Pathophysiological Insights Derived by Natural History and Motor Function of Spinal Muscular Atrophy - 20/12/12
, Steve Vucic, MBBS, PhD 1, 3, Heather M. Johnston, MBChB 2, Desirée du Sart, MBBS, PhD 4, Matthew C. Kiernan, MBBS, PhD, DSc 1, 5
Reprint requests: Michelle A. Farrar, MBBS, Neurosciences Research Australia, PO Box 1165, Randwick, NSW 2031, Australia.Abstract |
Objective |
To examine the natural history of spinal muscular atrophy (SMA) to gain further insight into the clinical course and pathogenesis.
Study design |
Survival pattern, age of onset, and ambulatory status were retrospectively analyzed in 70 patients with SMA with deletions of the survival motor neuron 1 genes that presented to a specialized neuromuscular clinic. The Kaplan-Meier method was used to obtain survival curves. Hammersmith Functional Motor Scale-Expanded and abductor pollicis brevis compound muscle action potential amplitudes were assessed in 25 of the surviving cohort and correlated with survival motor neuron 2 copy number.
Results |
Survival probabilities at ages 1, 2, 4, 10, 20, and 40 years were 40%, 25%, 6%, and 0%, respectively, for patients with SMA type 1; 100%, 100%, 97%, 93%, 93%, and 52% for patients with SMA type 2 and all patients with SMA type 3 were alive (age range 7-33 years). There were significant associations between age of onset and long-term outcome, specifically survival in SMA type 1 (P < .01) and Hammersmith Functional Motor Scale-Expanded (P < .0001), and compound muscle action potential (P = .001) in SMA types 2 and 3. Motor function in patients with long-standing SMA reduced over prolonged periods or remained stable. Survival motor neuron 2 copy number related to continuing changes in motor function with age.
Conclusion |
The natural history of SMA suggests considerable early loss of motor neurons, with severity related to differences in the number of remaining motor neurons. As the ensuing chronic course in milder phenotypes suggests relative stability of remaining motor neurons, the maximal therapeutic window presents early.
Le texte complet de cet article est disponible en PDF.Keyword : CMAP, HFMS-E, SMA, SMN, SMN1, SMN2
Plan
| M.F. received grant support from the National Health and Medical Research Council of Australia (Medical Postgraduate Scholarship, ID568915). S.V. serves on the scientific advisory board for Novartis, Merck Serono Australia, and Bayer Schering Australia, and as a medical consultant for Merck Serono Australia. M.K. serves as Editor in Chief of the Journal of Neurology, Neurosurgery and Psychiatry (BMJ Group). The other authors declare no conflicts of interest. |
Vol 162 - N° 1
P. 155-159 - janvier 2013 Retour au numéro
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