int Med that "A consistent, very early event is a symptoms until subjected to trauma, makes 198 1;94:293-301. breakdown of the blood-brain barrier which causative assumptions that our study data do is largely repaired over weeks, leading to not support. Bates replies: marked changes in the size of acute lesions" With regard to his comments concerning I am grateful to Professor Plum for emphasis- and by Compston' who wrote, "Blood-brain the validity of statistical methods, we believe ing the important exclusions in the Inter- barrier damage is necessary early in the that it is common scientific practice to national Study on Prognosis in Non-trau- development of focal demyelination". generalise on the basis of data obtained in matic Coma and appreciate his comments One cannot expect that all, or even most representative samples of a group. The cal- relating to the use of unfavourable early signs. MS patients will have exacerbations follow- culation of annual exacerbation rates was for I did not intend to suggest that clinical or ing trauma, since it is a common experience the convenience of the reader; the chi-square laboratory indicators of poor outcome were for MS patients to have repeated viral infec- calculations were done on actual exacerba- not to be used as part of the process to make tions without changes in the course of their tion numbers during periods at risk and not decisions in patient management, and am disease. at risk for trauma, not on the annual rates. very conscious of what Professor Plum refers The relationship between trauma to the Our study tested the hypothesis, advanced to as the "downside statistical feature" of head, neck or back that I have supported, is by others, that trauma, including peripheral prolonging an insentient life and the con- based upon clinical, neuropathological, and trauma, could cause exacerbations ofMS. We sequent burden on the family. My purpose experimental evidence which were reviewed are happy to see that Dr Poser agrees that was rather to emphasise that predictors of in 1986' and based on the obligatory step of peripheral trauma, at least, can be dismissed poor outcome should not be used as the sole the alteration of the blood-brain barrier for as a cause. He continues to believe, however, factor in making decisions about life support, the formation of the MS lesion. This has now that CNS trauma that causes a breach in the though they should be used in discussions been amply documented. blood-brain barrier can cause new lesions in with relatives of the patient and with our Additional problems seemed to have MS. The anecdotal case reports that form the colleagues in helping to arrive at an appro- plagued this study: for reasons which are not clinical basis for his belief are selected from priate clinical decision. explained, symptoms alone are not recog- large numbers of cases where there is no http://jnnp.bmj.com/ nised as exacerbations. Nevertheless, diplo- temporal relationship between trauma and pa, paresthesiae and vertigo, classic symp- exacerbation and cannot be accepted as valid toms of MS are quite often unaccompanied evidence that trauma is a risk factor in MS. by objective changes in the neurological We agree that if trauma were a causative A prospective study of physical trauma examination. It is curious that Sibley et al factor that all traumas would not be followed and multiple sclerosis used 48 hours' duration for an exacerbation by excacerbations, since many new lesions of as opposed to the more generally accepted 24 MS are symptomatic. However, a study such I read with great interest the article by Sibley hours.6 Finally, it is difficult to draw any as ours should have shown a higher propor- et al.' Because of my own involvement in this conclusions from data given on the basis of tion of excacerbations when at risk for on September 24, 2021 by guest. Protected copyright. particular problem, I wish to make the mean annual exacerbation rates for the sim- trauma in 170 patients over a five year period following comments. ple reason that exacerbations in MS are never since the frequency of trauma was high. There can be no more difficult task than to uniformly distributed; periods of complete The Multiple Sclerosis NMR Group at conduct epidemiological surveys of multiple quiescence lasting several years not uncom- Queen Square has found that in some sclerosis (MS) because of its unpredictability monly occur after a series ofseveral exacerba- patients gadolinium leakage may precede and symptomatic variability. It is therefore tions within a single year. other evidence of new lesion formation; they unsuitable for measurements with the yard- CHARLES M POSER attribute this to , not to trau- sticks currently at hand. Indeed, to design an Department ofNeurology, ma.' Certainly barrier breakdown due to the Harvard Medical School, epidemiologically valid study, it would be Boston, MA, USA perivenular inflammatory lesions is an early necessary to match MS patients (not just event, but we believe that the cause of this healthy controls) for age, sex, ethnic origin, 1 Sibley WA, Bamford CR, Clark K, Smith MS, inflammatory response is unknown and our duration and geographic sites of residence, Laguna JF. A Prospective study of physical data suggest that trauma is not a factor in living and socio-economic environment, trauma and multiple sclerosis. Y Neurol Neu- new lesion formation. duration and of type of rosurg Psychiatry 1991;54:584-9. severity disease, 2 Schoenberg B. Neurological epidemiology. New Our decision to define exacerbations on clinical course, stage of activity, and number York: Raven Press, 1978;1 1, 43. the basis of objective neurological changes and location oflesions using modern imaging 3 McDonald I, Barnes D. Lessons from magnetic only are in keeping with the Schumacher techniques such as MRI. It would be neces- resonance imaging in multiple sclerosis. Committee criteria for Trends Neurosci 1989;12:376-9. definition of a sary to consider not only patients who have 4 Compston A. Immunological aspects of multi- relapse.2 The 48 hour minimum duration of already been diagnosed as having MS, but ple sclerosis. In: MatthewsW (ed) McAlpine's new symptoms was an arbitrary departure also those who have been symptomatic but Multiple Sclerosis, 2nd ed. Edinburgh: Chur- from the Schumacher criteria to help ensure not yet recognised as well as all those chill-livingstone, 1991; 330. patients 5 Poser C. The pathogenesis of multiple sclerosis: that fluctuations in symptoms due to whose symptoms of underlying MS will not a critical reappraisal. Acta Neuropathol and other physiological factors were not appear until they are subjected to trauma. 1986;71: 1-10. counted erroneously as exacerbations. Matters arising 525 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.6.524-b on 1 June 1992. Downloaded from Dr Poser and his colleagues have not often dramatically so, than in the asympto- first third of the book comprises technical attempted any type of epidemiological study matic carriers, or patients with unrelated information about regional cerebral blood to show a relationship between trauma and illnesses. flow measurement using single photon emis- MS. The evidence he cites for a positive In the black South African patient sion tomography (SPET), data analysis and relationship is largely speculative and anec- described by Gledhill, et al' the titres of interpretation of images. It is clearly and dotal. While we agree with him that a HTLV-I antibodies in the serum and CSF simply presented and has been made inter- "perfect" epidemiological study in MS is were extremely high and the diagnostic cate- esting by the authors. The next third consists difficult to design and execute, this fact gory into which he fell viz: TSP or MS, is of examples of SPET in a variety of cerebral should not deter those who would design heavily dependent upon the weight one gives disorders including , , reasonable studies to find out what actually to an episode of unilateral visual failure that , and Parkinson's disease. happens in this illness. was irreversible and the improvement The final third consists of 34 case studies of observed. Whatever the diagnosis, this case is patients with a number of clinical disorders, 1 Kermode AG, Thompson AJ, Tofts P, et al. Breakdown of the blood-brain barrier pre- exceptional. often comparing SPET images with CT, cedes symptoms and other MRI signs of new MRI and angiography investigations. lesions in multiple sclerosis. Brain 1990; 1 Gledhill RF, Dessein PH, Sneider P. Antibody The book has a wealth of information and 113:1477-89. to HTLV-I in a black South African with a 2 Schumacher GA, Beebe G, Kibler RF, et al. neurological disorder resembling multiple a delightful array of colour images which are Problems in experimental trials of therapy sclerosis. SAfrMed3' 1989;75:147-8. very pleasing to the eye. It demonstrates in multiple sclerosis; report by the panel on clearly the results of SPET in cerebral imag- the evaluation of experimental trials of thera- ing and, as such, will be of particular interest py in multiple sclerosis. Ann NY Acad Sci 1 965;122:552-68. Neuropathological features of Alz- to readers of this journal. It has a remarkably heimer's disease in non-demented Par- low price despite the very high quality of kinsonian patients representations on the scans. Two minor quibbles-the clinical descriptions ofsome of I was interested to read about the two cases the disorders are rather simplistic especially Multiple sclerosis, tropical spastic para- reported by Daniel and Lees.' Both of the in view of the readership at which the book is paresis and HTLV-I infection patients had neuropathological features of aimed. Second, a sentence or two of what Alzheimer's disease and nigral loss but clin- future developments may hold for SPET A course without remissions(s) and ically had dopa responsive . would have been very interesting and would relapse(s) was the one clinical feature that However, one of the interesting features of have put the book into perspective. distinguished human T-cell lymphotrophic their condition that may help distinguish All in all, I highly recommend this book. virus type-I (HTLV-I) associated tropical such patients from those with idiopathic Had it not landed on my desk, I was even spastic paraparesis (TSP) invariably from Parkinson's disease, is the speed with which considering buying it myself-quite an multiple sclerosis (MS) in the series of cases they develop involuntary movements related admission for someone of my ethnic origin. reported by Rudge et al.' We do not consider to therapy. In both of their cases the patients ALISTAIR BURNS this to be an absolute rule since we have developed abnormal movements within 12 reported a patient with HTLV-I associated and six months ofstarting oral levadopa. This TSP who did indeed manifest such a pattern may relate to their combined pathology of Focus on Parkinson's Disease. Edited by of illness.2 nigral loss with striatal plaques and neurofi- T CARACENI AND G NAPPI (Pp 235;Price L We should perhaps emphasise3 that our brillary tangles. It will therefore be of interest 78,000). 1991. Milan, Masson, S.p.A. ISBN patient was an African, born and raised in to see ifpatients who develop early dyskinetic 88 214 2057 4 Swaziland where the very occurrence of MS movements with levadopa have similar neu- is quite uncertain. Also, corticosteroids were ropathology. This account of the papers presented at a not given, an intervention that might have ROGER BARKER postgraduate course concerning Parkinson's Department ofExperimental Psychology, contributed to the relapsing-remitting course Cambridge CB2 3EB, UK and extrapyramidal diseases held at Trem- in a case of HTLV-I associated myelopathy ezzo, Italy in April of 1990 comprehensively described recently by McKendall et al.' 1 Daniel SE, Lees AJ. Neuropathological features covers the pathophysiology of akinesia and RF GLEDHILL ofAlzheimer's disease in non-demented Park- hyperkinesia, the aetiology of Parkinson's insonian patients. J Neurol Neurosurg Psy- Department ofInternal Medicine, disease, the multiple system atrophies and Faculty ofMedicine and Health Sciences, chiatry 1991;54:972-5. United Arab Emirates University, current problems and potential develop- http://jnnp.bmj.com/ AlAin, UAE ments in therapy. All but 17 of the 56 PH DESSEIN contributors are from Italy and thus to a Department ofMedicine, University of the Witwatersrand, considerable degree the book represents an Johannesburg, South Africa BOOK authoritative Italian statement concerning Correspondence to: Professor Gledhill. this important group of movement disorders. It is a most impressive account and the 1 Rudge P, Ali A, Cruickshank JK. Multiple REVIEWS sclerosis, tropical spastic paraparesis and balanced content reflects not only the excel- HTLV-I infection in Afro-Caribbean patients lence of the contributors but also the edito-

in the United Kingdom. J Neurol Neurosurg rial skills of Professors Caraceni and Nappi. on September 24, 2021 by guest. Protected copyright. Psychiatry 1991;54:689-94. The text the 2 Gledhill RF, Sneider P, Dessein PH. Antibody All titles reviewed here are available from the is gratifyingly free of irritating to HTLV-I in a black South African with a BMJ Bookshop, PO Box 295, London defects often associated with precipitate pub- neurological disorder resembling multiple WC1H 9TE. Prices include postage in the lication of proceedings and manages to be sclerosis. S AfrMed J 1989;75:147-8. both comprehensive and succinct. Partic- 3 Poser CM, Roman GC, Vernant J-C. Multiple United Kingdom and for members of the sclerosis on HTLV-I myelitis? Neurology British Forces Overseas, but overseas cuto- ularly impressive is an account of the renais- 1990;40: 1020-2. mers should add £2 per item for postage and sance of interest in the subthalamic nucleus 4 McKendall RR, Oas J, Lairmore MD. HTLV-I in the organization of basal ganglia function associated myelopathy endemic inTexas-born packing. Payment can be made by cheque in residents and isolation of virus from CSF sterling drawn on a United Kingdom bank, by Rondot, the biochemistry of Parkinson's cells. Neurology 1991;41:831-6. or by credit card (Mastercard, Visa or Amer- disease by Gerlach and Reiderer, and Duvoi- ican Express) stating card number, expira- sin's critique of genetic and epidemiological Rudge et al reply: tory date, and your full name. factors. Other impressive surveys cover the neuropsychology of the parkinsonian syn- It is true that there are patients with HTLV- dromes, primary autonomic failure, single I positive tropical spastic paraparesis, who do photon emmission computer tomography not show a progressive course, but they are Brain Blood Flow in Neurology and and the management of late complications of exceptional. In fact, the major clinical prob- Psychiatry. Clinician's Guide to Nuclear Parkinson's disease. Perhaps because of the lem is differentiating patients with multiple Medicine Series. By DC COSTA AND PJ ELL rapidity of recent developments, the chapter sclerosis from those with TSP when the Series Editor: Pj ELL (Pp 182 Illustrated; on adrenal medullary implants is not the course is progressive. Such a situation arises Price £14.95). 1991. Edinburgh, Churchill strongest or most critical but does illustrate in HTLV-I endemic areas where the two Livingstone. ISBN 0 443 04282 9 the breadth of topics covered. The book is conditions co-exist, for example Brazil. Obvi- printed in Italy and not surprisingly is ele- ously a small proportion of the population This is a compact volume in the series gantly produced and the print is agreeable to will have HTLV-I antibodies in their serum, "Clinicians Guide to Nuclear Medicine" read. but as a rule in TSP the titres are higher, which is edited by the second author. The GERALD STERN