NEUROPSYCHOLOGICAL PERFORMANCE OF CHILDREN WITH DUCHENNE MUSCULAR DYSTROPHY AND SPINAL MUSCLE ATROPHY

Neuropsychological examinations were conducted on 39 boys with Duchenne muscular dystrophy (DMD) and 12 children with spinal muscular atrophy (SMA). There were no significant group differences in the pattern or level of test-score profiles, indicating that the performances of the two patient groups were very similar. However, pattern analysis indicated that while scores on verbal and non-verbal intelligence tests were within the average range for the children with DMD, there were deficits on tests of immediate memory.     

PROTEIN SYNTHESIS IN MUSCLE CULTURES FROM PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY

Muscle samples for cultures were obtained from the quadriceps by open biopsy under local anesthesia in five patients with early stage of Duchenne muscular dystrophy (DMD) and 10 controls. Primary cultures were grown in Eagle's Minimum Essential Medium (MEM) with 20 per cent fetal calf serum. After 4 weeks, cells were trypsinized, counted, sub-cultured for 5 days in MEM with 5 per cent horse serum and finally incubated for 4 h with (³H) leucine. Total protein synthesis showed a significant decrease (half of control values) only in muscle cultures from patients with DMD. Addition of calcium chloride alone or with A23187 ionophore normalized this defect in protein synthesis. By contrast, myosin heavy chain synthesis was measured and found normal in all patients.     

SERIAL POSITION MEMORY OF BOYS WITH DUCHENNE MUSCULAR DYSTROPHY

Ten male patients with Duchenne muscular dystrophy (DMD) and 10 age-matched controls were tested with the WISC-R and a memory test requiring recall of the serial positions of drawings of easily named objects. After statistically controlling for differences in IQ, the two groups did not differ in their ability to recall the most recently presented items. However, the DMD patients were severely impaired in remembering items presented early in the list. The DMD patients also performed poorly on the WISC-R subtests Digit Span and Arithmetic. This pattern of impairment is discussed in terms of possible verbal mediation and attentional deficits.     

LANGUAGE AND LEARNING DISORDERS OF OLDER BOYS WITH DUCHENNE MUSCULAR DYSTROPHY

The IQs of 25 males with Duchenne muscular dystrophy were determined and the results were pooled with those for 76 others reported in the literature to examine the relationship between IQ and age. Verbal IQ was significantly lower than Performance IQ among the younger boys, but not the older. The distribution of Verbal IQ of the older boys was bimodal, suggesting that a verbal deficit persists in some cases. Detailed examination of the cognitive and reading skills of 15 older patients revealed a similar pattern of deficient phonological processing and reading skills in about half of this group.     

INTERVIEWS WITH PARENTS OF BOYS SUFFERING FROM DUCHENNE MUSCULAR DYSTROPHY

Parents from 53 families of boys with Duchenne muscular dystrophy were interviewed to explore their reactions to the diagnosis and the effects of the disease on family life. The findings are discussed in terms of the problems reported by the parents, their experiences at the time of diagnosis, their views on neonatal screening, the effects on the marital relationship, on siblings and on the affected boys themselves, and the parents' need for better information about the disorder.     

PSYCHIATRIC DISORDER AMONG BOYS WITH DUCHENNE MUSCULAR DYSTROPHY

The prevalence of psychiatric disorder in 23 boys with Duchenne muscular dystrophy was assessed and compared to a matched control group. Dysthymic disorder and major depressive disorder occurred significantly more often among DMD boys than controls. Older boys with DMD were at greater risk of depressive disorder than younger boys. Possible aetiological factors and approaches to management are discussed.     

SPINAL FUSION IN DUCHENNE MUSCULAR DYSTROPHY

Sixty-eight patients from a clinical population of 183 patients with Duchenne muscular dystrophy underwent posterior spinal fusion with instrumentation for progressive spinal deformity. Pulmonary complications were the most common postoperative problem, occurring in 17 per cent of the patients. A 35 per cent normal forced vital capacity was a reliable indicator of pulmonary complication risk. The patients with surgically stabilized spines were more comfortable in the later years of life and easier to care for, but deteriorating pulmonary function was not affected by the spinal fusion. The average age at death for the 29 boys who underwent spinal fusion was 18.3 years, which was similar to that of the 58 boys with scoliosis. Factors that improved the patients' quality of life included segmental instrumentation, fusion from T2 to the pelvis, correcting or balancing scoliosis, creating normal sagittal plane alignment and correcting pelvic obliquity.     

FIBROBLAST CULTURES IN DUCHENNE MUSCULAR DYSTROPHY

Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-(³H)-proline for 24 hours. Intracellular collagen incorporation was significantly decreased (2.2 ×) and extracellular collagen incorporation significantly increased (1.8 ×) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts.     

MUSCLE FIBRE SIZE AND SHAPE IN DUCHENNE MUSCULAR DYSTROPHY

Watkins S.C. & Cullen M.J. (1982) Neuropathology and Applied Neurobiology 8, 11–17
Muscle fibre size and shape in Duchenne muscular dystrophy
A method for measuring fibre area and shape which obviates variabilities inherent in diameter measuring techniques was applied to dystrophic and normal human muscle. It was seen that the mean fibre area in patients with Duchenne muscular dystrophy (DMD) increases with age at a greater rate than that of the controls until approximately 5 years-of-age, when it decreases rapidly. This is due to an increasing population of small regenerating, regenerated or split fibres. The shape of fibres was expressed as a form factor and it was seen that the fibres measured from DMD biopsies were less regular in shape than the controls due to constraints placed on the normal growth of regenerating fibres by the proliferation of connective tissue.     

COMMUNICATION WITHIN FAMILIES ABOUT DUCHENNE MUSCULAR DYSTROPHY

An interview with parents of 23 boys with Duchenne muscular dystrophy (DMD) suggested that communication within families about the disorder presented difficulties for both parents and the boys. Spouses rarely discussed the condition and for many this was not a problem area but a way of coping by dealing only with the present. More problematic was the inability for parents and affected boys to communicate about the disorder. Lack of communication occasionally was responsible for carriers not being informed about the genetic nature of the disorder. Possible reasons for these patterns of communication are discussed and some approaches to helping families of boys with DMD are suggested.     

RESPIRATORY MUSCLE TRAINING IN DUCHENNE MUSCULAR DYSTROPHY

Eighteen boys with Duchenne muscular dystrophy were entered into trials to assess the effects of specific ventilatory strength and endurance training programmes. The findings showed an improvement in ventilatory muscle endurance but not in strength as a result of specific respiratory muscle training. The clinical significance of these findings is uncertain, however, and needs further evaluation.     

DUCHENNE MUSCULAR DYSTROPHY IN YOUNG GIRLS?

Four cases (three sporadic, one familial) of muscular dystrophy (MD) in young girls are presented. The clinical picture was similar to Duchenne MD with onset around two years of age, muscle weakness of pelvic girdle, pseudohypertrophy of the calves (2 cases), contractures of Achilles tendons. Later on, weakness of shoulder girdle and neck flexors developed. Progression was slow. Electrocardiogram was normal in all cases. Buccal smear was positive and serum creatine phosphokinase was high in all cases. Histological biopsy findings (vastus lateralis) were typical for muscular dystrophy with extensive proliferation of endomysial connective tissue. In vitro amino acid incorporation of muscle ribosomes (vastus lateralis) revealed a sixfold increase in the activity of total polyribosomes. Both collagen and noncollagen synthesis of the heavy polyribosomes were significantly increased in all patients. Supplementation of these polyribosomes with normal muscle soluble enzymes restored the synthesis of collagen to control values in one case. The ribosomal findings in our cases are very similar to those found in male Duchenne MD and suggest they might belong to its autosomal recessive variant.     

HISTOCHEMICAL FIBRE TYPING AND ULTRASTUCTURE OF THE SMALL FIBRES IN DUCHENNE MUSCULAR DYSTROPHY

Fibre type differentiation was carried out on 20 biopsies from Duchenne Muscular Dystrophy (DMD) sufferers using the acid-preincubated reaction for myofibrillar ATPase. Fibres, classified as either type 1, type 2 or 2C, were counted and their minimum diameters (least fibre axis) measured. Particular attention was paid to the population of small fibres that becomes increasingly prominent with the increasing age of the patient. Type 1 fibres were always predominant in the fibre population as a whole. The numbers of type 2 fibres declined with the increasing age of the patients while the numbers of 2C fibres increased. All fibre types were represented in the population of small fibres and the ratio of the numbers of types 1:2:2C fibres was approximately 1:1:3. Ultrastructural examination of the small fibres showed them to be at varying stages of regeneration and differentiation. The continuous presence of regenerating fibres in DMD while the muscles are wasting implies that while regeneration can be initiated it becomes increasingly constrained or restricted as the disease progresses. The cause of this restriction and whether it is related to the basic genetic lesion is unknown. It is suggested that the accumulation of fibrous connective tissue interferes with growth, either directly, in the formation of pseudomyotendinous junctions, or indirectly, by reducing nutrient exchange with the vascular system.     

PROLONGATIÓN OF WALKING IN DUCHENNE MUSCULAR DYSTROPHY WITH LIGHTWEIGHT ORTHOSES; REVIEW OF 57 CASES

Fifty-seven boys with Duchenne muscular dystrophy aged between 6 years 3 months and 13 years 6 months, who were at the point of losing the ability to walk or had recently done so, were fitted with lightweight knee-ankle-foot orthoses to re-establish walking. 47 walked well and independently in their orthoses, achieving good stability and confidence. 20 are still ambulant; the other 27 stopped walking at intervals ranging from eight to 48 months. Prolongation of walking prevented the development of scoliosis, joint contractures and deformities and also benefited the boys psychologically.