Paradoxical metabolic acidosis after vomiting in children with spinal muscular atrophy: A report of 9 patients.

BACKGROUND: Spinal muscular atrophy (SMA) is a hereditary neuromuscular disease that progresses toward restrictive respiratory failure due to muscle paralysis. We observed that SMA patients presented with a specific clinical and laboratory profile, consisting of severe metabolic acidosis following an episode of mild vomiting. This is an unusual, little-known, and life-threatening situation for these patients, as hyperventilation induced by metabolic acidosis can lead to exhaustion and to death by mixed acidosis. OBJECTIVE: The aim of our study was to describe this paradoxical acidosis after vomiting in SMA patients and to discuss the physiological basis of this condition. METHODS: We conducted a retrospective single-center study reviewing the clinical and laboratory data of SMA patients who were hospitalized in the intensive care unit for severe metabolic acidosis after vomiting. RESULTS: Our cohort comprised 11 cases. On arrival, the median pH of the patients was 7.23 with a median bicarbonate concentration of 11.7 mmol/L and almost half of them (45 %) had ketone bodies in the blood and/or urine. The median correction time was 24 h for pH and 48 h for bicarbonate concentrations after receiving intravenous hydration with a glucose solution. CONCLUSIONS: We suggest that SMA patients are particularly sensitive to ketoacidosis induced by fasting, even after a few episodes of mild vomiting. Moreover, they have a low buffering capacity due to their severe amyotrophy, which favors metabolic acidosis. They must be quickly hydrated through a glucose-containing solution to avoid exhaustion, mixed acidosis, and death.

Lung volume recruitment and airway clearance for children at home in France.

BACKGROUND: Airway clearance (ACT) and lung volume recruitment (LVR) techniques are used to manage bronchial secretions, increase cough efficiency and lung/chest wall recruitment, to prevent and treat respiratory tract infections. The aim of the study was to review the prescription of ACT/LVR techniques for home use in children in France. METHODS: All the centers of the national pediatric noninvasive ventilation (NIV) network were invited to fill in an anonymous questionnaire for every child aged ≤20 years who started a treatment with an ACT/LVR device between 2022 and 2023. The devices comprised mechanical in-exsufflation (MI-E), intermittent positive pressure breathing (IPPB), intrapulmonary percussive ventilation (IPV), and/or invasive mechanical ventilation (IMV)/NIV for ACT/LVR. RESULTS: One hundred and thirty-nine patients were included by 13 centers. IPPB was started in 83 (60 %) patients, MI-E in 43 (31 %) and IPV in 30 (22 %). No patient used IMV/NIV for ACT/LVR. The devices were prescribed mainly by pediatric pulmonologists (103, 74 %). Mean age at initiation was 8.9 ± 5.6 (0.4-18.5) years old. The ACT/LVR devices were prescribed mainly in patients with neuromuscular disorders (n = 66, 47 %) and neurodisability (n = 37, 27 %). The main initiation criteria were cough assistance (81 %) and airway clearance (60 %) for MI-E, thoracic mobilization (63 %) and vital capacity (47 %) for IPPB, and airway clearance (73 %) and repeated respiratory exacerbations (57 %) for IPV. The parents were the main carers performing the treatment at home. CONCLUSIONS: IPPB was the most prescribed technique. Diseases and initiation criteria are heterogeneous, underlining the need for studies validating the indications and settings of these techniques.

Non-invasive respiratory support in children and young adults with complex medical conditions in pediatric palliative care.

OBJECTIVE: Dyspnoea and sleep-disordered breathing (SDB) are common in children with life-limiting conditions but studies on treatment with non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) are scarce. The aim of the study was to describe children treated with long-term NIV/CPAP within a paediatric palliative care programme in France. METHODS: Cross-sectional survey on children and young adults with complex medical conditions treated within the French paediatric NIV network with long-term NIV/CPAP. Characteristics of the patients were analysed and patient-related outcome measures of NIV/CPAP benefit were reported. RESULTS: The data of 50 patients (68% boys), median age 12 (0.4-21) years were analysed. Twenty-three (46%) patients had a disorder of the central nervous system and 5 (10%) a chromosomal anomaly. Thirty-two (64%) patients were treated with NIV and 18 (36%) with CPAP. NIV/CPAP was initiated on an abnormal Apnoea-Hypopnoea Index in 18 (36%) of the patients, an abnormal nocturnal gas exchange alone in 28 (56%), and after an acute respiratory failure in 11 (22%) of the patients. Mean objective NIV/CPAP adherence was 9.3±3.7 hours/night. NIV/CPAP was associated with a decrease in dyspnoea in 60% of patients, an increase in sleep duration in 60% and in sleep quality in 74%, and an improvement in parents' sleep in 40%. CONCLUSIONS: In children with life-limiting conditions, long-term NIV/CPAP may be associated with relief of dyspnoea, an improvement of SDB and an improvement in parents' sleep.

Pediatric long-term noninvasive respiratory support in children with central nervous system disorders.

RATIONALE: The use of long-term noninvasive respiratory support is increasing in children along with an extension of indications, in particular in children with central nervous system (CNS) disorders. OBJECTIVE: The aim of this study was to describe the characteristics of children with CNS disorders treated with long-term noninvasive respiratory support in France. METHODS: Data were collected from 27 French pediatric university centers through an anonymous questionnaire filled for every child treated with noninvasive ventilatory support ≥3 months on 1st June 2019. MAIN RESULTS: The data of 182 patients (55% boys, median age: 10.2 [5.4;14.8] years old [range: 0.3-25]) were collected: 35 (19%) patients had nontumoral spinal cord injury, 22 (12%) CNS tumors, 63 (35%) multiple disabilities, 26 (14%) central alveolar hypoventilation and 36 (20%) other CNS disorders. Seventy five percent of the patients were treated with noninvasive ventilation (NIV) and 25% with continuous positive airway pressure (CPAP). The main investigations performed before CPAP/NIV initiation were nocturnal gas exchange recordings, alone or coupled with poly(somno)graphy (in 29% and 34% of the patients, respectively). CPAP/NIV was started in an acute setting in 10% of the patients. Median adherence was 8 [6;10] hours/night, with 12% of patients using treatment <4 h/day. Nasal mask was the most common interface (70%). Airway clearance techniques were used by 31% of patients. CONCLUSION: CPAP/NIV may be a therapeutic option in children with CNS disorders. Future studies should assess treatment efficacy and patient reported outcome measures.

Perioperative complications after posterior spinal fusion versus minimally invasive fusionless surgery in neuromuscular scoliosis: a comparative study.

INTRODUCTION: Early-onset scoliosis is a common deformity in neuromuscular disease. When conservative treatment becomes ineffective, several surgical options can be proposed. The most common technique is posterior spinal fusion (PSF) consisting of performing a multiple segmental instrumentation with pedicular screws on the full spine associated with decortication and bone graft. Minimally invasive fusionless surgery (MIFS) is an alternative to correct and fix definitively the spine without graft. The objective of this study was to compare early surgical inpatient period between PSF and MIFS in neuromuscular scoliosis. MATERIAL AND METHODS: 140 NMS operated by PSF or MIFS between 2012 and 2017 was retrospectively reviewed. The following data were compared between groups: general characteristics (age, sex, etiology), preoperative preparation (halo traction, noninvasive ventilation or tracheostomy), Cobb angle and pelvic obliquity correction, use of drugs (vasopressor and/or inotropes, expansion fluids, transfusion and volumes), postoperative complications, and need of noninvasive ventilation. RESULTS: 75 patients were managed by PSF with a mean age of 14.3 ± 2.3y and 65 by MIFS with a mean age of 11.8 ± 3y. Average pelvic obliquity and major curve correction were similar postoperatively. Intraoperative blood transfusion was significantly more common in PSF group (OR, 14; 95% CI [6.3-33.0]). Vasopressors were used non-significantly more often in the PSF group and expansion fluids similar in the two groups. PSF group had more overall complications (OR, 4.6; 95% CI [2.3-9.8]), more infections (OR, 3.6; 95% CI [1.5-9.3]) and more hemodynamic complications (OR, 4.1; 95% CI [1.4-15.1]). Average intubation duration was 5 days in the PSF and 4 days in MIFS (p = 0.05). CONCLUSION: In this series of neuromuscular patients, the complication rate was reduced in MIFS comparatively to PSF, with lower blood transfusion and less infections.

Long term noninvasive ventilation and continuous positive airway pressure in children with neuromuscular diseases in France.

The aim of the study was to describe the characteristics of children with neuromuscular diseases treated with long term noninvasive ventilation or continuous positive airway pressure in France. On June 1st 2019, 387 patients (63% boys, mean age 11.2 ± 5.5 years) were treated with long term noninvasive ventilation/continuous positive airway pressure. Thirty three percent of patients had spinal muscular atrophy, 30% congenital myopathy/dystrophy, 20% Duchenne muscular dystrophy, 7% Steinert myotonic dystrophy, and 9% other neuromuscular diseases. Ninety-four percent of patients were treated with long term noninvasive ventilation and 6% with continuous positive airway pressure. Treatment was initiated electively for 85% of patients, mainly on an abnormal overnight gas exchange recording (38% of patients). Noninvasive ventilation/continuous positive airway pressure was initiated during a respiratory exacerbation in 15% of patients. Mean duration of noninvasive ventilation/continuous positive airway pressure was 3.3 ± 3.1 years. Mean objective long term noninvasive ventilation/continuous positive airway pressure use was 8.0 ± 3.1 h/24. Spinal muscular atrophy, congenital myopathy/dystrophy, and Duchenne muscular dystrophy represented 83% of children with neuromuscular diseases treated with long term noninvasive ventilation in France. Screening for nocturnal hypoventilation was satisfactory as noninvasive ventilation /continuous positive airway pressure was predominantly initiated electively.

Minimally Invasive Fusionless Surgery for Scoliosis in Spinal Muscular Atrophy: Long-term Follow-up Results in a Series of 59 Patients.

BACKGROUND: Treatment of spinal muscular atrophy (SMA) scoliosis has evolved in the last decade, with the emergence of fusionless surgical techniques that allow correction of the deformity before the end of growth spurt. These techniques are expected to delay definitive spine fusion and preserve trunk growth. PURPOSE: The aim was to evaluate long-term clinical, radiologic, and respiratory outcomes of a minimally invasive fusionless surgery (MIFLS) in SMA scoliosis. METHODS: All children affected with SMA scoliosis who underwent MIFLS in our department from 2011 to 2019 were included. The instrumentation consisted in a bilateral sliding rod construct from T1 to the sacrum, anchored proximally by double-hook claws and distally by iliosacral screws. Clinical, genetic, respiratory and radiographic data were retrospectively reviewed. A patient's satisfaction survey was performed. RESULTS: A total of 59 children with genetic confirmation of SMA (9SMA1c, 47SMA2, and 3SMA3) underwent MIFLS at a mean age of 11±1.9 years. All of them were nonwalker at the time of surgery. Twenty-six were treated with intrathecal Nusinersen. Mean follow-up was 5.2 years (2 to 9.6 y). Mean major coronal curve improved from 79±15 to 41±16 degrees and pelvic obliquity decreased from 24±11 to 5.9±4 degrees. Mean space available for lung improved from 77% to 93%. Mechanical or infectious complications occurred in 9 patients, with removal of the implant in 1. 6 children required unplanned surgeries. Postoperative bracing was needed in 13 children. Mean gain weight 3 years after the first surgery was 6 kg. 91.5% of patients had a positive satisfaction of the surgery. There was no significant impact in respiratory function postoperatively. Only 30 children required rod lengthening procedures, with a mean interval between procedures of 1.9 years (0.5 to 3.7 y). No arthrodesis was required at last follow-up in any patient. CONCLUSION: Bipolar MIFLS in SMA preserves spinal and thoracic growth without interference with respiratory function. It provides a significant correction of spinal deformity and pelvic obliquity, having a reduced rate of complications. The correction of spinal deformity was maintained at long term, not requiring definitive fusion at the end of growth. LEVEL OF EVIDENCE: Level IV.

Paediatric long term continuous positive airway pressure and noninvasive ventilation in France: A cross-sectional study.

OBJECTIVE: To describe the characteristics of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in France. DESIGN: Cross-sectional national survey. SETTING: Paediatric CPAP/NIV teams of 28 tertiary university hospitals in France. PATIENTS: Children aged <20 years treated with CPAP/NIV since at least 3 months on June 1st, 2019. INTERVENTION: An anonymous questionnaire was filled in for every patient. RESULTS: The data of 1447 patients (60% boys), mean age 9.8 ± 5.8 years were analysed. The most frequent underlying disorders were: upper airway obstruction (46%), neuromuscular disease (28%), disorder of the central nervous system (13%), cardiorespiratory disorder (7%), and congenital bone disease (4%). Forty-five percent of the patients were treated with CPAP and 55% with NIV. Treatment was initiated electively for 92% of children, while 8% started during an acute illness. A poly(somno)graphy (P(S)G) was performed prior to treatment initiation in 26%, 36% had a P(S)G with transcutaneous carbon dioxide monitoring (PtcCO2), while 23% had only a pulse oximetry (SpO2) with PtcCO2 recording. The decision of CPAP/NIV initiation during an elective setting was based on the apnea-hypopnea index (AHI) in 41% of patients, SpO2 and PtcCO2 in 25% of patients, and AHI with PtcCO2 in 25% of patients. Objective adherence was excellent with a mean use of 7.6 ± 3.2 h/night. Duration of CPAP/NIV was 2.7 ± 2.9 years at the time of the survey. CONCLUSION: This survey shows the large number of children treated with long term CPAP/NIV in France with numerous children having disorders other than neuromuscular diseases.

Levosimendan as Rescue Therapy for Acute Heart Failure in a Patient with Duchenne Muscular Dystrophy.

The longer survival of patients with Duchenne muscular dystrophy due to advances in clinical care has increased the incidence of Duchenne muscular dystrophy-associated cardiomyopathy, a nearly consistent feature in the third decade of life. A 26-year-old patient with Duchenne muscular dystrophy experienced severe acute heart failure triggered by pneumonia. Levosimendan was effective in improving heart function.

De novo LMNA mutations cause a new form of congenital muscular dystrophy.

OBJECTIVE: To describe a new entity of congenital muscular dystrophies caused by de novo LMNA mutations. METHODS: Fifteen patients presenting with a myopathy of onset in the first year of life were subjected to neurological and genetic evaluation. Histopathological and immunohistochemical analyses were performed for all patients. RESULTS: The 15 patients presented with muscle weakness in the first year of life, and all had de novo heterozygous LMNA mutations. Three of them had severe early-onset disease, no motor development, and the rest experienced development of a "dropped head" syndrome phenotype. Despite variable severity, there was a consistent clinical pattern. Patients typically presented with selective axial weakness and wasting of the cervicoaxial muscles. Limb involvement was predominantly proximal in upper extremities and distal in lower extremities. Talipes feet and a rigid spine with thoracic lordosis developed early. Proximal contractures appeared later, most often in lower limbs, sparing the elbows. Ten children required ventilatory support, three continuously through tracheotomy. Cardiac arrhythmias were observed in four of the oldest patients but were symptomatic only in one. Creatine kinase levels were mild to moderately increased. Muscle biopsies showed dystrophic changes in nine children and nonspecific myopathic changes in the remaining. Markedly atrophic fibers were common, most often type 1, and a few patients showed positive inflammatory markers. INTERPRETATION: The LMNA mutations identified appear to correlate with a relatively severe phenotype. Our results further broaden the spectrum of laminopathies and define a new disease entity that we suggest is best classified as a congenital muscular dystrophy (LMNA-related congenital muscular dystrophy, or L-CMD).