Giovanni Baranello

Bone and Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease, leading to progressive denervation atrophy in the involved skeletal muscles. Bone status has been poorly studied. We assessed bone metabolism, bone mineral density (BMD) and fractures in 30 children (age range 15-171 months) affected by SMA types 2 and 3. Eighteen children (60%) had higher than normal levels of CTx (bone resorption marker); 25-OH vitamin D was in the lower range of normal (below 20 ng/ml in 9 children and below 12 ng/ml in 2). Lumbar spine BMAD (bone mineral apparent density) Z-score was below -1.5 in 50% of children. According to clinical records, four children had sustained four peripheral fractures; on spine X-rays, we observed 9 previously undiagnosed vertebral fractures in 7 children. There was a significant inverse regression between PTH and 25-OH D levels, and a significant regression between BMC and BMAD values and the scores of motor-functional tests. Even if this study could not establish the pathogenesis of bone derangements in SMA, its main findings - reduced bone density, low 25OH vitamin D levels, increased bone resorption markers and asymptomatic vertebral fractures also in very young patients - strongly suggest that even young subjects affected by SMA should be considered at risk of osteopenia and even osteoporosis and fractures.

Efficacy of oral pharmacological treatments in dyskinetic cerebral palsy: a systematic review

To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP).

Spinal Muscular Atrophy, types I and II: What are the differences in body composition and resting energy expenditure?

Summary Background & aims Different neuromuscular functional domains in types I and II Spinal Muscular Atrophy (SMAI and SMAII) could lead to differences in body composition (BC) and resting energy expenditure (REE). Their identification could provide the key to defining appropriate strategies in clinical dietary management, but data comparing SMAI and SMAII in terms of BC and REE are not yet available. We measured total and regional fat (FM), lean (LBM), mineral (BMC) masses, body water (total, intra- and extra-cellular, TBW, ICW, ECW) and REE in a sample of SMAI and II children, matched for age and sex, and also adjusting for body size to compare these features of the two SMA phenotypes. Methods 15 SMAI and 15 SMAII children, (M/F = 9/6 vs 9/6, age 3.6 ± 1.9 vs 3.5 ± 1.8 years, p = 0.99), confirmed genetically, were measured as follows: Anthropometric measurements [Body Weight (BW), Supine Length (SL), Arm Length (AL), Femur Length (FL), Tibia Length (TL)], Dual x-ray Energy Absorptiometry (DEXA) [total and segmental FM, LBM, FFM, and BMC], Bioelectrical impedance (BIA) [TBW, ICW, ECW] and Indirect Calorimetry (REE, respiratory quotients) were collected by the same trained dietician. BW, SL and Body Mass Index (BMI) Z-scores were calculated according to CDC Growth Charts (2000). Results SMA children had high percentages of FM and a lower percentage of TBW and ECW compared to the respective reference values for sex and age, whereas the BMC percentages did not differ, even splitting the two phenotypes. SMA I children had a lower BW and BMI-Z score compared to children with SMA II, but similar total and segmental FM. On the contrary, total FFM and LBM were significantly lower in SMAI (7290.0 ± 1729.1 g vs 8410.1 ± 1508.4 g; 6971.8 ± 1637.1 g vs 8041.7 ± 1427.7 g, p = 0.039, p = 0.037, respectively), particularly at the trunk level. Arm BMC also resulted significantly lower in SMAI. The measured REE values were similar (684 ± 143 kcal/day vs 703 ± 122 Kcal/day p = 0.707) whereas REE per FFM unit was higher in SMA I children than in SMA II (95 ± 12 kcal/FFMkg vs 84 ± 11 kcal/FFMkg p = 0.017). Conclusions This study has shown that BW and BMI Z-score measurements alone can be misleading in assessing nutritional status, particularly in SMAI. The differences between SMAI and II in total and regional BC are related only to FFM, LBM and BMC, and seem to be more linked to the magnitude of neurofunctional impairment rather than to the nutritional status derangement. SMA I and SMA II children can have different energy requirements in relation to their specific BC and hypermetabolism of FFM. Based on these results, our recommendation is to use direct BC and REE measurements in the nutritional care process until SMA-specific predictive equations become available.

Body composition in children and young patients affected by chronic diseases

We analyzed body composition (DXA, Hologic) in 334 young patients (aged 3-24 years) with chronic diseases, most of them on longterm glucocorticoid (GC) treatment, and monitored its changes over 3 to 14 years (6.9±6.2 years). Bone Mineral Content (BMC), Fat Mass (FM) and Fat-Free Mass (FFM) were measured on Total Body Less Head (TBLH), trunk, upper limbs, lower limbs. Regional values of BMC, FM, FFM were expressed as percentages of total and compared with ageand sexmatched healthy Italian controls. Body Mass Index (BMI) was also measured.