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International collaborative study of the spinal muscular atrophies. Part 1. Analysis of clinical and laboratory data
Insights
Early onset spinal muscular atrophy (SMA) before age 4, especially if motor milestones are missed, indicates a poor prognosis. Diagnostic markers include EMG and neurogenic atrophy on muscle biopsy.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Spinal muscular atrophy (SMA) presents with significant variability in age of onset.
- Early childhood onset, particularly before 4 years, is common and associated with worse outcomes.
Purpose of the Study:
- To delineate the clinical and diagnostic features of spinal muscular atrophy.
- To identify prognostic indicators and reliable diagnostic criteria for SMA.
Main Methods:
- Analysis of clinical presentation, including age of onset, motor development, and physical examination findings.
- Evaluation of diagnostic tools such as electromyography (EMG), muscle biopsy (histology and histochemistry), and serum creatine kinase levels.
Main Results:
- Onset before 4 years, inability to sit without support, proximal muscle weakness, and reduced muscle tone are key features.
- EMG findings (spontaneous activity, increased motor unit potential) and routine neurogenic atrophy on histology are reliable diagnostic markers.
- Serum creatine kinase is often normal, and CSF chemistry is consistently normal.
Conclusions:
- Prognosis is significantly worse for early-onset SMA (before 4 years) and those with delayed motor milestones.
- Neurogenic atrophy on routine histology and specific EMG findings are crucial for SMA diagnosis.
- Clinical presentation and diagnostic test results aid in predicting disease severity and guiding management.
Abstract:
There is considerable variation in age of onset, though in over three-quarters of cases onset is before 4 years of age. A febrile episode, often of viral origin, may be present at the time of onset and might possibly be of aetiological significance, perhaps by precipitating the disease in a genetically predisposed individual. Reduced fetal movements and floopiness at birth are present in about one third of those cases where the onset is in early childhood. It would seem that when the onset is before 4 years of age, and particularly if the child has never been able to sit without support, the prognosis is much worse than in cases where the onset is after the age of 4 years. The proximal limb muscles are predominantly affected and muscle tone is usually reduced but pseudohypertrophy is uncommon. Rarely are the cranial nerves affected. Muscle fasiculations are present in about half the cases. Almost 10% of cases appear to be mentally retarded. With regard to the EMG findings, spontaneous activity, reduced full effort pattern increased potential amplitude and duration and increased motor unit territory appear to be the most reliable diagnostic criteria. Routine histological evidence of neurogenic atrophy seems to be a more reliable diagnostic criterion than muscle histochemistry. However, this may be only reflect the way in which the data were selected, that is, from cases where a muscle biopsy showed evidence of neurogenic atrophy on routine histology. Finally the serum level of creatine kinase is rarely very high and in more than half the cases it is normal. The CSF chemistry is always normal.