Hypoventilation and sleep hypercapnia in a case of congenital variant-like Rett syndrome.

BACKGROUND: Breathing disturbances are often a primary clinical concern especially during wakefulness of the classic form of Rett syndrome, but data for atypical forms are lacking. CASE PRESENTATION: We report the case of a 20-month-old female affected by Rett syndrome with congenital variant-like onset, characterized by severe hypotonia and neurodevelopment impairment. She presented hypoventilation, persistent periodic breathing, and sustained desaturation during sleep, without obstructive or mixed events. Pulse oximetry and capnography during wakefulness were strictly normal. To the best of our knowledge, this is the first case of a patient affected by a congenital variant of Rett syndrome presenting sleep hypercapnia. Hypotonia may play a major role in the genesis of hypoventilation and hypoxemia in our patient. Non-invasive ventilation led to quality-of-life improvements. CONCLUSIONS: Thus, we suggest screening patients with congenital-like Rett syndrome through transcutaneous bedtime carbon dioxide and oxygen monitoring. Moreover, assisted control mode was a breakthrough to achieve adequate ventilation in our case.

Lung ultrasound: A useful additional tool in clinician's hands to identify pulmonary atelectasis in children with neuromuscular disease.

INTRODUCTION AND OBJECTIVES: Patients with neuromuscular disease (NMD) are often exposed to ionizing radiations which could be reduced if a noninvasive and reliable diagnostic method is identified. The major aim of this study was to compare the use of chest X-ray (CXR) with lung ultrasound (LUS) in pediatric patients with NMD, to identify pulmonary atelectasis (PA). MATERIALS AND METHODS: A prospective study was conducted on children affected by NMD. In all patients who underwent CXR, a LUS was also performed and results compared for the assessment of PA. RESULTS: Forty children affected by NMD were enrolled. Spinal muscular atrophy type 1 was the most common NMD, followed by spinal muscular atrophy type 2 and congenital myopathies. More than half of the subjects presented PA, more prevalent in the lung left lower lobes. LUS agreed with CXR results (negative or positive for atelectasis) in 31 patients (77.5%). In two patients, an agreement evaluation was not possible due to non-conclusive LUS. Conversely, LUS disagreed with CXR in seven patients, four of which were positive for atelectasis. If only complete agreement was considered, the statistical analysis between CXR and LUS showed: LUS sensitivity of 57%, LUS specificity of 82%, positive predictive value 80%, negative predictive value 61%. CONCLUSIONS: This study suggests that the use of LUS should be recommended to early identify PA and reduce frequent ionizing exposition of these fragile patients. Finally, our study also suggests that LUS can provide relevant information for clinicians and respiratory physiotherapists.

'Amish Nemaline Myopathy' in 2 Italian siblings harbouring a novel homozygous mutation in Troponin-I gene.

Amish Nemaline Myopathy is a severe form of nemaline myopathy associated to mutation in TNNT1 gene, firstly reported among the Old Order Amish. Here we report two Italian siblings who manifested, by the age of 7 months, progressive and severe muscle weakness and wasting, respiratory insufficiency, pectus carinatum deformity and failure to thrive. Muscle biopsy was consistent with nemaline myopathy and novel homozygous missense mutation in TNNT1 was found. Our cases expand the mutational spectrum of TNNT1, confirm the invariable peculiar clinical phenotype also outside the Amish population, and suggest that TNNT1 should be considered for molecular analysis in NM patients with chest deformities and progressive contractures.

Transition to adult care in young people with neuromuscular disease on non-invasive ventilation.

BACKGROUND: Long-term mechanical ventilation (LTV) with non-invasive ventilation (NIV) prolongs survival in patients with Neuromuscular Diseases (NMDs). Transition from paediatric to adult healthcare system is an undervalued and challenging issue for children with chronic conditions on mechanical ventilation. METHODS: this retrospective study aims to compare issues of young adults in age to transition to adult care (≥ 15 years old) affected by NMDs on NIV in two different Paediatric Respiratory Units in two different countries: Bambino Gesù Children's Hospital, Research Institute, (Rome, Italy) (BGCH) and the Paediatric Respiratory Unit of the Royal Brompton Hospital (London, UK) (RBHT). RESULTS: The median (min-max) age at starting ventilation was significantly different in the two groups (16 years old vs 12, p = 0.0006). We found significant difference in terms of median age at the time of observation (18 (15-22) vs 17 (15-19) years, p = 0.0294) and of type of referral (all the patients from the BGCH group were referred to paediatric services (n = 15, 100%), median age 18 (15-22); only 6 patients, in the RBHT group, with a median age 15.50 (15-17) years, were entirely referred to paediatric service). We found different sleep-disordered breathing assessments 6 full Polysomnographies, 7 Cardio-Respiratory Polygraphies and 2 oximetry with capnography (SpO2-tcCO2) studies in the BCGH group, while all patients of RBHT group were assessed with an SpO2-tcCO2 study. All patients from both groups underwent multidisciplinary assessment. CONCLUSIONS: In conclusion, patients with NMDs on NIV in age to transition to adult require complex multidisciplinary management: significant efforts are needed to achieve the proper transition to adult care.

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

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.