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Immunosuppressive treatment in multiple sclerosis
278
Immunosuppressive Treatment in Multiple Sclerosis,
b y P. D e l m o t t e , O. R. H o m m e s
a n d R . G o n s e t t e ( E d s . ) , 2 2 4 p a g e s , E u r o p e a n P r e s s , G h e n t , 1977, B f r 1 5 5 0 . - - ( E u r o p e a n c o u n t r i e s ) , Bfr. 1 8 0 0 . - - n o n - E u r o p e a n
countries).
This volume consists of a report of the Workshop held at the Nationaal Centrum for Multiple Sclerose, Melsbroeck, Belgium, in April t977 and has been published with commendable promptitude. After summary accounts of the possible role of immunological factors in the aetiology of M S and of the immunosuppressant agents available, the main topic of the effects of such treatment is launched. The reviewer must confess to a severe sense of disappointment. In a number of centres large numbers of patients have been treated with various regimes ofazathioprine, cyclophosphamide, levamisoleand steroids, with frequent claims of arrest of the disease or reduction in relapse rate. In not one of these studies was any attempt made to compare the results with concurrently observed controls and "blind" assessment of the results was naturally impossible. Many authors go to some lengths to justify the use of the patients as their own controls but evidently feel somewhat uneasy about doing so. Anyone who has been engaged in the long-term assessment of patients with MS will be conscious of the subjective nature of the decision as to what constitutes a relapse rather than an increased awareness of symptoms from fatigue or heat. The assessment of the clinical state, apart from gross changes, also presents great obstacles to objectivity unless phenomena are actually measured, rather than graded or scored. In any serious attempt at treatment of MS a randomised blind controlled trial is surely essential. Only one such is reported in the present volume, no doubt reflecting the great difficulties of organisation involved. Mertin and Knight report the design of a controlled trial of anti-lymphocytic globulin but do not present results as the code has not yet been broken. Unfortunately, there appears to have been some doubt about the potency of the initial batch of A L G but the design of the trial appears admirable. If similar methods had been used in the assessment of other forms of immunosuppression we would by now have learnt whether these are effective or not. The claims made for the different regimes described at this workshop cannot be regarded as being supported by scientific evidence. W. B. Matthews
Antiepileptic Drug Monitoring, b y
C. G a r d n e r - T h o r p e ,
D . J a n z , H . M e i n a r d i a n d C. E.
P i p p e n g e r ( E d s . ) , vii ÷ 388 p a g e s , 119 i l l u s t r a t i o n s , 102 t a b l e s , P i t m a n M e d i c a l , T u n b r i d g e W e l l s , K e n t , 1977, £ 16.00. This is basically the proceedings of a "workshop" on the estimation of anti-convulsants in body fluids. Its readership will be dual and somewhat disparate laboratory scientists and clinicians. The book's presentation of laboratory work is useful as an indication of new techniques and their difficulties, and as a guide to the more detailed references needed to bring them into use. For clinicians it may also allow some assessment of the reliability of the results they must use in treatment. However, on the general theme of anti-convulsant estimations they may also ask other questions. Neurologists are increasingly beset by the problems of the exact site and method of drug action within the nervous system. For instance do anticonvulsants simply reduce epileptic firing by direct action on discharging neurones, or is the process more complex with stimulated inhibitory activity inpinging on the discharge? Again, how do drug levels in the brain, and perhaps in differing parts, which must be the final site ofanti-convulsanl action, relate to those in serum and CSF? What may account for the unexpected and large fluctuations sometimes reported? Is it solely the primary drug itself or perhaps some of its breakdown products which are responsible for the anti-convulsant activity ? Some of these questions are at least partly answered. The first is perhaps more for detailed neurophysiological or neuropharmacological study. However, on the distribution of drug levels, a correlation of synchronous estimations in brain, CSF and plasma gives valuable confirmation of still rather scanty work suggesting some linear relation. While the possible technical reasons for fluctuations are well dealt with, other increasingly important factors such as enzyme induction (or inhibition) is little mentioned. Further definition is needed of the potentially wide range of factors which may operate this mechanism. Drug interaction and substrate competition are discussed, but not indexed and thus difficult to find. Consideration is also given to the activity of metabolites and this information is more easily located as part of the index entry of pharmacokinetics. An appendix gives a useful index of anti-convulsants by trade and official name. All those concerned with the management of epilepsy will find parts of this book helpful: but some of its reports require critical assessment before being applied to patients. It is sad that its high price may limit the range of purchasers. C. W. M. Whitty
Immunosuppressive Treatment in Multiple Sclerosis,
b y P. D e l m o t t e , O. R. H o m m e s
a n d R . G o n s e t t e ( E d s . ) , 2 2 4 p a g e s , E u r o p e a n P r e s s , G h e n t , 1977, B f r 1 5 5 0 . - - ( E u r o p e a n c o u n t r i e s ) , Bfr. 1 8 0 0 . - - n o n - E u r o p e a n
countries).
This volume consists of a report of the Workshop held at the Nationaal Centrum for Multiple Sclerose, Melsbroeck, Belgium, in April t977 and has been published with commendable promptitude. After summary accounts of the possible role of immunological factors in the aetiology of M S and of the immunosuppressant agents available, the main topic of the effects of such treatment is launched. The reviewer must confess to a severe sense of disappointment. In a number of centres large numbers of patients have been treated with various regimes ofazathioprine, cyclophosphamide, levamisoleand steroids, with frequent claims of arrest of the disease or reduction in relapse rate. In not one of these studies was any attempt made to compare the results with concurrently observed controls and "blind" assessment of the results was naturally impossible. Many authors go to some lengths to justify the use of the patients as their own controls but evidently feel somewhat uneasy about doing so. Anyone who has been engaged in the long-term assessment of patients with MS will be conscious of the subjective nature of the decision as to what constitutes a relapse rather than an increased awareness of symptoms from fatigue or heat. The assessment of the clinical state, apart from gross changes, also presents great obstacles to objectivity unless phenomena are actually measured, rather than graded or scored. In any serious attempt at treatment of MS a randomised blind controlled trial is surely essential. Only one such is reported in the present volume, no doubt reflecting the great difficulties of organisation involved. Mertin and Knight report the design of a controlled trial of anti-lymphocytic globulin but do not present results as the code has not yet been broken. Unfortunately, there appears to have been some doubt about the potency of the initial batch of A L G but the design of the trial appears admirable. If similar methods had been used in the assessment of other forms of immunosuppression we would by now have learnt whether these are effective or not. The claims made for the different regimes described at this workshop cannot be regarded as being supported by scientific evidence. W. B. Matthews
Antiepileptic Drug Monitoring, b y
C. G a r d n e r - T h o r p e ,
D . J a n z , H . M e i n a r d i a n d C. E.
P i p p e n g e r ( E d s . ) , vii ÷ 388 p a g e s , 119 i l l u s t r a t i o n s , 102 t a b l e s , P i t m a n M e d i c a l , T u n b r i d g e W e l l s , K e n t , 1977, £ 16.00. This is basically the proceedings of a "workshop" on the estimation of anti-convulsants in body fluids. Its readership will be dual and somewhat disparate laboratory scientists and clinicians. The book's presentation of laboratory work is useful as an indication of new techniques and their difficulties, and as a guide to the more detailed references needed to bring them into use. For clinicians it may also allow some assessment of the reliability of the results they must use in treatment. However, on the general theme of anti-convulsant estimations they may also ask other questions. Neurologists are increasingly beset by the problems of the exact site and method of drug action within the nervous system. For instance do anticonvulsants simply reduce epileptic firing by direct action on discharging neurones, or is the process more complex with stimulated inhibitory activity inpinging on the discharge? Again, how do drug levels in the brain, and perhaps in differing parts, which must be the final site ofanti-convulsanl action, relate to those in serum and CSF? What may account for the unexpected and large fluctuations sometimes reported? Is it solely the primary drug itself or perhaps some of its breakdown products which are responsible for the anti-convulsant activity ? Some of these questions are at least partly answered. The first is perhaps more for detailed neurophysiological or neuropharmacological study. However, on the distribution of drug levels, a correlation of synchronous estimations in brain, CSF and plasma gives valuable confirmation of still rather scanty work suggesting some linear relation. While the possible technical reasons for fluctuations are well dealt with, other increasingly important factors such as enzyme induction (or inhibition) is little mentioned. Further definition is needed of the potentially wide range of factors which may operate this mechanism. Drug interaction and substrate competition are discussed, but not indexed and thus difficult to find. Consideration is also given to the activity of metabolites and this information is more easily located as part of the index entry of pharmacokinetics. An appendix gives a useful index of anti-convulsants by trade and official name. All those concerned with the management of epilepsy will find parts of this book helpful: but some of its reports require critical assessment before being applied to patients. It is sad that its high price may limit the range of purchasers. C. W. M. Whitty