- Email: [email protected]
The "Floppy" Infant
294
have a successful future, technical methods must take account of the fact that access to cerebral vessels is often obtained in the depths of a cleft, and that quite small vessels may be involved. The angle through which instruments can be moved may be only a few degrees, and if working parts have to be tiny they must be at the tip of a long instrument. End-to-end junction of small vessels with each other or with grafts cannot depend under such circumstances on some magical kind of manual dexterity: manoeuvres must be brought within the range of normal movements of the hand. With the aid of perfusion the surgeon may be enabled to work in leisurely fashion with an empty segment or vessel. " When we look back," WRIGHT says, " to the state of heart surgery fifteen years ago and compare it with the present, we can feel encouraged and predict that, with increased interest and improved technics, vascular surgery of the brain will show great strides in the next decade." Such an advance will not be accomplished without blood, sweat,
is
to
toil, and tears. The
"Floppy"
Infant
IDENTIFYING the
pathological change that underlies widespread hypotonia of the skeletal muscles in infants can be one of the most perplexing problems for the paediatrician or neurologist. The late Dr. J. G. GREENspent the last few months of his life in the United on this question; and his work with colleagues at the National Institute of Neurological Diseases and Blindness, Bethesda, has now been
FIELD
States, where he worked
reported.1 This group of workers suggest that cases of this fall into four principal groups, which vary considerably in prognosis: (1) infantile spinal muscular nature
atrophy (Werdnig-Hoffmann disease), a progressive disorder which is eventually fatal 2 3; (2) congenital muscular dystrophy4 5, which is also progressive, though less rapidly so than spinal atrophy; (3) " central core disease ",6 in which the muscular weakness is stationary, neither progressing nor improving as the patient grows older; and (4) " benign congenital hypotonia" , 78 in which there is steady improvement and eventual recovery. In their experience, muscle biopsy is the only really effective means of distinguishing between these disease entities or syndromes, and it may thus give information of the greatest prognostic value. Patients with infantile spinal muscular atrophy have widespread weakness and hypotonia of the skeletal muscles. Usually the proximal limb muscles are affected first, but eventually weakness is generalised, the respiratory and pharyngeal muscles are involved, and fasciculation is seen in the tongue. The deep tendon reflexes are lost early in the disease. Muscle biopsy reveals characteristic groups of uniformly atrophic fibres alongside others which are normal. 1. Greenfield, J. G., Cornman, T., Shy, G. M. Brain, 1958, 2. Werdnig, G. Arch. Psychiat. Nervenkr. 1891, 22, 437. 3. Hoffmann, J. ibid. 1892, 22, 644. 4. Batten, F. E. Brain, 1903, 26, 147. 5. Turner, J. W. A. ibid. 1949, 72, 25. 6. Shy, G. M., Magee, K. R. ibid. 1956, 79, 610. 7. Oppenheim, H. Mschr. Psychiat. Neurol. 1900, 8, 232. 8. Walton, J. N. Lancet, 1956, i, 1023.
81, 461.
Congenital muscular dystrophy is rare; as a rule muscular weakness and hypotonia are comparatively slight in infancy and are confined to the proximal limb muscles. Weakness tends to progress slowly as the child develops, but occasionally deterioration is more rapid. Muscle biopsy shows an excess of endomysial collagen and fat, variation in muscle-fibre size, fragmentation and phagocytosis of some muscle-fibres, and even areas of inflammation and fibre regeneration. Patients with the " central core disease ", which hitherto has been described in only one family, also have muscular weakness and hypotonia, predominantly of proximal limb muscles, from birth. As the child grows the weakness remains unchanged, and there is no apparent progression throughout life. All the deep tendon reflexes in these cases are generally present. Muscle biopsy shows a characteristic abnormality: the fibres are generally larger than normal and contain, in transverse section, a central core of closely packed myofibrils which stain blue, instead of the normal purple, with Gomori’s trichrome stain. "
Finally, patients with " benign congenital hypotonia also have weakness and hypotonia of proximal limb muscles from birth, but never as severely as in WerdnigHoffmann disease, despite the fact that the respiratory muscles are sometimes involved; the tendon reflexes are usually retained, though they may be depressed. Although affected children are late in reaching the normal physical milestones and may not walk until the latter part of the second year or the third year of life, they improve steadily and eventually recover completely. Muscle biopsy reveals either completely normal muscle or a uniform reduction in diameter of the muscle fibres.
As GREENFIELD et al. point out, infantile hypotonia may also be symptomatic of cerebral, skeletal, and metabolic disorders-a feature to which WALTON9 has also drawn attention-but in these infants muscle biopsy will show no abnormality. They consider briefly the syndrome of widespread muscular atrophy and contractures which has been entitled arthrogryphosis multiplex congenita, but insist that this cannot be regarded as a distinctive disease since microscopic examination may indicate a myopathic lesion in some cases but a neuropathic lesion in others.
This work, although an important step forward, still leaves many questions unanswered. It is true that the muscle-biopsy findings in Werdnig-Hoffmann disease are usually unequivocal; but the existence of a genuine congenital muscular dystrophy remains in doubt, and the syndrome of benign congenital hypotonia has yet to be precisely defined. In WALTON’S 10 series of cases which were regarded as examples of benign congenital hypotonia, half the patients recovered completely; while half, though improving up to a point, had smallness and weakness of some muscles throughout life, thus resembling clinically (though not pathologically) the patients with " central core disease ". GREENFIELD et al. suggest that those of WALTON’S cases which recovered incompletely should properly be regarded as examples of muscular dystrophy, even though the weakness was not progressive and muscle-biopsy specimens in several showed no abnor9. 10.
Walton, J. N. Proc. R. Soc. Med. 1956, 49, Walton, J. N. J. Neurol. Psychiat. 1957, 20,
107. 144.
295
there is no place in GREENFIELD’S classification for the condition which KRABBE 11 has entitled " congenital universal muscular hypoplasia ", and which is clinically similar to WALTON’S " benign with incomplete recovery " and to congenital5 hypotonia " TURNER’S benign congenital myopathy ". One serious difficulty is that the pathological responses of muscle, observed by conventional histological techniques, are extremely limited; and similar appearances may result from several diseases of different aetiology. Perhaps newer techniques, including histochemistry and electron microscopy, will throw additional light on these fascinating but perplexing problems. For the present, however, the physician who classifies his cases of infantile hypotonia according to the findings outlined in the careful study by the Bethesda workers will make relatively few mistakes in forecasting the outcome of the illness.
mality. Furthermore,
A "Chest Service" IN 1956, discussing the proposal that a comprehensive chest service " should be evolved from the present system of chest clinics in this country, we remarked that it is hard to believe that diseases of the respiratory system, other than tuberculosis, differ so much in social significance that they need a service that cannot be "
"
provided by the general hospital." 12 A year later we suggested that " it would seem better to graft developments in chest medicine on to the local general medical structure, rather than on to the more rigid structure of the tuberculosis service" .13 The Joint Tuberculosis Council has now published a report on the subject.14 The Council recommends that " the integration with general medicine which has already begun should be continued ". Future consultant appointments to chest clinics and chest outpatient departments should include membership of the medical staff of a major general hospital, with charge of beds; and further efforts should be made to bring chest clinics " within the curtilage of general hospitals". Tuberculosis " must no longer be dealt with by a body of physicians isolated from general medicine ". There must be a department of chest medicine in, or attached to, each teaching hospital. The staffing structure of the " chest service requires urgent revision to bring it into line with the staffing structure of general medicine ". The proposals in this carefully compiled report are different from the ill-defined concept of a considerably " comprehensive chest service " that we previously criticised. We agree that efforts should be made to establish chest medicine as a specialty within the existing general hospital structure (as, no doubt, it already is in some areas); and the Council’s recommendations seem on the whole to represent a reasonable way of bringing this about. But the concept of consultants in diseases of the chest being on the staffs of general hospitals is quite different from the idea that the existing chest clinics should be developed into " a 11. Krabbe, K. H. Nord. Med. 1947, 35, 1756; Acta psychiat., Kbh. 1958, 33, 94. 12. Lancet, 1956, i, 272. 13. ibid. 1957, ii, 478. 14. Joint Tuberculosis Council: a Report on the Future Service for Tuberculosis and Diseases of the Chest. 1958. 1s. 6d.
service for diseases of the chest ". Chest clinics differ in one important respect from outpatient departments: they are designed to deal with an infectious disease that can be prevented. As the report states, special techniques have been built up for this purpose, including family care, lengthy follow-up, cooperation with public-health departments, and sociomedical and rehabilitation services. The report also says that these services are available in general medical departments, though here they do not suffice for the care of tuberculous patients. But, as far as we know, it has not been suggested that general medical departments should look after tuberculous patients. The crux of the problem, however, is the diagnosis and care of patients with non-tuberculous respiratory diseases. Can this work be done efficiently in hospital outpatient and inpatient departments, or does it require chest clinics, with their special techniques developed to deal with tuberculosis ? According to the report, the number of new patients not having tuberculosis seen at chest clinics in the North East Metropolitan hospital region in 1957 was 54,716-an increase of 24% on the number seen in 1953. At eighteen clinics in various regions during one winter month in 1958, 22% of the 3059 new patients had respiratory tuberculosis, 3% had neoplasms, 5% had cardiovascular disease, 27% chronic and 30% acute respiratory disease, and 13% other unspecified conditions. Clearly the proportion of new patients with non-tuberculous disorders seen at chest clinics is increasing, and much of the diagnostic work is concerned with non-tuberculous disease; but the majority of patients with these conditions are probably sent to the clinics for a chest X-ray to exclude tuberculosis and cancer, rather than to obtain a consultant’s advice on the treatment of chronic bronchitis or acute respiratory infection. This diagnostic work could, we believe, be done in hospital outpatient and inpatient departments, adequately staffed and under the control of consultants with special training in respiratory diseases: the special structure of a chest clinic is not required. No facts are available on the volume and type of treatment (including the help given by health visitors and tuberculosis care organisers) given to patients without tuberculosis at the chest clinics. What proportion, for instance, of the 27% with chronic nontuberculous respiratory disease require, or obtain, help that could not be given by general practitioners and suitably staffed hospital outpatient and almoners’ departments ? It seems likely that most of the 30% with acute respiratory disease required no hospital treatment at all. How many of the 5% with cardiovascular disorders were referred to cardiological or general medical outpatient departments ? Only 3% of the patients in the sample were found to have neoplasms. Possibly a quarter of these received surgical treatment, and others would probably be sent to radiotherapy departments. It is, indeed, difficult to see what part of the treatment of non-tuberculous respiratory illness could not be carried out in chest departments of general hospitals or, in many cases, in general medical departments. Is it seriously claimed, for instance, that the treatment of pneumonia or chronic bronchitis requires a unique set
have a successful future, technical methods must take account of the fact that access to cerebral vessels is often obtained in the depths of a cleft, and that quite small vessels may be involved. The angle through which instruments can be moved may be only a few degrees, and if working parts have to be tiny they must be at the tip of a long instrument. End-to-end junction of small vessels with each other or with grafts cannot depend under such circumstances on some magical kind of manual dexterity: manoeuvres must be brought within the range of normal movements of the hand. With the aid of perfusion the surgeon may be enabled to work in leisurely fashion with an empty segment or vessel. " When we look back," WRIGHT says, " to the state of heart surgery fifteen years ago and compare it with the present, we can feel encouraged and predict that, with increased interest and improved technics, vascular surgery of the brain will show great strides in the next decade." Such an advance will not be accomplished without blood, sweat,
is
to
toil, and tears. The
"Floppy"
Infant
IDENTIFYING the
pathological change that underlies widespread hypotonia of the skeletal muscles in infants can be one of the most perplexing problems for the paediatrician or neurologist. The late Dr. J. G. GREENspent the last few months of his life in the United on this question; and his work with colleagues at the National Institute of Neurological Diseases and Blindness, Bethesda, has now been
FIELD
States, where he worked
reported.1 This group of workers suggest that cases of this fall into four principal groups, which vary considerably in prognosis: (1) infantile spinal muscular nature
atrophy (Werdnig-Hoffmann disease), a progressive disorder which is eventually fatal 2 3; (2) congenital muscular dystrophy4 5, which is also progressive, though less rapidly so than spinal atrophy; (3) " central core disease ",6 in which the muscular weakness is stationary, neither progressing nor improving as the patient grows older; and (4) " benign congenital hypotonia" , 78 in which there is steady improvement and eventual recovery. In their experience, muscle biopsy is the only really effective means of distinguishing between these disease entities or syndromes, and it may thus give information of the greatest prognostic value. Patients with infantile spinal muscular atrophy have widespread weakness and hypotonia of the skeletal muscles. Usually the proximal limb muscles are affected first, but eventually weakness is generalised, the respiratory and pharyngeal muscles are involved, and fasciculation is seen in the tongue. The deep tendon reflexes are lost early in the disease. Muscle biopsy reveals characteristic groups of uniformly atrophic fibres alongside others which are normal. 1. Greenfield, J. G., Cornman, T., Shy, G. M. Brain, 1958, 2. Werdnig, G. Arch. Psychiat. Nervenkr. 1891, 22, 437. 3. Hoffmann, J. ibid. 1892, 22, 644. 4. Batten, F. E. Brain, 1903, 26, 147. 5. Turner, J. W. A. ibid. 1949, 72, 25. 6. Shy, G. M., Magee, K. R. ibid. 1956, 79, 610. 7. Oppenheim, H. Mschr. Psychiat. Neurol. 1900, 8, 232. 8. Walton, J. N. Lancet, 1956, i, 1023.
81, 461.
Congenital muscular dystrophy is rare; as a rule muscular weakness and hypotonia are comparatively slight in infancy and are confined to the proximal limb muscles. Weakness tends to progress slowly as the child develops, but occasionally deterioration is more rapid. Muscle biopsy shows an excess of endomysial collagen and fat, variation in muscle-fibre size, fragmentation and phagocytosis of some muscle-fibres, and even areas of inflammation and fibre regeneration. Patients with the " central core disease ", which hitherto has been described in only one family, also have muscular weakness and hypotonia, predominantly of proximal limb muscles, from birth. As the child grows the weakness remains unchanged, and there is no apparent progression throughout life. All the deep tendon reflexes in these cases are generally present. Muscle biopsy shows a characteristic abnormality: the fibres are generally larger than normal and contain, in transverse section, a central core of closely packed myofibrils which stain blue, instead of the normal purple, with Gomori’s trichrome stain. "
Finally, patients with " benign congenital hypotonia also have weakness and hypotonia of proximal limb muscles from birth, but never as severely as in WerdnigHoffmann disease, despite the fact that the respiratory muscles are sometimes involved; the tendon reflexes are usually retained, though they may be depressed. Although affected children are late in reaching the normal physical milestones and may not walk until the latter part of the second year or the third year of life, they improve steadily and eventually recover completely. Muscle biopsy reveals either completely normal muscle or a uniform reduction in diameter of the muscle fibres.
As GREENFIELD et al. point out, infantile hypotonia may also be symptomatic of cerebral, skeletal, and metabolic disorders-a feature to which WALTON9 has also drawn attention-but in these infants muscle biopsy will show no abnormality. They consider briefly the syndrome of widespread muscular atrophy and contractures which has been entitled arthrogryphosis multiplex congenita, but insist that this cannot be regarded as a distinctive disease since microscopic examination may indicate a myopathic lesion in some cases but a neuropathic lesion in others.
This work, although an important step forward, still leaves many questions unanswered. It is true that the muscle-biopsy findings in Werdnig-Hoffmann disease are usually unequivocal; but the existence of a genuine congenital muscular dystrophy remains in doubt, and the syndrome of benign congenital hypotonia has yet to be precisely defined. In WALTON’S 10 series of cases which were regarded as examples of benign congenital hypotonia, half the patients recovered completely; while half, though improving up to a point, had smallness and weakness of some muscles throughout life, thus resembling clinically (though not pathologically) the patients with " central core disease ". GREENFIELD et al. suggest that those of WALTON’S cases which recovered incompletely should properly be regarded as examples of muscular dystrophy, even though the weakness was not progressive and muscle-biopsy specimens in several showed no abnor9. 10.
Walton, J. N. Proc. R. Soc. Med. 1956, 49, Walton, J. N. J. Neurol. Psychiat. 1957, 20,
107. 144.
295
there is no place in GREENFIELD’S classification for the condition which KRABBE 11 has entitled " congenital universal muscular hypoplasia ", and which is clinically similar to WALTON’S " benign with incomplete recovery " and to congenital5 hypotonia " TURNER’S benign congenital myopathy ". One serious difficulty is that the pathological responses of muscle, observed by conventional histological techniques, are extremely limited; and similar appearances may result from several diseases of different aetiology. Perhaps newer techniques, including histochemistry and electron microscopy, will throw additional light on these fascinating but perplexing problems. For the present, however, the physician who classifies his cases of infantile hypotonia according to the findings outlined in the careful study by the Bethesda workers will make relatively few mistakes in forecasting the outcome of the illness.
mality. Furthermore,
A "Chest Service" IN 1956, discussing the proposal that a comprehensive chest service " should be evolved from the present system of chest clinics in this country, we remarked that it is hard to believe that diseases of the respiratory system, other than tuberculosis, differ so much in social significance that they need a service that cannot be "
"
provided by the general hospital." 12 A year later we suggested that " it would seem better to graft developments in chest medicine on to the local general medical structure, rather than on to the more rigid structure of the tuberculosis service" .13 The Joint Tuberculosis Council has now published a report on the subject.14 The Council recommends that " the integration with general medicine which has already begun should be continued ". Future consultant appointments to chest clinics and chest outpatient departments should include membership of the medical staff of a major general hospital, with charge of beds; and further efforts should be made to bring chest clinics " within the curtilage of general hospitals". Tuberculosis " must no longer be dealt with by a body of physicians isolated from general medicine ". There must be a department of chest medicine in, or attached to, each teaching hospital. The staffing structure of the " chest service requires urgent revision to bring it into line with the staffing structure of general medicine ". The proposals in this carefully compiled report are different from the ill-defined concept of a considerably " comprehensive chest service " that we previously criticised. We agree that efforts should be made to establish chest medicine as a specialty within the existing general hospital structure (as, no doubt, it already is in some areas); and the Council’s recommendations seem on the whole to represent a reasonable way of bringing this about. But the concept of consultants in diseases of the chest being on the staffs of general hospitals is quite different from the idea that the existing chest clinics should be developed into " a 11. Krabbe, K. H. Nord. Med. 1947, 35, 1756; Acta psychiat., Kbh. 1958, 33, 94. 12. Lancet, 1956, i, 272. 13. ibid. 1957, ii, 478. 14. Joint Tuberculosis Council: a Report on the Future Service for Tuberculosis and Diseases of the Chest. 1958. 1s. 6d.
service for diseases of the chest ". Chest clinics differ in one important respect from outpatient departments: they are designed to deal with an infectious disease that can be prevented. As the report states, special techniques have been built up for this purpose, including family care, lengthy follow-up, cooperation with public-health departments, and sociomedical and rehabilitation services. The report also says that these services are available in general medical departments, though here they do not suffice for the care of tuberculous patients. But, as far as we know, it has not been suggested that general medical departments should look after tuberculous patients. The crux of the problem, however, is the diagnosis and care of patients with non-tuberculous respiratory diseases. Can this work be done efficiently in hospital outpatient and inpatient departments, or does it require chest clinics, with their special techniques developed to deal with tuberculosis ? According to the report, the number of new patients not having tuberculosis seen at chest clinics in the North East Metropolitan hospital region in 1957 was 54,716-an increase of 24% on the number seen in 1953. At eighteen clinics in various regions during one winter month in 1958, 22% of the 3059 new patients had respiratory tuberculosis, 3% had neoplasms, 5% had cardiovascular disease, 27% chronic and 30% acute respiratory disease, and 13% other unspecified conditions. Clearly the proportion of new patients with non-tuberculous disorders seen at chest clinics is increasing, and much of the diagnostic work is concerned with non-tuberculous disease; but the majority of patients with these conditions are probably sent to the clinics for a chest X-ray to exclude tuberculosis and cancer, rather than to obtain a consultant’s advice on the treatment of chronic bronchitis or acute respiratory infection. This diagnostic work could, we believe, be done in hospital outpatient and inpatient departments, adequately staffed and under the control of consultants with special training in respiratory diseases: the special structure of a chest clinic is not required. No facts are available on the volume and type of treatment (including the help given by health visitors and tuberculosis care organisers) given to patients without tuberculosis at the chest clinics. What proportion, for instance, of the 27% with chronic nontuberculous respiratory disease require, or obtain, help that could not be given by general practitioners and suitably staffed hospital outpatient and almoners’ departments ? It seems likely that most of the 30% with acute respiratory disease required no hospital treatment at all. How many of the 5% with cardiovascular disorders were referred to cardiological or general medical outpatient departments ? Only 3% of the patients in the sample were found to have neoplasms. Possibly a quarter of these received surgical treatment, and others would probably be sent to radiotherapy departments. It is, indeed, difficult to see what part of the treatment of non-tuberculous respiratory illness could not be carried out in chest departments of general hospitals or, in many cases, in general medical departments. Is it seriously claimed, for instance, that the treatment of pneumonia or chronic bronchitis requires a unique set