Neuromuscular diseases are a heterogeneous group of disorders affecting muscles and peripheral nerves, leading to progressive muscle weakness and functional impairment. Muscle MRI facilitates the assessment of muscle pathology, but current analysis relies on time-consuming manual segmentation or subjective visual scoring. Validation across diverse patient populations and imaging protocols is lacking in existing automated methods. Deep learning segmentation methods were developed to quantify intramuscular fat infiltration and muscle volume across all lower limb muscles using heterogeneous multi-site data. Three convolutional neural network architectures (U-Net, U-Net + + , and Attention U-Net + +) were evaluated on a multi-site dataset comprising 27,858 slices from 797 muscle MRI scans across 376 patients, spanning 12 neuromuscular diseases and 12 international sites. Thirty-two individual muscles across pelvis, thigh, and lower leg regions were segmented. High accuracy was achieved by all architectures (DSC = 0.97). Leave-One-Site-Out experiments revealed strong generalisability across sites (average DSC = 0.96). Automated fat quantification placed 90.9% of muscles within one point of ground truth on standard visual scales and correlated strongly with quantitative fat fraction measurements (r = 0.995, p < 0.001). High correlation with ground truth was demonstrated by cross-sectional area predictions (r = 0.94, p < 0.001). Diverse imaging protocols were handled with minimal preprocessing. Accuracy equivalent to observer variability was achieved by automated segmentation, potentially eliminating the need for manual correction in large-scale applications.

BackgroundWheelchair users with muscular dystrophy face health challenges from their condition, sedentary lifestyle, and wheelchair use. While exercise benefits are well-documented in healthy individuals, its effects in wheelchair users with muscular dystrophy are underexplored: low muscle mass might limit exercise benefits. This study investigates benefits and adverse events of assisted leg cycling to improve fatigue, pain, constipation, and quality of life in wheelchair users with muscular dystrophy.MethodsWheelchair users with muscular dystrophy were tested at baseline, after a 10-week control period, and after 10 weeks of assisted leg cycling (20 minutes, 3 times/week). Efficacy outcomes were changes in fatigue, lower back/leg pain, constipation, and quality of life. Secondary outcomes included changes in exercise performance, cardiovascular response, and metabolic health. A 1.5-year follow-up of voluntary training evaluated long-term effects.ResultsNineteen participants enrolled; two dropped out. Lower back pain and fatigue decreased and physical quality of life improved. Constipation did not change overall but improved in more than half of participants. HbA1c decreased by 2 mmol/mol, mainly in two participants with diabetes. Blood lipids, leg pain, cycling time, and power output showed no changes. Benefits persisted or improved over 1.5 years in participants with a high adherence.DiscussionAssisted cycling may reduce lower back pain, improve quality of life, and possibly decrease fatigue and constipation in wheelchair users with muscular dystrophy. Furthermore, exercise likely lowers HbA1c, particularly in individuals with diabetes. These findings suggest that assisted cycling is a feasible health intervention for wheelchair users with muscular dystrophy.

The ADAPT phase 3 trial (NCT03669588) showed efgartigimod was well tolerated and efficacious in acetylcholine receptor antibody–positive (AChR-Ab +) patients with generalized myasthenia gravis (gMG). This analysis utilized data from the ADAPT trial to investigate the efficacy and safety of efgartigimod in different patient subgroups. ADAPT included a broad population of AChR-Ab + participants who received a stable dose of ≥ 1 (any) treatment for gMG and were randomized 1:1 to efgartigimod (10 mg/kg) or placebo (administered as four once-weekly infusions per cycle) for 26 weeks. Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) responder rates in cycles 1 and 2, and rates of treatment-emergent adverse events (TEAEs) were analyzed in the following patient subgroups: history of nonsteroidal immunosuppressive treatment (NSIST), concomitant use of gMG treatments throughout the study, and baseline patient and disease characteristics, including time since diagnosis, age, baseline MG-ADL score, body mass index (BMI), sex, and prior thymectomy. In total, 129 AChR-Ab + participants were included (efgartigimod, n = 65; placebo, n = 64). Across all subgroups, higher MG-ADL and QMG responder rates were observed in participants treated with efgartigimod versus placebo during cycles 1 and 2. Rates of TEAEs were similar between participants treated with efgartigimod and placebo, regardless of concomitant gMG treatment type. Similar to outcomes observed in the ADAPT overall population, efgartigimod was well tolerated and efficacious across a broad range of patients, regardless of NSIST treatment history, concomitant use of gMG treatments, or baseline patient and disease characteristics. ClinicalTrials.gov: NCT03669588 (registered September 13, 2018).

Cardiac involvement is increasingly recognized in women carrying pathogenic variants in the dystrophin (DMD) gene, both Duchenne and Becker-associated, but the long-term natural history of cardiac structure, function, and conduction abnormalities in this group is not well understood. We conducted a prospective 7-year follow-up study to investigate the evolution of ventricular function, myocardial fibrosis, and arrhythmias. 34 women with confirmed pathogenic DMD gene variants (19 predicted to cause Duchenne muscular dystrophy and 15 Becker muscular dystrophy) underwent assessments after a mean of 7 years. Evaluations included cardiac magnetic resonance imaging with late gadolinium enhancement, 24-h Holter monitoring, 12-lead electrocardiography (ECG), cardiac biomarkers, and clinical examinations. At the group level, left ventricular ejection fraction (LVEF) remained stable over follow-up (p = 0.403). Six women had a ≥ 5

Mitochondrial diseases are complex conditions that can affect many organs, and patients may be seen by doctors from various clinical specialities. Currently, treatments are primarily supportive; however, this review finds that identifying the underlying genetic cause is becoming increasingly important as new targeted therapies are under development. Additionally, recent advances in reproductive technologies, such as pre-implantation testing and mitochondrial replacement therapy, may offer additional options for affected patients.

Generalized myasthenia gravis (gMG) is an autoimmune disorder that is marked by fluctuating muscle weakness and poor health-related quality of life (HRQoL). This pre-specified analysis of the phase 3 Vivacity-MG3 study (NCT04951622) assessed the effect of nipocalimab (fully human anti-FcRn monoclonal antibody) on HRQoL in patients with gMG. Seropositive adults (anti-AChR/anti-MuSK/anti-LRP4) with gMG were randomized (1:1) to intravenous nipocalimab (30 mg/kg loading, followed by 15 mg/kg every 2 weeks) or placebo, in addition to standard-of-care (SOC) for 24 weeks. The Myasthenia Gravis-Quality-of-Life 15-item revised scale (MG-QoL15r), Neuro-QoL Fatigue, EQ-5D-5L, Patient Global Impression (PGI) of Severity-Fatigue (PGI-S), and PGI-Change Fatigue (PGI-C) were used to measure patient-reported HRQoL. Nipocalimab + SOC improved MG-QoL15r scores versus placebo + SOC (Least square (LS) mean change –5.87 vs –4.42; difference –1.45). By week 2, the fatigue had improved (–10 points) and continued to improve during the double-blind phase; LS mean change in Neuro-QoL Fatigue was –13.17 vs –10.02 (difference: –3.15) over weeks 22–24. Nipocalimab showed greater improvements at week 24 than placebo in EQ-5D-5L index values (0.13 vs 0.07), VAS scores (14.55 vs 7.27) and PGI-C perceived fatigue status (56.5

Serum antibodies to muscle specific kinase (MuSK) are present in a proportion of patients with acetylcholine receptor antibody seronegative myasthenia gravis (SNMG), but their reported frequencies in different populations vary. From 2002, serum samples were sent to Oxford for MuSK antibody testing from 35 centres in 6 continents. MuSK antibodies were identified in 143/465 (30.8%) previously untested SNMG sera. They were not identified in 147 adult acetylcholine receptor antibody positive patients or in 63 adult ocular MG patients. As expected from subsequent reports, the MuSK antibody positive patients differed in gender, clinical severity, bulbar predominance and treatment requirements from the 322/465 (69.2%) MuSK antibody negative SNMG patients, but they were improved following the more aggressive treatments received, although still showing bulbar predominance. Similar features were seen in the 42 childhood cases tested (17/42 (40%) MuSK-Ab positive from 18 centres); although numbers were small there was bulbar predominance that persisted after the treatments that were more extensive than those given to the juvenile SNMG patients. Although found in each continent, MuSK-MG showed an unexpected and surprising distribution. The frequency of MuSK-Abs within individual centres varied in the Northern Hemisphere with a clear north-south gradient from 0% to 47% in Europe and North America. There were fewer cohorts from Asia but data from 11 publications, including five from East and South East Asia, confirmed a latitudinal distribution of MuSK-Ab frequency consistent with a Gaussian curve peaking at 40 degrees North, and trending towards very low frequencies above this latitude in Europe and below this latitude in South East Asia. Thus, MuSK-Abs, that are predominantly IgG4 rather than IgG1 subclass, show a striking and unexpected relationship with latitude in the Northern Hemisphere. The results raise interesting questions regarding the environmental and genetic factors involved, with possible relevance also for the increasing number of IgG4 antibody-mediated neurological disorders, including forms of neuropathy and autoimmune encephalitis.

Physical performance can be improved in aerobic athletes and breath-hold divers (BHD) by limb exposure to repetitive ischemia: remote ischemic conditioning (RIC). RIC protects against cardiac ischemia, and its blood-borne transferable substrate could be lactate. Accordingly, lactate added to whale blood increases oxygen unloading and adult seals possess higher cardiac lactate dehydrogenase activity (LDHa) than terrestrial mammals. Because BHD and adult diving mammals share adaptations to hypoxia, including lactate metabolization during apnea, we hypothesized that BHD compared to BMI/VO2max-matched aerobic controls have higher LDHa and lactate added to blood from BHD unloads oxygen more efficiently. Six BHD and six matched aerobic controls underwent RIC: three cycles of 5-min inflation and 4-min deflation of a blood pressure cuff on the dominant arm, maximum apnea after three submaximal apneas (BHD only), and a VO2max-test. Blood-samples were collected from the nondominant radial artery and the vena basilica of the dominant arm at rest, before termination of the three interventions, and for LDHa. Blood gases were compared to samples added lactate or placebo suspension. BHD had ⁓30% higher cardiac/erythrocyte LDHa compared to controls (p < 0.05). Lactate added to arterial blood from BHD after RIC increased oxygen unloading (p < 0.05). PaO2 decreased ⁓66% during apnea (375+/-49 s; p < 0.001; BHD only). We conclude that 1 (erythrocyte- and cardiac-LDHa is higher in BHD compared to matched controls, and 2) lactate facilitates oxygen-unloading in blood from BHD after RIC, similar to diving mammals.

Mitochondrial diseases are complex conditions that can affect many organs, and patients may be seen by doctors from various clinical specialities. Currently, treatments are primarily supportive; however, this review finds that identifying the underlying genetic cause is becoming increasingly important as new targeted therapies are under development. Additionally, recent advances in reproductive technologies, such as pre-implantation testing and mitochondrial replacement therapy, may offer additional options for affected patients.

Mitochondrial myopathy (MM) represents a group with a broad phenotypic spectrum which complicates the diagnostic process. This study investigated whether plasma lactate changes following a 12-min walk test (12MWT) and 20-min recovery could be a diagnostic screening tool for MM. Thirty patients with MM and 19 healthy controls (HC) participated. Total walking distance and heart rate during the test were measured, along with plasma lactate at rest, after exercise, and during recovery. For the latter, we calculated the area under the curve (AUC). The results were compared between groups. MM patients walked shorter (1082 m [994-1143] m vs. 1349 m [1149-1435], p = 0.0005) and had higher resting lactate (1.7 ± 1.2 mmol/L vs. 0.9 ± 0.3 mmol/L, p = 0.003). No significant difference in plasma lactate was observed after exercise. Plasma lactate AUC during recovery was similar between groups. Thus, the 12MWT is not a reliable screening tool for MM as changes in plasma lactate during exercise and recovery did not differentiate MM from HC.

BACKGROUND AND OBJECTIVE:Women carrying pathogenic DMD gene variants can develop muscle affection, such as muscle weakness and fat replacement. The long-term progression of the muscle involvement is unknown. This study investigates the 6.5-year changes in muscle function and -fat fraction in women carrying pathogenic DMD gene variants to enhance understanding of disease progression and its natural history. METHODS:Muscle structure and -function were investigated at baseline and after 6.5 years in 34 women carrying pathogenic DMD gene variants (19 predicted to confer Duchenne Muscular Dystrophy (DMD), 15 Becker Muscular Dystrophy (BMD)). After a clinical evaluation, muscle fat fraction was assessed using Dixon MRI, muscle strength with isokinetic dynamometry, and muscle biomarkers with blood samples for creatine kinase and myoglobin. RESULTS:Muscle fat fraction in the lower back, thigh, and calf increased significantly over 6.5 years. The average increases were generally less than 2%, but some carriers with significant baseline abnormalities experienced a more substantial increase in fat fraction, reaching as high as 31%. Although overall disease progression did not differ significantly between DMD and BMD carriers, all women who showed rapid progression were DMD carriers. Small but significant changes occurred in muscle strength and biomarkers. DISCUSSION:The progression of muscle involvement in women carrying pathogenic DMD gene variants is generally slow. However, those with severe baseline abnormalities on MRI-often associated with a lower age of symptom onset-experience a more rapid progression of muscle fat fraction, suggesting that baseline MRI findings could help predict future disease progression in this population.

BACKGROUND:Autoantibody-mediated complement activation drives pathology in acetylcholine receptor (AChR) antibody-positive generalised myasthenia gravis. Newer targeted therapies lower overall antibody concentrations or inhibit complement activity. We aimed to evaluate an siRNA (cemdisiran) targeting complement component 5 (C5) as monotherapy and in combination with a C5 antibody (pozelimab) in generalised myasthenia gravis. METHODS:NIMBLE is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 86 centres in 13 countries. We enrolled patients aged 18 years or older with a diagnosis of generalised myasthenia gravis, positive serology for anti-AChR or anti-LRP4 antibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or greater. Patients were randomly allocated to receive cemdisiran monotherapy (600 mg every 12 weeks; cemdisiran group), pozelimab monotherapy (200 mg every 4 weeks; pozelimab group), combined cemdisiran (200 mg every 4 weeks) and pozelimab (200 mg every 4 weeks; combination group), or placebo, all administered subcutaneously, during a 24-week double-blind treatment period. The primary endpoint was change from baseline in MG-ADL scores at week 24, assessed in the modified intention-to-treat (mITT) primary analysis set (the first 245 randomly allocated patients who received any dose of study treatment and had at least one post-baseline assessment). A prespecified hierarchal statistical testing strategy was used; multiplicity was controlled for comparisons of cemdisiran versus placebo and combination versus placebo (pozelimab was not statistically tested against placebo and was used only to assess the contribution of components to the combination treatment). Safety was mainly assessed by recording of treatment-emergent adverse events in all patients who received any dose of study treatment. This study is registered with ClinicalTrials.gov (NCT05070858); the current status is active, not recruiting. FINDINGS:Between Jan 20, 2022 and July 18, 2025, 390 participants were screened and, as of the data cut-off presented in this report (July 8, 2025), 284 were randomly allocated to the cemdisiran group (79 [28%] patients), pozelimab group (50 [18%]), combination group (80 [28%]), and placebo group (75 [26%]). Of 277 patients who received any study treatment, 263 (95%) completed the double-blind treatment period. In the mITT primary analysis set, at week 24, the least-squares mean change from baseline in MG-ADL total score was -4·5 (SE 0·4) in the cemdisiran group (n=64), -4·0 (0·4) in the combination group (n=67), and -2·2 (0·5) in the placebo group (n=59). Placebo-adjusted least-squares mean differences in MG-ADL score at week 24 were -2·3 (SE 0·7; 95% CI -3·6 to -1·0; p=0·0005) in the cemdisiran group and -1·7 (0·7; -3·0 to -0·4; p=0·0086) in the combination group. The proportion of participants with at least one adverse event during the double-blind treatment period was 54 (69%) of 78 in the cemdisiran group, 65 (81%) of 80 in the combination group, 40 (82%) of 49 in the pozelimab group, and 54 (77%) of 70 in the placebo group. The most common adverse event in the cemdisiran group was upper respiratory tract infection (nine [12%] of 78 patients), which occurred at a similar incidence in the placebo group (eight [11%] of 70). No serious or meningococcal infections occurred in the cemdisiran group. Adverse events leading to treatment discontinuation occurred in two participants (3%) in the placebo group and one participant (2%) in the pozelimab group. No deaths occurred during the double-blind treatment period. Two deaths occurred after the double-blind treatment period, one of which was assessed as treatment-related by the investigator but not treatment-related by the sponsor. INTERPRETATION:Cemdisiran monotherapy and combination therapy were effective in the treatment of generalised myasthenia gravis, and were generally well tolerated. Subcutaneous dosing of cemdisiran, administered every 3 months, could provide a convenient treatment approach for generalised myasthenia gravis. FUNDING:Regeneron Pharmaceuticals.

BackgroundX-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) are rare neuromuscular disorders characterized by severe weakness and respiratory impairment and have recently been the focus of therapeutic development. Robust baseline data are essential to understand disease trajectories and enable trial readiness. We present baseline clinical, functional, and biomarker findings from the terminated Unite-CNM trial (NCT04033159), a basket study of the antisense oligonucleotide DYN101, designed to modulate DNM2 expression in adolescents and adults with XLMTM or ADCNM.MethodsScreening and baseline evaluations included medical history, patient-reported outcomes, quantitative muscle strength and motor function, respiratory testing, muscle ultrasound and histology, and biomarker analyses (DNM2 protein, creatinine, creatine kinase, cystatin C, myostatin, and microRNAs) in plasma and muscle.ResultsTwenty-six patients were screened (15 DNM2, 11 MTM1); 14 entered the study. Patient-reported measures highlighted swallowing challenges and variable personal goals. Baseline respiratory impairment was variable in DNM2 and female MTM1 patients but consistently reduced in males with MTM1 (FVC% and FEV1% stable over follow-up to 78 weeks). MFM32 scores were similar across genotypes and sexes, while Myogrip strength was reduced versus age norms yet stable longitudinally. Muscle pathology was comparable across groups. Biomarker analyses showed altered DNM2 protein, reduced myostatin, and specific abnormalities in creatinine, creatine kinase, cystatin C, and microRNAs.ConclusionThis dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizes the importance of baseline data for ultrarare disease trials, and highlights the need for protocol flexibility in response to safety signals and disruptions (e.g. COVID-19).

BACKGROUND:Losmapimod is an orally administered small molecule and selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor able to reduce aberrant expression of DUX4 in vitro and thereby potentially slowing disease progression in patients with facioscapulohumeral muscular dystrophy (FSHD). OBJECTIVE:This global, randomized, placebo-controlled, double-blind phase 3 study in patients with FSHD1 and FSHD2 examined the efficacy and safety of losmapimod over a 48-week treatment period compared to placebo (NCT05397470, EUDRACT 2022-000389-16). METHODS:The primary endpoint was change in quantification of reachable workspace (RWS) expressed as relative surface area (RSA). Other endpoints included measures of muscle composition (fat content and lean muscle) using magnetic resonance imaging (MRI), muscle strength using quantitative dynamometry, and quality of life measures. RESULTS:130 participants received losmapimod and 130 participants received placebo, with 252 participants completing the 48-week treatment period. There were no statistically significant differences between groups in change in RSA and all secondary efficacy endpoints from baseline to Week 48. Losmapimod treatment was well-tolerated, and most adverse events were mild. CONCLUSIONS:Losmapimod was generally well tolerated with a favorable safety profile at a dose of 15 mg twice daily. Although none of the efficacy endpoints were met, study design and data from the study may inform future studies of FSHD therapies.

Importance:Uncontrolled generalized myasthenia gravis (gMG) can lead to exacerbations that often warrant rescue therapy (RT) use, especially in moderate to severe cases. Inebilizumab, a monoclonal antibody that depletes cluster of differentiation 19+ B cells, demonstrated efficacy and safety in patients with gMG enrolled in the Myasthenia Gravis Inebilizumab Trial (MINT); the present analysis evaluated its effect on exacerbations and RT use. Objective:To examine the effect of inebilizumab on exacerbations, including RT use, in participants enrolled in MINT. Design, Setting, and Participants:MINT was a phase 3, international, randomized, placebo-controlled trial that enrolled participants between August 2020 and November 2023. The randomized controlled period was 52 weeks for the anti-acetylcholine receptor antibody positive (AChR+) subpopulation and 26 weeks for the anti-muscle-specific kinase antibody positive (MuSK+) subpopulation with an optional 3-year open-label extension. Participants were enrolled at 81 academic and nonacademic sites in 18 countries. MINT screened 485 patients with gMG (AChR+ or MuSK+) and enrolled adult participants with Myasthenia Gravis Activities of Daily Life (MG-ADL) scores of 6-10. This prespecified analysis was conducted between September 2024 and March 2025. Interventions:Participants were randomized 1:1 to either inebilizumab or placebo and underwent a protocol-specified corticosteroid taper to 5 mg per day or less. Main Outcomes and Measures:The frequency of exacerbations, defined as myasthenic crisis, worsening of individual MG-ADL scores, or RT use (intravenous immunoglobulin or plasma exchange). Results:MINT enrolled 238 participants. The mean (SD) age at baseline was 47.5 (15.3) years, 144 (61%) were female, and the mean (SD) MG-ADL score was 9.1 (2.8). Inebilizumab reduced the risk of exacerbations compared with placebo in the combined population by week 26 (hazard ratio [HR], 0.41; 95% CI, 0.24-0.70), in the AChR+ subpopulation by week 52 (HR, 0.39; 95% CI, 0.23-0.68), and in the MuSK+ subpopulation by week 26 (HR, 0.21; 95% CI, 0.06-0.79). Conclusions and Relevance:In this prespecified analysis of a randomized clinical trial, inebilizumab treatment reduced exacerbation rate, including RT use, in participants with gMG who underwent a protocol-specified corticosteroid taper during MINT. These findings further support the clinical benefits of inebilizumab in AChR+ and MuSK+ gMG. Trial Registration:ClinicalTrials.gov Identifier: NCT04524273.

AIMS:Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder with substantial healthcare resource utilization (HRU) and high economic burden. This study evaluated HRU, costs, and predictors of high-cost events in adults with gMG, using data from VIVACITY-MG3. METHODS:Post-hoc analyses used the primary efficacy dataset from VIVACITY-MG3, a randomized, double-blind, placebo-controlled study of nipocalimab and standard-of-care (SoC) versus placebo and SoC in seropositive adults with gMG. HRU endpoints included hospital admissions (HA), emergency department visits (EDV), and hospital days. Logistic regression analysis identified clinical and demographic HA/EDV predictors. Hospital costs per patient per year (PPPY) were estimated using United States (US) cost data from published sources and from a claims database, adjusted to 2024 US dollars. RESULTS:Among 153 patients, nipocalimab numerically reduced the proportion experiencing ≥1 all-cause (9.1% vs 15.8%) and gMG-related (3.9% vs 7.9%) HA/EDV events versus placebo. The incidence rate of HA/EDV events was 51% numerically lower with nipocalimab. Mean hospital stay duration was numerically shorter with nipocalimab for all-cause (8.4 vs 14.6 days) and gMG-related admissions (11.2 vs 17.6 days). All-cause and gMG-related hospital days per 100 patient-years were statistically significantly reduced by 60% and 68% with nipocalimab, respectively. Estimated cost offsets for reduced HRU were $10,860-$13,253 PPPY. Multivariate analysis identified worsening in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score and higher baseline Quantitative Myasthenia Gravis (QMG) respiratory total score as independent predictors. Patients switching from placebo to nipocalimab in the VIVACITY-MG3 open-label extension experienced a 64% reduction in hospital days PPPY. LIMITATIONS AND CONCLUSION:Study limitations include the post-hoc nature of the analysis and the relatively short study duration. Nipocalimab added to SoC significantly reduces overall HRU and associated costs in adults with gMG, particularly by lowering rates and severity of HA/EDV events. Clinical deterioration and high baseline disease severity independently predict high-cost events.

Abstract Background There is currently limited data to guide treatment selection, dosing, combination strategies and sequencing in the management of myasthenia gravis (MG). Additionally, MG symptoms are heterogenous between people and with time, requiring an individualized treatment approach. As such, successful patient-physician communication is key. This Delphi project was undertaken by MG specialists and patient representatives to explore their opinion on improving MG management via effective physician-patient communication and collaboration approach. Methods This mixed-methods study was conducted in two phases. In Phase I, seven MG specialists and two patient representatives contributed to idea generation. Relevant insights informed the development of the Phase II Delphi survey. A panel of 16 MG specialists and seven patient representatives participated in a two-round Delphi survey. Consensus was defined as ≥ 70% agreement or disagreement on a 6-point Likert scale. Participants responded to the survey from what they considered an ideal scenario, regardless of their real-world experience. Results Consensus was achieved on 89% of all statements. Key areas of alignment were – importance of incorporating patient preferences on quality of life (QoL), sustained symptom control, route of administration, and side effects profile. Both groups agreed that current clinical practices insufficiently integrate mental health considerations and patient engagement remains suboptimal. Two key areas of misalignment were – patient representative and physicians had different perspective on how well physicians understood patient preferences and both groups showed different interpretations of side effects (adverse reaction versus issues of tolerability). Conclusion This Delphi consensus found that while physician and patient representatives shared similar perspectives these were not always reflected in current clinical practice due to differences in understanding of patient preferences. Prioritizing structured conversations on QoL, treatment expectations, and side effect were found important for physicians while improving access to information, openly communicating and actively participating in treatment decisions were key outcomes for patients. This study lays a valuable foundation for deepening conversations and alignment on key topics in MG management among the medical, patient and caregiving communities.