Survival analysis of spinal muscular atrophy type I

Abstract

PurposeThe life expectancy of patients with spinal muscular atrophy (SMA) type I is generally considered to be less than 2 years. Recently, with the introduction of proactive treatments, a longer survival and an improved survival rate have been reported. In this study, we analyzed the natural courses and survival statistics of SMA type I patients and compared the clinical characteristics of the patients based on their survival periods.MethodsWe reviewed the medical records of 14 pediatric patients diagnosed with SMA type I during a 9-year period. We examined the demographic and clinical characteristics of these patients, calculated their survival probabilities, and plotted survival curves as on the censoring date, January 1, 2010. We also compared the characteristics of the patients who died before the age of 24 months (early-death, ED group) and those who survived for 24 months or longer (long-survival, LS group).ResultsThe mean survival time was 22.8±2.0 months. The survival probabilities at 6 months, 12 months, 18 months, 24 months, and 30 months were 92.9%, 92.9%, 76.0%, 76.0%, and 65.1%, respectively. Birth weight was the only factor that showed a statistically significant difference between the ED and LS groups (P=0.048).ConclusionIn this study, the survival probabilities at 2 years were far greater than expected. Because of the limited number of patients and information in this study, the contribution of improved supportive care on longer survival could not be clarified; this may be elucidated in larger cohort studies.

Healthcare utilisation in children with SMA type 1 treated with nusinersen: a single centre retrospective review

“…Parents of a twelfth child declined nusinersen and the child died at 3 months of age. The median (range) number of nusinersen doses was 6 4–8. Nine children received mask ventilation and two children were ventilated via tracheostomy (TIV).…”

“…Until recently, SMA1 was the most common genetic disease resulting in death in infancy 4. Affected children usually present with symptoms before 6 months of age and historically died from respiratory failure by the age of 2 years 5…”

Demographic characteristics of SMA type 1 patients at a tertiary center in Turkey

“…The diagnostic criteria for SMA reviewed in 1999 by the European Neuromuscular Center and motor skills were added as an important criterium; according to the new criteria, SMA type 1 patients are unable to sit unassisted, and the onset of the disease is in the prenatal period or within the first six postnatal months [15]. The life expectancy in SMA type 1 patients is less than 2 years [10]; however, recent studies have shown that the prognosis for SMA type 1 patients born after 1995 is better than for the ones born before 1995 [9]. In a cohort study of SMA type 1 patients, approximately 10% are reported to have lived beyond 5 years [3].…”

Placental development in a mouse model of spinal muscular atrophy

“…SMA is mainly characterized by the loss of alpha-motor neurons, leading to atrophy in the lower limbs and trunk muscles. However, restoration of SMN expression only in motor neurons is not sufficient to rescue SMN mice, nor does knocking out SMN in only motor neurons and oligodendrocytes phenocopy the whole-body loss of SMN[3,4]. Defects in heart, lung, pancreas[1,5,6,7], and liver have been identified in humans and in mouse models of SMA 1 .…”

“…In a small study, birth weight was the only significant predictor of survival longer than 24 months in patients with SMA[4], suggesting that intrauterine growth may be related to prognosis. Similarly, in the mouse model of severe SMA (Smn -/- SMN2 tg/tg ), a subset of pups are born underweight, and these die at, or shortly after birth 11 .…”