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Modern concepts in brain tumour therapy — Laboratory and clinical investigations
299 to see cases over the next few years. It is timely therefore to have a review of tuberculous meningitis, its presentation and pathology. In this small m o n o g r a p h Dr. Parsons has presented a very clear account of the current understanding o f the disease, its behaviour and treatment. He makes the point that early recognition of micro-bacteria in the CSF of a patient is crucial and can lead to early treatment but one feels he is a little optimistic in his hopes for genuine positive results despite recent advent of fluorescent microscopy. It is as well to bear in mind that any lymphocytic meningitis should be suspected as tuberculous, until conclusively proved otherwise. In m a n y cases in this country the diagnosis remains in doubt until positive culture or guinea pig inoculation have confirmed it and these cases are best treated with triple therapy in the interim. Dr. Parsons gives a full account of the antibiotics available, their advantages and disadvantages. He discusses the case for intrathecal treatment discussing the dangers and risks in addition to the theoretical advantages. Unfortunately he does not give us his own opinion. Fuller accounts of tuberculous meningitis and its various features are available in the writings from the Indian Subcontinent but this little m o n o g r a p h is a useful synopsis and at 55 pages can very quickly be absorbed. Recent experience has indicated that hydrocephalus is often an unrecognised, early complication in this disease. The advent of CAT scanning has shown this very clearly and perhaps if the book runs into a second edition Dr. Parsons might advise an early search for and prophylactic treatment of the hydrocephalus. J. B. Foster
Current Neurology, Vol. 2, by H.R. Tyler and D. M. Dawson (Eds.), 531 pages,
illustrated, Houghton Mifflin Professional Publishers, Boston, MA, 1979, US $ 34.00 (in U.S.A.), US $ 42.50 (elsewhere). This is the second volume of the justifiably highly praised new series of neurological text books. The editors, Richard Tyler and David Dawson with their team of distinguished contributors intend to cover the whole field of neurology recurrently in a two or three year cycle a formidable task which they have tackled with skill and enthusiasm. This second volume contains what they call "'up-dates", i.e., summaries of recent research work on topics covered in detail in the first volume. These require studying in conjunction with previous chapters which are much more detailed and of course, this means that the discerning reader will have to purchase the whole series and not merely individual volumes ! This reviewer finds it a difficult task to select chapters for special mention and is merely reflecting his own clinical interest when he highlights the discussion on "Myasthenic Syndromes" by Bernard Patten and the excellent review of "'The Heart and Neurological Disorders" by Martin Samuels. The "up-date'" on Huntington's disease - - this reviewer's choice, as the outstanding chapter in Volume l, is especially well written and worthy of praise. The whole book is admirably presented with clear illustrations and references that are as upto-date as is possible. It is too comprehensive for beginners, but is, as the authors state, a thorough source of reference and a most readable survey on recent research work in neurology. This reader has certainly been "'hooked" and looks forward with keen anticipation to the next volume. R . G . Lascelles
Modern Concepts in Brain Tumour Therapy - - Laboratory and Clinical Investigations, by A. E. Evans, iv + 220 pages, 62 illustrations, 72 tables, Castle House Publications Ltd., Tunbridge Wells, Kent, 1979, £ 25.00. This book is a collection of the papers presented at a Symposium held in Atlanta in February 1976 which was sponsored by the National Cancer Institute. At the end of each section the ensuing discussion, or at least part of it, is reported verbatim. The papers are arranged in sections which can be summarised broadly as: animal studies with pharmacodynamics and cell kinetics; pathology; diagnostic methods:
300 surgical m a n a g e m e n t ; chemotherapy, radiotherapy and prognostic l:actors: current Brain T u m o u r Study Group activities. In a field which is in a state of constant change this book may be of considerable value in its attempt to bring together the different aspects of this difficult subject upon which so much current work depends. Therefore the sections which deal with basic studies in pharmacodynamics, cell kinetics, animal models and the chemical- and virus-induced tumours are likely to be of more laboratory reference value than some of the later papers which report therapeutic trials in which the results have not been of any major significance and which have been superseded by later works. Amongst the papers in the earlier sections of the book that on "'Chemical- and Virus-lnduced Brain Turnouts'" is an extremely valuable and succinct review of the subject with 63 references, and this particular chapter will continue to provide laboratory and clinical workers with a ready source of basic references. The next chapter on "Animal Models of Brain Tumours'" is of similar value but there is inevitable reduplication of some material. The chapter on "'Pharmacodynamics and the Blood Brain Barrier" is less successful probably because the complexity of the subject demands much fuller treatment particularly for readers not working in this field. Work on cell kinetics is summarised and new rapid methods for the estimation of kinetic parameters described. The five papers which can bc grouped broadly under the heading of Pathology, provide a very uneven review and here, as in later sections of the book, problems concerning the purpose and design of symposia and their publication begin to arise. It seems strange that 19 pages should be devoted to the pathology of radiation damage to the normal brain of the monkey, while only 6 arc given to the controversial and crucial problem of the nomenclatures of gliomas, which continues to cause considerable difficulty when allocating patients to treatment arms particularly in multi-centre lrials. Fortunately this theme is developed more cogently in the paper on pathologic tumour type and response to treatment, and the favourable lector of age (adults below 40) which correlates with the lower incidence of transition to glioblastoma multiformc is noted. The paper on autopsy pathology from patients treated by the Brain T u m o u r Study Group is valuable in revealing the problems and deficiencies in obtaining comprehensive and meaningful material. Thus it is surprising and indeed disappointing to find that of 523 patients studied until death only 110 had autopsies of whom histologic sections from only 53 were available. Furthermore autopsy protocols were received in only 31 patients. In the light of these figures it is surprising that the authors feel able to comment upon a comparison of histology of the original biopsy specimens and that of the autopsy specimens, and ~i)r similar reasons upon the ultimate causes of death. However. the comments upon greater degrees of anaplasia, endothelial proliferation and necrosis in autopsy specimens compared to the earlier surgical specimens arc helpful in underlining the grave difficulties in using autopsy and not surgical material in assessing methods of '~reatmcnt; sadly this practice continues in some 1979 publications. In the section on diagnostic radiology attention is drawn to the contmt6ng value of radio-isotope scanning which is complementary to CT scanning, particularly when determining recurrence of turnout growth. The papers on CSF steroids and polyamines in relation to brain m m o u r s are essentially reports of studies without applicable conclusions. The later papers in the book deal with various aspects of clinical trials and much of the work has been published elsewhere and will be already familiar to those working in these fields. The problem of writing or speaking for a particular audience is evident in the paper on surgical management which contributes little for neurosurgeons, but which may be of some value t\)r those not familiar with neurosurgical practice. Unfortunately the presentation of the material is remarkably uncritical : t o conclude that "aggressive surgical removal of malignant brain tumours ...can be performed with low mortality and morbidity rates in carefully selected patients" in the face of table 5 (p. 141) which indicates that only 13 of 28 patients with glioblastoma so managed "in the past 2 years" were surviving is somcwhal incongruous. Fortunately it is admitted that the "'presentation does not establish the value of radical surgery in the treatment of malignant gliomas". The paper on corticosteroid therapy is very valuable and the statement that "'corticosteroids influence and therefore obscure every known index of clinical response to brain t u m o u r chemotherapy'" is disregarded too frequently by lhose designing and reporting clinical trials. Indeed, although the importance of control of steroids is admitted in the following paper (needle biopsy, corticosteroids and radiotherapy), rigid control was not instituted and it is difficult to draw any meaningful conclusions. It is therefore encouraging that in the survey of current activities of the Bruin T u m o u r Study Group, a study of the anti-neoplastic effect of steroids is being undertaken. The later papers in the book deal with therapeutic trials including hyperbaric oxygen, radiotherapy, nitrosurcas and methotrcxate and discuss prognostic factors and criteria ol" response to treatment. Much of the work has bccn published
301 elsewhere and is uneven particularly in matters of statistical significance, and is not likely to be of lasting reference value. The points made in the discussion section are generally of passing interest only, and much is anecdotal, and an expression of opinion which does not always merit publication. Dr. Michael Walker comments (p. 199) "A pressing need exists for tightly controlled studies that clearly define the characteristics of the patient population and that will develop therapeutic data which, though at first may not reflect dramatic gains will provide a basis for the planning of future studies". Certainly these sentiments will be echoed by all those working seriously in these fields. The difficulty with a publication such as Modern Concepts in Brain Tumour Therapy is to assess its place in the light of Dr. Walker's comment, and inevitably there must be reservations. Sadly, some of the material does not merit re-reading, especially that which contains expressions of opinion without factual basis, whereas the earlier sections do provide a valuable reference source. Finally it is difficult to understand why well over three years has elapsed between the presentation o f the papers and their publication. John Garfield
Muscle, Nerve and Brain Degeneration Proceedings of a Symposium of the Foundation for Life Sciences, Sydney, 12-16 February, 1979) (International Congress Series, No. 473), by A.D. Kidman and J.K. Tomkins (Eds.), x + 230 pages, illustrated, Excerpta Medica, Amsterdam, 1979, US $ 41.50, Dfl 85.00. This Australian symposium, diffusely entitled Muscle, Nerve and Brain Degeneration, contains two types of contribution. A group of well-selected research professors from the Northern Hemisphere provide an analysis of the present state of their chosen fields, pointing out potential lines of research. Dubowitz covers genetic muscle disorders, emphasising the associated respiratory and bulbar problems in early life which may confront the neuropaediatrician. Bradley, on the aetiology of amyotrophic lateral sclerosis, refers particularly to the role of pancreatic insufficiency and viral immunology of the small bowel. Where the aetiology is known, following lead poisoning, poliomyelitis or associated with neoplasia, the ALS is more benign and predominantly of LMN type. Thesleff finds a correlation between particle endocytosis, sarcotubular lysozyme activation and calcium perturbations in muscle; thus it is possible that micropinocytosis, potentially controllable by drugs or by endogenous mechanisms, may function as an inducer of degenerative changes in skeletal muscle. Terry's descriptive and histological discussion of Alzheimer's disease precedes Davison's histochemical analysis. As yet the most significant histochemical change found in Alzheimer's disease is a 65% reduction of choline acetyltransferase activity. The research papers which form the Antipodean contribution are more uneven. Only one is concerned in any way with dementia: Rees discusses the identification of neuronal inclusions before outlining work on the intracerebral injection of suramin in rats to provide an experimental model for mucopolysaccharide storage diseases. Kidman gives a well rounded presentation of the role of satellite cells in axonal metabolism ; and Gage and Barry discuss the properties of endplate channels in relation to acetylcholine receptors and cation permeability. However, the most fruitful research described appertains to muscle disease. Tomas and Ballard are concerned with measures which could prevent the failure of premature infants to conserve protein. Tomkins and Collins discuss the potential of leupeptin as a protease inhibitor. And Jeffrey's studies on the increased concentration of membrane-bound carbohydrate following denervation suggest an excellent research programme. In publishing this symposium the organisers appear to have two basic aims: to stimulate further research in Australasia and to bridge the equatorial communication barrier. They may well succeed in their first objective. E. M. R. Critchley
Current Neurology, Vol. 2, by H.R. Tyler and D. M. Dawson (Eds.), 531 pages,
illustrated, Houghton Mifflin Professional Publishers, Boston, MA, 1979, US $ 34.00 (in U.S.A.), US $ 42.50 (elsewhere). This is the second volume of the justifiably highly praised new series of neurological text books. The editors, Richard Tyler and David Dawson with their team of distinguished contributors intend to cover the whole field of neurology recurrently in a two or three year cycle a formidable task which they have tackled with skill and enthusiasm. This second volume contains what they call "'up-dates", i.e., summaries of recent research work on topics covered in detail in the first volume. These require studying in conjunction with previous chapters which are much more detailed and of course, this means that the discerning reader will have to purchase the whole series and not merely individual volumes ! This reviewer finds it a difficult task to select chapters for special mention and is merely reflecting his own clinical interest when he highlights the discussion on "Myasthenic Syndromes" by Bernard Patten and the excellent review of "'The Heart and Neurological Disorders" by Martin Samuels. The "up-date'" on Huntington's disease - - this reviewer's choice, as the outstanding chapter in Volume l, is especially well written and worthy of praise. The whole book is admirably presented with clear illustrations and references that are as upto-date as is possible. It is too comprehensive for beginners, but is, as the authors state, a thorough source of reference and a most readable survey on recent research work in neurology. This reader has certainly been "'hooked" and looks forward with keen anticipation to the next volume. R . G . Lascelles
Modern Concepts in Brain Tumour Therapy - - Laboratory and Clinical Investigations, by A. E. Evans, iv + 220 pages, 62 illustrations, 72 tables, Castle House Publications Ltd., Tunbridge Wells, Kent, 1979, £ 25.00. This book is a collection of the papers presented at a Symposium held in Atlanta in February 1976 which was sponsored by the National Cancer Institute. At the end of each section the ensuing discussion, or at least part of it, is reported verbatim. The papers are arranged in sections which can be summarised broadly as: animal studies with pharmacodynamics and cell kinetics; pathology; diagnostic methods:
300 surgical m a n a g e m e n t ; chemotherapy, radiotherapy and prognostic l:actors: current Brain T u m o u r Study Group activities. In a field which is in a state of constant change this book may be of considerable value in its attempt to bring together the different aspects of this difficult subject upon which so much current work depends. Therefore the sections which deal with basic studies in pharmacodynamics, cell kinetics, animal models and the chemical- and virus-induced tumours are likely to be of more laboratory reference value than some of the later papers which report therapeutic trials in which the results have not been of any major significance and which have been superseded by later works. Amongst the papers in the earlier sections of the book that on "'Chemical- and Virus-lnduced Brain Turnouts'" is an extremely valuable and succinct review of the subject with 63 references, and this particular chapter will continue to provide laboratory and clinical workers with a ready source of basic references. The next chapter on "Animal Models of Brain Tumours'" is of similar value but there is inevitable reduplication of some material. The chapter on "'Pharmacodynamics and the Blood Brain Barrier" is less successful probably because the complexity of the subject demands much fuller treatment particularly for readers not working in this field. Work on cell kinetics is summarised and new rapid methods for the estimation of kinetic parameters described. The five papers which can bc grouped broadly under the heading of Pathology, provide a very uneven review and here, as in later sections of the book, problems concerning the purpose and design of symposia and their publication begin to arise. It seems strange that 19 pages should be devoted to the pathology of radiation damage to the normal brain of the monkey, while only 6 arc given to the controversial and crucial problem of the nomenclatures of gliomas, which continues to cause considerable difficulty when allocating patients to treatment arms particularly in multi-centre lrials. Fortunately this theme is developed more cogently in the paper on pathologic tumour type and response to treatment, and the favourable lector of age (adults below 40) which correlates with the lower incidence of transition to glioblastoma multiformc is noted. The paper on autopsy pathology from patients treated by the Brain T u m o u r Study Group is valuable in revealing the problems and deficiencies in obtaining comprehensive and meaningful material. Thus it is surprising and indeed disappointing to find that of 523 patients studied until death only 110 had autopsies of whom histologic sections from only 53 were available. Furthermore autopsy protocols were received in only 31 patients. In the light of these figures it is surprising that the authors feel able to comment upon a comparison of histology of the original biopsy specimens and that of the autopsy specimens, and ~i)r similar reasons upon the ultimate causes of death. However. the comments upon greater degrees of anaplasia, endothelial proliferation and necrosis in autopsy specimens compared to the earlier surgical specimens arc helpful in underlining the grave difficulties in using autopsy and not surgical material in assessing methods of '~reatmcnt; sadly this practice continues in some 1979 publications. In the section on diagnostic radiology attention is drawn to the contmt6ng value of radio-isotope scanning which is complementary to CT scanning, particularly when determining recurrence of turnout growth. The papers on CSF steroids and polyamines in relation to brain m m o u r s are essentially reports of studies without applicable conclusions. The later papers in the book deal with various aspects of clinical trials and much of the work has been published elsewhere and will be already familiar to those working in these fields. The problem of writing or speaking for a particular audience is evident in the paper on surgical management which contributes little for neurosurgeons, but which may be of some value t\)r those not familiar with neurosurgical practice. Unfortunately the presentation of the material is remarkably uncritical : t o conclude that "aggressive surgical removal of malignant brain tumours ...can be performed with low mortality and morbidity rates in carefully selected patients" in the face of table 5 (p. 141) which indicates that only 13 of 28 patients with glioblastoma so managed "in the past 2 years" were surviving is somcwhal incongruous. Fortunately it is admitted that the "'presentation does not establish the value of radical surgery in the treatment of malignant gliomas". The paper on corticosteroid therapy is very valuable and the statement that "'corticosteroids influence and therefore obscure every known index of clinical response to brain t u m o u r chemotherapy'" is disregarded too frequently by lhose designing and reporting clinical trials. Indeed, although the importance of control of steroids is admitted in the following paper (needle biopsy, corticosteroids and radiotherapy), rigid control was not instituted and it is difficult to draw any meaningful conclusions. It is therefore encouraging that in the survey of current activities of the Bruin T u m o u r Study Group, a study of the anti-neoplastic effect of steroids is being undertaken. The later papers in the book deal with therapeutic trials including hyperbaric oxygen, radiotherapy, nitrosurcas and methotrcxate and discuss prognostic factors and criteria ol" response to treatment. Much of the work has bccn published
301 elsewhere and is uneven particularly in matters of statistical significance, and is not likely to be of lasting reference value. The points made in the discussion section are generally of passing interest only, and much is anecdotal, and an expression of opinion which does not always merit publication. Dr. Michael Walker comments (p. 199) "A pressing need exists for tightly controlled studies that clearly define the characteristics of the patient population and that will develop therapeutic data which, though at first may not reflect dramatic gains will provide a basis for the planning of future studies". Certainly these sentiments will be echoed by all those working seriously in these fields. The difficulty with a publication such as Modern Concepts in Brain Tumour Therapy is to assess its place in the light of Dr. Walker's comment, and inevitably there must be reservations. Sadly, some of the material does not merit re-reading, especially that which contains expressions of opinion without factual basis, whereas the earlier sections do provide a valuable reference source. Finally it is difficult to understand why well over three years has elapsed between the presentation o f the papers and their publication. John Garfield
Muscle, Nerve and Brain Degeneration Proceedings of a Symposium of the Foundation for Life Sciences, Sydney, 12-16 February, 1979) (International Congress Series, No. 473), by A.D. Kidman and J.K. Tomkins (Eds.), x + 230 pages, illustrated, Excerpta Medica, Amsterdam, 1979, US $ 41.50, Dfl 85.00. This Australian symposium, diffusely entitled Muscle, Nerve and Brain Degeneration, contains two types of contribution. A group of well-selected research professors from the Northern Hemisphere provide an analysis of the present state of their chosen fields, pointing out potential lines of research. Dubowitz covers genetic muscle disorders, emphasising the associated respiratory and bulbar problems in early life which may confront the neuropaediatrician. Bradley, on the aetiology of amyotrophic lateral sclerosis, refers particularly to the role of pancreatic insufficiency and viral immunology of the small bowel. Where the aetiology is known, following lead poisoning, poliomyelitis or associated with neoplasia, the ALS is more benign and predominantly of LMN type. Thesleff finds a correlation between particle endocytosis, sarcotubular lysozyme activation and calcium perturbations in muscle; thus it is possible that micropinocytosis, potentially controllable by drugs or by endogenous mechanisms, may function as an inducer of degenerative changes in skeletal muscle. Terry's descriptive and histological discussion of Alzheimer's disease precedes Davison's histochemical analysis. As yet the most significant histochemical change found in Alzheimer's disease is a 65% reduction of choline acetyltransferase activity. The research papers which form the Antipodean contribution are more uneven. Only one is concerned in any way with dementia: Rees discusses the identification of neuronal inclusions before outlining work on the intracerebral injection of suramin in rats to provide an experimental model for mucopolysaccharide storage diseases. Kidman gives a well rounded presentation of the role of satellite cells in axonal metabolism ; and Gage and Barry discuss the properties of endplate channels in relation to acetylcholine receptors and cation permeability. However, the most fruitful research described appertains to muscle disease. Tomas and Ballard are concerned with measures which could prevent the failure of premature infants to conserve protein. Tomkins and Collins discuss the potential of leupeptin as a protease inhibitor. And Jeffrey's studies on the increased concentration of membrane-bound carbohydrate following denervation suggest an excellent research programme. In publishing this symposium the organisers appear to have two basic aims: to stimulate further research in Australasia and to bridge the equatorial communication barrier. They may well succeed in their first objective. E. M. R. Critchley