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Segmental body composition in young children with SMA type 2: Correlation with motor function abilities
Abstracts 2017 / Neuromuscular Disorders 27 (2017) S96–S249 skeletal muscle lipid metabolic defects are present in SMA. A thorough characterization of gross, histological and molecular changes in the liver and skeletal muscle from SMA model mice was performed. Progressively paler livers were noted in Smn2B/- mice as they aged, a possible sign of fatty liver. Haematoxylin and eosin staining showed a dramatic decrease in cellular density in P19 Smn2B/- livers, potentially because of fatty infiltration. Fatty acid quantification and profiling highlighted a 25-fold increase in triglycerides, a 6-fold increase in cholesterol esters, and misregulation of all other lipids classes, albeit to a milder extent. Of note, fatty acid profiles in each lipid class were altered. Microarray analysis of fatty acid metabolism pathways revealed major changes in mRNA of both liver and muscle of symptomatic mice. About 50% of the 84 genes analysed were misregulated, 25 of which were changed in both muscle and liver, while 15 and 17 changes were specific to the muscle and the liver, respectively. Taken together, these results provide further evidence in metabolic defects in SMA. Further investigation will be required to establish the primary mechanism of these lipid metabolic defects and understand whether they lead to additional co-morbidities in SMA patients. http://dx.doi.org/10.1016/j.nmd.2017.06.149
P.120 Segmental body composition in young children with SMA type 2: Correlation with motor function abilities G. Baranello 1, M. Arnoldi 1, R. Zanin 1, R. Masson 1, C. Mastella 2, R. De Amicis 3, A. Battezzati 3, S. Bertoli 3 1 Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 2 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 3 University of Milan, Milan, Italy
S133
SMA is a recessive disorder caused by mutations in the SMN1 gene characterised by progressive muscle weakness and atrophy. The clinical subtypes are based on age of onset and maximum motor milestones achieved. SMA2 patients present after 6 months and are able to sit but never achieve the ability to walk. Feeding difficulties and malnutrition have been described. The aim of this study is to assess nutrition in SMA2 and its impact on management and motor function. This is a retrospective study reviewing medical records of SMA2 patients followed at the Dubowitz neuromuscular centre (2008–2017). Main parameters reviewed: nutritional status, need for gastrostomy, bone health and Hammersmith functional motor scale (HFMS). Sixty-two patients (median age 10 years; range 2–23) met the inclusion criteria. The mean age of onset was 10.6 months (range 3–18). 6 patients presented before 6 months but were included because their clinical course was consistent with SMA2. Half of our population was underweight (50%; 31/62) while 11% of patients were overweight (7/62). Nearly half (42%; 26/62) needed nutritional supplements of which 42% (11/26) eventually required gastrostomy. Almost one quarter of patients underwent gastrostomy (24%; 15/ 62) at a mean age of 5.7 years. 33% of these had laparoscopic fundoplication for gastroesophageal reflux. Reasons for gastrostomy: risk of aspiration (40%), malnutrition (47%) and respiratory or gastrointestinal problems (20%). Vitamin D insufficiency was detected in 24/62 patients (39%). The maximum HFMS achieved in patients needing gastrostomy (range 1–33/40; median 8.5; mean 12.91) was significantly lower than in patients not requiring gastrostomy (range 3–37/40; median 21.5; mean 19.25) (p < 0.027). To conclude, ensuring adequate nutrition is an important aspect of SMA2 management and affects quality of life. The proportion of patients needing gastrostomy was higher than in previously published series, and broadly correlated with the severity of the functional involvement observed in these children. http://dx.doi.org/10.1016/j.nmd.2017.06.151
The aim of the present study was to investigate the correlation between fat mass (FM) and fat-free mass (FFM), measured by total and segmental body dual energy x-ray absorptiometry (DEXA), and the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Upper limb module (ULM). 40 children with SMA type 2 (mean age 4.07 ± 1.90 years) were included in the study. Total FFM and FM were not correlated with HFMSE scores. However, when we investigated the correlation of segmental FFM and FM with motor function scores, we found that lower limbs FFM was significantly correlated with HFMSE scores (r = 0.375; p = 0.017), while no correlations were found between upper limbs FFM and HFMSE (r = 0.050; p = 0.756) or ULM (r = 0,154; p = 0,392). When we divided the whole cohort into LowFunctioning (HFMSE < 12) and High-Functioning (HFMSE > 12) children, we found that the Low-Functioning group had lower upper and lower limbs FFM, and higher upper and lower limbs FM, compared to the High-Functioning group. To our knowledge this is the first study investigating the correlation between total and segmental body composition and motor function in young children with SMA 2. The present study demonstrated that segmental lean mass at the lower limbs was correlated with global motor function abilities, as assessed by the HFMSE, and that segmental lean and fat mass was significantly different when children were stratified by level of functional abilities. These data further highlight the validity of HFMSE as an outcome measure in SMA, and may be helpful in monitoring the effects of therapeutic strategies. http://dx.doi.org/10.1016/j.nmd.2017.06.150
P.121 Nutritional status of a large cohort of children with spinal muscular atrophy type 2 (SMA2) L. Schottlaender 1, M. Scoto 2, N. Imbrigiotta 1, T. Davis 3, M. Main 3, P. Munot 3, A. Sarkozy 3, A. Manzur 3, F. Muntoni 2 1 UCL Great Ormond Street Institute of Child Health, London, UK; 2 UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK; 3 Great Ormond Street Hospital, London, UK
P.122 Autonomic nervous system involvement in spinal muscular atrophy type 1, 2 and 3 S. Messina 1, M. Sframeli 1, G. Vita 2, C. Stancanelli 3, C. Terranova 3, E. Rizzo 3, F. Cavallaro 3, P. Girlanda 3, G. Vita 3 1 University Hospital of Messina-Nemo Sud Clinical Centre, Messina, Italy; 2 Nemo Sud Clinical Centre, Messina, Italy; 3 University Hopsital of Messina, Messina, Italy Spinal muscular atrophy (SMA) is a selective lower motor neuron disease. There are emerging data indicating the involvement of additional systems, such as the autonomic nervous system (ANS), in SMA 1. The main reported symptoms are tremors and sweating with a correlation with the severity of clinical phenotype. We studied 30 patients with type 1, 2 and 3 SMA (n:10 for each group), with a broad age range and followed regularly in a multidisciplinary setting. We evaluated also age- and sex-matched healthy controls. Symptoms of autonomic dysfunction were assessed using the Composite autonomic symptom scale (COMPASS 31) and specific autonomic tests. They comprise of: Head-up tilting (HUT), Valsalva manoeuvre, deep breathing and cold pressure tests and skin sympathetic reflex. Moreover, we tested the plasma and urinary levels of catecholamines and sudomotor dysfunction with the novel Sudoscan technique. A significant number of patients/caregivers (26/30) reported symptoms of ANS dysfunction, mainly with gastrointestinal involvement. Eleven patients could perform a complete HUT test, the other patients were evaluated on reaching the sitting position from supine due to severe lower limbs contractures. All patients with type 1 SMA and most of patients with type 2 SMA experienced orthostatic intolerance symptoms during tilt test. Moreover, we showed high supine level of epinephrine at baseline and no significant rising of norepinephrine after tilt compared to controls. At variance, the dosage of catecholamines on the 24-hour urine protein test did not confirm differences with controls. Only in the less severe patients (8/30), we were able to perform Valsalva manoeuvre, deep breathing and cold pressure tests, showing normal results. Skin sympathetic reflex and Sudoscan test were normal. Our results suggest the novel hypothesis
P.120 Segmental body composition in young children with SMA type 2: Correlation with motor function abilities G. Baranello 1, M. Arnoldi 1, R. Zanin 1, R. Masson 1, C. Mastella 2, R. De Amicis 3, A. Battezzati 3, S. Bertoli 3 1 Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 2 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 3 University of Milan, Milan, Italy
S133
SMA is a recessive disorder caused by mutations in the SMN1 gene characterised by progressive muscle weakness and atrophy. The clinical subtypes are based on age of onset and maximum motor milestones achieved. SMA2 patients present after 6 months and are able to sit but never achieve the ability to walk. Feeding difficulties and malnutrition have been described. The aim of this study is to assess nutrition in SMA2 and its impact on management and motor function. This is a retrospective study reviewing medical records of SMA2 patients followed at the Dubowitz neuromuscular centre (2008–2017). Main parameters reviewed: nutritional status, need for gastrostomy, bone health and Hammersmith functional motor scale (HFMS). Sixty-two patients (median age 10 years; range 2–23) met the inclusion criteria. The mean age of onset was 10.6 months (range 3–18). 6 patients presented before 6 months but were included because their clinical course was consistent with SMA2. Half of our population was underweight (50%; 31/62) while 11% of patients were overweight (7/62). Nearly half (42%; 26/62) needed nutritional supplements of which 42% (11/26) eventually required gastrostomy. Almost one quarter of patients underwent gastrostomy (24%; 15/ 62) at a mean age of 5.7 years. 33% of these had laparoscopic fundoplication for gastroesophageal reflux. Reasons for gastrostomy: risk of aspiration (40%), malnutrition (47%) and respiratory or gastrointestinal problems (20%). Vitamin D insufficiency was detected in 24/62 patients (39%). The maximum HFMS achieved in patients needing gastrostomy (range 1–33/40; median 8.5; mean 12.91) was significantly lower than in patients not requiring gastrostomy (range 3–37/40; median 21.5; mean 19.25) (p < 0.027). To conclude, ensuring adequate nutrition is an important aspect of SMA2 management and affects quality of life. The proportion of patients needing gastrostomy was higher than in previously published series, and broadly correlated with the severity of the functional involvement observed in these children. http://dx.doi.org/10.1016/j.nmd.2017.06.151
The aim of the present study was to investigate the correlation between fat mass (FM) and fat-free mass (FFM), measured by total and segmental body dual energy x-ray absorptiometry (DEXA), and the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Upper limb module (ULM). 40 children with SMA type 2 (mean age 4.07 ± 1.90 years) were included in the study. Total FFM and FM were not correlated with HFMSE scores. However, when we investigated the correlation of segmental FFM and FM with motor function scores, we found that lower limbs FFM was significantly correlated with HFMSE scores (r = 0.375; p = 0.017), while no correlations were found between upper limbs FFM and HFMSE (r = 0.050; p = 0.756) or ULM (r = 0,154; p = 0,392). When we divided the whole cohort into LowFunctioning (HFMSE < 12) and High-Functioning (HFMSE > 12) children, we found that the Low-Functioning group had lower upper and lower limbs FFM, and higher upper and lower limbs FM, compared to the High-Functioning group. To our knowledge this is the first study investigating the correlation between total and segmental body composition and motor function in young children with SMA 2. The present study demonstrated that segmental lean mass at the lower limbs was correlated with global motor function abilities, as assessed by the HFMSE, and that segmental lean and fat mass was significantly different when children were stratified by level of functional abilities. These data further highlight the validity of HFMSE as an outcome measure in SMA, and may be helpful in monitoring the effects of therapeutic strategies. http://dx.doi.org/10.1016/j.nmd.2017.06.150
P.121 Nutritional status of a large cohort of children with spinal muscular atrophy type 2 (SMA2) L. Schottlaender 1, M. Scoto 2, N. Imbrigiotta 1, T. Davis 3, M. Main 3, P. Munot 3, A. Sarkozy 3, A. Manzur 3, F. Muntoni 2 1 UCL Great Ormond Street Institute of Child Health, London, UK; 2 UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK; 3 Great Ormond Street Hospital, London, UK
P.122 Autonomic nervous system involvement in spinal muscular atrophy type 1, 2 and 3 S. Messina 1, M. Sframeli 1, G. Vita 2, C. Stancanelli 3, C. Terranova 3, E. Rizzo 3, F. Cavallaro 3, P. Girlanda 3, G. Vita 3 1 University Hospital of Messina-Nemo Sud Clinical Centre, Messina, Italy; 2 Nemo Sud Clinical Centre, Messina, Italy; 3 University Hopsital of Messina, Messina, Italy Spinal muscular atrophy (SMA) is a selective lower motor neuron disease. There are emerging data indicating the involvement of additional systems, such as the autonomic nervous system (ANS), in SMA 1. The main reported symptoms are tremors and sweating with a correlation with the severity of clinical phenotype. We studied 30 patients with type 1, 2 and 3 SMA (n:10 for each group), with a broad age range and followed regularly in a multidisciplinary setting. We evaluated also age- and sex-matched healthy controls. Symptoms of autonomic dysfunction were assessed using the Composite autonomic symptom scale (COMPASS 31) and specific autonomic tests. They comprise of: Head-up tilting (HUT), Valsalva manoeuvre, deep breathing and cold pressure tests and skin sympathetic reflex. Moreover, we tested the plasma and urinary levels of catecholamines and sudomotor dysfunction with the novel Sudoscan technique. A significant number of patients/caregivers (26/30) reported symptoms of ANS dysfunction, mainly with gastrointestinal involvement. Eleven patients could perform a complete HUT test, the other patients were evaluated on reaching the sitting position from supine due to severe lower limbs contractures. All patients with type 1 SMA and most of patients with type 2 SMA experienced orthostatic intolerance symptoms during tilt test. Moreover, we showed high supine level of epinephrine at baseline and no significant rising of norepinephrine after tilt compared to controls. At variance, the dosage of catecholamines on the 24-hour urine protein test did not confirm differences with controls. Only in the less severe patients (8/30), we were able to perform Valsalva manoeuvre, deep breathing and cold pressure tests, showing normal results. Skin sympathetic reflex and Sudoscan test were normal. Our results suggest the novel hypothesis