Predictive factors and screening strategy for obstructive sleep apnea in patients with advanced multiple sclerosis.

BACKGROUND: Obstructive sleep apnea (OSA) screening questionnaires have been evaluated in Multiple Sclerosis (MS) but not yet validated in patients with advanced disease. The aim of this study is to identify OSA predictive factors in advanced MS and to discuss screening strategies. METHODS: Oximetry data from 125 patients were retrospectively derived from polysomnographic reports. Univariate and multivariate analysis were used to determine predictive factors for OSA. A two-level screening model was assessed combining the oxygen desaturation index (ODI) and a method of visual analysis. RESULTS: multivariate analysis showed that among the clinical factors only age and snoring were associated with OSA. Usual predictive factors such as sleepiness, Body mass index (BMI) or sex were not significantly associated with increased Apnea Hypopnea Index (AHI). The ODI was highly predictive (p < 0.0001) and correctly identified 84.1 % of patients with moderate OSA and 93.8 % with severe OSA. The visual analysis model combined with the ODI did not outperform the properties of ODI used alone. CONCLUSION: As the usual clinical predictors are not associated with OSA in patients with advanced MS, questionnaires developed for the general population are not appropriate in these patients. Nocturnal oximetry seems a pertinent, ambulatory and accessible method for OSA screening in this population.

Nusinersen treatment in adults with severe spinal muscular atrophy: A real-life retrospective observational cohort study.

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. METHODS: We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was

[Factors associated with the type of mask used during nocturnal NIV in patients with neuromuscular disorders]. / Facteurs associés au masque de ventilation non invasive nocturne chez les patients neuromusculaires adultes.

In subjects with neuromuscular diseases (NMD), the choice of facemask is essential for successful long-term noninvasive ventilation (NIV). While nasal masks usually represent the first line of treatment, almost a third of our subjects with NMD use an oro-nasal interface. Factors associated with the choice of mask remain poorly understood. We provide an original analysis of a previous prospective, multi-centric, Franco-Belgian survey investigating the factors associated with the type of nocturnal mask used in 116 adult NMD subjects treated with NIV. In these patients oro-nasal mask use was more often associated with non-Duchenne muscular dystrophy, older subjects, higher body mass index, better upper limb autonomy allowing independent mask removal and shorter periods of ventilation. Controlled prospective studies are needed to compare the efficacy and tolerance of different interfaces in this specific population.

Respiratory rehabilitation in multiple sclerosis: A narrative review of rehabilitation techniques.

BACKGROUND: Respiratory disorders in multiple sclerosis (MS) are an important issue. They can occur early during the course of the disease, are associated with the neurological impairment, and can lead to pneumonia and respiratory failure, which are the main causes of death in advanced MS. Prevailing impaired expiratory muscles and cough abilities has been demonstrated in this population and might constitute a specific target for rehabilitation interventions. However, international guidelines lack recommendations regarding respiratory rehabilitation in MS. Here we performed a systematic review of the published literature related to respiratory rehabilitation in MS. METHODS: We searched the databases MEDLINE via PubMed, PEDro and Cochrane Library for English or French reports of clinical trials and well-designed cohorts published up to December 2016 with no restriction on start date by using the search terms "multiple sclerosis", "respiratory rehabilitation", "respiratory muscle training", "lung volume recruitment", "cough assistance", and "mechanical in-exsufflation". Literature reviews, case reports and physiological studies were excluded. The Maastricht criteria were used to assess the quality of clinical trials. We followed the Oxford Centre for Evidence-Based Medicine guidelines to determine level of evidence and grade of recommendations. RESULTS: Among the 21 reports of studies initially selected, 11 were retained for review. Seven studies were randomized controlled trials (RCTs), 2 were non-RCTs, and 2 were observational studies. Respiratory muscle training (inspiratory and/or expiratory) by use of a portable resistive mouthpiece was the most frequently evaluated technique, with 2 level-1 RCTs. Another level-1 RCT evaluated deep-breathing exercises. All reviewed studies evaluated home-based rehabilitation programs and focused on spirometric outcomes. The disparities in outcome measures among published studies did not allow for a meta-analysis and cough assistance devices were not evaluated in this population. CONCLUSION: Although respiratory muscle training can improve maximal respiratory pressure in MS and lung volume recruitment can slow the decline in vital capacity, evidence is lacking to recommend specific respiratory rehabilitation programs adapted to the level of disability induced by the disease.

Respiratory impairment in multiple sclerosis: a study of respiratory function in wheelchair-bound patients.

BACKGROUND AND PURPOSE: Respiratory disorders are a major cause of morbidity and mortality in multiple sclerosis (MS). Mainly reported in walking patients, they are poorly explored when walking is severely impaired. To characterize respiratory impairment in patients with advanced MS. METHODS: From 2012 to 2015, patients with MS with an Expanded Disability Status Scale (EDSS) score of ≥7 who were referred for functional and rehabilitation evaluation underwent pulmonary function tests to study lung volumes, cough efficacy and respiratory muscle pressures. RESULTS: Among 73 patients with a median EDSS score of 8 [7.5; 8.5], 72.6% had impaired respiratory function with a mean vital capacity (VC) of 57.9 ± 33.5% of theoretical value. Severe impairment (VC < 50%) was found for 34 (46.6%) patients. Cough was impaired in 45 (61.6%) patients, with a mean cough peak flow of 3.14 ± 1.9 L/s and severe impairment (cough peak flow < 2.67 L/s) in 27 (37.0%) patients. Overall, the results suggested predominant expiratory muscle dysfunction and non-predominant diaphragm impairment. EDSS score was correlated with VC but not with any other clinical data. CONCLUSION: Restrictive respiratory failure is frequent in severely impaired patients with MS, predominantly involves expiratory muscles, does not involve diaphragm weakness and is associated with cough impairments.

[Enzyme replacement therapy of lysosomal storage diseases]. / Thérapies enzymatiques substitutives des maladies lysosomales.

Extraction and purification of an acid ß-glucosidase from human placenta (alglucerase) for the treatment of Gaucher disease, replaced a few years later by a recombinant enzyme (imiglucérase, Cerezyme(®)), has paved the way to the development of enzyme replacement therapies (ERT) for the treatment of lysosomal storage diseases (LSD) among which Fabry disease for which the long-term efficacy of the two currently available preparations (agalsidase alfa, Replagal(®) and Fabrazyme(®)) is still being investigated. Mucopolysaccharidosis (MPS) type I (Hurler and Scheie diseases), II (Hunter syndrome) and VI (Maroteaux-Lamy disease) also benefit from ERT using laronidase (Aldurazyme(®)), idursulfase (Elaprase(®)) and galsulfase (Naglazyme(®)), respectively. ERT reduces the hepatosplenomegaly and improves the physical and respiratory capacities of MPS patients with a globally acceptable safety profile although the possibility of infusion-associated should always be kept in mind. Alglucosidase alpha (Myozyme(®)) improves the cardiomyopathy and life expectancy of infants suffering from Pompe disease and is under evaluation for the treatment of the juvenile and adult forms of the disease. CNS involvement remains a major challenge for many LSD and innovative research and approaches are needed to address the fact that recombinant enzymes do not cross the blood-brain barrier and therefore are not expected to lead to any improvement in CNS damages, except if alternative routes such as intrathecal administration would be developed. Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.

Relation between corset use and lung function postural variation in spinal cord injury.

Corsets are widely used to improve trunk stability in patients with spinal cord injury (SCI) and can improve respiratory function. The aim of the present study was to identify predictors of respiratory benefits from wearing a corset in SCI patients. In a prospective observational study, respiratory function was tested in the supine and upright seated position with and without a corset in 36 SCI patients who regularly used a corset. SCI patients who no longer used a corset were matched to users on sex, injury level and severity. Vital capacity (VC) did not differ between users and nonusers in the supine position. In users, contrary to nonusers, VC increased significantly in the supine position compared to the seated position (increase of 0.43+/-0.39 versus -0.05+/-0.32 L in nonusers; p<0.0001). Corset use was associated with a significant VC increase in the upright position (2.13+/-0.71 L without versus 2.41+/-0.69 L with the corset; p<0.001). The VC increase with the corset in the upright position correlated significantly with the VC increase induced by being supine, compared to sitting without the corset. The VC increase induced in SCI patients by lying supine may predict the effects of wearing a corset. The long-term effects of corset use should be evaluated.

[Diffuse interstitial pneumonitis with acute respiratory failure]. / Une pneumopathie infiltrante diffuse avec insuffisance respiratoire aiguë

Drug-induced pneumonia due to ibuprofen is exceptional. We report the case of hypoxic interstitial pneumonitis with eosinophilic alveolitis induced by ibuprofen. The resolution was spontaneously obtained by the stop of this drug.

[Critical evaluation and predictive value of clinical presentation in out-patients with acute community-acquired pneumonia]. / 07--analyse critique et valeurs prédictives des signes de pneumonies aiguës communautaires en médecine ambulatoire.

Diagnostic probability of community-acquired pneumonia (CAP) depends on data related to age and clinical and radiological findings. The critical evaluation of data in the literature leads to the following conclusions: 1) the prevalence of CAP in a given population with acute respiratory disease is 5% in outpatients and 10% in an emergency care unit. This could be as low as 2% in young people and even higher than 40% in hospitalized elderly patients; 2) the collection of clinical data is linked to the way the patient is examined and to the expertise of the clinician. The absolute lack of "vital signs" has a good negative predictive value in CAP; presence of unilateral crackles has a good positive predictive value; 3) there is a wide range of X-ray abnormalities: localized alveolar opacities; interstitial opacities, limited of diffused. The greatest radiological difficulties are encountered in old people with disorders including chronic respiratory or cardiac opacities and as a consequence of the high prevalence of bronchopneumonia episodes at this age; 4) among patients with lower respiratory tract (LRT) infections, the blood levels of leukocytes, CRP and procalcitonine are higher in CAP patients, mainly when their disease has a bacterial origin. Since you have not a threshold value reliably demonstrated in large populations with LRT infections or acute respiratory disease, presence or absence of these parameters could only be taken as a slight hint for a CAP diagnosis.

Characteristics of tracheostomy phonation valves.

Phonation valves are commonly used devices that allow the restoration of speech in tracheostomised patients. However, their use should not compromise the physiological benefit of tracheostomy. Six commercialised phonation valves were studied in a dynamic set-up simulating a respiratory frequency of 20 breaths.min(-1), a tidal volume of 0.5 L and a peak flow rate of 0.5 L.s(-1). Resistance and additional work of breathing (WOB) were calculated. In 10 tracheostomised patients, evaluations using no phonation valve (baseline), and the most and one of the least resistive valves were carried out. Respiratory patterns and gas exchanges were recorded. Inspiratory difficulty was evaluated using the modified Borg scale. Valves displayed a wide array of resistance ranging 1.3-5.9 cmH2O.L(-1).s(-1). Additional WOB varied with a ratio of 4.4 between the best and the worst valve. While the different clinical conditions did not modify respiratory patterns and gas exchanges, a significant effect on the Borg scale rating was observed using ANOVA and post hoc analysis of baseline versus worst valve and one of the best valves versus worst valve. In conclusion, the variety of aerodynamic characteristics of phonation valves should be considered when choosing the device, according to the underlying condition of the patients benefiting from their use.

Significance of phrenic nerve electrophysiological abnormalities in Guillain-Barré syndrome.

The authors investigated whether the amplitude and latency of diaphragm compound muscle action potential helped predict respiratory failure in Guillain-Barré syndrome. Both variables were significantly but weakly correlated with vital capacity (VC) and were similar in unventilated (n = 60) and ventilated (n = 10) patients. In ventilated patients, motor loss severity, progression, and VC reduction were significantly greater, and bulbar dysfunction was more common. Predicting respiratory failure must rely on clinical features and VC.

[Optimising speech during artificial ventilation]. / Optimisation de la phonation sous ventilation artificielle.

Speech is an essential component of quality of life for patients treated with long term mechanical ventilation. Therefore trying to improve phonation should always sought by physicians treating these patients. We review the different tools and techniques available in order to restore speech for patients with home mechanical ventilation whether ventilation is done continuously or not.

[Acute forms of diffuse interstitial hypoxemic pneumonia in immunocompetent patients]. / Les formes aiguës des pneumopathies infiltrantes diffuses hypoxémiantes de l'immunocompétent.

The large majority of patients with acute respiratory failure present diffuse pulmonary opacities resulting from pulmonary embolism, intra-alveolar hemorrhage, or a classical cause of ARDS. In a small number of patients however, these opacities correspond to diffuse interstitial pneumonia. This should be suspected in light of the context, the time of formation, and the unusual respiratory and/or extrarespiratory signs. If there is a clinical doubt, thoracic scan and bronchoalveolar lavage should be performed together with infectious and immunology tests. Treatment depends on the cause and/or the type of lesion.

[Long term domiciliary mechanical ventilation in patients with neuromuscular disease (indications, establishment and follow up)]. / Ventilation mécanique a domicile et au long cours des patients neuromusculaires (indication, mise en place et surveillance).

UNLABELLED: Neuromuscular diseases represent a heterogeneous group of pathologies which common feature is the development of a restrictive ventilatory failure. BACKGROUND: Respiratory insufficiency of neuromuscular origin manifests itself by functional symptoms that must be carefully searched for in the history, such as headaches, sleep disorders, or dyspnoea of effort, sometimes very mild, or in severe cases associated with orthopnoea. Follow up should be multi-disciplinary. On the respiratory level regular measurement of blood gases, vital capacity, maximum inspiratory and expiratory pressures as well as sleep studies, will detect the criteria for mechanical ventilation (hypercarbia > 45 mm Hg, nocturnal desaturation < 88%, vital capacity < 60%, PImax < 60 cm H2O). STATE OF THE ART: The establishment of mechanical ventilation is a major decision for patients with neuromuscular disease because of the important physical, psychological, social and sometimes financial consequences. The patients and their family must be instructed precisely in order to obtain the best possible observation and compliance. The establishment requires a stay in hospital of several days to optimise the choice of ventilator, its settings, and connections. The link with the organisation managing the domiciliary ventilation is fundamental in ensuring follow up after discharge from hospital. Techniques of cough assistance must be taught to each neuromuscular patient requiring mechanical ventilation. CONCLUSION: Ventilation of neuromuscular patients requires careful evaluation of the indications and rigorous follow up by a multidisciplinary team with wide experience of this type of disease.

Spectrum of CD4 to CD8 T-cell ratios in lymphocytic alveolitis associated with methotrexate-induced pneumonitis.

The present study was conducted to confirm the presence of severe lymphocytic alveolitis and to determine the factors responsible for the very different alveolar CD4 to CD8 T-cell ratios (CD4/ CD8) described in methotrexate-induced pneumonitis (MTX-pneumonitis). Clinical and radiologic findings, as well as bronchoalveolar lavage (BAL) data, including CD4 and CD8 subset analysis, were retrospectively reviewed for patients hospitalized between 1985 and 2000 for MTX-pneumonitis. BAL cell counts from patients with MTX-pneumonitis (cases) were compared with those from patients receiving MTX but who did not have evidence of MTX toxicity (MTX-exposed patients) and those from healthy subjects (control subjects). Nineteen BAL were performed in 14 consecutive cases of MTX-pneumonitis. MTX was given for various underlying diseases. All cases presented a subacute diffuse interstitial pneumonitis that recovered, with MTX discontinuation and/or initiation of adjunctive steroid therapy. At the time of diagnosis, BAL cell counts in MTX-pneumonitis indicated severe lymphocytic alveolitis when compared with MTX-exposed patients and control subjects and moderate neutrophil alveolitis compared with control subjects. The lymphocytic alveolitis resulted from an increase in both CD4 and CD8 lymphocyte cell counts. Nevertheless, alveolar CD4/ CD8 T-cell ratios ranged from 0.4 to 9.6. CD4/CD8 values correlated positively with lymphocyte counts but negatively with time elapsed between last MTX administration and BAL and with steroid cumulative dose received by the patients. Severe lymphocytic alveolitis was confirmed in our series of MTX-pneumonitis. The between-patient variation in CD4/CD8 T-cell ratios may reflect the large range of time intervals between last MTX administration and BAL evaluation and the use of adjunctive steroid therapy.

Evaluation of the biocompatibility of titanium-tantalum alloy versus titanium.

To evaluate the biocompatibility of a new titanium-tantalum alloy, with qualities superior to titanium alone, for use in oral implantology, fibroblast and epithelial cell lines were grown on plastic, titanium, copper, and titanium-tantalum supports. Studies using scanning electron microscopy, flow cytometry, and cytotoxicity assays were conducted to compare the different supports. Scanning electron microscopic observations showed high densities of fibroblasts and epithelial cells with well-developed attachment systems in the form of cytoplasmic projections. Cell densities were lower on titanium and titanium-tantalum surfaces than on plastic. Cell numbers, as determined by cytotoxicity assays, were significantly higher on plastic than on titanium or titanium-tantalum surfaces while fibroblasts proliferated better than epithelial cells on both metal surfaces. Flow cytometric analyses of cell cycles did not reveal any significant variations in the distribution of cells among the cycle phases on the three materials. We found no differences with regard to the parameters studied between titanium and the titanium-tantalum alloy.