Search

Introduction/aims: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD., Methods: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests., Results: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001)., Discussion: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD., (© 2021 Wiley Periodicals LLC.)

Background: In patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders., Purpose: We aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency., Materials and Methods: We included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver., Results: A total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years [25; 50] and the median FVC was 34% of predicted [18; 55]. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p <0.0001) and the left hemidiaphragm (r = 0.63 p = 0.0008). Right sniff peak TDI velocity was also significantly associated with FVC (r = 0.72, p<0.0001) and with sniff nasal pressure (r = 0.66 p<0.0001). Sniff diaphragm ultrasound using either TM mode or TDI displayed significant accuracy for predicting FVC<60% with an area under curve (AUC) reaching 0.93 (p<0.0001) for the right sniff diaphragm ultrasound in TM mode and 0.86 (p<0.001) for right peak diaphragm TDI velocity., Conclusion: Sniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Diaphragm is the main inspiratory respiratory muscle and little is known about diaphragm ultrasound in facio-scapula-humeral muscular dystrophy, a neuromuscular disease characterized by an asymmetric skeletal muscle involvement., Patient Concerns: Diaphragm function evaluation DIAGNOSIS:: Diaphragm muscle weakness attested by the drop of vital capacity (VC) value from sitting position (74%) to supine position (46%)., Interventions: A diaphragm ultrasound was performed in supine position, from the anterior subcostal window OUTCOMES:: We found an opposite side to side hemi diaphragm displacement, either during sniff maneuver or during deep inspiration maneuver, showing a cranial abnormal reduced motion of the right hemi diaphragm whereas the left hemi diaphragm moved caudally., Lessons: Diaphragm weakness may be present with an asymmetric pattern and an opposite motion during inspiration or sniff manoeuver in facio-scapula-humeral muscular dystrophy. A future study with a systematic evaluation of a greater number of FSHD1 patients will be necessary to characterize this population.

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function. However, there are only a few studies using diaphragm ultrasound (US) in DMD., Purpose: We aimed to assess diaphragm ultrasound patterns in DMD, their relationship with age and their association with home mechanical ventilation (HMV)., Methods: We included DMD patients followed at Raymond Poincaré Hospital who benefited from diaphragm ultrasound and pulmonary function tests., Results: There were 110 DMD patients and 17 male sex-matched healthy subjects included. In all, 94% of patients were permanent wheelchair users. Median body mass index (BMI) was 18 kg/m2. DMD patients disclosed a reduced forced vital capacity (VC) (12% of predicted value), and 78% of patients were on HMV. In patients, right and left diaphragmatic motions on deep inspiration were reduced and end expiratory diaphragm thickness was borderline normal. In patients, right and left diaphragmatic thickening fractions (TF) were reduced 12.7% and 15.5%, respectively. Age and end expiratory thickness were significantly inversely associated (p = 0.005 for the right diaphragm, p = 0.018 for the left diaphragm). Diaphragm TF was significantly inversely associated with age (p = 0.001 for the right side, p < 0.0001 for the left side). Right and left inspiratory diaphragm motions were significantly inversely associated with age (p < 0.0001)., Conclusion: This study describes the severity of diaphragm dysfunction in patients with DMD. Diaphragm US may be a non-invasive outcome measure for DMD.

Respiratory muscles are classically involved in neuromuscular disorders, leading to a restrictive respiratory pattern. The diaphragm is the main respiratory muscle involved during inspiration. Ultrasound imaging is a noninvasive, radiation-free, accurate and safe technique allowing assessment of diaphragm anatomy and function. The authors review the pathophysiology of diaphragm in neuromuscular disorders, the methodology and indications of diaphragm ultrasound imaging as well as possible pitfalls in the interpretation of results.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with respiratory muscle weakness and respiratory failure. Non-invasive ventilation alleviates respiratory symptoms and prolongs life, but is a palliative intervention. Slowing the deterioration of diaphragm function before respiratory failure would be desirable. We aimed to assess whether early diaphragm pacing could slow down diaphragm deterioration and would therefore delay the need for non-invasive ventilation., Methods: We did a multicentre, randomised, controlled, triple-blind trial in patients with probable or definite ALS in 12 ALS centres in France. The main inclusion criterion was moderate respiratory involvement (forced vital capacity 60-80% predicted). Other key eligibility criteria were age older than 18 years and bilateral responses of the diaphragm to diagnostic phrenic stimulation. All patients were operated laparoscopically and received phrenic stimulators. Clinicians randomly assigned patients (1:1) to receive either active or sham stimulation with a central web-based randomisation system (computer-generated list). Investigators, patients, and an external outcome allocation committee were masked to treatment. The primary outcome was non-invasive ventilation-free survival, analysed in the intention-to-treat population. Safety outcomes were also assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01583088., Findings: Between Sept 27, 2012, and July 8, 2015, 74 participants were randomly assigned to receive either active (n=37) or sham (n=37) stimulation. On July 16, 2015, an unplanned masked analysis was done after another trial showed excess mortality with diaphragm pacing in patients with hypoventilation (DiPALS, ISRCTN 53817913). In view of this finding, we analysed mortality in our study and found excess mortality (death from any cause) in our active stimulation group. We therefore terminated the study on July, 16, 2015. Median non-invasive ventilation-free survival was 6·0 months (95% CI 3·6-8·7) in the active stimulation group versus 8·8 months (4·2-not reached) in the control (sham stimulation) group (hazard ratio 1·96 [95% CI 1·08-3·56], p=0·02). Serious adverse events (mainly capnothorax or pneumothorax, acute respiratory failure, venous thromboembolism, and gastrostomy) were frequent (24 [65%] patients in the active stimulation group vs 22 [59%] patients in the control group). No treatment-related death was reported., Interpretation: Early diaphragm pacing in patients with ALS and incipient respiratory involvement did not delay non-invasive ventilation and was associated with decreased survival. Diaphragm pacing is not indicated at the early stage of the ALS-related respiratory involvement., Funding: Hospital Program for Clinical Research, French Ministry of Health; French Patients' Association for ALS Research (Association pour la Recherche sur la Sclérose Latérale Amyotrophique); and Thierry de Latran Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Late-onset Pompe disease, for which enzyme replacement therapy is available, induces progressive diaphragmatic weakness. Monitoring diaphragmatic function is therefore crucial but is hindered by the need to insert esophageal and gastric probes. Vital capacity (VC), inspiratory capacity, maximal inspiratory pressure, and sniff nasal pressure are noninvasive measurements but reflect only global inspiratory-muscle function. Diaphragmatic function may be assessable noninvasively based on abdominal contribution to breathing and abdominal volume change during the VC maneuver (AVC-VC), obtained by 3-dimensional chest-wall analysis. In 11 patients, we assessed the relationships between the above-listed noninvasive variables and the invasively measured Gilbert index reflecting the diaphragmatic contribution to breathing (ratio of gastric pressure over transdiaphragmatic pressure swings during spontaneous breathing). Only abdominal contribution to breathing and AVC-VC correlated significantly with the Gilbert index (R = 0.977, P = 0.0001; and R = 0.944, P = 0.001 respectively). AVC-VC correlated significantly with transdiaphragmatic pressure swing during the sniff maneuver (R = 0.743, P = 0.0009) and with phrenic magnetic stimulation (R = 0.610, P = 0.046). Repeat testing 1 year later in the first 6 patients showed concordant changes in abdominal contribution to breathing, Gilbert index, and VC. Abdominal contribution to breathing and AVC-VC are reliable and noninvasive indices of diaphragmatic function in Pompe disease, and therefore hold promise as clinical monitoring tools., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The objective was to determine whether optoelectronic plethysmography (OEP) can detect asymmetric ventilation related to unilateral or asymmetric diaphragmatic weakness, suggesting usefulness as a diagnostic tool., Methods: Thirteen patients with suspected asymmetric diaphragmatic weakness based on dyspnea and hemidiaphragm elevation on the chest radiograph were studied as well as three patients with maltase acid deficiency (a cause of symmetrical diaphragmatic weakness). The transdiaphragmatic pressure response to unilateral magnetic stimulation (lateral twitch transdiaphragmatic pressure [latPdiTw]) and the diaphragm compound muscle action potentials (CMAPs) elicited by transcutaneous electrical stimulation of each phrenic nerve as well as OEP were performed., Results: The CMAPs and latPdiTw showed unilateral or predominantly unilateral diaphragmatic weakness in nine of the 13 patients. By OEP, the affected side of the thorax and abdomen contributed &lt; 45% of the inspiratory capacity in each of these nine patients, whereas no asymmetry was noted in the other four patients or in the three patients with maltase acid deficiency. All patients preferred OEP over CMAP or latPdiTw., Conclusions: OEP detected asymmetric ventilation in all patients diagnosed with unilateral diaphragm weakness and in no patients without this diagnosis. Thus, OEP is an effective noninvasive alternative that is preferred by the patients over CMAP response and latPdiTw.

We hypothesized that peak values of oesophageal (Poes) and transdiaphragmatic pressure (Pdi) swings during a maximal sniff manoeuvre and a maximal static inspiratory manoeuvre (Muller manoeuvre) are comparable or give complementary information for assessing diaphragmatic and global inspiratory muscle strength. We studied 98 patients with suspected diaphragmatic dysfunction. Poes and Pdi swings were measured during maximal sniff manoeuvres (sniff), maximal Muller manoeuvres (max), and cervical magnetic phrenic nerve stimulation (cervical Tw). Eighty eight patients were able to perform both volitional manoeuvres. Among them, mean Poes sniff was significantly higher than mean Poes max (48.7+/-28.7 cm H(2)O vs. 42.9+/-27.4 cm H(2)O, p<0.05) and mean Pdi sniff was higher than mean Pdi max (49.2+/-35.1cm H(2)O vs. 42.9+/-33.3 cm H(2)O, respectively, p=0.05). Cervical Pdi Tw correlated better with Pdi sniff (p<0.0001, r=0.62) than with Pdi max (p<0.0001, r=0.44). Poes and Pdi swings were greatest during the sniff manoeuvre in 42 patients (48%) and during the Muller manoeuvre in 29 patients (33%). Among the 17 remaining patients, nine had the greatest Poes swing during a maximal sniff manoeuvre and the greatest Pdi swing during a maximal static inspiratory manoeuvre; the opposite occurred in the other eight patients. The combination of Muller manoeuvre and sniff manoeuvre increased the diagnosis of normal diaphragmatic strength from 18 patients (20%) to 21 patients (24%), and the additional analysis of cervical Pdi Tw further increased the diagnosis of normal diaphragmatic strength to 27 patients (31%). In conclusion, though sniff manoeuvre gave significantly higher values than Muller manoeuvre, both volitional manoeuvres and cervical Pdi Tw are complementary and should be used in combination to evaluate diaphragmatic muscle strength.

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.

Functional imaging studies in normal humans have shown that the supplementary motor area (SMA) and the primary motor cortex (PMC) are coactivated during various breathing tasks. It is not known whether a direct pathway from the SMA to the diaphragm exists, and if so what properties it has. Using transcranial magnetic stimulation (TMS) a site at the vertex, representing the diaphragm primary motor cortex, has been identified. TMS mapping revealed a second area 3 cm anterior to the vertex overlying the SMA, which had a rapidly conducting pathway to the diaphragm (mean latency 16.7 +/- 2.4 ms). In comparison to the vertex, the anterior position was characterized by a higher diaphragm motor threshold, a greater proportional increase in motor-evoked potential (MEP) amplitude with voluntary facilitation and a shorter silent period. Stimulus-response curves did not differ significantly between the vertex and anterior positions. Using paired TMS, we also compared intracortical inhibition/facilitation (ICI/ICF) curves. In comparison to the vertex, the MEP elicited from the anterior position was not inhibited at short interstimulus intervals (1-5 ms) and was more facilitated at long interstimulus intervals (9-20 ms). The patterns of response were identical for the costal and crural diaphragms. We conclude that the two coil positions represent discrete areas that are likely to be the PMC and SMA, with the latter wielding a more excitatory effect on the diaphragm.