Neuromuscular Disease Patients Research Articles

Hypercapnia is not excluded by normoxia in neuromuscular disease patients: implications for oximetry

BackgroundPulse oximetry is widely used in the assessment of chronic respiratory failure (CHRF) in neuromuscular disease (NMD) patients. CHRF is the major cause of morbidity and mortality, necessitating early diagnosis and intervention. Guidelines suggest an arterial blood gas (ABG) is indicated if oxygen saturations (SpO2)≤94% in the absence of lung disease. However, hypercapnia with normoxia (SpO2≥95%) has been observed on ABGs of patients with NMD, in particular those with motor neurone disease (MND).MethodsA single-centre retrospective audit of room-air ABGs in stable hypercapnic chronic respiratory failure (CHRF) patients from 1990–2020 was performed. Patients with parenchymal lung disease were excluded. Patients were grouped into three main categories: non-NMD, other-NMD and MND.FindingsTwo-hundred and ninety-seven ABGs with hypercapnia from 180 patients with extrinsic restrictive lung disease were analysed. No patients with non-NMD, 54% of other-NMD and 36% of MND patients demonstrated hypercapnia with normoxia (χ261.33; p<0.001). The potential mechanism is proposed to be a difference in calculated respiratory quotient (RQ). If the A-a gradient is assumed to be normal, the calculated RQ was significantly higher in MND patients and other-NMD patients compared with non-NMD patients (estimated-marginal-mean 0.99 [95%CI 0.94–1.03]; 0·86 [95%CI 0.76–0.96]; 0·73 [95%CI 0.63—0.83] respectively; p<0.001) by mixed-model analysis.InterpretationHypercapnia is not excluded with normal oximetry in NMD patients and may be due to an elevated RQ. This has implications in the diagnosis and monitoring of respiratory insufficiency in NMD patients with oximetry alone.FundingDr Emma Gray received an NHMRC Postgraduate Scholarship.

Sleep disordered breathing assessment in patient with slowly progressive neuromuscular disease

BackgroundSleep-disordered breathing (SDB) is common in patients with neuromuscular diseases (NMD). Focusing on hypercapnia may lead to the neglect of other SDB such as obstructive and/or central sleep apnea syndrome (SAS). Our objectives were to assess the risk of inappropriate SDB management according to different screening strategies and to evaluate the prevalence and determinants of isolated and overlapping sleep apnea in patients with slowly progressive NMD. MethodsThis monocentric, cross-sectional, retrospective study analyzed medical records of adult NMD patients referred to a sleep department. Diagnostic strategies, including respiratory polygraphy (RP), nocturnal transcutaneous capnography (tcCO2), and blood gases (BG), were assessed for their performance in diagnosing SDB. Demographics and pulmonary function test results were compared between patients with or without SDB to identify predictors. ResultsAmong the 149 patients who underwent a full diagnostic panel (RP + tcCO2 + BG), 109 were diagnosed with SDB. Of these, 33% had isolated SAS, and central apneas were predominant. Using single diagnostic strategies would lead to inappropriate SDB management in two thirds of patients. A combination of 2 diagnostic tools resulted respectively in 21.1, 22.9 and 42.2 % of inappropriate SDB management for RP + tcCO2, RP + BG and tcCO2 + BG. ConclusionThe significant prevalence of sleep apnea syndrome in patients with slowly progressive NMD highlights the need for increased awareness among clinicians. Improved diagnostics involve a systematic approach addressing both sleep apnea and diurnal and nocturnal alveolar hypoventilation to avoid inappropriate management and limit the consequences of SDB.

Peri-partum respiratory management of pregnant women with neuro-muscular disorders: a prospective observational study (IT-NEUMA-Pregn study)

BackgroundPregnant women with neuromuscular diseases (NMDs) often display respiratory muscle impairment which increases the risk for pulmonary complications (PCs). The aim of this study was to identify pregnant NMDs patients with pulmonary risk factors and to apply in these women non-invasive ventilation (NIV) combined with mechanical insufflation-exsufflation (MI-E) in the peri-partum period.MethodsWe conducted a multicenter observational study on women with NMDs undergoing cesarean section or spontaneous labor in a network of 7 national hospitals. In these subjects we applied a protocol for screening and preventing PCs, and we evaluated PCs rate, maternal and neonatal outcome.ResultsTwenty-four patients out of the 94 enrolled pregnant women were at risk for PCs and were trained or retrained to use NIV and/or MI-E before delivery. After delivery, 17 patients required NIV with or without MI-E. Despite nine out of the 24 women at pulmonary risk developed postpartum PCs, none of them needed reintubation nor tracheostomy. In addition, the average birth weight and Apgar score were normal. Only one patient without pulmonary risk factors developed postpartum PCs.ConclusionThis study showed the feasibility of applying a protocol for screening and treating pregnant NMDs women with pulmonary risk. Despite a PCs rate of 37% was observed in these patients, maternal and neonatal outcome were favorable.

The Safety of a High-Flow Nasal Cannula in Neuromuscular Disease Patients with Acute Respiratory Failure: A Retrospective Case-Series Study.

(1) Background: Although Non-Invasive Ventilation (NIV) is effective in preventing mortality and endotracheal intubation in patients with Acute Respiratory Failure (ARF) linked to a neuromuscular disorder, its efficacy can be affected by patient intolerance. A High-Flow Nasal Cannula (HFNC) appears to have a significant advantage over NIV as far as patient tolerance is concerned. The aim of the study was to investigate HFNC's safety profile in a group of consecutive Neuromuscular Disease (NMD) patients intolerant to NIV who were admitted to an Intermediate Respiratory Care Unit (IRCU) for ARF. (2) Methods: The clinical course of nine NMD patients intolerant to NIV and switched to HFNC was reported. HFNC was provided during daytime hours and NIV during the night-time to the NIV-intolerant patients. HFNC was utilized 24 h a day in those patients who were intolerant of even nocturnal NIV. (3) Results: HFNC was simple to use and it was well tolerated by all of the patients. Three out of nine patients experienced treatment failure, consisting of the need for ETI and/or death during their IRCU stay. The remaining 6 had a favorable outcome. Treatment failure was linked to the utilization of HFNC 24 h a day. (4) Conclusion: HFNC during the daytime hours, together with nocturnal NIV, seems to be a safe therapeutic approach for NMD patients with ARF. A round-the-clock use of HFNC tends to be linked to a high likelihood of failure.

The Impact of Fatty Infiltration on MRI Segmentation of Lower Limb Muscles in Neuromuscular Diseases: A Comparative Study of Deep Learning Approaches.

Deep learning methods have been shown to be useful for segmentation of lower limb muscle MRIs of healthy subjects but, have not been sufficiently evaluated on neuromuscular disease (NDM) patients. Evaluate the influence of fat infiltration on convolutional neural network (CNN) segmentation of MRIs from NMD patients. Retrospective study. Data were collected from a hospital database of 67 patients with NMDs and 14 controls (age: 53 ± 17 years, sex: 48 M, 33 F). Ten individual muscles were segmented from the thigh and six from the calf (20 slices, 200 cm section). A 1.5 T. Sequences: 2D T1 -weighted fast spin echo. Fat fraction (FF): three-point Dixon 3D GRE, magnetization transfer ratio (MTR): 3D MT-prepared GRE, T2: 2D multispin-echo sequence. U-Net 2D, U-Net 3D, TransUNet, and HRNet were trained to segment thigh and leg muscles (101/11 and 95/11 training/validation images, 10-fold cross-validation). Automatic and manual segmentations were compared based on geometric criteria (Dice coefficient [DSC], outlier rate, absence rate) and reliability of measured MRI quantities (FF, MTR, T2, volume). Bland-Altman plots were chosen to describe agreement between manual vs. automatic estimated FF, MTR, T2 and volume. Comparisons were made between muscle populations with an FF greater than 20% (G20+) and lower than 20% (G20-). The CNNs achieved equivalent results, yet only HRNet recognized every muscle in the database, with a DSC of 0.91 ± 0.08, and measurement biases reaching -0.32% ± 0.92% for FF, 0.19 ± 0.77 for MTR, -0.55 ± 1.95 msec for T2, and - 0.38 ± 3.67 cm3 for volume. The performances of HRNet, between G20- and G20+ decreased significantly. HRNet was the most appropriate network, as it did not omit any muscle. The accuracy obtained shows that CNNs could provide fully automated methods for studying NMDs. However, the accuracy of the methods may be degraded on the most infiltrated muscles (>20%). 4. Stage 1.

Telemedicine in Neuromuscular Diseases During Covid-19 Pandemic: ERN-NMD European Survey.

Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients' homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is limited due to difficulties evaluating subtle neurological signs such as mild weakness or sensory deficits. The COVID-19 pandemic has disrupted healthcare delivery worldwide, necessitating rapid measures implementation by health care providers (HCPs) to protect patients from acquiring SARS-CoV-2 while maintaining the best care and treatment. Given the challenges faced by remote healthcare assistance of NMD patients, we aim to evaluate the use of TM in NMD during the COVID-19 pandemic. Based on the Model for Assessment-of-Telemedicine-Applications (MAST), we conducted a survey amongst clinicians of the ERN EURO NMD (European-Reference-Network-for-Rare-Neuromuscular-Diseases). Based on 42 responses over 76 expected ones, our results show that the COVID-19 pandemic significantly increased the number of HCPs using TM (from 60% to 100%). The TM types most used during the COVID-19 period are teleconsultation and consultation by phone, particularly in the context of symptoms worsening in NMD patients with COVID-19 infection. Most European HCPs were satisfied when using TM but as a complementary option to physical consultations. Many responses addressed the issue of technical aspects needing improvement, particularly for elderly patients who need caregivers' assistance for accessing the TM platform. TM has been essential during COVID-19, but its use still presents some limitations for NMD patients with cognitive deficits or for first-time diagnosis. Thus, TM should be used as complement to, rather than substitute, for face-to-face consultations.

Prevalence of co-morbidity and history of recent infection in patients with neuromuscular disease: A cross-sectional analysis of United Kingdom primary care data.

People with neuromuscular disease (NMD) experience a broader range of chronic diseases and health symptoms compared to the general population. However, no comprehensive analysis has directly quantified this to our knowledge. We used a large UK primary care database (Clinical Practice Research Datalink) to compare the prevalence of chronic diseases and other health conditions, including recent infections between 23,876 patients with NMD ever recorded by 2019 compared to 95,295 age-sex-practice matched patients without NMD. Modified Poisson regression estimated Prevalence Ratios (PR) to summarise the presence of the disease/condition ever (or for infections in 2018) in NMD patients versus non-NMD patients. Patients with NMD had significantly higher rates for 16 of the 18 conditions routinely recorded in the primary care Quality and Outcomes Framework (QOF). Approximately 1-in-10 adults with NMD had ≥4 conditions recorded (PR = 1.39, 95%CI 1.33-1.45). Disparities were more pronounced at younger ages (18-49). For other (non-QOF) health conditions, significantly higher recorded levels were observed for rarer events (pulmonary embolism PR = 1.96 95%CI 1.76-2.18, hip fractures PR = 1.65 95%CI 1.47-1.85) as well as for more common primary care conditions (constipation PR = 1.52 95%CI 1.46-1.57, incontinence PR = 1.52 95%CI 1.44-1.60). The greatest co-morbidity burden was in patients with a myotonic disorder. Approximately 1-in-6 (17.1%) NMD patients had an infection recorded in the preceding year, with the risk of being hospitalised with an infection nearly double (PR = 1.92, 95%CI 1.79-2.07) compared to non-NMD patients. The burden of chronic co-morbidity among patients with NMD is extremely high compared to the general population, and they are also more likely to present in primary and secondary care for acute events such as infections.

Cardiopulmonary Exercise Testing for Patients With Neuromuscular Disease and Limited Mobility

ABSTRACTBackgroundPatients with neuromuscular disease (NMD) have progressive muscle weakness and limited mobility that contributes to a sedentary lifestyle. A sedentary lifestyle often leads to deconditioning and decreases cardiorespiratory fitness (CRF). Cardiopulmonary exercise testing (CPX) is the gold standard for the evaluation of CRF but has not been widely applied in patients with NMD.MethodsPatients with NMD were recruited from the Neuromuscular Clinic at the Stanford Neurosciences Health Center at Stanford University. Matched controls were recruited by staff from the local community by word of mouth. All participants performed CPX using a wheelchair-accessible total body trainer and a wearable metabolic cart system to volitional exhaustion.ResultsParticipants with NMD and limited mobility (n = 37) were able to perform high-quality CPX with no adverse events or safety concerns of comparable quality to controls. Average respiratory exchange ratio for NMD patients was 1.08 ± 0.16, and average rating of perceived exertion was 18 ± 2 compared with 1.16 ± 0.12 and 18 ± 2 for controls, respectively (P = 0.17 and P = 0.78, respectively). Patients with NMD on average showed markedly reduced percent predicted VO2max and impaired ventilatory efficiency.ConclusionHigh-quality CPX in patients with NMD may reveal distinct physiological profiles that may lead to a better understanding of pathology in these individuals. CPX on total body trainers may be a viable method for improving exercise prescription for patients with NMD.

Ventilatory, phonatory and swallowing impairments in advanced neuromuscular disease patients

PurposeTo analyze the ventilatory, phonatory and swallowing impairments and their relation with physical status in a group of advanced Neuromuscular Disease (NMD). MethodsA cross-sectional observational study was utilized 48 participants from the Association of NMD of Granada (Granada, España), university clinical research, University of Granada. A total of 24 advanced NMD patients and 24 healthy controls matched for age and sex were recruited. Advanced NMD patients were divided in two groups according to the level of their overall physical status (NMD higher physical status group or NMD lower physical status group). Hand grip strength, ventilatory, phonatory and swallowing features were analyzed. ResultsThere were significant differences (p<.05) among NMDs groups in ventilatory function. There were significant differences (p<.05) between NMDs groups in ventilatory, phonatory and swallowing function. Finally, there were significant differences (p<.05) among advanced NMDs groups in swallowing function and orofacial evaluation. ConclusionPatients with lower physical status have higher risk of suffer ventilatory, phonatory and swallowing complications after diagnosis of NMD.Registered in the Clinical Trials reference: NCT04473612.

Caregivers of Neuromuscular Patients Living with Tracheostomy during COVID-19 Pandemic: Their Experience.

Background: During a pandemic, tracheostomy management in neuromuscular disease (NMD) patients can be complex. Methods: Using a multicentre, multiple case study approach, we sought perspectives through semi-structured interviews via hybrid quali-quantitative analysis. The qualitative analysis involved a semi-structured interview and the quantitative analysis the completion of a battery of questionnaires. Aim: To investigate the caregivers’ experiences, burden and beliefs regarding tracheostomy during the Italian COVID-19 pandemic. The following instruments were administered: Connor and Davidson Resilience Scale (CD-RISC-25); Acceptance and Action Questionnaire-II (AAQ-II); State-Trait Anxiety Inventory (STAI); Langer Mindfulness Scale (LMS); Zarit Burden Interview (ZBI). Results: Fifty-three caregivers (62.3% female, mean age 52.2 (SD = 18.2)) participated in the study. The more resilient the carers, the more they were psychologically flexible (r = 0.380, p = 0.014) and able to cope adaptively with the emergency (r = 0.378, p < 0.006). Similarly, perceived control was higher the more resilient they were (r = 0.897, p < 0.001). The main emotions emerging were isolation and loneliness (15; 34.88%). The perception of tracheostomy meant that it could be seen as a lifesaver or as a condemnation. Similarly, the relationship with health professionals moves from satisfaction to a feeling of abandonment over the course of the pandemic. Conclusions: These findings offer a unique opportunity to understand the point of view of caregivers of NMD patients living with tracheotomy during the COVID-19 pandemic, when going to the hospital may have been hampered.

Mental health challenges and digital platform opportunities in patients and families affected by pediatric neuromuscular diseases - experiences from Switzerland.

Receiving the diagnosis of a severe disease may present a traumatic event for patients and their families. To cope with the related challenges, digital interventions can be combined with traditional psychological support to help meet respective needs. We aimed to 1) discuss the most common consequences and challenges for resilience in Neuro Muscular Disease patients and family members and 2) elicit practical needs, concerns, and opportunities for digital platform use. We draw from findings of a transdisciplinary workshop and conference with participants ranging from the fields of clinical practice to patient representatives. Reported consequences of the severe diseases were related to psychosocial challenges, living in the nexus between physical development and disease progression, social exclusion, care-related challenges, structural and financial challenges, and non-inclusive urban design. Practical needs and concerns regarding digital platform use included social and professional support through these platforms, credibility and trust in online information, and concerns about privacy and informed consent. Furthermore, the need for safe, reliable, and expert-guided information on digital platforms and psychosocial and relationship-based digital interventions was expressed. There is a need to focus on a family-centered approach in digital health and social care and a further need in researching the suitability of digital platforms to promote resilience in the affected population. Our results can also inform city councils regarding investments in inclusive urban design allowing for disability affected groups to enjoy a better quality of life.

CARDIOPULMONARY RESPONSE TO EXERCISE IN PATIENTS WITH NEUROMUSCULAR DISEASE

BACKGROUND Standard of care for patients with neuromuscular disease (NMD) includes exercise testing and exercise therapy. The focus of exercise in this group is to respond to muscular skeletal pathologies related to NMD, improve general health and fitness and health related quality of life. Cardiopulmonary exercise testing CPX is the gold standard for assessing cardiorespiratory fitness, but the use of CPX has been limited in NMD, especially for those patients with low mobility. We present our data on peak CPX and submaximal A6MCT exercise testing in patients with NMD and limited mobility. METHODS We prospectively recruited and consented consecutive patients who were performing outpatient physical therapy at the Neuromuscular Clinic at Stanford University Hospital. Patients performed CPX to volitional exhaustion on a total body trainer and/ or A6MCT at highest pace possible for six minutes on an ergometer. Respiratory gas data were collected on a breath-by-breath basis and analyzed after applying a rolling 30 second average filter. Collected data were compared and contrasted between CPX and A6MCT and compared to normative data and controls. RESULTS There were no complications or adverse events during the study, and data quality was adequate for CPX and A6MCT and comparable to controls. Average respiratory exchange ratio (RER) for patients with NMD was 1.08±0.16 and average rating of perceived exertion (RPE) was 18.4±2.1 compared to 1.16±0.12 and 18.1±2.0 for controls. NMD patients on average showed markedly reduced percent predicted VO2 max (55.6±24.9 percent predicted) and impaired ventilatory efficiency. CONCLUSIONS Quality exercise testing is possible and worthwhile in patients with NMD and low mobility. Especially CPX may offer strong and standard assessment of CRF which may provide valuable clinical data both specific to NMD and nonspecific to improve outcomes. Although a commonly performed procedure, A6MCT would need more study to illustrate its utility for patients with NMD.

A fact‐finding survey of medical care provided to neuromuscular disease patients at the National Center of Neurology and Psychiatry in Japan

AbstractSubjectThe aim of the present study was to conduct a fact‐finding survey of medical care practices that are provided to neuromuscular diseases (NMDs) patients and to identify the placement rate and timing of implementation for each of the diseases.MethodAll 3756 NMD patients who were admitted to the Neurology ward between April 2015 and March 2020 were included. This was a retrospective survey of specific medical care practices (percutaneous endoscopic gastrostomy (PEG) and tracheotomy) implemented.ResultsThe results showed that 325 patients (8.7%) had PEG placements, and 78 patients (2.1%) had tracheotomies. When the course of each disease from onset to medical care was examined, the diseases for which medical care was received soon after onset were MND, MSA, DLB, and progressive supranuclear palsy, whereas muscular dystrophy, myopathy, and Parkinson's disease (PD) were diseases with a relatively long time between disease onset and medical care. Discussion: In conducting the fact‐finding survey on medical care practices for NMD, the following were taken into consideration: (i) difficulty in conducting the investigation due to NMD being a rare disease; (ii) existence of a difference in age of onset and progression of the diseases; and (iii) differences in treatment environments due to disparities in treatment policies among medical institutions providing medical care and local support systems.ConclusionsThe course of medical care provision for NMD patients varied depending on the disease, and the difference in the time course of progression of symptoms greatly impacted patients' decision making.

Factors associated with the severity of COVID-19 outcomes in people with neuromuscular diseases: Data from the International Neuromuscular COVID-19 Registry.

Clinical outcome information on patients with neuromuscular diseases (NMDs) who have been infected with SARS-CoV-2 is limited. The aim of this study was to determine factors associated with the severity of COVID-19 outcomes in people with NMDs. Cases of NMD, of any age, and confirmed/presumptive COVID-19, submitted to the International Neuromuscular COVID-19 Registry up to 31 December 2021, were included. A mutually exclusive ordinal COVID-19 severity scale was defined as follows: (1) no hospitalization; (2) hospitalization without oxygenation; (3) hospitalization with ventilation/oxygenation; and (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs) for severe outcome, adjusting for age, sex, race/ethnicity, NMD, comorbidities, baseline functional status (modified Rankin scale [mRS]), use of immunosuppressive/immunomodulatory medication, and pandemic calendar period. Of 315 patients from 13 countries (mean age 50.3 [±17.7] years, 154 [48.9%] female), 175 (55.5%) were not hospitalized, 27 (8.6%) were hospitalized without supplemental oxygen, 91 (28.9%) were hospitalized with ventilation/supplemental oxygen, and 22 (7%) died. Higher odds of severe COVID-19 outcomes were observed for: age ≥50 years (50-64 years: OR2.4, 95% confidence interval [CI] 1.33-4.31; >64 years: OR4.16, 95% CI 2.12-8.15; both vs. <50 years); non-White race/ethnicity (OR1.81, 95% CI 1.07-3.06; vs. White); mRS moderately severe/severe disability (OR 3.02, 95% CI 1.6-5.69; vs. no/slight/moderate disability); history of respiratory dysfunction (OR 3.16, 95% CI 1.79-5.58); obesity (OR 2.24, 95% CI 1.18-4.25); ≥3 comorbidities (OR 3.2, 95% CI 1.76-5.83; vs. ≤2; if comorbidity count used instead of specific comorbidities); glucocorticoid treatment (OR 2.33, 95% CI 1.14-4.78); and Guillain-Barré syndrome (OR 3.1, 95% CI 1.35-7.13; vs. mitochondrial disease). Among people with NMDs, there is a differential risk of COVID-19 outcomes according to demographic and clinical characteristics. These findings could be used to develop tailored management strategies and evidence-based recommendations for NMD patients.

Ultrasonography Assessment Based on Muscle Thickness and Echo Intensity in Post-Polio Patients.

There is nospecific designed diagnostic test for post-poliomyelitis syndrome. The most important symptoms of this syndrome are new loss of muscle strength and more fatigue. Previous studies have investigated muscle ultrasound parameters to distinguish neuromuscular disease patients from healthy controls. The aim of this study was to investigate if muscle thickness and echo intensity measured by ultrasound can discriminate post-poliomyelitis syndrome patients from healthy controls. A total of 29 post-polio patients and 27 healthy controls participated in this cross-sectional study. Anthropometric measures, muscle thickness, echo intensity using B-mode ultrasound in rectus femoris and biceps brachii muscles, and muscle strength test data were collected. Muscle thickness in rectus femoris was significantly lower in post-poliomyelitis patients than in healthy controls, but not in biceps brachii. Echo intensity in rectus femoris and biceps brachii was higher in post-poliomyelitis syndrome patients than in healthy controls. Correlations were found between muscle thickness and strength in the upper and lower limbs. The results of the present study showed that muscle thickness in rectus femoris and echo intensity in rectus femoris and biceps brachii can discriminate post-poliomyelitis syndrome patients from healthy controls. A better assessment is possible because it can observe differences and relevant parameters in this clinical population.

SARS-CoV-2 antibody response to the second COVID-19 vaccination in neuromuscular disease patients under immune modulating treatment

Einer erfolgreichen Impfung (adäquater Anstieg der Anti-S[Spike]-Protein-Antikörper) gegen SARS-CoV‑2 (engl. severe acute respiratory syndrome coronavirus type 2) wird ein suffizienter Schutz gegen einen schweren Verlauf von COVID-19 (engl. coronavirus disease 2019) zugeschrieben. Bei Patient*innen mit chronisch-inflammatorischen Erkrankungen (engl. „chronic inflammatory diseases“ [CID]) und Immunsuppression ist der Impferfolg weiterhin im wissenschaftlichen Diskurs. Daher evaluierten wir bei Patient*innen mit einer neuromuskulären Erkrankung (NME), die zu regelmäßigen Infusionen von Immunglobulinen in unserer neurologischen Tagesklinik/Ambulanz vorstellig wurden, 2 Wochen nach vollständiger Immunisierung die Antikörpertiter gegen das S1 (S1-Untereinheit des Spike-Proteins) -Antigen von SARS-CoV‑2. Unsere Daten zeigen, dass Patient*innen mit einer chronischen autoimmunen NME und gleichzeitiger immunsuppressiver bzw. immunmodulierender Therapie nach einer Impfung sowohl mit einem mRNA- als auch mit einem Vektorimpfstoff eine Antikörperantwort aufwiesen. Im Vergleich zu gesunden Proband*innen zeigte sich eine vergleichbare Anzahl an Serokonversionen durch die Impfung. Eine Korrelation zwischen Immunglobulindosierung und Impfantwort sowie Infusionsintervall und Impfantwort ließ sich nicht feststellen. Demgegenüber zeigte jedoch insbesondere die Kombination aus Mycophenolatmofetil (MMF) und Prednisolon eine signifikante Reduktion der spezifischen Antikörpersynthese.

Neuromuscular diseases and their cardiac manifestations under the spectrum of cardiovascular imaging.

Neuromuscular diseases (NMDs) include a broad spectrum of disorders that affect motor unit in every possible site, extending from the cell body of peripheral nerves to the muscle. The different lesion sites make this group of inherited disorders difficult to diagnose. Many NMDs, especially those involving skeletal muscles, can present significant cardiovascular complications, ranging from rhythm disturbances to the development of dilated or hypertrophic cardiomyopathy. Heart disease represents a major cause of morbidity and mortality among NMD patients, underlining the vital need for further familiarization with the pathogenesis and assessment of cardiac involvement. Cardiovascular imaging is the cornerstone for the evaluation of heart disorders in NMDs, with conventional echocardiography still offering a portable, affordable, and easily accessible solution. Meanwhile, newer echocardiographic techniques such as speckle tracking imaging in combination with cardiac magnetic resonance add new insights into further substrate characterization. The purpose of this review is to offer a brief presentation of the main NMDs and their cardiovascular complications, as well as the presentation of data that highlight the importance of cardiovascular imaging in early diagnosis, monitoring, and prognosis of these patients. Lastly, the authors provide a simple guide about which clinical features, imaging findings, and follow-up plan to adopt in each myopathic disorder.

Myocardial strain analysis by cardiac magnetic resonance 3D feature-tracking identifies subclinical abnormalities in patients with neuromuscular disease and no overt cardiac involvement.

Cardiovascular magnetic resonance (CMR) is valuable for the detection of cardiac involvement in neuromuscular diseases (NMDs). We explored the value of 2D- and 3D-left ventricular (LV) myocardial strain analysis using feature-tracking (FT)-CMR to detect subclinical cardiac involvement in NMD. The study included retrospective analysis of 111 patients with NMD; mitochondrial cytopathies (n = 14), Friedreich's ataxia (FA, n = 27), myotonic dystrophy (n = 27), Becker/Duchenne's muscular dystrophy (BMD/DMD, n = 15), Duchenne's carriers (n = 6), or other (n = 22) and 57 age- and sex-matched healthy volunteers. Biventricular volumes, myocardial late gadolinium enhancement (LGE), and LV myocardial deformation were assessed by FT-CMR, including 2D and 3D global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and torsion. Compared with the healthy volunteers, patients with NMD had impaired 2D-GCS (P < 0.001) and 2D-GRS (in the short-axis, P < 0.001), but no significant differences in 2D-GRS long-axis (P = 0.101), 2D-GLS (P = 0.069), or torsion (P = 0.122). 3D-GRS, 3D-GCS, and 3D-GLS values were all significantly different to the control group (P < 0.0001 for all). Especially, even NMD patients without overt cardiac involvement (i.e. LV dilation/hypertrophy, reduced LVEF, or LGE presence) had significantly impaired 3D-GRS, GCS, and GLS vs. the control group (P < 0.0001). 3D-GRS and GCS values were significantly associated with the LGE presence and pattern, being most impaired in patients with transmural LGE. 3D-FT CMR detects subclinical cardiac muscle disease in patients with NMD even before the development of replacement fibrosis or ventricular remodelling which may be a useful imaging biomarker for early detection of cardiac involvement.

Multiple breath washout lung function reveals ventilation inhomogeneity unresponsive to mechanical assisted cough in patients with neuromuscular disease

BackgroundRespiratory involvement defines the clinical outcome of neuromuscular diseases (NMD). The lung clearance index (LCI) is a marker of lung ventilation inhomogeneity and indicates small airway disease. It is determined by mulitple breath washout lung function (MBW). The merit of LCI is undisputed for primary lung diseases like cystic fibrosis, but its role in NMD is unclear.MethodsWe investigated the role of MBW in patients with NMD and the effect of two different tracer gases and cough assist devices on the LCI. Patients and controls performed MBW with nitrogen (N2) and sulfur hexafluoride (SF6), whereas the latter analysis was repeated after the use of a cough assist device in the NMD group. LCI was compared to forced vital capacity (FVC) and peak cough flow (PCF).Results24 NMD patients (12 Duchenne Muscular Dystrophy, 8 Spinal Muscular Atrophy, 4 other NMDs) and 15 healthy controls were enrolled. In the NMD group, overall LCI N2 was higher than LCI SF6 (9.67 ± 1.56 vs. 8.71 ± 1.47; mean ± SD; p < 0.033). In controls, LCI N2 did not differ significantly from LCI SF6 (7.03 ± 0.37 vs. 7.05 ± 0.67; p = 0.882). Both LCI N2 and LCI SF6 were significantly higher in NMD patients as in controls (9.67 ± 1.56 vs. 7.03 ± 0.37, p < 0.001, and 8.71 ± 1.478.65 vs. 7.05 ± 0.67, p < 0.001). In the NMD group, both LCI N2 and LCI SF6 showed a negative correlation to FVC (r = − 0.525; p = 0.008 and r = − 0.526; p = 0.008, respectively) and PCF (r = − 0.590; p = 0.002 and r = − 0.641; p = 0.001, respectively). LCI N2 and LCI SF6 correlated well in the NMD group. LCI SF6 did not change significantly after the use of the cough assist in NMD patients (n = 22; 8.65 ± 1.52 pre vs. 8.79 ± 2.03 post, p = 0.667).ConclusionLung involvement of patients with neuromuscular diseases goes beyond weakness of respiratory muscles. MBW with both N2 and SF6 is suitable to detect ventilation inhomogeneity in NMD patients with respiratory impairment. Cough assist devices with low to moderate pressure levels do not immediately improve the LCI.

Changing Paradigm of Care of Neuromuscular Diseases in the COVID-19 Pandemic: A Scoping Review

In the current clinical scenario, people living with neuromuscular diseases (NMD) represent a vulnerable category with a high risk of severe course of COVID-19. Management of NMDs has become a challenge since most of them are chronic, disabling, progressive, and/or require immunosuppressive drugs. This scoping review aims to bring forth crucial queries for general neurologists and specialists dealing with NMD patients in the time of COVID-19 and highlight the research areas in a novel pandemic situation.