1046 strated filamentous tumour cells.
cytoplasmic staining in individual cultured a
Department of Pathology and Immunology, Monash University Medical School, Melbourne 3181, Australia.
B. H. TOH H. K. MULLER M. N. CAUCHI
INFANTILE SPASMS AND SUBSEQUENT APPEARANCE OF TUBEROUS SCLEROSIS SYNDROME
SIR,-In 1841 The Lancet published a letter from Dr W. J. West’ "on a peculiar form of infantile convulsions". This described an illness in his own son whom he had taken to London for a consultation with Sir Charles Clarke who had already seen four similar cases of what he called "the salaam convulsion". This clinical syndrome is now well recognised and consists of repetitive massive spasms involving the muscles of the neck, trunk, and limbs, either in extension or flexion, each lasting a second or so and occurring in bouts of 10 to 50 or more attacks. Infantile spasms are mostly seen between 6 and 18 months of age and are usually accompanied by regression of motor and mental skills and often by gross multifocal abnormalities (hypsarrhythmia) on the electroencephalogram (E.E.G.). Infantile spasms are a common early manifestation of the tuberous sclerosis syndrome (T.S.S.).2 Such spasms were an early clinical manifestation in thirty-three out of a group of fifty cases in which the full picture of T.s.s. eventually devel-
oped.3 Because the proportion of patients with infantile spasms in whom T.s.s. eventually develops was not known we carried out a survey of all children referred to the Hospital for Sick Children for neurophysiological investigations of possible or probable infantile spasms in the years 1972 and 1973. E.E.G. abnormalities were classified and the clinical notes of these ninety-three patients were scrutinised for confirmation of seizures, the mental defect, skin lesions (poorly pigmented
trunk and limbs, fibroangiomatous lesions of the face often called adenoma sebaceum, shagreen patches), phakoma, intracerebral calcifications, or other evidence ofT.s.s. from neuroradiological investigations. The presence of at least three of the above main clinical features in any child at follow-up was regarded as diagnostic of T.s.s. At referral twenty-five were less than 6 months old, forty-eight were between 6 months and 2 years, and twenty-two were between 2 years and 5 years. Out of ninety-three cases, thirty-nine were excluded either because the history of infantile spasms had not been substantiated (twenty cases) or because in the clinical notes there was no mention of any examination of the skin (twenty-six cases, with an overlap of seven cases). The remaining fifty-four cases all had definite evidence of infantile spasms, skull X-rays had been carried out as well as E.E.G. studies, and the skin had been inspected. Out of this group 85% had mental defect (forty-six cases) and three were doubtfully subnormal. 40% had definite skin changes (twentytwo cases) and nearly 6% (three cases) had intracranial calcifications on X-ray. In this group 26% (fourteen cases) had three or more features undoubtedly diagnostic of T.S.S., while a further 18% (ten further cases) had less obvious but similar features. It seems therefore probable, at least in our material, that amongst those babies presenting with infantile spasms as an early clinical manifestation 2 to 4 years ago, over 25% have already developed various features which are diagnostic of the T.s.s. The above data were collected over a relatively short period, and as the remaining children grow older more obvious diagnostic features of the T.s.s. may vappear in a larger proareas on
portion of cases. 1. West, W J Lancet, 1840/1841, i, 724. Rovere, M, Hoare, R. D., Pampiglione, G. Devl. Med. Child Neurol. 1964, 6, 149. 3. Pampiglione G., Evans, P. R., Harris, R., Moynahan, E. J in Atti delle
2 Della
Conferenze di
aggiornamento
Gaggi); p 73 Bologna, 1968.
Societâ Italiana E.E.G.
(edited by
A.
The following points should be considered in any child with possible history of infantile spasms:
(1) Careful notes should be kept about the precise features of any seizures witnessed by competent observers. If possible further details should be obtained about the sequence of events and the family history. E.E.G. investigations should be carried out at an early phase for consideration of early corticotrophin therapy and repeated at appropriate intervals (preferably 10 and 30 days after starting the drug, as well as 6, 12, 24 months later to check on progress). (2) The skin should be carefully inspected for poorly pigmented areas during infancy, while in older children facial fibroangiomatous lesions (adenoma sebaceum) should not be missed: differentiation from acne may be difficult during adolescence and the two conditions may coexist. In case of doubt the opinion of a dermatologist interested m the field should be sought, remembering that the absence as well as the presence of such lesions should be noted. (3) Ophthalmoscopic examinations should be repeated every few years. (4) In infancy a single skull X-ray rarely reveals intracranial calcifications ofr.s.s., while after the age of 2-4 years the chances increase. If possible therefore skull X-rays should be repeated at the age of 6-12 years. (5) Any post-mortem examination may be of very limited value unless the brain is studied by an interested neuropathologist prepared to carry out detailed histological studies. We wish to draw attention to the complex evolution of these clinical phenomena which have important prognostic and genetic implications and we would be pleased to learn from our colleagues about their experience with similar cases. Department of Neurophysiology, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH.
G. PAMPIGLIONE E. PUGH
THYROTOXICOSIS ASSOCIATED WITH SPLENIC ATROPHY
SIR,-We noted with interest that 2 of the 12 patients with
splenic atrophy described by Dr Wardrop and his colleagues (July 5, p. 4) also had thyrotoxicosis. Although the association of splenic atrophy with coeliac disease is well recognised,’ the association with thyrotoxicosis is poorly documented.2 We report 3 more cases of thyrotoxicosis associated with splenic atrophy. Case 1.-A 54-year-old woman with a history of goitre since girlhood first presented with thyrotoxicosis and severe bilateral exophthalmos in 1963. In 1968 she was referred because of inadequate antithyroid-drug control of her thyrotoxicosis. Serum-thyroxine was greater than 20g/dl (normal 5-5-ll-5[ig/dl), free-thyroxine index greater than 30 (normal 4-14), antithyroglobulin antibody (haemagglutination and latex slide test) positive, long-acting thyroid stimulator (L.A.T.S.) negative (kindly performed by Dr D. D. Adams). She had bilateral infiltrative ophthalmopathy, a moderate-sized diffusely enlarged thyroid, and pallor. The hsemaglobin was 6g/dl, and the blood-film showed anisocytosis, poikilocytosis, target cells, Microspherocytes, and scanty Howell-Jolly bodies. The bone-marrow showed a lack of iron stores with a normoblastic hyperplastic picture. Serumiron was 8µg/dl (normal 55-190µg/dl), serum-iron-binding capacity was 384g/dl (normal 250-420jjtg/dl), serum-folate 2.2ng/ml (normal 7-16ng/ml). Serum vitamin B12, calcium, and carotene were normal, as were the D-xylose-absorption test and fsecal-fat excretion. Banummeal and follow-through-enema examinations were normal. The anaemia responded to parenteral and oral iron therapy. Later studies including a 99’"Tc-sulphur-colloid scan and chromium-51heat- damaged red cell studies confirmed splenic atrophy. The thyrotoxicosis was permanently controlled with 5mCi iodine-131 administered in June, 1968. Case 2.-A 43-year-old woman presented in April, 1975, with moderately severe thyrotoxicosis, total serum-thyroxine l!’6d! (normal 3-5-lOjjtg/dI), free-thyroxine index greater than 30 (normal
4-12), antithyroglobulin-haemagglutination test positive, thyroid-antimicrosomal-immunofluorescent-antibody negative. A moderately enlarged diffuse goitre was present, and there was no significant ophthalmopathy. She was not antmic (haemaglobin 12.1g/dl), but a blood-film showed anisocytosis with target cells and some Howell-Jolly 1. 2.
K. T., Read, A. E. Gut, 1966, 7, 140 1908, 58, 441.
McCarthy, C. F., Fraser, I. D., Evan, Schur,
H. Wien. med. Wschr.
cytoplasmic staining in individual cultured a
Department of Pathology and Immunology, Monash University Medical School, Melbourne 3181, Australia.
B. H. TOH H. K. MULLER M. N. CAUCHI
INFANTILE SPASMS AND SUBSEQUENT APPEARANCE OF TUBEROUS SCLEROSIS SYNDROME
SIR,-In 1841 The Lancet published a letter from Dr W. J. West’ "on a peculiar form of infantile convulsions". This described an illness in his own son whom he had taken to London for a consultation with Sir Charles Clarke who had already seen four similar cases of what he called "the salaam convulsion". This clinical syndrome is now well recognised and consists of repetitive massive spasms involving the muscles of the neck, trunk, and limbs, either in extension or flexion, each lasting a second or so and occurring in bouts of 10 to 50 or more attacks. Infantile spasms are mostly seen between 6 and 18 months of age and are usually accompanied by regression of motor and mental skills and often by gross multifocal abnormalities (hypsarrhythmia) on the electroencephalogram (E.E.G.). Infantile spasms are a common early manifestation of the tuberous sclerosis syndrome (T.S.S.).2 Such spasms were an early clinical manifestation in thirty-three out of a group of fifty cases in which the full picture of T.s.s. eventually devel-
oped.3 Because the proportion of patients with infantile spasms in whom T.s.s. eventually develops was not known we carried out a survey of all children referred to the Hospital for Sick Children for neurophysiological investigations of possible or probable infantile spasms in the years 1972 and 1973. E.E.G. abnormalities were classified and the clinical notes of these ninety-three patients were scrutinised for confirmation of seizures, the mental defect, skin lesions (poorly pigmented
trunk and limbs, fibroangiomatous lesions of the face often called adenoma sebaceum, shagreen patches), phakoma, intracerebral calcifications, or other evidence ofT.s.s. from neuroradiological investigations. The presence of at least three of the above main clinical features in any child at follow-up was regarded as diagnostic of T.s.s. At referral twenty-five were less than 6 months old, forty-eight were between 6 months and 2 years, and twenty-two were between 2 years and 5 years. Out of ninety-three cases, thirty-nine were excluded either because the history of infantile spasms had not been substantiated (twenty cases) or because in the clinical notes there was no mention of any examination of the skin (twenty-six cases, with an overlap of seven cases). The remaining fifty-four cases all had definite evidence of infantile spasms, skull X-rays had been carried out as well as E.E.G. studies, and the skin had been inspected. Out of this group 85% had mental defect (forty-six cases) and three were doubtfully subnormal. 40% had definite skin changes (twentytwo cases) and nearly 6% (three cases) had intracranial calcifications on X-ray. In this group 26% (fourteen cases) had three or more features undoubtedly diagnostic of T.S.S., while a further 18% (ten further cases) had less obvious but similar features. It seems therefore probable, at least in our material, that amongst those babies presenting with infantile spasms as an early clinical manifestation 2 to 4 years ago, over 25% have already developed various features which are diagnostic of the T.s.s. The above data were collected over a relatively short period, and as the remaining children grow older more obvious diagnostic features of the T.s.s. may vappear in a larger proareas on
portion of cases. 1. West, W J Lancet, 1840/1841, i, 724. Rovere, M, Hoare, R. D., Pampiglione, G. Devl. Med. Child Neurol. 1964, 6, 149. 3. Pampiglione G., Evans, P. R., Harris, R., Moynahan, E. J in Atti delle
2 Della
Conferenze di
aggiornamento
Gaggi); p 73 Bologna, 1968.
Societâ Italiana E.E.G.
(edited by
A.
The following points should be considered in any child with possible history of infantile spasms:
(1) Careful notes should be kept about the precise features of any seizures witnessed by competent observers. If possible further details should be obtained about the sequence of events and the family history. E.E.G. investigations should be carried out at an early phase for consideration of early corticotrophin therapy and repeated at appropriate intervals (preferably 10 and 30 days after starting the drug, as well as 6, 12, 24 months later to check on progress). (2) The skin should be carefully inspected for poorly pigmented areas during infancy, while in older children facial fibroangiomatous lesions (adenoma sebaceum) should not be missed: differentiation from acne may be difficult during adolescence and the two conditions may coexist. In case of doubt the opinion of a dermatologist interested m the field should be sought, remembering that the absence as well as the presence of such lesions should be noted. (3) Ophthalmoscopic examinations should be repeated every few years. (4) In infancy a single skull X-ray rarely reveals intracranial calcifications ofr.s.s., while after the age of 2-4 years the chances increase. If possible therefore skull X-rays should be repeated at the age of 6-12 years. (5) Any post-mortem examination may be of very limited value unless the brain is studied by an interested neuropathologist prepared to carry out detailed histological studies. We wish to draw attention to the complex evolution of these clinical phenomena which have important prognostic and genetic implications and we would be pleased to learn from our colleagues about their experience with similar cases. Department of Neurophysiology, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH.
G. PAMPIGLIONE E. PUGH
THYROTOXICOSIS ASSOCIATED WITH SPLENIC ATROPHY
SIR,-We noted with interest that 2 of the 12 patients with
splenic atrophy described by Dr Wardrop and his colleagues (July 5, p. 4) also had thyrotoxicosis. Although the association of splenic atrophy with coeliac disease is well recognised,’ the association with thyrotoxicosis is poorly documented.2 We report 3 more cases of thyrotoxicosis associated with splenic atrophy. Case 1.-A 54-year-old woman with a history of goitre since girlhood first presented with thyrotoxicosis and severe bilateral exophthalmos in 1963. In 1968 she was referred because of inadequate antithyroid-drug control of her thyrotoxicosis. Serum-thyroxine was greater than 20g/dl (normal 5-5-ll-5[ig/dl), free-thyroxine index greater than 30 (normal 4-14), antithyroglobulin antibody (haemagglutination and latex slide test) positive, long-acting thyroid stimulator (L.A.T.S.) negative (kindly performed by Dr D. D. Adams). She had bilateral infiltrative ophthalmopathy, a moderate-sized diffusely enlarged thyroid, and pallor. The hsemaglobin was 6g/dl, and the blood-film showed anisocytosis, poikilocytosis, target cells, Microspherocytes, and scanty Howell-Jolly bodies. The bone-marrow showed a lack of iron stores with a normoblastic hyperplastic picture. Serumiron was 8µg/dl (normal 55-190µg/dl), serum-iron-binding capacity was 384g/dl (normal 250-420jjtg/dl), serum-folate 2.2ng/ml (normal 7-16ng/ml). Serum vitamin B12, calcium, and carotene were normal, as were the D-xylose-absorption test and fsecal-fat excretion. Banummeal and follow-through-enema examinations were normal. The anaemia responded to parenteral and oral iron therapy. Later studies including a 99’"Tc-sulphur-colloid scan and chromium-51heat- damaged red cell studies confirmed splenic atrophy. The thyrotoxicosis was permanently controlled with 5mCi iodine-131 administered in June, 1968. Case 2.-A 43-year-old woman presented in April, 1975, with moderately severe thyrotoxicosis, total serum-thyroxine l!’6d! (normal 3-5-lOjjtg/dI), free-thyroxine index greater than 30 (normal
4-12), antithyroglobulin-haemagglutination test positive, thyroid-antimicrosomal-immunofluorescent-antibody negative. A moderately enlarged diffuse goitre was present, and there was no significant ophthalmopathy. She was not antmic (haemaglobin 12.1g/dl), but a blood-film showed anisocytosis with target cells and some Howell-Jolly 1. 2.
K. T., Read, A. E. Gut, 1966, 7, 140 1908, 58, 441.
McCarthy, C. F., Fraser, I. D., Evan, Schur,
H. Wien. med. Wschr.
