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FOLIC ACID AND NEUROPATHY IN EPILEPSY
146
glomeruli. In other contexts, transplantation antibodies are not necessarily non-existent when they are not totipotent and, as the late Peter Gorer used to point out repeatedly, this would cause no surprise except to a select band of transplanters. Department of Surgery, Royal Postgraduate Medical School, Ducane Road, London W.12.
W. J. DEMPSTER
MEDICAL STUDENTS AND GENERAL PRACTICE SIR,-We should like to congratulate Dr. Pearson and his colleagues, whose article appeared last week (p. 81), for drawing attention once more to the inadequacies of present methods of teaching in general practice in a large proportion of our medical schools. Their survey leaves one with the impression that most attachment schemes are ill-conceived afterthoughts in which medical students in their 5th or final year are shown something of the peculiarities of general practice in an unstructured, unsupervised way with little participation by the staff of the medical school itself. It is possible that a postal inquiry is not the best method of eliciting facts of the type they sought and in this medical school at least the teaching of general and community practice is not of the type they describe. The 1967 recommendations of the General Medical Council were to a large extent anticipated in Newcastle in 1964 when, despite the absence of a department of general practice or of social medicine, a course in family and community medicine was instituted as a component part of the revised medical curriculum.1 All lst-year clinical students take part, and the course is evolving at regular meetings of the teaching group in the light of experience on the part of the teachers and of the, feed-back of criticism and suggestion by the students. The group consists of 12 general practitioners appointed as clinical tutors in family medicine by the university, 2 doctors from public health, 6 hospital consultants from a variety of disciplines led by a faculty subcommittee which has included 3 general practitioners, and the professors of pxdiatrics, obstetrics, and industrial health, together with other senior members of the university. The general practitioners are carefully selected members of partnership and group practices, able to devote two mornings each week to teaching without too much distraction by routine practice work. They follow a planned, though flexible, teaching programme which emphasises the personal, emotional, and Students are psychological aspects of family medicine. attached in pairs to one of the practices and are expected during their 5 weeks to keep records of the clinical cases they see and in particular to become involved with and study in depth a particular family situation. They present this study at the final seminar of the course held in the teaching hospital and attended by both the community and the hospital based doctors of the group. The student therefore has 10 compulsory sessions in general practice, and in addition attends on a voluntary basis, evening surgeries, antenatal clinics, and emergency calls, as well as spending additional time " working up " his family. Alternate mornings are spent in community medicine. During this time the student is offered experience of a wide range of community services and visits with members of the " domiciliary team "-the health visitor, the district nurse, and the social worker. He studies child-health services in clinic and school, rehabilitation, mental health, public health in the environment, and community geriatrics. Regular seminars during this part of the course, conducted by one of us, enable the student to correlate these two aspects of medicine in the community. In addition to this course, which takes place during the 1st clinical year, the student may spend one of his elective periods in his 2nd or 3rd clinical year in general practice. Over the past 3 years a total of 10 students have been attached full-time for periods ranging from 3 weeks to 3 months to a variety of general practitioners in more distant parts of the region. There is careful briefing by members of the teaching 1.
Walker, J. H., Barnes, H. G. Br. med. J. 1966, ii,
1129.
group, and every effort is made to ensure that there is nothing " amateur or haphazard " about these attachments. In addition to this planned clinical experience in general and community practice, the student meets during the systematiclecture part of his medical training a variety of general practitioners whose special interests are appropriate to the particular topic being taught. During the course dealing with diseases of the respiratory tract, a general practitioner lectures upon and discusses the presentation and management of upper-respiratory-tract infection, another the social consequences of chronic bronchitis, and a third the management of asthma in the home. If our scheme does not constitute " a bold innovation," we feel that in Newcastle at least considerable progress has been made. One valuable by-product has been the establishment of collaborative community research projects: these have involved the university departments of psychological medicine, public health, industrial health and medical statistics, midwifery, and child health, the M.R.C. growth and reproduction unit, and a number of general
practitioners. These activities are creating the atmosphere of a " third faculty", through which students are seeing the challenge and the fascination of practice in the community in all its aspects. University Department of Public Health, Medical School, Newcastle upon Tyne 1
ANDREW SMITH
JOHN H. WALKER.
FOLIC ACID AND NEUROPATHY IN EPILEPSY SiR,ŃIwas interested to read the observations of Dr. Horwitz and his colleagues. Since the inferences drawn are controversial, I should like to present an alternative
interpretation. The incidence of peripheral neuropathy in what I assume be a random group of epileptics, treated for 10 years or more with anticonvulsants, must be very much higher than in patients with any other disorder of unrelated xtiology. Since the anticonvulsant therapy was the most likely common denominator, it would seem reasonable to attribute the neuropathy to the anticonvulsants. The evidence that the dementia, cerebellar degeneration, and neuropathy sometimes seen in drug-treated epileptics may be due to interference with folate metabolism deserves consideration. I, and other observers,2have noted that folic acid sometimes provokes epilepsy in folate-deficient anticonvulsanttreated epileptic patients. Lately a folate-deficient patient (serum-folate 0-75 ng. per ml., red-blood-cell folate 75 ng. per ml., cerebrospinal fluid (C.S.F) folate 5 ng. per ml.) died in uncontrolled status epilepticus after being treated orally with folic acid. These observations suggest that folic acid affects the central nervous system. Moreover there is evidence that anticonvulsants interfere with folate metabolism within the nervous system, since the C.S.F.-folate level in drug-treated epileptics is statistically significantly lower than in control patients.4The only two documented anticonvulsant-treated epileptics with signs and symptoms suggestive of cerebellar degeneration, in whom c.s.F.-folate concentration has been assayed, both had very low c.s.F.-folate levels.46 Clinical reports of patients with neuropyschiatric disorders improving after oral folic-acid therapy are subject to errors of observer bias. The electrophysiological techniques employed by Dr. Horwitz and his colleagues are more objective, and are to be commended. If further studies are contemplated I believe it would be more valuable to compare the electrodiagnostic findings with the c.s.F.-folate activity. D. G. WELLS. Epsom, Surrey.
to
1. 2. 3. 4. 5. 6.
Horwitz, S. J., Klipstein, F. A., Lovelace, R. Lancet, 1967, ii, 1305. Chanarin, I., Laidlaw, J., Loughridge, L. W., Mollin, D. L. Br. med. J. 1960, i, 1099. Reynolds, E. H. Lancet, 1967, i, 1086. Wells, D. G., Casey, H. J. Br. med. J. 1967, iii, 834. Reynolds, E. H., Chanarin, I. Unpublished. Wells, C. Proc. R. Soc. Med. 1965, 58, 721.
glomeruli. In other contexts, transplantation antibodies are not necessarily non-existent when they are not totipotent and, as the late Peter Gorer used to point out repeatedly, this would cause no surprise except to a select band of transplanters. Department of Surgery, Royal Postgraduate Medical School, Ducane Road, London W.12.
W. J. DEMPSTER
MEDICAL STUDENTS AND GENERAL PRACTICE SIR,-We should like to congratulate Dr. Pearson and his colleagues, whose article appeared last week (p. 81), for drawing attention once more to the inadequacies of present methods of teaching in general practice in a large proportion of our medical schools. Their survey leaves one with the impression that most attachment schemes are ill-conceived afterthoughts in which medical students in their 5th or final year are shown something of the peculiarities of general practice in an unstructured, unsupervised way with little participation by the staff of the medical school itself. It is possible that a postal inquiry is not the best method of eliciting facts of the type they sought and in this medical school at least the teaching of general and community practice is not of the type they describe. The 1967 recommendations of the General Medical Council were to a large extent anticipated in Newcastle in 1964 when, despite the absence of a department of general practice or of social medicine, a course in family and community medicine was instituted as a component part of the revised medical curriculum.1 All lst-year clinical students take part, and the course is evolving at regular meetings of the teaching group in the light of experience on the part of the teachers and of the, feed-back of criticism and suggestion by the students. The group consists of 12 general practitioners appointed as clinical tutors in family medicine by the university, 2 doctors from public health, 6 hospital consultants from a variety of disciplines led by a faculty subcommittee which has included 3 general practitioners, and the professors of pxdiatrics, obstetrics, and industrial health, together with other senior members of the university. The general practitioners are carefully selected members of partnership and group practices, able to devote two mornings each week to teaching without too much distraction by routine practice work. They follow a planned, though flexible, teaching programme which emphasises the personal, emotional, and Students are psychological aspects of family medicine. attached in pairs to one of the practices and are expected during their 5 weeks to keep records of the clinical cases they see and in particular to become involved with and study in depth a particular family situation. They present this study at the final seminar of the course held in the teaching hospital and attended by both the community and the hospital based doctors of the group. The student therefore has 10 compulsory sessions in general practice, and in addition attends on a voluntary basis, evening surgeries, antenatal clinics, and emergency calls, as well as spending additional time " working up " his family. Alternate mornings are spent in community medicine. During this time the student is offered experience of a wide range of community services and visits with members of the " domiciliary team "-the health visitor, the district nurse, and the social worker. He studies child-health services in clinic and school, rehabilitation, mental health, public health in the environment, and community geriatrics. Regular seminars during this part of the course, conducted by one of us, enable the student to correlate these two aspects of medicine in the community. In addition to this course, which takes place during the 1st clinical year, the student may spend one of his elective periods in his 2nd or 3rd clinical year in general practice. Over the past 3 years a total of 10 students have been attached full-time for periods ranging from 3 weeks to 3 months to a variety of general practitioners in more distant parts of the region. There is careful briefing by members of the teaching 1.
Walker, J. H., Barnes, H. G. Br. med. J. 1966, ii,
1129.
group, and every effort is made to ensure that there is nothing " amateur or haphazard " about these attachments. In addition to this planned clinical experience in general and community practice, the student meets during the systematiclecture part of his medical training a variety of general practitioners whose special interests are appropriate to the particular topic being taught. During the course dealing with diseases of the respiratory tract, a general practitioner lectures upon and discusses the presentation and management of upper-respiratory-tract infection, another the social consequences of chronic bronchitis, and a third the management of asthma in the home. If our scheme does not constitute " a bold innovation," we feel that in Newcastle at least considerable progress has been made. One valuable by-product has been the establishment of collaborative community research projects: these have involved the university departments of psychological medicine, public health, industrial health and medical statistics, midwifery, and child health, the M.R.C. growth and reproduction unit, and a number of general
practitioners. These activities are creating the atmosphere of a " third faculty", through which students are seeing the challenge and the fascination of practice in the community in all its aspects. University Department of Public Health, Medical School, Newcastle upon Tyne 1
ANDREW SMITH
JOHN H. WALKER.
FOLIC ACID AND NEUROPATHY IN EPILEPSY SiR,ŃIwas interested to read the observations of Dr. Horwitz and his colleagues. Since the inferences drawn are controversial, I should like to present an alternative
interpretation. The incidence of peripheral neuropathy in what I assume be a random group of epileptics, treated for 10 years or more with anticonvulsants, must be very much higher than in patients with any other disorder of unrelated xtiology. Since the anticonvulsant therapy was the most likely common denominator, it would seem reasonable to attribute the neuropathy to the anticonvulsants. The evidence that the dementia, cerebellar degeneration, and neuropathy sometimes seen in drug-treated epileptics may be due to interference with folate metabolism deserves consideration. I, and other observers,2have noted that folic acid sometimes provokes epilepsy in folate-deficient anticonvulsanttreated epileptic patients. Lately a folate-deficient patient (serum-folate 0-75 ng. per ml., red-blood-cell folate 75 ng. per ml., cerebrospinal fluid (C.S.F) folate 5 ng. per ml.) died in uncontrolled status epilepticus after being treated orally with folic acid. These observations suggest that folic acid affects the central nervous system. Moreover there is evidence that anticonvulsants interfere with folate metabolism within the nervous system, since the C.S.F.-folate level in drug-treated epileptics is statistically significantly lower than in control patients.4The only two documented anticonvulsant-treated epileptics with signs and symptoms suggestive of cerebellar degeneration, in whom c.s.F.-folate concentration has been assayed, both had very low c.s.F.-folate levels.46 Clinical reports of patients with neuropyschiatric disorders improving after oral folic-acid therapy are subject to errors of observer bias. The electrophysiological techniques employed by Dr. Horwitz and his colleagues are more objective, and are to be commended. If further studies are contemplated I believe it would be more valuable to compare the electrodiagnostic findings with the c.s.F.-folate activity. D. G. WELLS. Epsom, Surrey.
to
1. 2. 3. 4. 5. 6.
Horwitz, S. J., Klipstein, F. A., Lovelace, R. Lancet, 1967, ii, 1305. Chanarin, I., Laidlaw, J., Loughridge, L. W., Mollin, D. L. Br. med. J. 1960, i, 1099. Reynolds, E. H. Lancet, 1967, i, 1086. Wells, D. G., Casey, H. J. Br. med. J. 1967, iii, 834. Reynolds, E. H., Chanarin, I. Unpublished. Wells, C. Proc. R. Soc. Med. 1965, 58, 721.