Myasthenie.comAssociation de malades de la Myasthénie et leurs familles.2024-03-27T11:00:00+01:00https://www.myasthenie.com/feed2024-03-27T11:00:00+01:002024-03-27T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154152#p154152J Neurol Neurosurg Psychiatry. 2024 Mar 27:jnnp-2023-333097. doi: 10.1136/jnnp-2023-333097. Online ahead of print.
ABSTRACT
BACKGROUND: Incidence and prevalence rates of myasthenia gravis (MG) vary considerably across studies, and mortality risk is rarely addressed. We examined the prevalence and incidence rates, mortality and factors associated with mortality with MG.
METHOD: This was a registry linkage study based on nationwide health and administrative registries of Denmark, Finland and Sweden (populations of 5.9, 5.6 and 10.5 million, respectively). Patients with MG were identified based on International Classification of Diseases codes from inpatient and outpatient specialised care registries. Yearly prevalence, incidence and mortality rates in relation to the total background population were calculated from 2000 to 2020 (study period). The causes of death and factors associated with mortality were addressed separately.
RESULTS: The overall incidence of MG was 1.34 (95% CI 1.27 to 1.41), 1.68 (95% CI 1.60 to 1.75) and 1.62 (95% CI 1.56 to 1.68) per 100 000, and the overall prevalence per 100 000 was 18.56 (95% CI 18.31 to 18.81), 20.89 (95% CI 20.62 to 21.16) and 23.42 (95% CI 23.21 to 23.64) in Denmark, Finland and Sweden, respectively. The overall standardised mortality ratio (SMR) was 1.32 (95% CI 1.23 to 1.42) among patients with MG in Denmark, 1.23 (95% CI 1.15 to 1.33) in Finland, and 1.20 (95% CI 1.14 to 1.26) in Sweden, with higher SMR observed in women than men. Annual incidence and prevalence increased over time, whereas the SMR remained stable. The most common causes of death were MG, chronic ischaemic heart disease and acute myocardial infarction.
CONCLUSIONS: This population-based study from three Nordic countries highlights the need for improved care of patients with MG, especially young women.
Source: https://pubmed.ncbi.nlm.nih.gov/3853805 ... t9+e462414
]]>2024-03-27T11:00:00+01:002024-03-27T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154151#p154151Cells. 2024 Mar 21;13(6):556. doi: 10.3390/cells13060556.
ABSTRACT
Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies target structures within the neuromuscular junction, affecting neuromuscular transmission. Muscle-specific tyrosine kinase receptor-associated MG (MuSK-MG) is a rare, often more severe, subtype of the disease with different pathogenesis and specific clinical features. It is characterized by a more severe clinical course, more frequent complications, and often inadequate response to treatment. Here, we review the current state of knowledge about potential pathomechanisms of the MuSK-MG and their therapeutic implications as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of myasthenia gravis.
Source: https://pubmed.ncbi.nlm.nih.gov/3853440 ... t9+e462414
]]>2024-03-27T11:00:00+01:002024-03-27T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154150#p154150Cells. 2024 Mar 14;13(6):508. doi: 10.3390/cells13060508.
ABSTRACT
Myasthenia gravis (MG) is a prototypical autoimmune disease of the neuromuscular junction (NMJ). The study of the underlying pathophysiology has provided novel insights into the interplay of autoantibodies and complement-mediated tissue damage. Experimental autoimmune myasthenia gravis (EAMG) emerged as a valuable animal model, designed to gain further insight and to test novel therapeutic approaches for MG. However, the availability of native acetylcholine receptor (AChR) protein is limited favouring the use of recombinant proteins. To provide a simplified platform for the study of MG, we established a model of EAMG using a recombinant protein containing the immunogenic sequence of AChR in mice. This model recapitulates key features of EAMG, including fatigable muscle weakness, the presence of anti-AChR-antibodies, and engagement of the NMJ by complement and a reduced NMJ density. Further characterization of this model demonstrated a prominent B cell immunopathology supported by T follicular helper cells. Taken together, the herein-presented EAMG model may be a valuable tool for the study of MG pathophysiology and the pre-clinical testing of therapeutic applications.
Source: https://pubmed.ncbi.nlm.nih.gov/3853435 ... t9+e462414
]]>2024-03-27T11:00:00+01:002024-03-27T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154149#p154149Ann Pharmacother. 2024 Mar 27:10600280241239048. doi: 10.1177/10600280241239048. Online ahead of print.
ABSTRACT
OBJECTIVE: The aims of this article are to review the clinical aspects of rozanolixizumab, to describe clinical trial results that led to the drug's approval, and to examine the impact on patient care to aid clinical decision making.
DATA SOURCES: A PubMed search was conducted using the terms Rystiggo™, rozanolixizumab, rozanolixizumab therapy, and myasthenia gravis. The most recent prescribing information was also used for information relating to the drug and for identification of pertinent studies.
STUDY SELECTION/DATA EXTRACTION: Phase I, II, and III randomized controlled trials were all eligible for inclusion. Meeting abstracts and articles focusing on the use of rozanolixizumab or any indication other than generalized myasthenia gravis were excluded from this article.
DATA SYNTHESIS: Food and Drug Administration approval of rozanolixizumab is based on the phase III MycarinG study in patients with generalized myasthenia gravis. A phase II trial explored initial clinical efficacy and safety pertaining to the dose and frequency of rozanolixizumab across 2 treatment periods in patients with moderate to severe myasthenia gravis.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: Rozanolixizumab is the first therapy approved to treat patients positive for both types of antibodies, anti-acetylcholine receptor or anti-muscle-specific tyrosine kinase, in generalized myasthenia gravis.
CONCLUSION/RELEVANCE: The approval of rozanolixizumab represents an advancement in therapy for generalized myasthenia gravis. The provision of individualized, targeted, and well-tolerated treatment is valuable for the patients whose myasthenia gravis is not well controlled and who are seeking a medication with a rapid onset of action to improve their symptoms and overall quality of life.
Source: https://pubmed.ncbi.nlm.nih.gov/3853373 ... t9+e462414
]]>2024-03-27T11:00:00+01:002024-03-27T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154148#p154148SAGE Open Med. 2024 Mar 25;12:20503121241229591. doi: 10.1177/20503121241229591. eCollection 2024.
ABSTRACT
BACKGROUND: In Vietnam, there is limited research on the role of nerve conduction in myasthenia gravis and its association with clinical features.
OBJECTIVE: This study aims to describe the electrophysiological features in patients with myasthenia gravis.
METHODS: This descriptive study was conducted from September 2019 to December 2021. The study included 33 myasthenia gravis patients who sought medical consultation or received inpatient treatment during this period. The Myasthenia Gravis Foundation of America classifies myasthenia gravis into five groups: I, IIa, IIb, IIIa, IIIb, IVa, IVb, and V. Notably, Group I involves pure ocular weakness, whereas Group a primarily impacts limb and axial muscles, and Group b mainly affects bulbar and respiratory muscles.
RESULTS: The study revealed that motor and sensory nerve conduction in the upper and lower limbs were within normal limits for the patient group under evaluation. Repetitive nerve stimulation testing at a frequency of 3 Hz showed positive results in 66.7% of myasthenia gravis patients. Myasthenia gravis patients displayed distinct clinical symptoms, with ptosis being the most common (87.9%). Myasthenia Gravis Foundation of America classification indicated the highest proportion in subgroup IIa (24.2%), with myasthenia gravis predominating in limb and axial muscles (Group a) observed in 51.5% of cases. Needle electromyography showed no abnormalities in myasthenia gravis patients. There was an association between acetylcholine receptor antibody titers and the results of the 3 Hz repetitive nerve stimulation test in myasthenia gravis patients, with a significance of p = 0.002.
CONCLUSION: Nerve conduction studies should be performed in patients with suspected neuromuscular disorders to aid in differential diagnosis and definitive diagnosis of myasthenia gravis.
BACKGROUND: Myasthenia gravis is a rare chronic autoimmune neuromuscular disorder mainly caused by autoantibodies to the nicotinic acetylcholine receptor. Cholesterol is an essential molecule that affects the distribution and proper functioning of this receptor. Several reports have described the potential worsening of myasthenia gravis in patients treated with statins.
CASE PRESENTATION: The patient was an obese 72 years old man, past smoker, diagnosed with ischaemic heart disease, type 2 diabetes mellitus and lipid metabolism disorder. Statin treatment was not implemented because of chronic myasthenia gravis and PCSK9i monotherapy [Repatha (evolucamab), 140 mg] was implemented to treat dyslipidaemia. Within 24 h after the first dose of PCSK9i the patient developed severe muscle weakness, joint pain, fever, and general discomfort, lasting for several days. Despite strong advice against the second dose administration, this was self-administered approximately 2 weeks later, leading to report significant worsening of the muscle problems, leading to the patient admittion to the neurology department where he was being treated for myasthenia gravis attack.
CONCLUSION: Based on the neurologist's conclusion, it can be assumed that in this case, treatment with PCSK9i resulted in significant worsening of the patient's chronic disease.
"All United for MG", au sein de laquelle nous sommes engagés, poursuit son combat avec ardeur à l'échelle européenne,
Depuis son lancement en 2023, notre coalition s'est dévouée sans relâche à sensibiliser sur la Myasthénie Grave (MG) et à défendre les droits des patients et de leurs aidants. Aujourd'hui, nous vous appelons à vous unir à nous en signant une pétition essentielle.
Pourquoi une pétition ?
Cette initiative vise à interpeller la prochaine Commission Européenne pour l'adoption d'un nouveau Plan des Maladies Rares, crucial pour faire face aux défis que pose la MG. Cette maladie auto-immune rare, qui affecte les muscles, rend chaque geste quotidien extrêmement difficile pour ceux qui en souffrent.
Grâce au soutien sans faille de membres éminents du Parlement Européen, de professionnels de santé engagés, et de groupes de plaidoyer, notre appel à l'action lancé l'année dernière a déjà laissé sa marque. Via la plateforme change.org, nous visons à rassembler entre 5 000 et 10 000 signatures. Cette démarche symbolique représente bien plus : c'est un cri pour une compréhension approfondie et un soutien renforcé envers les victimes de la MG et d'autres maladies rares.
Des personnalités influentes, telles que Stelios Kympouropoulos et le Professeur Jan De Bleecker, ont souligné l'importance vitale de cette sensibilisation et de notre initiative "All United for MG" pour améliorer concrètement la qualité de vie des individus touchés.
Cette pétition n'est pas juste un appel à l'action ; elle est un puissant levier pour amplifier la voix des maladies rares dans l'arène politique, incitant à un changement positif durable dans leur prise en charge. Rejoignez-nous dans ce combat pour la reconnaissance, le soutien et une vie meilleure pour tous les affectés par ces conditions. Votre signature compte !
Ensemble, faisons entendre notre voix. Signez, partagez et engagez-vous pour un futur où les maladies rares ne seront plus des ombres dans notre société. Merci pour votre soutien inestimable. Pour signer la pétition, cliquez sur les 3 barres puis sur le bouton "Agir",
Ensemble, nous pouvons faire la différence !
]]>2024-03-26T11:00:00+01:002024-03-26T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154145#p154145Neuropediatrics. 2024 Mar 26. doi: 10.1055/s-0044-1782675. Online ahead of print.
ABSTRACT
Congenital myasthenic syndrome-25 (CMS-25) is an autosomal recessive neuromuscular disorder caused by a homozygous mutation in VAMP1 gene. To date, only eight types of allelic variants in VAMP1 gene have been reported in 12 cases of CMS-25. Here, we report on an 8-year-old boy with motor developmental delay, axial hypotonia, myopathic face, muscle weakness, strabismus, ptosis, pectus carinatum, kyphoscoliosis, joint contractures, joint laxity, seizures, and recurrent nephrolithiasis. He also had feeding difficulties and recurrent aspiration pneumonia. Brain magnetic resonance imaging at 20 months of age showed left focal cerebellar hypoplasia. Genetic analysis revealed a homozygous missense variant of c.202C > T (p.Arg68Ter) in the VAMP1 gene. Treatment with oral pyridostigmine was started, which resulted in mild improvement in muscle strength. Salbutamol syrup was added a few months later, but no significant improvement was observed. This case report presents novel findings such as focal cerebellar hypoplasia and nephrolithiasis in VAMP1-related CMS-25. Consequently, this case report extends the clinical spectrum. Further studies are needed to expand the genotype-phenotype correlations in VAMP1-related CMS-25.
Source: https://pubmed.ncbi.nlm.nih.gov/3853136 ... t9+e462414
]]>2024-03-26T11:00:00+01:002024-03-26T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154144#p154144Ann Surg Oncol. 2024 Mar 26. doi: 10.1245/s10434-024-15194-z. Online ahead of print.
ABSTRACT
BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection.
METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis.
RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036).
CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.
INTRODUCTION: Early-onset (EOMG) and late-onset (LOMG) are distinct groups of MG patients. It is unclear if treatment strategies and treatment-related adverse events may differ according to the age of MG onset.
METHODS: This single-center retrospective study includes all MG patients followed at a tertiary center since 2007. We reviewed the electronic clinical records.
RESULTS: In total, 212 patients were identified, 142 (67.0%) females, with a median disease duration of 10 years. The median age of symptom onset was 42.0 (26.0-64.5) years, with 130 (61.3%) EOMG cases and 82 (38.7%) LOMG. EOMG were more frequently female, had longer disease duration and often more generalized MG (p < 0.001). Comorbidities were significantly more frequent in LOMG (67.1%) compared to EOMG (53.1%) (p = 0.002). Steroid-related adverse effects motivating the switch to steroid-sparing agents (82.0%) were different between groups, with hypertension, hypercholesterolemia, diabetes mellitus and malignancies being more common in LOMG. At the same time, osteoporosis and dyspepsia were more frequent in EOMG (p < 0.001). The most common first-line choice was azathioprine (45.8%), and rituximab was used in 4 patients (1.9%).
CONCLUSION: Our study shows that treatment modalities are similar between EOMG and LOMG, while steroid-related adverse events appear to be distinct.
Source: https://pubmed.ncbi.nlm.nih.gov/3852903 ... t9+e462414
]]>2024-03-26T11:00:00+01:002024-03-26T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154141#p154141J Neurol. 2024 Mar 25. doi: 10.1007/s00415-024-12293-5. Online ahead of print.
ABSTRACT
Recommendations for the treatment of myasthenia gravis (MG) have been difficult to develop because of limited evidence from large randomized controlled trials. New drugs and treatment approaches have recently been shown to be effective in phase 3 studies in seropositive generalized (g) MG. One such drug is efgartigimod, a human-Fc-fragment of IgG1, with a high affinity for the endosomal FcRn. We conducted a multicenter study to evaluate the real-world clinical and safety effects of efgartigimod in 22 gMG patients. We evaluated the strategies for the timing of re-treatment with it. The participants received a total of 59 efgartigimod -treatment cycles. The median number of cycles was 2 (range 1-6). Twenty patients (86.3%) improved by at least 2 MG-ADL points after the first treatment cycle. The median MG-ADL score at baseline was 6.5 (range: 3-17) and 2.5 (range: 0-9) post-treatment (p < 0.001). A consistent improvement of at least 2 points in the MG-ADL score after each cycle occurs in 18 patients. The effect duration of the treatment was usually between 4 and 12 weeks. Two major clinical patterns of treatment response were found. Treatment with efgartigimod was also associated with significant reductions of prednisone doses Overall, the treatment was safe and associated with only minor adverse events. The single fatality was apparently due tosevere respiratory failure. We found that efgartigimod is clinically effective, may be used as a steroid sparing agent and is generally safe for gMG patients. We recommend a personalized preventive treatment approach until clinical stabilization, followed by discontinuation and periodic evaluations.
le quatrième épisode de notre série consacrée au système immunitaire "Les thérapies immunosuppressives "
En attendant, vous pouvez retrouver toutes nos vidéos sur notre chaine YouTube en cliquant sur l'image ci-dessous
]]>2024-03-25T11:00:00+01:002024-03-25T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154135#p154135AACE Clin Case Rep. 2023 Dec 18;10(2):52-54. doi: 10.1016/j.aace.2023.12.004. eCollection 2024 Mar-Apr.
ABSTRACT
BACKGROUND/OBJECTIVE: Type 1 diabetes (T1D) and myasthenia gravis (MG) are autoimmune conditions that rarely co-occur. Here, we report a child with MG who subsequently developed T1D.
CASE REPORT: An 11-year-old girl with seropositive MG diagnosed at 4 years of age presented with muscle pain, cramps, and weight loss of 3.5 kg over 4 months. Her MG was in remission on daily pyridostigmine. She denied polyuria, polydipsia, recent illnesses, or other medications. She was prepubertal and had stable vitals with normal systemic examination. Initial work up for a probable diagnosis of rhabdomyolysis showed hyperglycemia and glucosuria. She had ketosis without acidosis. Diabetes autoantibodies were positive (anti-glutamic acid decarboxylase antibody 113.5 IU/mL (reference range < 5 IU/mL), anti-zinc transporter 8 antibody > 500 U/mL (reference range < 15 IU/mL)). Screening for autoimmune thyroid disease and celiac disease was negative. Patient was diagnosed with T1D and was started on subcutaneous insulin.
DISCUSSION: The co-existence of MG and T1D is rare. All the 4 prior reported patients from Europe were diagnosed with T1D prior to or concurrently with MG. In contrast, our patient was first diagnosed with MG and subsequently diagnosed with T1D 7 years later.
CONCLUSIONS: Consider screening for T1D in patients with MG and offering treatment to those above 8 years and older with stage 2 T1D to delay its onset. Along with other causes, T1D should also be considered when patients with MG present with nonspecific symptoms such as fatigue and weight loss.
Source: https://pubmed.ncbi.nlm.nih.gov/3852385 ... t9+e462414
]]>2024-03-25T11:00:00+01:002024-03-25T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154134#p154134Expert Opin Pharmacother. 2024 Mar 25:1-14. doi: 10.1080/14656566.2024.2332610. Online ahead of print.
ABSTRACT
INTRODUCTION: Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with neuromuscular symptoms of varying severity and significant morbidity. The mainstay of treatment in MG is mitigation of the immune cascade with steroids and non-steroidal immunosuppressive therapies. The therapeutic strategies in MG are transitioning from broad and indiscriminate immunosuppression to novel agents targeting key steps in MG pathogenesis, including T cell activation, B cell proliferation, complement activation, maintenance of pathogenic antibody production, and proinflammatory cytokine production.
AREAS COVERED: In this review, an overview of the pathogenesis of MG and traditional MG therapies is presented, followed by a discussion of the novel MG drugs that have been evaluated in phase 3 clinical trials with an emphasis on those which have received regulatory approval.
EXPERT OPINION: Novel MG therapeutics belonging to the classes of complement inhibitors, neonatal Fc receptor (FcRn) inhibitors and B cell depletors, as well as the other emerging MG drugs in the pipeline constitute promising treatment strategies with potentially better efficacy and safety compared to the conventional MG treatments. However, further long-term research is needed in order to optimize the implementation of these new treatment options for the appropriate patient populations.
Source: https://pubmed.ncbi.nlm.nih.gov/3852350 ... t9+e462414
]]>2024-03-25T11:00:00+01:002024-03-25T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154133#p154133J Oncol Pharm Pract. 2024 Mar 24:10781552241240734. doi: 10.1177/10781552241240734. Online ahead of print.
ABSTRACT
INTRODUCTION: Immune checkpoint inhibitors (ICIs) can cause a spectrum of adverse events known as immune-related adverse events (irAEs) that resemble autoimmune responses. Immune-mediated myasthenia gravis (MG) is a rare and serious neurologic adverse event that has been associated with ICIs requiring prompt treatment. In the Jehovah's Witness population, typical management of these adverse events may not be options, and alternative treatment choices would be needed.
CASE REPORT: 73-year-old Jehovah's Witness patient with high-grade undifferentiated pleiomorphic sarcoma who developed immune-mediated MG approximately 4 weeks after initiation of pembrolizumab. On the day of admission, the patient presented with a three-day history of worsening ptosis, right greater than left. He was later found to be seronegative for MG.
MANAGEMENT AND OUTCOME: The patient required therapy with pyridostigmine, steroids, and agreed to plasma exchange (PLEX) prior to discharge. He achieved near resolution of his neurologic symptoms, and pembrolizumab was discontinued. He later underwent radical resection of the left thigh soft tissue sarcoma and superficial inguinal lymph node dissection. He is now on active surveillance.
DISCUSSION: While neurologic adverse events typically present 6 weeks after initiation of ICIs, MG has been reported occurring as early as 4 weeks after initiation. This rare and serious adverse event requires prompt treatment, and clinicians need to be aware of the alternative treatment options in this unique patient population. Early conversations regarding blood products and factions must be had to develop a treatment plan in accordance with the patient's personal decisions.
Source: https://pubmed.ncbi.nlm.nih.gov/3852342 ... t9+e462414
]]>2024-03-25T11:00:00+01:002024-03-25T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154132#p154132Eur J Neurol. 2024 Mar 24:e16280. doi: 10.1111/ene.16280. Online ahead of print.
ABSTRACT
BACKGROUND: Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert-derived consensus recommendations for good practice.
METHODS: A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub-committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence-based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1-10.
RESULTS: Eighteen expert- and evidence-based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG-ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State ) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG-ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds.
CONCLUSIONS: This process provided evidence- and expert consensus-based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients.
BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG.
METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk.
RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk.
CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.
The concomitant presentation of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis is well documented. In the course of Graves disease (GD), symptomatic transient neuromuscular junction disorder may occur due to the effect of thyroid hormones at the neuromuscular synapse. Diagnostic clues are the clinical and electrophysiologic remission synchronous with restoration of euthyroidism. Furthermore, the occurrence of thymic hyperplasia in GD poses further diagnostic and therapeutic considerations. These points are discussed in the case report of a 43-year-old male patient suffering from TAO and transient neuromuscular junction disorder due to GD.
BACKGROUND: Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT-M) could be used to prevent the potential birth of CMS-affected children is unclear.
METHODS: Application of WES (whole-exome sequencing) for carrier testing and guidance for the PGT-M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed.
RESULTS: The family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS-affected child was successfully prevented, allowing the family to have offspring devoid of disease-associated variants and exhibiting a normal phenotype.
CONCLUSION: This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families.
Source: https://pubmed.ncbi.nlm.nih.gov/3851126 ... t9+e462414
]]>2024-03-20T11:00:00+01:002024-03-20T11:00:00+01:00https://www.myasthenie.com/viewtopic.php?p=154125#p154125Rinsho Shinkeigaku. 2024 Mar 20. doi: 10.5692/clinicalneurol.cn-001945. Online ahead of print.
ABSTRACT
A 79-year-old woman who presented ptosis and dysphagia were admitted to our hospital. Anti-acetylcholine receptor antibodies and anti-P/Q-type VGCC antibodies were both positive. Electrophysiological examination showed postsynaptic pattern which supported myasthenia gravis. She did not meet the diagnostic criteria for Lambert-Eaton myasthenic syndrome (LEMS). In cases which these antibodies coexist, careful electrophysiological evaluation is required for the diagnosis. In addition, although anti-P/Q-type VGCC antibodies have been specific to LEMS, patients with these antibodies represent various symptoms other than LEMS. Low and middle titer of the antibodies may be not specific to LEMS.