132
psychotherapy, which had previously been impossible; psychosurgery is by no means a last-resort " treatment.
to
Dr Challacombe’s observations
"
so
Controlled trials will
no
doubt clear the air around British
psychosurgery, and one can only compliment the psychiatrists for their important action. Department of Neurosurgery, University Central Hospital,
LAURI V. LAITINEN.
00260 Helsinki 26, Finland.
CŒLIAC DISEASE
SIR,-We read with interest the report by Dr Challacolleagues (June 14, p. 1345). They describe
combe and his
15-month-old child who had a normal small-intestinal on biopsy whilst having an average intake of gluten (6 g.) in his diet for age. Normal " daily intake of wheat protein for children aged 1-3 years is 5-7 g.1i When he was given a high gluten intake of 30 g. daily (i.e., twice the average adult intake) he had aggravation of his symptoms and a second biopsy was abnormal although not flat. There was thus evidence of intolerance to a high gluten intake in this child, but whether this is permanent or transient has not yet been established. We consider that it is premature to diagnose cceliac disease-i.e., permanent gluten intolerance-in this child. We therefore cannot yet agree with their statement, based upon this case-report, that " coeliac disease may be found in association with a histologically normal small intestinal mucosa if tissue is sampled from only one site " for the following a
mucosa
"
Queen Elizabeth Hospital for Children,
’
(4) Of children in whom we have established the diagnosis of coeliac disease by showing mucosal healing on a gluten-free diet and mucosal relapse on a gluten-containing diet, in all except In the one exception one the mucosa was flat on initial biopsy. the mucosa was severely abnormal. The much less severe mucosal abnormality demonstrated by Dr Challacombe on his second biopsy we have not yet seen at the time of initial biopsy in any child established to have cceliac disease. We have commonly seen such appearances in children with delayed recovery following acute gastroenteritis with subsequent return to normal mucosal architecture on a normal gluten-containing diet with normal mucosa more than two years after return to a gluten-containing diet. Francis, D. E. M. Diets for Sick Children. Oxford, 1975. Visakorpi, J. K. in Coeliac Disease (edited by W. Th. J. M. Hekkens and A. S. Peña). Leiden, 1974. 3. Kilby, A. Unpublished. 4. Thompson, H. Clins Gastroent. 1974, 3, 171. 5.Walker-Smith, J. A. Gut, 1972, 13, 17. 6. Schreiber, D. S., Blacklow, N. R., Trier, J. S. New Engl. J. Med. 1973, 288, 1318. 1. 2.
ANNE KILBY.
AMANTADINE IN CHOREA SiR,—Reports of the successful treatment of Huntington’s chorea with levodopa 1,2 prompted us to assess the effectiveness of another antiparkinsonian drug, amantadine, in 13 patients with choreiform movements, including 6 with Huntington’s chorea. The assessment of the effectiveness of the drug was based on three factors: (1) the subjective impressions of the medical and nursing staff involved; (2) the opinions of the patients themselves together with those of their relatives; and (3), in 3 cases only, assessment of films of the patient taken before, during, and after and restarting drug treatment. Since the dopamine concentration in the basal ganglia of post-mortem brain tissue has recently been reported to be elevated in cases of Huntington’s chorea in which rigidity was prominentwe determined the urinary excretion of homovanillic acid (H.V.A.) 4 in our patients both before and after the administration of amantadine. In addition, urine was analysed for 5-hydroxyindoleacetic acid (5-H.I.A.A.)5 since we had previously found urinary6 5-H.I.A.A. to be elevated in 7 cases of Huntington’s chorea. 24-hour urine samples were collected from 12 of the 13 patients before beginning amantadine and a second collection was made from 10 patients soon after the start of amantadine (100 or 200 mg. a day) therapy. The urines were collected under standardised dietary conditions, all foodstuffs known to affect the excretion of monoamine metabolites being excluded. In 3 patients involuntary movements decreased notably. In 2 of these the changes were confirmed by studying the films; in the 3rd case the changes in the film were less convincing, but the patient insisted that he had maintained a useful improvement for more than a year after commencing therapy. In a further 6 cases improvement was marginal but nevertheless sufficient in some instances to justify continued therapy. There was no correlation between the clinical response to amantadine and either the pre-drug or the post-drug urinary excretion of amine metabolites. Thus in our study there did not appear to be an association between the effect of therapy and H.V.A., as had been observed with respect to cerebrospinal-fluid H.V.A. levels and the response to levodopa in Huntington’s chorea.2 We conclude therefore that some patients with chorea
stopping
after
challenge.’
to
JOHN WALKER-SMITH
London E2 8PS.
reasons:
post-mortem studies of adult cceliac disease.’ There is also evidence that such a patchy lesion may occur in both children and adults who have other enteropathies such as that associated with gastroenteritis. 5,6 However, we do have some evidence, using a double-port capsule, that a flat mucosa and a less severely abnormal mucosa (severe partial villous atrophy) may be adjacent when two biopsies are done simultaneously in children with cceliac disease who have relapsed histologically after a gluten
of great interest
disease on the basis of these lesser abnormalities of smallintestinal mucosa which in our experience are most often due to causes other than coeliac disease. This field is now increasingly complex since the use of the technique of small-intestinal biopsy in children has become widespread. This confirms us in our view that such investigations should, if possible, be performed in special centres such as that provided by Dr Challacombe, where long-term follow-up with serial biopsies can be performed.
SMALL-INTESTINAL HISTOLOGY IN
(1) When their child has subsequently been reinvestigated an interval, the mucosal lesion, shown to heal, and then to relapse after gluten challenge, only then can the diagnosis of permanent gluten intolerance be said to have been established.’ (2) It is possible in view of their suggestion of a patchy proximal small-intestinal lesion in coeliac disease that their second biopsy merely reflected such variation in mucosal morphology. We have seen a similar range of mucosal morphology using a double-porthole biopsy capsule,3 providing two simultaneous adjacent biopsies in children with delayed recovery following gastroenteritis. (3) We are unaware of any data yet published documenting a patchy (i.e., non-uniform) mucosal abnormality on proximal small-intestinal biopsy of children with completely untreated coeliac disease, although there is evidence of such patchiness in
are
paediatric gastroenterologists, and in time it may be established that this child, in fact, does have coeliac disease. If this is so, this is a very important and exciting observation and it will have far-reaching implications for the diagnosis of coeliac disease, but we are concerned that other clinicians who perform occasional biopsies may as a result of reading Dr Challacombe’s letter now diagnose cceliac
,
1.
Tan, B. K., Leijnse-Ybema, H. J.,
v.
d. Brand, H. J. Lancet, 1972, i,
903. 2. 3. 4. 5. 6.
Schenk, G., Leijnse-Ybema, H. J. ibid. 1974, i, 364. Bird, E. D., Iversen, L. L. ibid. p. 463. Sato, T. L. J. Lab. clin. Med. 1965, 66, 517. MacFarlane, P. S., Dalgliesh, C. E., Dutton, R. W., Lennox, L., Nyhus, L. M., Smith, A. N. Scott. med. J. 1956, 1, 148. McNamee, B., Kelvin, A. S., Turnbull, M. J. ibid. 1971, 16, 247.
psychotherapy, which had previously been impossible; psychosurgery is by no means a last-resort " treatment.
to
Dr Challacombe’s observations
"
so
Controlled trials will
no
doubt clear the air around British
psychosurgery, and one can only compliment the psychiatrists for their important action. Department of Neurosurgery, University Central Hospital,
LAURI V. LAITINEN.
00260 Helsinki 26, Finland.
CŒLIAC DISEASE
SIR,-We read with interest the report by Dr Challacolleagues (June 14, p. 1345). They describe
combe and his
15-month-old child who had a normal small-intestinal on biopsy whilst having an average intake of gluten (6 g.) in his diet for age. Normal " daily intake of wheat protein for children aged 1-3 years is 5-7 g.1i When he was given a high gluten intake of 30 g. daily (i.e., twice the average adult intake) he had aggravation of his symptoms and a second biopsy was abnormal although not flat. There was thus evidence of intolerance to a high gluten intake in this child, but whether this is permanent or transient has not yet been established. We consider that it is premature to diagnose cceliac disease-i.e., permanent gluten intolerance-in this child. We therefore cannot yet agree with their statement, based upon this case-report, that " coeliac disease may be found in association with a histologically normal small intestinal mucosa if tissue is sampled from only one site " for the following a
mucosa
"
Queen Elizabeth Hospital for Children,
’
(4) Of children in whom we have established the diagnosis of coeliac disease by showing mucosal healing on a gluten-free diet and mucosal relapse on a gluten-containing diet, in all except In the one exception one the mucosa was flat on initial biopsy. the mucosa was severely abnormal. The much less severe mucosal abnormality demonstrated by Dr Challacombe on his second biopsy we have not yet seen at the time of initial biopsy in any child established to have cceliac disease. We have commonly seen such appearances in children with delayed recovery following acute gastroenteritis with subsequent return to normal mucosal architecture on a normal gluten-containing diet with normal mucosa more than two years after return to a gluten-containing diet. Francis, D. E. M. Diets for Sick Children. Oxford, 1975. Visakorpi, J. K. in Coeliac Disease (edited by W. Th. J. M. Hekkens and A. S. Peña). Leiden, 1974. 3. Kilby, A. Unpublished. 4. Thompson, H. Clins Gastroent. 1974, 3, 171. 5.Walker-Smith, J. A. Gut, 1972, 13, 17. 6. Schreiber, D. S., Blacklow, N. R., Trier, J. S. New Engl. J. Med. 1973, 288, 1318. 1. 2.
ANNE KILBY.
AMANTADINE IN CHOREA SiR,—Reports of the successful treatment of Huntington’s chorea with levodopa 1,2 prompted us to assess the effectiveness of another antiparkinsonian drug, amantadine, in 13 patients with choreiform movements, including 6 with Huntington’s chorea. The assessment of the effectiveness of the drug was based on three factors: (1) the subjective impressions of the medical and nursing staff involved; (2) the opinions of the patients themselves together with those of their relatives; and (3), in 3 cases only, assessment of films of the patient taken before, during, and after and restarting drug treatment. Since the dopamine concentration in the basal ganglia of post-mortem brain tissue has recently been reported to be elevated in cases of Huntington’s chorea in which rigidity was prominentwe determined the urinary excretion of homovanillic acid (H.V.A.) 4 in our patients both before and after the administration of amantadine. In addition, urine was analysed for 5-hydroxyindoleacetic acid (5-H.I.A.A.)5 since we had previously found urinary6 5-H.I.A.A. to be elevated in 7 cases of Huntington’s chorea. 24-hour urine samples were collected from 12 of the 13 patients before beginning amantadine and a second collection was made from 10 patients soon after the start of amantadine (100 or 200 mg. a day) therapy. The urines were collected under standardised dietary conditions, all foodstuffs known to affect the excretion of monoamine metabolites being excluded. In 3 patients involuntary movements decreased notably. In 2 of these the changes were confirmed by studying the films; in the 3rd case the changes in the film were less convincing, but the patient insisted that he had maintained a useful improvement for more than a year after commencing therapy. In a further 6 cases improvement was marginal but nevertheless sufficient in some instances to justify continued therapy. There was no correlation between the clinical response to amantadine and either the pre-drug or the post-drug urinary excretion of amine metabolites. Thus in our study there did not appear to be an association between the effect of therapy and H.V.A., as had been observed with respect to cerebrospinal-fluid H.V.A. levels and the response to levodopa in Huntington’s chorea.2 We conclude therefore that some patients with chorea
stopping
after
challenge.’
to
JOHN WALKER-SMITH
London E2 8PS.
reasons:
post-mortem studies of adult cceliac disease.’ There is also evidence that such a patchy lesion may occur in both children and adults who have other enteropathies such as that associated with gastroenteritis. 5,6 However, we do have some evidence, using a double-port capsule, that a flat mucosa and a less severely abnormal mucosa (severe partial villous atrophy) may be adjacent when two biopsies are done simultaneously in children with cceliac disease who have relapsed histologically after a gluten
of great interest
disease on the basis of these lesser abnormalities of smallintestinal mucosa which in our experience are most often due to causes other than coeliac disease. This field is now increasingly complex since the use of the technique of small-intestinal biopsy in children has become widespread. This confirms us in our view that such investigations should, if possible, be performed in special centres such as that provided by Dr Challacombe, where long-term follow-up with serial biopsies can be performed.
SMALL-INTESTINAL HISTOLOGY IN
(1) When their child has subsequently been reinvestigated an interval, the mucosal lesion, shown to heal, and then to relapse after gluten challenge, only then can the diagnosis of permanent gluten intolerance be said to have been established.’ (2) It is possible in view of their suggestion of a patchy proximal small-intestinal lesion in coeliac disease that their second biopsy merely reflected such variation in mucosal morphology. We have seen a similar range of mucosal morphology using a double-porthole biopsy capsule,3 providing two simultaneous adjacent biopsies in children with delayed recovery following gastroenteritis. (3) We are unaware of any data yet published documenting a patchy (i.e., non-uniform) mucosal abnormality on proximal small-intestinal biopsy of children with completely untreated coeliac disease, although there is evidence of such patchiness in
are
paediatric gastroenterologists, and in time it may be established that this child, in fact, does have coeliac disease. If this is so, this is a very important and exciting observation and it will have far-reaching implications for the diagnosis of coeliac disease, but we are concerned that other clinicians who perform occasional biopsies may as a result of reading Dr Challacombe’s letter now diagnose cceliac
,
1.
Tan, B. K., Leijnse-Ybema, H. J.,
v.
d. Brand, H. J. Lancet, 1972, i,
903. 2. 3. 4. 5. 6.
Schenk, G., Leijnse-Ybema, H. J. ibid. 1974, i, 364. Bird, E. D., Iversen, L. L. ibid. p. 463. Sato, T. L. J. Lab. clin. Med. 1965, 66, 517. MacFarlane, P. S., Dalgliesh, C. E., Dutton, R. W., Lennox, L., Nyhus, L. M., Smith, A. N. Scott. med. J. 1956, 1, 148. McNamee, B., Kelvin, A. S., Turnbull, M. J. ibid. 1971, 16, 247.
