Maria Beatrice Chiarini Testa

Survival of Patients With Spinal Muscular Atrophy Type 1

BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a progressive disease and is usually fatal in the first year of life. METHODS: A retrospective chart review was performed of SMA1 patients and their outcomes according to the following choices: letting nature take its course (NT); tracheostomy and invasive mechanical ventilation (TV); continuous noninvasive respiratory muscle aid (NRA), including noninvasive ventilation; and mechanically assisted cough. RESULTS: Of 194 consecutively referred patients enrolled in this study (103 males, 91 females), NT, TV, and NRA were chosen for 121 (62.3%), 42 (21.7%), and 31 (16%) patients, respectively. Survival at ages 24 and 48 months was higher in TV than NRA users: 95% (95% confidence interval: 81.8%–98.8%) and 67.7% (95% confidence interval: 46.7%–82%) at age 24 months (P < .001) and 89.43% and 45% at age 48 months in the TV and NRA groups, respectively (P < .001). The choice of TV decreased from 50% (1992–1998) to 12.7% (2005–2010) (P < .005) with a nonstatistically significant increase for NT from 50% to 65%. The choice of NRA increased from 8.1% (1999–2004) to 22.7% (2005–2010) (P < .001). CONCLUSIONS: Long-term survival outcome is determined by the choice of the treatment. NRA and TV can prolong survival, with NRA showing a lower survival probability at ages 24 and 48 months.

Sleep-disordered breathing in spinal muscular atrophy types 1 and 2

Chiarini Testa MB, Pavone M, Bertini E, Petrone A, Pagani M, Cutrera R: Sleep-disordered breathing in spinal muscular atrophy types 1 and 2. Am J Phys Med Rehabil 2005;84:666–670. Objective: Our aim was to assess the respiratory pattern during sleep in patients affected by spinal muscular atrophy types 1 and 2 and to compare their apnea-hypopnea indices with those of controls. Design: All consecutively referred patients underwent polysomnography. Sleep stages were defined as either wake, quiet sleep (QS), or active sleep (AS). As measures of thoracoabdominal coordination, we measured: phase angle during QS and AS (Ph Angle QS and AS), phase relation during inspiration and expiration during QS and AS: (Ph RIB QS, Ph RIB AS, Ph REB QS; Ph REB AS) and the apnea-hypopnea index. Results: The 14 consecutively referred infants and small children (age, 11.7 ± 11.4 mos) showed a higher apnea-hypopnea index (P < 0.001), Ph Angle QS (P < 0.001), Ph Angle AS (P < 0.001), Ph RIB QS (P < 0.001), Ph RIB AS (P < 0.001), Ph REB QS (P < 0.001), and Ph REB AS (P < 0.001) compared with 28 healthy controls (age, 10.1 ± 8.9 mos). Conclusions: Patients affected by types 1 and 2 spinal muscular atrophy had significantly higher apnea-hypopnea indices than controls. Thoracoabdominal asynchrony was present during the inspiratory and expiratory phases in both quiet and active sleep. Measures of thoracoabdominal coordination may be useful for the evaluation and monitoring of therapeutic interventions for these patients.

Noninvasive ventilation in children with spinal muscular atrophy types 1 and 2

Petrone A, Pavone M, Chiarini Testa MB, Petreschi F, Bertini E, Cutrera R: Noninvasive ventilation in children with spinal muscular atrophy types 1 and 2. Am J Phys Med Rehabil 2007;86:216–221. Objective: Our aim was to assess the efficacy of noninvasive ventilation (NIV) for the treatment of thoracoabdominal asynchrony during sleep in children with spinal muscular atrophy (SMA) types 1 and 2. Design: Nine subjects underwent assessment for sleep apnea/hypopnea index (AHI), mean oxyhemoglobin saturation (SpO2), oxygen desaturation index, transcutaneous carbon dioxide tension (tcpCO2), and mean phase angle during sleep as a measure of thoracoabdominal coordination. A second sleep study was performed with use of NIV. Results: The nine patients (7 mos of age, range 2–33) had a baseline AHI of 2.1 events per hour (range 0.5–55.8), oxygen desaturation index of 3.7 events per hour (range 1.6–46.1), mean tcpCO2 of 46 mm Hg (range 37–60), and phase angle of 127 degrees (range 72.7–151.7). Comparing baseline and NIV sleep studies, we found significant improvement in oxygen desaturation index (P < 0.010), mean tcpCO2 (P < 0.001), and phase angle (P < 0.001). For five patients, phase-angle improvement became significant when using high-span bilevel positive airway pressure (PAP). Conclusions: NIV improved sleep breathing parameters and thoracoabdominal coordination during sleep in SMA types 1 and 2. Phase-angle improvement correlated with bilevel PAP pressures. Phase angle may be useful for the evaluation and monitoring of therapeutic interventions such as NIV.

Sleep architecture in infants with spinal muscular atrophy type 1.

OBJECTIVE Few reports on sleep patterns of patients with spinal muscular atrophy type 1 (SMA1) have been published and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of infants with SMA1, compared with age- and sex-matched controls. METHODS Twelve SMA1 patients (six males, mean age 5.9 months) and 10 controls (five males, mean age 4.8 months) underwent full polysomnography to evaluate their sleep architecture and microstructure by means of the cyclic alternating pattern (CAP). RESULTS Compared with control children, SMA1 patients showed increased sleep latency and apnea/hypopnea index. CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes and of A2 and A3 indexes (number/h), indicating a dysfunction of the arousal system in these patients. CONCLUSION The results indicate the presence of an abnormality of sleep microstructure in SMA1 patients, characterized by a reduction of A2 and A3 CAP subtypes. We hypothesize that SMA1 patients have reduced arousability during non-rapid eye movement sleep, which could be interpreted as additional evidence of central nervous system involvement in this disease.

Predicted and measured resting energy expenditure in children with spinal muscular atrophy 2.

We investigated in children with spinal muscular atrophy type 2 the consistency of 4 different equations for predicting resting energy expenditure (REE) compared with measured REE by using indirect calorimetry. In patients with spinal muscular atrophy type 2, measured REE was lower than predicted. We also found a correlation between energy consumption and motor skills.

Sleep architecture in children with spinal muscular atrophy type 2.

OBJECTIVE There have been few published reports on the sleep patterns of patients with spinal muscular atrophy (SMA) type 2, and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of children with SMA type 2, compared with age-matched and sex-matched controls. METHODS Seventeen SMA type 2 children (seven males, mean age 4.2 years) and 12 controls (five males, mean age 5.0 years) underwent full polysomnography to evaluate sleep architecture and microstructure by means of the Cyclic Alternating Pattern (CAP). RESULTS Compared with the control children, the SMA type 2 patients showed a mild increase in the apnea/hypopnea index. Sleep was characterized by a decrease in the number of sleep stage shifts per hour, of percentage of stage N3, of stage R, and of sleep efficiency. On the contrary, significant increases of awakenings per hour, wake after sleep onset, and percentage of stage N1 were found. The CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes, and of A2 and A3 indexes. CONCLUSIONS The results indicated an abnormality of sleep macrostructure and microstructure in SMA type 2 patients, which was characterized by a reduction of A2 and A3 subtypes (low and high power arousals), supporting the concept of a decreased arousability in SMA type 2 patients. Similar to a previous report on SMA type 1, the findings might be additional proof of central nervous system involvement, although these alterations are less severe than those observed in infants with SMA type 1.

Who Influences Parents’ Decision on Life Support Treatments for Children with Spinal Muscular Atrophy Type 1?

Background: We aimed at assessing the influence of those who are part of the parents’ social network (family, friends and health professionals) when they are making decisions about nutritional and respiratory support treatments for their SMA 1 children. Methods: We prepared a 46-question questionnaire to explore the factors that influence parents’ decisions. The influence of the different persons, the degree of satisfaction with the treatment elected and the consistency between the treatment information and the child’s status were assessed by the parents using a Likert scale of ten (a higher score for a higher influence). Results: The secondary-care physicians have the main influence on parent’s decisions about nutritional support (mean=6.4) and about respiratory support (mean=5.8). This influence is higher among decisions about Percutaneous Endoscopic Gastrostomy (mean=8.0) and among decisions about Tracheostomy Ventilation (mean=8.0). The degree of satisfaction with the chosen treatment is high (mean=7.9), and consistency between information about treatment and development of the illness also has a high score (mean=8.3). The hospital ethics committee was involved in 13.3% of the cases. Conclusions: The secondary-care physician influences parents’ decisions about nutritional and respiratory support, particularly while choosing PEG and TV. The degree of satisfaction is very high regardless of the treatment chosen. The hospital ethics committee is not usually involved in the treatment decisions for SMA1 children. *Correspondence to: Fermín Jesús González-Melado, Pontifical John Paul II Institute for Studies on Marriage and Family, Lateran University, Piazza San Giovanni in Laterano, 4 00120 Vatican City, Rome, Italy, Tel: +34 630-438-796; Fax: +34 924 221 245; E-mail : ferminjgm@hotmail.com