Acquired Myasthenia Gravis Research Articles

Suspected Fluoroquinolone-Induced Exacerbation of Myasthenia Gravis in Dogs.

Acquired myasthenia gravis (MG) in dogs can present with focal or generalized weakness and is diagnosed by the presence of circulating antibodies to the acetylcholine receptor. Megaesophagus is the most common focal form of MG. Although exacerbation of MG has been associated with the use of fluoroquinolones in humans, it has not been previously described in dogs. The medical records of 46 dogs diagnosed with MG based on acetylcholine receptor antibody testing from 1997 to 2021 were retrospectively evaluated to identify any dogs who demonstrated exacerbation of MG after the administration of a fluoroquinolone. Exacerbation of MG, from focal to generalized, occurred in a median of 4.5 days after initiation of fluoroquinolone therapy in six dogs. In addition, one dog with generalized MG and megaesophagus developed pyridostigmine resistance subsequent to fluoroquinolone therapy. Marked improvement in generalized weakness was reported 36 hr after discontinuation of fluoroquinolone therapy alone in one dog and in combination with pyridostigmine in two dogs. Fluoroquinolone therapy was never stopped in three dogs who were euthanized because of severe weakness and one dog who died of respiratory arrest.

Feline acquired thymoma‐associated myasthenia gravis managed with surgery and therapeutic plasma exchange

AbstractA 3‐year‐old cat with thymoma‐associated myasthenia gravis underwent thymectomy. Skeletal muscle weakness deteriorated after surgery, and the cat became non‐ambulatory tetraparetic. A higher dose of pyridostigmine failed to improve the weakness. Therapeutic plasma exchange was performed twice, 4 and 8 weeks after surgery, with continued pyridostigmine treatment. Improvement in clinical signs was noted after each therapeutic plasma exchange. Improvement was short‐lasting after the first and long‐lasting after the second session. The dose of pyridostigmine was reduced 4 and 21 months after thymectomy without relapse. Thirty‐two months after thymectomy, the cat remained in clinical remission with continued pyridostigmine treatment, but serum anti‐acetylcholine receptor antibody titre remained elevated (2.0 nmol/L). This is the first report of therapeutic plasma exchange in a cat with acquired thymoma‐associated myasthenia gravis. Therapeutic plasma exchange may be considered an additional immune‐modulating option to medical treatment in cats with acquired myasthenia gravis.

Clinical features and outcome of acquired myasthenia gravis in 94 dogs.

BackgroundFactors known to be associated with outcome of acquired myasthenia gravis (MG) in dogs are limited.Hypothesis/ObjectivesOf dogs with MG, advancing age and comorbid neoplasia are associated with poor long‐term prognosis and low rates of remission.AnimalsNinety‐four client‐owned dogs with MG diagnosed by acetylcholine receptor antibody (AChR Ab) assay between 2001 and 2019 from a university clinic and 3 private clinics in the United States.MethodsCases were retrospectively evaluated and data were collected to determine clinical signs, treatment, and response to therapy defined by means of a clinical scoring rubric. Immunological remission was defined as a return of the AChR Ab concentration to <0.6 nmol/L. Multivariable binary logistic regression analysis was used to identify clinical criteria predicting remission.ResultsAn anticholinesterase drug was used to treat 90/94 (96%) dogs, which in 63/94 (67%) was the sole treatment; other drugs included immune modulators. Clinical remission (lack of clinical signs ≥4 weeks after treatment cessation) was observed in 29 (31% [95% confidence interval (CI): 22.4‐40.8%]) dogs, clinical response (lack of clinical signs on treatment) in 14 (15% [95% CI: 9.0‐23.6%]) dogs, clinical improvement (on treatment) in 24 (26% [95% CI: 17.8‐35.2%]) dogs, and no clinical improvement in 27 (29% [95% CI: 20.5‐38.6%]) dogs. Immunological remission was observed in 27/46 (59%) dogs, with clinical remission in all 27. Younger age (P = .04) and comorbid endocrine disease (P = .04) were associated with clinical remission. Initial AChR Ab concentration (P = .02) and regurgitation (P = .04) were negatively associated with clinical remission.Conclusions and Clinical ImportanceClinical remission in MG is less likely in older dogs and dogs presenting with regurgitation or high initial AChR Ab concentration, but more likely in younger dogs and dogs with comorbid endocrine disease.

The clinical utility of neostigmine administration in the diagnosis of acquired myasthenia gravis.

To assess the clinical utility of neostigmine methylsulfate administration in the diagnosis of suspected acquired myasthenia gravis (MG) in dogs and cats. Retrospective study (2017-2019). Five university teaching hospitals and 2 private referral hospitals. Twenty-two dogs and 3 cats. Criteria for inclusion were clinical signs consistent with acquired MG, performance of a neostigmine challenge and acetylcholine receptor antibody titers. None. The route of neostigmine administration was recorded. Response to neostigmine challenge was determined via sequential evaluation of muscle strength and ambulation following administration of neostigmine methylsulfate. Response to neostigmine challenge was compared to acetylcholine receptor antibody titers, which were used as the biochemical gold standard in this study. Sixteen out of 22 dogs were diagnosed with acquired MG. Thirteen of 16 had a strong positive response to neostigmine challenge whereas 3 of 16 had no response. Two out of 3 dogs with polymyositis also had a strong positive response to neostigmine challenge. Weak positive results were seen with intracranial neoplasia (n=1) and a dog with dilated cardiomyopathy and coxofemoral joint disease (n=1). One cat was diagnosed with acquired MG and had a positive response to neostigmine challenge. Two cats had no response to neostigmine challenge and were diagnosed with alternate conditions. Two cats were premedicated with glycopyrrolate, one of which had a mild adverse response to neostigmine challenge (sialorrhea and mild transient tremors). Three out of 22 dogs had minimal adverse effects (sialorrhea and 1 dog with muscle tremors). The neostigmine challenge appears to be safe and viable alternative to the previously utilized edrophonium challenge, particularly when weak positive responses are considered negative for acquired MG. Polymyositis cases may have a false positive response to neostigmine challenge.

SY4.2. Seronegative myasthenia gravis: Auto-antibody profiles and clinical features

Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by antibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. However, serological tests based on novel assays and recently identified antigens are not available for routine clinical practice in many regions where the overall frequency and features of seronegative MG according to antibody have not been determined yet. Recently, we performed a multi-centers study in South Korea to investigate the clinical features and autoantibody profiles in adult patients seronegative for AChR antibodies. Serological tests included the antibodies to MuSK (Muscle-specific tyrosine kinase), LRP4 (Lipoprotein receptor- related protein 4), and clustered AChR, In this talk, an overview will be presented that covers the results of our recent study and what is currently known on seronegative MG in Asia from basic epidemiology and clinical features through to treatments.

Мyasthenia gravis complicated by comorbid pathology

Acquired myasthenia gravis is a rare pathology of the spectrum of neuromuscular disorders and is characterized by the production of autoantibodies to various components of the neuromuscular synapse. The clinical picture is based on typical symptoms: dynamic ptosis, oculomotor dysfunction, diplopia, masticatory muscle weakness, pathological muscle fatigue, in case of dominance of oropharyngeal muscle weakness, patients complain of dysphagia, dysarthria, dyspnea resulting from insolvency.. This variant of the disease is the most dangerous, as it is characterized by a high risk of myasthenic crisis. In addition, the course of myasthenia gravis may be complicated by the development of comorbid pathology, which can be classified into four main groups. These include causal conditions in the development of diseases with a single mechanism of development for myasthenia gravis, such as cross‑autoimmune damage to the heart muscle. The group of complications of myasthenia includes myasthenic, cholinergic and mixed crises. Unrelated diseases are competitive, so in the elderly, myasthenia gravis is accompanied by a wide range of chronic diseases, such as hypertension, diabetes and others. The last group that should be targeted is intercurrent diseases — acute pathologies that develop against the background of myasthenia. Infectious diseases involving the most vulnerable respiratory system are potentially dangerous in the latter group. Knowledge of these potential factors of decompensation of myasthenia gravis will predict the development and timely diagnose the pathology. Timely treatment in a life‑threatening condition can be critical, since myasthenia gravis differs significantly from other diseases of the neuromuscular system in the rate of critical decompensation and the difficulty of normalizing the patient’s severe condition.

MYASTHENIA & RELATED DISORDERS: P.33 Clinical features and evolution of juvenile myasthenia gravis in an Israeli cohort

Myasthenia Gravis (MG), an autoimmune neurological disease, is more frequently found amongst adults than amongst children. Our research provides data on the clinical symptoms, forms of MG, effective treatment, the presence of thymoma and the effect of thymectomy in children with MG in Israel. The database of a tertiary pediatric medical center was retrospectively reviewed for patients under 18 years of age diagnosed between the years 2000-2020 with either ocular or systemic acquired myasthenia gravis.

Acquired myasthenia gravis in a dog a case report

Neuromuscular diseases are uncommon in the clinical routine of dogs and cats and their diagnosis is a challenge for the veterinarian. Thus, this paper reports the clinical diagnosis and established therapy in a four-year-old female without a defined breed with a history of ataxia and tetraparesis, especially after exercise. Due to the history and clinical signs presented, acquired myasthenia gravis was suspected and the therapeutic diagnosis was chosen using anticholinesterase neostigmine, for being simpler, faster and more accessible. The patient presented a significant improvement in clinical status after administration of neostigmine intramuscularly, returning to normal ambulatory activity after administration of the drug intravenously, thus making possible the diagnosis of the disease. Treatment was instituted using pyridostigmine bromide associated with corticosteroid in a immunosuppressive dose for a period of six months, observing complete remission of the clinical signs without recurrences until the present moment.

Long-term outcome of cats with acquired myasthenia gravis without evidence of a cranial mediastinal mass.

BackgroundAcquired myasthenia gravis (AMG) is increasingly recognized in cats, yet information regarding the natural history of the disease, treatment, and outcome including occurrence of immune and spontaneous remission remains limited.ObjectiveTo determine the long‐term outcome of cats with AMG without evidence of a cranial mediastinal mass (CMM).AnimalsEight cats diagnosed with AMG without evidence of a CMM.MethodsRetrospective case series. The medical records of cats diagnosed with AMG between 2005 and 2018 from 2 veterinary referral hospitals were reviewed for inclusion. Inclusion criteria consisted of a diagnosis of AMG, thoracic imaging, serum biochemistry including measurement of creatine kinase, and a CBC. Exclusion criteria were the presence of an identifiable CMM, or administration of methimazole or carbimazole.ResultsAll cats had an excellent long‐term outcome, achieving immune remission within 6 months of diagnosis, including 4 cats that did not receive any treatment and whose natural course of disease involved spontaneous remission. Clinical presentation was heterogeneous, and skeletal muscle weakness and fatigability induced or exacerbated by the wheelbarrow exercise stress test were the most consistent abnormalities associated with AMG.Conclusion and Clinical ImportanceCats diagnosed with AMG without evidence a CMM have a favorable outcome and frequently achieve immune remission. Moreover, the natural history of AMG in cats includes spontaneous remission when there is no evidence of a CMM. Attempting to rule out the presence of a CMM therefore refines prognosis, and treatment is not always necessary in this disease population.

Feline myasthenia gravis: a review

Myasthenia gravis is an immune mediated disorder of neuromuscular transmission. Both an acquired and a congenital form have been reported in cats. Generalised weakness is considered a hallmark of myasthenia gravis, but in cats, due to their sedentary nature, this may not be as evident as in dogs. Feline acquired myasthenia gravis is associated with a significant incidence of cranial mediastinal masses, and a lower percentage of associated megaoesophagus than myasthenia gravis in dogs. The diagnosis of acquired myasthenia gravis remains challenging for the clinician, and there are currently no evidence-based treatment protocols. Reports describing outcomes in acquired feline myasthenia gravis are conflicting, with survival rates ranging from 42–85%. Data concerning the rate of spontaneous remission in feline acquired myasthenia gravis is limited, however the reported incidence appears low (9.2%). Recently, a mutation affecting the COLQ gene has been identified in the Sphynx and Devon Rex breeds, demonstrating a genetic basis to feline congenital myasthenia gravis.

Management and resolution of acquired myasthenia gravis in a carbimazole-treated hyperthyroid domestic shorthair cat

An 11-year-old male neutered domestic shorthair cat presented with acute onset signs of generalised weakness and neck ventroflexion. He had been diagnosed with hyperthyroidism two months previously and been treated...

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation.

Data on antibody profile in myasthenia gravis (MG) from India are limited. To investigate antibody profile in patients with MG and their clinical correlates. Patients of MG (n=85, M:F::1.1:1, mean age: 39.29±17.3years, mean symptom duration: 72.94±91.8months) were evaluated for clinical features, MG foundation of America (MGFA) score, response to treatment, and outcome at last follow-up. Antibodies to acetylcholine receptor (AChR), muscle-specific kinase (MUSK), titin and ryanodine receptor (RYR) were analysed using ELISA. Based on the regional distribution of weakness, the cohort could be categorized as: generalized: 60, ocular: 16 and oculo-bulbar: 9. Sixty patients were followed up for a mean duration of 26.74±13.8months. Outcome at last follow-up was as follows: remission-22, no remission-33 and dead-5. AChR and MUSK antibodies were detected in 58 and 8 patients, respectively. Frequency of generalized MG, worse MGFA score during the disease course and thymomatous histology significantly correlated with presence of AChR-antibodies, though outcome at last follow-up was comparable between AChR-antibody positive and negative groups. Patients with MUSK antibodies had oculo-bulbar or generalized MG and frequent respiratory crisis, but majority improved or remitted with treatment. Titin antibodies were detected in 31.8% and RYR antibodies in 32.9%. Their presence did not correlate with age at onset of MG, severity or presence of thymoma. This report highlights the spectrum of antibodies in MG in an Indian cohort. AChR-antibody positivity correlated with clinical severity. Outcome was good in majority of MUSK antibody-positive MG. The role of other antibodies, complementary vs epiphenomenon, remains open.

Myasthenia gravis: current status of antibody diagnostics and aspects on refractory myasthenia gravis

Acquired myasthenia gravis (MG) is an autoimmune disease that leads to fluctuating muscle weakness and fatigue, caused by circulating antibodies against different structures of the neuromuscular junction. In most patients, antibodies against acetylcholine receptor (AChR) can be detected. In a smaller proportion of patients with and without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin, cortactin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. With current therapy, most patients achieve a stable condition with good quality of life and normal life expectancy. Nevertheless, 10 to 15 % of patients fail to respond ad equately to current therapies and are defined as refractory myasthenia gravis. Their clinical course is characterized by recurrent episodes of severe, acute deterioration, which sometimes appear life threatening. This article gives an overview of the current state of myasthenic antibody diagnostics and recommended treatment of refractory myasthenia gravis.

Myasthenia gravis seronegative for acetylcholine receptor antibodies in South Korea: Autoantibody profiles and clinical features

Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.

The application of multi-post joint assessment and early sequential rehabilitation training in patients with ICU mechanical ventilation

Objective To observe the effect of early sequential rehabilitation training based on multi-post joint assessment and collaboration in ICU mechanical ventilation patients. Methods Since April 2016, our hospital has adopted the early sequential rehabilitation training model based on multi-post joint assessment and collaboration to implement rehabilitation treatment for ICU mechanical ventilation patients.Fifty-nine patients who underwent mechanical ventilation were selected before (from October 2015 to March 2016) and after(from April to September 2016) the application, and the case group was set as the control group and the experimental group respectively.The differences between the two groups of ICU mechanical ventilation cases were compared with those of the two groups. Results The muscle strength, Barthel index score and nursing satisfaction score of the ICU mechanical ventilation cases were significantly higher than those in the control group, and the incidence of the ICU was significantly lower than that in the control group, and the differences were statistically significant (P<0.05). Conclusions The early rehabilitation training combined with the evaluation of sequential pattern and collaboration based on post ICU patients with mechanical ventilation rehabilitation therapy can significantly reduce the risk of ICU in patients with acquired myasthenia gravis patients, improve muscle strength and self-care ability, and improve nursing satisfaction. Key words: Evaluation; ICU; Mechanical ventilation; Early rehabilitation training

Evaluation of coexisting polymyositis in feline myasthenia gravis: A case series

Acquired myasthenia gravis (MG) is relatively uncommon in cats. In humans, MG may be associated with other immune-mediated disorders, in particular polymyositis (PM). In this study, we described in-depth electrodiagnostic findings and pathological changes in muscles of cats diagnosed with MG, and assessed the presence of concurrent PM. Six cats with confirmed acetylcholine receptor antibody seropositive MG, and two suspected cases with clinical signs and electrophysiological changes consistent with MG, were reviewed. All animals presented with severe typical signs of generalized weakness and/or fatigability, resembling late-onset MG in humans, in addition to regurgitation. Five cats presented a cranial mediastinal mass, with 3 confirmed as thymoma. Repetitive nerve stimulation revealed a decrement of the compound muscle action potential in all tested cases, starting from low frequencies of stimulation. Serum creatine kinase activity was increased in 6/8 cats. Muscle biopsies performed in 5 cats revealed varying degrees of mixed mononuclear cell infiltrates, positive for the leukocyte markers CD3/CD4/CD8 and CD11b. Further MHC-1/C5b-9 positive sarcolemmal deposits were identified in all tested cases, with or without thymoma. This study documents an association of MG and PM in cats, and provides further support for feline MG as a relevant animal model of human MG.

Association of early onset myasthenia gravis in Newfoundland dogs with the canine major histocompatibility complex class I

Acquired Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder whose development in humans has been associated with the Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA). There is a form of early onset MG (EOMG) in Newfoundland dogs that mimics the clinical presentation in humans and appears to have familial inheritance. Genotyping of three classical Dog Leukocyte Antigen (DLA) class II genes, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in 16 Newfoundlands with EOMG and 46 unaffected Newfoundlands, identified DLA-DQB1 *00301 (p-value = 0.0051 OR: 7.41) as a risk locus for the development of EOMG in this breed. In order to further investigate the extent of the association to the entire MHC region, 208 additional SNPs were genotyped in two phases. Both a risk locus for EOMG to the DLA class I (chr12: 458483–506460) and a protective locus for EOMG susceptibility that extends outside of the DLA class I (chr12: 89701–475348) were identified. Four additional dog breeds with an elevated risk for the development of MG were SNP genotyped, but no shared or significant associations were found. MHC involvement in canine MG disease manifestation overlaps with loci identified in human studies and highlights the value of dogs as a model for genetic studies of naturally occurring diseases.

Clinical and genetic basis of congenital myasthenic syndromes.

Neuromuscular junction disorders represent a wide group of neurological diseases characterized by weakness, fatigability and variable degrees of appendicular, ocular and bulbar musculature involvement. Its main group of disorders includes autoimmune conditions, such as autoimmune acquired myasthenia gravis and Lambert-Eaton syndrome. However, an important group of diseases include congenital myasthenic syndromes with a genetic and sometimes hereditary basis that resemble and mimick many of the classic myasthenia neurological manifestations, but also have different presentations, which makes them a complex clinical, therapeutic and diagnostic challenge for most clinicians. We conducted a wide review of congenital myasthenic syndromes in their clinical, genetic and therapeutic aspects.

Thymectomy for Myasthenia Gravis

Acquired myasthenia gravis, a disorder of neuromuscular transmission, results from the binding of autoantibodies to acetylcholine receptors. The

Acquired myasthenia gravis in a domestic shorthair cat with cranial mediastinal mass

Acquired myasthenia gravis in a domestic shorthair cat with cranial mediastinal mass