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its relationship to vermal hypoplasia in autism.’ Archives of Neurology, 46, 689-694.

20. Gaffney, G. R.. Kupermah, S., Tsai, L., Minchin, S. (1989) ‘Forebrain structure in infantile autism.’ Journal of the American Academy of Child and Adolescent Psychiatry, 28, 534-537.

21. Piven, J., Berthier, M.. Starkstein, S., Nehme, E., Pearlson, G., Folstein, S. (1990) ‘Magnetic resonance imaging evidence for a defect of cerebral cortical development in autism.’ American Journal of Psychiatry, 147, 734-739.

22. Ritvo, E. R.. Garber, H. J. (1988) ‘Cerebellar hypoplasia and autism.’ New England Journal of Medicine, 318, 1152. (Letter.)

23. Kleiman, M. D., Neff, S., Rosman. N. P. (1990) ‘The brain in infantile autism: is the cerebellum really abnormal?’ Annals of Neurology, 28, 422. (Abstract.)

24. Reiss, A. L. (1988) ‘Cerebellar hypoplasia and autism.’ New England Journal of Medicine, 319, 1152-1153. (Letter.)

25. Reiss, A. L., Aylward, E., Freund, L., Joshi, P., Bryan, R. N. (1991) ‘Neuroanatomy of fragile X syndrome: the posterior fossa.’ Annals of Neurology, 29,26-32.

26. Holroyd, S., Reiss, A. L., Bryan, R. N. (1991) ‘Autistic features in Joubert syndrome: a genetic disorder with agenesis of the cerebellar vermis.’ Biological Psychiatry, 29, 287-294.

27. Weinberger, D. R., Kleinman. J. E. M., Luchins, D. J.. Bigelow, L. B.. Wyatt, R. J. (1980) ‘Cerebellar pathology in schizophrenia: a controlled postmortem study.’ American Journal of Psychiatry, 137, 359-361.

28. Darby, J. K. (1976) ‘Neuropathologic aspects of psychosis in children.’ Journal of Autism and Childhood Schizophrenia, 6, 339-352.

29. Williams, R. S., Hauser, S. L., Purpura, D. P., DeLong, G. R., Swisher, C. N. (1980) ‘Autism and mental retardation: neuropathological studies performed in four retarded persons with autistic behaviour.’ Archives of Neurology. 37, 749-753.

30. human, M. L., Kemper, T. L. (1985) ‘Histo- anatomic observations of the brain in early infantile autism.’ Neurology, 35, 866-874.

31. Ritvo, E. R., Freeman, B. J., Scheibel, A. B., Duong, T.. Robinson, R., Guthrie, D., Ritvo, A. M. (1986) ‘Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the, UCLA-NSAC Autopsy Research Report. American Journal of Psychiatry. 143, 862-866.

32. Rumsey, J. M., Duara. R., Grady. C., Rapoport, J. L., Margolin, R. A., Rapoport, S. I., Cutler, N. R. (1985) ‘Brain metabolism

in autism: resting cerebral glucose utilization rates as measured with positron emission tomography.’ Archives of General Psychiatry, 42, 448-455.

33. Horowitz, B., Rumsey, J. M., Grady, C. L., Rapoport, S. I. (1988) ‘The cerebral metabolic landscape in autism: intercorrelations of regional glucose utilization.’ Archives of Neurology, 45, 749-755.

34. Gilman, S., Adams. K., Koeppe, R. A., Berent, S., Kluin, K. J., Modell, J. G., Kroll, P., Brunberg, J. A. (1990) ‘Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography.’ Annals of Neurology, 28,

35. Herold, S., Frakowiak, R. S. J., LeCouteur, A.. Rutter, M., Howlin, P. (1988) ‘Cerebral blood flow and metabolism of oxygen and glucose in young autistic adults.’ Psychological Medicine, 18, 823-831.

36. Coleman, M., Gillberg, C. (1985) The Biology of the Autistic Syndromes. New York:

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(1971) ‘The synaDtic organization of the malformed cerebefium induced by perinatal infection with feline panleucopenia virus (PLV): I. Elements forming the cerebellar glomeruli.’ Journal of Neuropathology and Experimental Neurology, 30, 196-205.

38. Nowakowski, R. S. (1987) ‘Basic concepts of CNS development. ’ Child Development, 58,

39. Rakic, P. (1971) ‘Neuron-glia relationship during granule cell migration in developing cerebellar cortex: a golgi and electron microscopic study in macacus rhesus.’ Journal of Comparative Neurology, 141, 283-312.

40. Hatten, M. E. (1990) ‘Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain.’ Trenak in the Neurosciences, 13, 179-184.

41. Andreasen, N. C. (Ed.) (1989) Brain Imaging Applications in Psychiatry. Washington, DC: American Psychiatric Press.

42. Duffy, F. H., Burchfield, J. L., Lombroso, C. T. (1979) ‘Brain electrical activity mapping (BEAM): a method for extending the clinical utility of EEG and evoked potential data.’ Annals of Neurologv, 7,421428.

43. Anninos, P. A., Tsagas, N., Adamopoulos, A. (1989) ‘A brain model theory for epilepsy and its treatment: experimental verification using SQUID measurements.’ In Cotterill, R. M. J. (Ed.) Models of Brain Function. Cambridge: Cambridge University Press. pp. 405-421.

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fication of the disease and the type affecting a particular child is of great importance. The parents are entitled to know the nature of the illness, the prognosis, and especially the genetic implications. Personal experience sug-

THE diagnosis of spinal muscular atrophy gests that spinal muscular atrophy, in is a depressing one, as its cause is particular, is a condition about which unknown and specific treatment parents sometimes are not advised on the unavailable. However, accurate identi- risks to subsequent children.

The Spinal Muscular Atrophies

Types of spinal muscular atrophy It is generally accepted that there are two main types, and a number of related disorders. In type I, or Werdnig- Hoffmann disease, the onset is from before birth to the end of the first six months of life’. In the former case the mother may well notice reduced fetal movements, and at birth there can be deformities of the limbs. The babies will be floppy, with a weak cry, and feeding and respiratory difficulties. Their move- ments remain very restricted, and hypotonia persists, with the baby lying in a frog-like position when supine. At this stage the differential diagnosis includes myopathies, but the presence of fasciculation, best seen in the tongue, will exclude primary muscle disorders. If the presentation is dominated by respiratory distress, it is possible that the underlying disorder will be unrecognised. Death usually occurs within the first three years.

Type 111, or Kugelberg-Welander disease, runs a longer course, with survival until the second or third decades. Onset is most often during the second year of life, but is very variable, as is the degree of weakness. This weakness affects the proximal more than the distal parts of the limbs, and fasciculation is often seen. Progression is usually slow, although not invariably so, and at some stage natural development may overtake the degener- ative changes, so that the child appears to improve. Affected children do learn to walk, but there is a great risk of skeletal deformities, especially scoliosis and kyphosis, and of equinovarus deformities of the feet if the child is not walking, unless these are prevented by providing adequate postural support. An inter- current illness can precipitate sudden deterioration, when fasciculation may be more easily detected. As in Duchenne muscular dystrophy, the child easily falls and has difficulty in getting up from the floor, and may ‘climb up’ his legs. When the upper limbs become involved there is often tremor of the hands. Also, while walking is still possible, the feet evert in spinal muscular atrophy, in contrast to the flat feet and toe-walking in muscular dystroph?. Tendon reflexes are sluggish or absent, and plantar responses may be extensor. Respiratory failure can occur,

even in the milder forms. Some children seem to fall between the

definitions of types I and 111, and they have been referred to as type 11, with onset before 15 months and usually survival beyond the age of four years3. However, distinction from type I11 is difficult, and the existence of this type has always been in doubt4.

The diagnosis can be confirmed by the three types of test most useful in neuromuscular disorders. Chemical tests show that the serum creatine kinase, often very raised in muscle diseases-especially so in Duchenne muscular dystrophy-is either normal or only slightly elevated in the spinal muscular atrophies. Characteristically, EMG findings in denervated muscles show evidence of fibrillation or fasciculation, and the most specific finding in this condition is spontaneous rhythmic muscle activity at a frequency of 5 to 15 per second, activated by voluntary effort. Also the residual motor-unit potentials are polyphasic and increased in amplitude and duration. With increased effort there is only a small increase in the frequency of the discharge, with little recruitment’. However, the most important of the tests is muscle biopsy. This must be taken from an affected muscle, but not one that is too degenerate. For young children a needle biopsy is preferable to an open biopsy. Considerable practise and experience is needed, and the technique has to be modified for infants, especially a reduction of the tip to window distance in the Bergstrom needle6. The specimen should be examined histologically and sometimes by chemical methods, and in spinal muscular atrophy it will show the features of denervation atrophy. Areas of small atrophic fibres are seen, as well as muscle fibres which are normal or slightly enlarged. Type 1 and 2 fibres cluster together, reflecting reinervation. Biopsies taken very early in life may be difficult to interpret.

There are a number of possibly related syndromes, such as juvenile amyotrophic lateral sclerosis, with evidence of both upper and lower motor-neuron lesions, and children presenting with bulbar palsy (Fazio-Londe disease), and some with dysarthria and external ophthalmoplegia;

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The mode of inheritance of the spinal muscular atrophies is varied. In type I it is almost always autosomal recessive, while in type 111, with onset after the age of two years, it can be autosomal recessive or autosomal dominant. In allied syndromes inheritance is also varied, and sometimes even sex-linked*.

Genetics of spinal muscular atrophy It is in the field of genetics that there is a ray of hope. BRZUSTOWICZ and colleaguesg mapped the gene for childhood-onset spinal muscular atrophy to chromosome 5q, in the region of ql 1 -2-13 - 3. Their conclusions were that SMA 5q presents with a broad spectrum of abnormalities, and that the severity of the disease is closely correlated with age at onset. Although there were exceptions, in most families the date of onset of the disease, the degree of disability, and the survival-time were very similar".

The same findings were reported by MELKI et al.". The locus seemed to be the same for types I1 and 111, which settled that argument. Although there are increased difficulties in investigating families affected by type I spinal muscular atrophy because of the early death of those with the disease, so that families with living affected siblings are not available for study, MELKI et al." have also shown that the gene responsible for the acute disorder is linked to the same locus.

Treatment of spinal muscular atrophy Although there is no specific treatment for these conditions, it does not mean, as with so many similar diseases, that the child and the family cannot be helped. When the condition is rapidly progressive, tube-feeding and pharangeal suction is often justifiable to alleviate unnecessary distress. In those types of spinal muscular atrophy with a better prognosis and likely survival for several decades, management must be carefully planned. One of the most important aims must be to keep the child mobile for as long as possible. The use of light calipers and well-fitting braces will do much to prevent deformities and to keep the child walking. The earlier

these are applied, if possible under the age of two years, the better they are tolerated; and it does seem logical to give the child as much assistance as possible at an age when so many fundamental motor skills are being acquired. In support of this plan of action, GRANATA et a1.I3 note the immediate advantages, both functional and psychological, and the effectiveness in preventing contractures and scoliosis over an average follow-up period of 2% years.

EVANS et all4 discuss the role of the orthopaedic surgeon in the management of the chronic forms of spinal muscular atrophy. 54 patients were reviewed on average 17 years after diagnosis, and divided into four groups depending on the severity of their physical disability. The most serious orthopaedic problem en- countered was scoliosis, which appeared early in life and sooner or later progressed rapidly, except in those with the ability to walk. Orthoses were provided for all the other children. Spinal fusion with Harrington rods was used on 11 occasions to prevent progressive scoliosis, and in one instance for severe lumbar hyper- lordosis. The fact that the operation can affect the ability to walk obviously does not apply to children who can no longer walk, and in any case this complication can often be avoided by the use of intensive physiotherapy and early resumption of activities. Severe con- tractures of the legs may also develop rapidly when the child is confined to a wheelchair. Physiotherapy can reduce these, and braces and crutches may be needed.

The contribution of the orthopaedic surgeon has also been reviewed by SCHWENIKER and GIBSON". Examin- ation of 57 patients at an average age of 11.5 years showed that 35 could not walk. The major orthopaedic problem was scoliosis, and nine of these children had had spinal fusion. 23 of the patients had been provided with spinal bracing and nine had had spinal fusion. Although eight of these were functionally worse after operation, seven gained in comfort and stability of the back. Apart from providing a treatment programme, fitting orthoses and advising on surgery, the surgeon must play a major part in the

diagnosis of this condition and in discussing the many related problems with the patient and the family. Particularly for those who do not have the strength to move a wheelchair, an upright mobility system with wheels of large diameter may be helpful. It can make breathing easier, prevent contractures of the leg joints, and lessen the risk of disuse osteoporosis’6.

When discussing the management of spinal muscular atrophy, ENG et al.” emphasise in the case of acute disorder the importance of parental support, with instruction on feeding and handling. Small, frequent oral feeds may be better tolerated, especially when there is respiratory distress; feeding through a nasogastric tube may sometimes be necessary, and even feeding through a gastrostomy. Treatment of constipation with glycerin suppositories may be needed, and also postural drainage and suctioning of the oropharynx. When the condition is a chronic one and the patient is not walking, posture and alignment will need attention, combined with exercises to prevent contractures; and parents can be taught to give breathing exercises.

There will also be difficulties to be solved in providing the children with suitable seats and wheelchairs, and experts will need to be consulted. The physiotherapist and occupational therapist will play key roles in terms of treatment and advice on equipment, suitable clothing and eating utensils; and in assessing progress and warning of developing contractures. The family as a whole will need support and advice, which can vary from suitable diets to prevent obesity, to toys that the child can manage, to ensuring that state benefits are claimed when applicable. Parents often can be unaware of the availability of these benefits’*. l9 and, for example, how to appeal if a mobility allowance has not been granted when the need seems to be evident. The health visitor and social worker can give a great deal of help, and can prevent the family feeling isolated in their distress.

These children are of average intelligence, and advice on suitable schooling may be needed from the psychology services. A school for physically handicapped children is often

the one of choice, not only from the academic point of view so that their education is geared to their probable abilities when they leave school, but also because of suitable out-of-school activities, which are often provided during term-time and during the holidays by these schools. A particular problem for children with spinal muscular atrophy is that, in distinction to those with cerebral palsy, for example, they are at only slightly greater risk of having specific learning difficulties than other children, and then only because of their physical disabilities. This may result in a lack of stimulation equal to their intelligence. Some children are able to manage in normal schools, although this may depend on the provision of an assistant to help the teacher.

Conclusions This condition in its acute form has an incidence in the Western world of about 1 in 20,000 live births. This yields a carrier frequency in the range of 1 in 60 to 1 in 80 in the population study by PEARN”. It is suggested that this high value may be due to the possibility of heterozygote advantage with increased fitness. It could be that in some way the anterior-horn cells of heterozygotes are protected against other diseases. Research into this condition has not been as intense as that into muscular dystrophy, with the discovery of the absent protein dystrophin in patients with Duchenne muscular dystroph?’. However, the hope is that now a gene has been mapped to chromosome 5 , this will lead to advances in both diagnosis and treatment. Meanwhile, parents of a child with spinal muscular atrophy must be given detailed genetic advice, in the hope of preventing the birth of further affected children. Often it may be an advantage to give this both verbally and in writing. To many parents, adoption may be a more acceptable alternative to the risks of another affected child.

NEIL GORDON Huntlywood, 3 Styal Road, Wilmslo w SK9 4AE.

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References 1. Pearn, J. H., Carter, C. O., Wilson, J. (1973)

‘The genetic identity of acute infantile spinal muscular atrophy.’ Brain, 85, 463470.

2. Moosa, A., Dubowitz, V. (1973) ‘Spinal muscular atroDhv in childhood: two clues to clinical diagnbsh.’ Archives of Disease in Childhood, 48, 386-390.

3. Fried, K., Emery, A. E. H. (1971) ‘Spinal muscular atrophy type 11. A separate clinid and genetic entity from type I (Werdnig-Hoffmann disease) and type I11 (Kugelberg-Welander disease).’ Clinical Genetics, 2, 203-209.

4. Gardner-Medwin, D. (1977) ‘Children with genetic muscular disorders.’ British Journal of Hospital Medicine, 17, 314-340.

5 . Buchthal, F., Olsen, P. 2. (1970) ‘Electro- myography and muscle biopsy in spinal muscular atrophy.’ Brain, 93, 15-30.

6. DiLiberti. J. H., D’Agnostino. A. N., Cole, G. (1988) ‘Needle muscle biopsy in infants and children.’ Journal of Pediatrics, 103, 566-570.

7. Bundey, S., Lovelace, R. E. (1975) ‘A clinical and genetic study of chronic proximal spinal muscular atrophy.’ Brain, 98, 455-472.

8 . Fischbeck, K. H., Ionasescu. V., Ritter, A. W.,Ionasescu, R., Davies, K., Ball, S., Bosch, P., Burns, T., Hausmanowa-Petrusewicz, I., Barkowska, J. et al. (1986) ‘Localization of the gene for X-linked spinal muscular atrophy.’ Neurology, 36, 1595-1598.

9. Brzustowicz, L. M., Lehner, T., Castilla, L. H., Penchaszadeh, G. H., Wilhelmsen, K. C., Daniels, R., Davies, K. E., Leppert, M., Ziter, F., Wood, D. et al. (1990) ‘Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5qll.2-13.3.’ Nature, 334, 540-541. (Letter.)

10. Munsat, T. L., Skerry, L., Korf, B., Pober, B., Schapira, Y., Gascon, G. G., Al-Rajeh, S. M., Dubowitz, V., Davies, K., Brzustowicz, L. M. et al. (1990) ‘Phenotypic heterogeneity of spinal muscular atrophy mapping t: chromosome 5q11.2-13.3 (SMA5q). Neurology, 40, 1831-1836.

11. Melki, J., Abdelhak, S., Sheth, P., Bachelot, M.-F., Burlet, P., Marcadet, A.. Aicardi. J.,

NOTICES

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Sixth Congress of the International Association and First Iberoamerican Congress of Pediatric Neurology Buenos Aires, 8th to 13th November 1991

The program for this joint meeting will follow the lines of previous ICNA meetings, including plenary lectures and symposia presented by leaders in the fields of paediatric neurology and the neurosciences. Satellite symposia and workshops are also being organized. Further information from Dr. Nester Chamoles, General Secretary, Sarmiento 1562 4” ‘F’ (1042), Buenos Aires, Argentina. Tel.: 54 1 35 6703/35 2798; Fax: 54 1 1 1 1678.

Barois, A., Carriere, J. P., Fardeau, M. et al. (1990) ‘Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q.’ Nature, 344, 767-768. (Letter.)

12. Melki, J.. Sheth, P., Abdelhak, S., Burlet, P., Bachelot, M.-F., Lathrop, M. G., Frezal, J., Munnich, A., Bachelot, M.-F., Burlet, P. et al. (1990) ‘Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14.’ Lancet, 336, 271 -273.

13. Granata, C., Cornelio, F., Bonfiglioli, S., Mattutini, P., Merlini, L. (1987) ‘Promotion of ambulation of patients with spinal muscular atrophy by early fitting of knee-ankle-foot orthoses. Developmental Medicine and Child Neurology, 29, 221-224.

14. Evans, G. A., Drennan, J. C., Russman, B. S. (1981) ‘Functional classification and ortho- paedic management of spinal muscular atrophy.’ Journal of Bone and Joint Surgery, 63B, 516522.

15. Schweniker, E. P., Gibson, D. A. (1976) ‘The orthopaedic aspects of spinal muscular atrophy.’ Journal of Bone and Joint Surgery,

16. Seigel, I. M., Silverman, M. (1984) ‘Upright mobility system for spinal muscular atrophy patients.’ Archives of Physical Medicine and Rehabilitation, 65, 418.

17. Eng, G. D., Binder, H.. Koch, B. (1984) ‘Spinal muscular atrophy: experience in diagnosis and rehabilitation management of 60 patients.’ Archives of Physical Medicine and Rehabilitation, 65, 549-553.

18. Ennals, S. (1991) ‘Attendance allowance.’ British Medical Journal, 302,228-230.

19. Ennals, S. (1991) ‘Mobility allowance.’ British Medical Journal, 302, 284-285.

20. Pearn, J. H. (1973) ‘The gene frequency of acute Werdnig-Hoffmann disease (SMA type I). A total population survey in north-east England.’ Journal of Medical Genetics, 10, -265.

21. Hoffman, E. P., Brown, R. H., Kunkel, L. M. (1987) ‘Dystrophin, the protein product of the Duchenne muscular dystrophy locus.’ Cell, 50, 9 19-928.

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Family Issues in Developmental Dis- abilities: 11th Annual Child Development Center Program New Orleans, 6th December 1991

To be held at Ochsner Medical Institutions, 1516 Jefferson Highway, New Orleans, Louisiana 70121. Further information from the Continuing Education Department. Tel.: (504) 838 3702.

45th Annual Meeting of the American Epilepsy Meeting Society Philadelphia, 6th to 11th December 1991

This meeting will be held at the Wyndham Franklin Plaza Hotel, with the American EEG Society. The scientific programme will commence on 9th December. Further information from the American Epilepsy Society, 638 Prospect Avenue, Hartford, Connecticut 06105-4298. Tel: (203) 232 4835; Fax: (203) 232 0819.