Treatment Of Myasthenia Research Articles

Innovations in myasthenia treatment: a stocktake

Innovations in myasthenia treatment: a stocktake

Myastenia gravis: features of epidemiology, pathogenesis, treatment and relation to thymomas

Мyasthenia gravis is a common disease, for adequate treatment of which early detection, knowledge of its clinical manifestations and possible methods of therapy is required. This review provides up-to-date information regarding the issues of myasthenia gravis. The aim of the paper: to systematize the latest scientific data on the pathogenesis, genetic characteristics, methods of treatment of myasthenia gravis, as well as to identify the relationship between myasthenia gravis and other diseases. The following databases were used to search for published studies: Pubmed, Web of Science, EBSCOhost and Scopus. The search was carried out in the time period from the date of establishment of the corresponding database until October 2022. Following search terms were used: “myasthenia gravis”, “myasthenia treatment”, “myasthenia epidemiological features”, “myasthenia and thymoma “myasthenia pathogenesis””. Тhe main studies on the epidemiology of myasthenia gravis are indicated, the key clinical forms and their pathogenetic characteristics, the relationship between myasthenia gravis and thymoma, and the main methods of treatment are also given.

Thymomas: Analysis of Histological Subtypes and Staging in Patients with Surgical Treatment in Two Reference Centers in Argentina

Background: Thymomas are a heterogeneous group of tumors which represent the most frequent tumor of the anterior mediastinum. Aims: To describe the clinical, histological, surgical and oncological characteristics of a cohort of patients with a diagnosis of thymoma surgically treated in two centers in Argentina and to evaluate the possibility of retrospectively implementing the 8th edition of TNM staging. Materials and Methods: 180 patients with thymoma surgically treated over a period of 41 years were studied. The following variables were analysed: age, sex, presence of myasthenia gravis at diagnosis, Masaoka staging (1994), TNM staging of thymus tumors, Histological classification (WHO 2015), neoadjuvant treatment with chemotherapy, post-operative radiation treatment and clinical evolution of myasthenia gravis defined according to the modified Osserman classification. Results: 96 men and 84 women were analysed. Median age 51 years (range 13-85). 85% of the patients analysed came from the public sphere. When analysing the institutional distribution by Masaoaka-Koga stage and TNM, a higher proportion of stages I was observed for both staging systems. Most myasthenic patients belonged to the WHO B2 histological classification (49%, p=0.04) and 15 patients received neoadjuvant treatment prior to surgery to improve the chances of resection, most of them classified as stages III of Masaoka (p=0.002) or IIIa of the TNM stage (p=0.001). 74 (46%) cases received post-operative RT when they presented Masaoka Koga stages II (p=0.000) and IIIa or more advanced TNM staging (p=0.000). 76% of the patients presented remission or stability of symptoms after surgical treatment and only 3/6 died due to myasthenic crisis in the immediate post-operative period. Conclusion: As reported in the literature, we have observed a higher frequency of B2 thymomas and their association with Myasthenia gravis. The histological criteria of the WHO 2015 classification, based on the ITMIG recommendations, favour precision in the definition of subtypes. The retrospective implementation of the 8th edition of TNM staging highlights the need to standardize protocols for pathological and surgical studies.

MYASTHENIA GRAVIS

Myasthenia gravis has a particular place among neurological diseases. The offered article gives information about the description, epidemiology, etiology, pathogenesis, classification, clinical course, diagnosis and differential diagnosis, treatment of myasthenia, and myasthenic crisis.

Myasthenia Crisis Vs Cholinergic Crisis: Challenges in Crisis Management Without Plasmapheresis or Intravenous Immunoglobulin (IVIG)

Introduction: Myasthenia gravis (MG) is an acquired autoimmune disorder clinically characterized by skeletal muscle weakness & fatigability on exertion with prevalence as high as 2–7 in 10,000 and women are affected more frequently than men (~3:2). Over 12-16% of generalized MG patients experience crisis once in their lifetime. A serious complication of myasthenia gravis is respiratory failure. This may be secondary to an exacerbation of myasthenia (myasthenia crisis) or to treatment with excess doses of a cholinesterase inhibitor (cholinergic crisis). Case Report: Thirty-two years old woman refereed from a private hospital to ED for further treatment with myasthenia in crisis, after nine days of treatment in the previous ICU. Patient already in intubation with mechanical ventilation and history of the treatment of a high dose of multiple anticholinesterase drugs and steroids without plasmapheresis or immunoglobulin intravenous. During admission, diarrhea was present, with no sign of GI infection. On the third day of admission, the patient performed a Spontaneous Breathing Trial and was a success then extubated. Then two day after extubation, the patient falls to respiratory failure and need mechanical ventilation. Anticholinesterase test was performed, and it shows no improvement in clinical signs, and diagnose as Cholinergic Crisis. After re-adjustment of anticholinesterase drug with a lower dose, clinically, the respiratory condition improved, and on the 10th day of admission, the patient was succeed extubated. At 12nd days of ICU admission, patient discharge from ICU. Discussion: Myasthenia and Cholinergic Crisis is a severe and life-threatening condition characterized by generalized muscle weakness with a respiratory compromise that requires ventilatory support. Respiratory failure may be present in the cholinergic crisis without cholinergic symptoms (miosis, diarrhea, urinary incontinence, bradycardia, emesis, lacrimation, or salivation). The most important management aspect of Myasthenia patients in crisis is the recognition and treatment of myasthenia vs cholinergic crisis.

Myasthenia Crisis Vs Cholinergic Crisis: Challenges in Crisis Management Without Plasmapheresis or Intravenous Immunoglobulin (IVIG)

Introduction: Myasthenia gravis (MG) is an acquired autoimmune disorder clinically characterized by skeletal muscle weakness & fatigability on exertion with prevalence as high as 2–7 in 10,000 and women are affected more frequently than men (~3:2). Over 12-16% of generalized MG patients experience crisis once in their lifetime. A serious complication of myasthenia gravis is respiratory failure. This may be secondary to an exacerbation of myasthenia (myasthenia crisis) or to treatment with excess doses of a cholinesterase inhibitor (cholinergic crisis). Case Report: Thirty-two years old woman refereed from a private hospital to ED for further treatment with myasthenia in crisis, after nine days of treatment in the previous ICU. Patient already in intubation with mechanical ventilation and history of the treatment of a high dose of multiple anticholinesterase drugs and steroids without plasmapheresis or immunoglobulin intravenous. During admission, diarrhea was present, with no sign of GI infection. On the third day of admission, the patient performed a Spontaneous Breathing Trial and was a success then extubated. Then two day after extubation, the patient falls to respiratory failure and need mechanical ventilation. Anticholinesterase test was performed, and it shows no improvement in clinical signs, and diagnose as Cholinergic Crisis. After re-adjustment of anticholinesterase drug with a lower dose, clinically, the respiratory condition improved, and on the 10th day of admission, the patient was succeed extubated. At 12nd days of ICU admission, patient discharge from ICU. Discussion: Myasthenia and Cholinergic Crisis is a severe and life-threatening condition characterized by generalized muscle weakness with a respiratory compromise that requires ventilatory support. Respiratory failure may be present in the cholinergic crisis without cholinergic symptoms (miosis, diarrhea, urinary incontinence, bradycardia, emesis, lacrimation, or salivation). The most important management aspect of Myasthenia patients in crisis is the recognition and treatment of myasthenia vs cholinergic crisis.

Ocular myasthenia gravis: A case series

Aim: To report the clinical profile of patients with myasthenia gravis (MG) at a tertiary eye care center in Tamil Nadu. Material and Methods: This is a retrospective case series of patients in a single center between February 2019 and March 2020. Result: We present a series of five cases of ocular myasthenia in the pediatric age group (0–16 years), comprising three males and two females. The patients had varied presentations on the initial examination. Conclusion: It is important to differentiate MG from other diagnostic mimics such as neurological causes such as cranial nerve palsy, myopathies, ocular pathologies, and neuromuscular junction pathologies such as botulism and brainstem tumors. Diagnosis and treatment of myasthenia is done as a team effort of ophthalmologist and neurologist. This study is to reinforce a vigilant lookout for this great masquerader.

МІАСТЕНІЯ – ТРУДНОЩІ ДІАГНОСТИКИ ТА ЛІКУВАННЯ (РОЗБІР КЛІНІЧНОГО ВИПАДКУ)

Myasthenia gravis is an autoimmune rapidly progressive disease characterized by a neuromuscular disorder due to the formation of autoantibodies to different epitopes of the peripheral neuromuscular device and is clinically manifested by pathological muscle fatigue and weakness. Diagnosis of myasthenia in the elderly is very problematic because doctors regard muscle weakness at this age as a symptom of other diseases. In addition, it may be combined with various pathological conditions. The article describes the presence of comorbid states in patients with myasthenia who were treated at the neurological department of Lviv regional clinical hospital in 2016-2018. 58% of patients with myasthenia, mainly older people, had comorbid diseases. Hypertensive heart disease (34%), ischemic heart disease (20%), diabetes mellitus (12%,) and small brain vessels disease (8%) were frequently observed. A case of late diagnosed generalized myasthenia in a 66-year-old woman with concomitant small vessels disease of the brain and diabetes mellitus is described. The patient was treated at the neurological department of Lviv regional clinical hospital in December 2018. For a long time, the patient had been treated of the small vessels disease, though main complaints were difficulties with speaking, swallowing, periodic double vision, ptosis, general weakness, weakness in the right leg, memory impairment, problems with walking and urination. The diagnosis of myasthenia was based on clinical manifestations, a positive reaction to acetylcholinesterase inhibitors, and detection of antibodies to acetylcholine receptors. Clinical manifestations of myasthenia, as well as apraxia of walking, disorders of urination and cognitive impairment due to vascular changes in the brain intensified the patient's disability and created the need for careful outside care and control of the drug intake. The positive influence of anticholinesterase drugs and prednisolone in the treatment of myasthenia was noted. The presence of diabetes mellitus is a relative contraindication to the administration of corticosteroids, but in the presence of comorbidity of generalized myasthenia and diabetes mellitus type II, prednisolone was used under constant monitoring of blood glucose by hypoglycemic agents. Thus, late-onset, severe comorbid diseases (small vessel disease of the brain, diabetes mellitus) complicate and delay the diagnosis of myasthenia and prescription of appropriate therapy.

Schwann cells sense and control acetylcholine spillover at the neuromuscular junction by α7 nicotinic receptors and butyrylcholinesterase.

Terminal Schwann cells (TSCs) are key components of the mammalian neuromuscular junction (NMJ). How the TSCs sense the synaptic activity in physiological conditions remains unclear. We have taken advantage of the distinct localization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at the NMJ to bring out the function of different ACh receptors (AChRs). AChE is clustered by the collagen Q in the synaptic cleft and prevents the repetitive activation of muscle nicotinic AChRs. We found that BChE is anchored at the TSC by a proline-rich membrane anchor, the small transmembrane protein anchor of brain AChE. When BChE was specifically inhibited, ACh release was significant depressed through the activation of α7 nAChRs localized on the TSC and activated by the spillover of ACh. When both AChE and BChE were inhibited, the spillover increased and induced a dramatic reduction of ACh release that compromised the muscle twitch triggered by the nerve stimulation. α7 nAChRs at the TSC may act as a sensor for spillover of ACh adjusted by BChE and may represent an extrasynaptic sensor for homeostasis at the NMJ. In myasthenic rats, selective inhibition of AChE is more effective in rescuing muscle function than the simultaneous inhibition of AChE and BChE because the concomitant inhibition of BChE counteracts the positive action of AChE inhibition. These results show that inhibition of BChE should be avoided during the treatment of myasthenia and the pharmacological reversal of residual curarization after anesthesia.

51. Myasthenia gravis – Identifying risk factors leading to a more severe course of the disease in a cohort of 45 patients

Introduction Myasthenia gravis is an autoimmune disease that causes neuromuscular transmission disorder manifested by muscle weakness and fatigue, in particular predilection muscle groups. Most cases are mediated by T lymphocyte-dependent polyclonal antibody directed against acetylcholine receptors. Approximately 10–15% of cases are etiological associated with thymoma. AChR antibodies in serum are detectable in 80–90% of patients. Of the remaining seronegative MG forms are most commonly detected antibodies to MuSK (30–70%) and especially in thymoma antistriatal, antititin and antiryanodin antibodies. Some cases are associated with low affinity antibodies against AChR. Diagnostic and therapeutic procedures in medicine has recently developed in a fast rate. The goal of our observations was to assess how the reflected developments in the area of the approach to patients with this diagnosis affected our department and to try identifying risk factors leading to a more severe course of the disease. Patients and methods The study included 45 patients (27 men, 18 women) followed in our department from 2009 to the present. The diagnosis was established on the basis of history, clinical examination and EMG findings. In this retrospective study was used material available in our archives. Results We present a cohort of patients with myasthenia gravis diagnosed and treated in our department. In our patients the EMG findings correspond with the severity of the disorder. We found that the higher titers of the antibodies against AChR led to a more severe course of the disease. Conclusion Despite advances in diagnosis and treatment of myasthenia, this still represents a challenge for physicians due to the relatively variable course and clinical findings. The aim of our study was to refer to this variability and point out not full understanding the pathogenesis of myasthenia. We determined risk factors leading to a more serious course of the disease in our patients.

Extracorporeal photochemotherapy in treatment of myasthenia

Aim: Estimation of extracorporeal photochemotherapy (EPCT) efficacy in myasthenic patients.

Factors Determining Response to Pyridostigmine or Steroid Treatment in Myasthenia Gravis (P04.096)

Objective: To identify factors impacting the response of myasthenic patients to anticholinesterase or steroid therapy. Background First-line treatment for myasthenia are steroids. Some patients do not respond and need to be switched to a non-steroid immunosuppressant. Pyridostigmine produces a symptomatic benefit, although frequently incomplete, needing addition of immunosuppressants. Identifying in advance patients not likely to respond to steroids, and those likely to have a complete response to pyridostigmine would help in avoiding unnecessary steroid therapy, preventing side effects and saving time. Design/Methods: Patients diagnosed with autoimmune myasthenia receiving pyridostigmine or steroids as the only treatment for myasthenia for at least 3 months were retrospectively recruited. Age, sex, distribution of symptoms, comorbid conditions, autoantibody titres, EMG results and co-administration of beta-blockers, benzodiazepines or beta-agonists were investigated as predictors for response to pyridostigmine or prednisone. Results: Ninety-five patients were included in the study. Fifty-nine patients were evaluated for response to pyridostigmine and 73 to prednisone. Forty-three patients had ocular myasthenia (OM) and 52 had generalized myasthenia (GM). Age, sex, comorbid conditions, antibody titres, EMG results, and benzodiazepines were not associated to the response to pyridostigmine or prednisone. Patients with OM were more likely to have a complete response to pyridostigmine than GM (p=0.02). Patients on Beta-Blockers were unlikely to respond to pyridostigmine (p=0.01). Patients on beta-agonists showed a trend to a better response to pyridostigmine, although not significant. Beta-blockers did not modify the response to prednisone. Conclusions: OM is more like to have a complete response to pyridostigmine than GM. In light of this, initiating therapy with pyridostigmine alone should be stressed for OM. Beta-blockers seem to have a negative impact on the response to pyridostigmine but not to prednisone. We suggest that Beta-blockers should be avoided when possible in patients with myasthenia treated only with pyridostigmine. If beta-blockers are necessary, inmunosuppression should not be delayed. Disclosure: Dr. Cabrera Serrano has nothing to disclose. Dr. Morgado has nothing to disclose. Dr. Benitez has nothing to disclose. Dr. Paradas Lopez has nothing to disclose.

Editorial: New drugs for Alzheimer's disease in Japan

Editorial: New drugs for Alzheimer's disease in Japan

Confusion and controversies in diagnosis and treatment of myasthenia

AbstractMyasthenia gravis is an afferent ocular motor mimic. The disease may appear with any pattern of pupil‐sparing, painless ocular misalignment with or without ptosis; accordingly, common mistaken diagnoses included CN3 palsy or internuclear ophthalmoplegia. Variability adds to diagnostic confusion, as patients may be asymptomatic and have a normal exam at certain stages in the disease. Clinical context remains the first diagnostic key, however, lab and electrophysiology are very helpful. Acetylcholine receptor antibodies are present in approximately 50% of ocular MG, but are highly specific. Single fiber EMG is perhaps the most sensitive test, being abnormal in approximately 90% of cases. Treatment is symptom dependent; pyridostigmine is often used as initial therapy and quite effective for ptosis and dysphagia, while additional immunosuppressives are often required for diplopia. We often initiate therapy with low dose every other day prednisone, and have a low threshold to add mycophenolate mofetil.

O24 Intravascular laser irradiation of blood in treatment of myasthenia

O24 Intravascular laser irradiation of blood in treatment of myasthenia

Traitement de la myasthénie auto-immune

Myasthenia gravis is the most common neuromuscular junction disorder and the best understood autoimmune disease of the nervous system. The autoimmune attack leads to decreased concentrations of the AChR and results in fatigability of skeletal muscles increasing with activity and improving with rest. The treatment of myasthenia has improved dramatically over the last few decades, with an increasing number of immunotherapies used in management although not all of them have been formally tested in double-blind, prospective trials. The principles of treatment consist in optimizing neuromuscular junction function by use of cholinesterase inhibitors, inducing an immunologic remission and then maintaining that remission by long-term immunotherapies. Prednisone and/or azathioprine are the most effective. Short-term immunotherapies, i.e. intravenous immunoglobulin or plasmapheresis, are indicated for disease exacerbation. For patients with nonthymomatous autoimmune myasthenia, the effectiveness of thymectomy remains uncertain. The overall objective of therapy is to enable patients to lead a normal life as rapidly as possible, while limiting side effects and costs if possible. Treatment should be individualized. The aggressiveness of therapy should be balanced against a number of factors including distribution of muscle involvement, rate of progression, degree of functional impairment, lifestyle choice, and coexisting disease. In all cases, adequate education, for the patient and the physician, is most helpful in facilitating management of this chronic disease.

Apport des échanges plasmatiques dans le traitement de la myasthénie : étude de 11 cas

The use of plasma exchange (PE) constituted an advance in the treatment of myasthenia. The objective of our study was to determine the relevance of PE in the treatment of myasthenia and to study the different complications which can be observed during PE. We studied retrospectively 11 patients who have generalized myasthenia and underwent PE. We used an intermittent flow cell separator and we performed PE three times a week. Biological assessment was performed before and after PE for all patients. The exchange volume was calculated according to the patient weight, gender and the value of hematocrit. Our series included six women and five men. The mean age at onset of the disease was 41.4+/-14.1 years (range: 18 to 68). Indication of PE was myasthenia crisis (eight cases), resistance to classic treatment (two cases) and exacerbation after thymectomy (one case). An improvement was observed rapidly in five cases and delayed in three cases. The remaining three patients did not improve. The most frequent side effects of PE were hypotension (four cases), heart arrhythmia (two cases) and hypoglycemia (one case). Three patients dead in the seven days after the first PE. PE represents an interesting tool to treat severe forms of myasthenia and improve prognosis. High incidence of complications in our series can be explained by the initial disease severity, the used method of PE, the existence of associated illness, and a long stay in intensive care unit.

Immunsuppressive Therapie - Myasthenia gravis

Immunosuppressive therapy of myasthenia gravis is important for long-term maintenance of remission with minimal side effects. Indication for immunosuppressive treatment is dependent on the severity and course of the disease, and has to take into account the effect of thymectomy which is eventually performed in early-onset generalized myasthenia. Azathioprin is the only drug formally approved for treatment of myasthenia. However, a variety of other immunosuppressants, such as cyclosporine, mycophenolate, cyclophosphamide, and tacrolimus, have also been shown to be effective and can be prescribed off-label as second-line treatment in cases with inefficacy or intolerable side effects of azathioprine.

Myasthenia gravis mimicking unilateral vocal fold paralysis at presentation

To demonstrate the importance of detailed clinical analysis in the differential diagnosis of unilateral vocal fold paralysis, and to provide an update on current knowledge and treatment of myasthenia gravis. A female patient presented with left unilateral vocal fold immobility. Diagnostic investigation revealed a 10 mm thyroid adenoma, but no other abnormality likely to cause unilateral vocal fold paralysis. Follow-up flexible endoscopy at three months showed laryngeal remobilisation with persistent left vocal fold bowing and vertical asymmetry of the vocal folds on phonation. Over the following months, voice quality varied between normal and breathy, with the breathy periods lasting from three days to one month. Laryngeal electromyography (EMG) showed a slight bilateral paradoxical activation of both posterior crico-arytenoid muscles on phonation. Magnetic resonance imaging of the brain and brainstem was normal. A diagnostic test for myasthenia gravis with intravenous edrophonium bromide (Tensilon) lead to an immediate improvement in voice quality. The patient was subsequently treated with pyridostigmine bromide, with complete resolution of dysphonia. Myasthenia gravis affecting the larynx may mimic unilateral vocal fold paresis or paralysis. A personal or family history of auto-immune disease, fluctuating symptoms, motor deficits in cranial nerve territories, and normal or subnormal laryngeal EMG results should lead the physician to reconsider a diagnosis of idiopathic unilateral vocal fold paralysis and to perform specific testing.

Myasthenia gravis: emerging new therapy options

Myasthenia gravis is probably the most thoroughly understood of all human autoimmune diseases. The basic mechanism of the disease is an antibody-mediated autoimmune attack that decreases the acetylcholine receptor density at the neuromuscular junction. Current therapies aim to restore the available acetylcholine receptors, deplete the autoantibodies or suppress the immune system. Prolonged drug treatment is required, but this carries a potential risk of severe adverse effects. Therefore, the ideal treatment for myasthenia would eliminate the abnormal autoimmune response without interfering with the immune system.