A 5-Year Follow-Up of Triple-Seronegative Myasthenia Gravis Successfully Treated with Tacrolimus Therapy

Tozawa, Takenori; Nishimura, Akira; Ueno, Tamaki; Kaneda, Daisuke; Miyanomae, Yuri; Chiyonobu, Tomohiro; Morimoto, Masafumi; Hosoi, Hajime

doi:10.1055/s-0037-1618591

Cited by 4 publications

(8 citation statements)

References 13 publications

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“…At 12 months follow-up, 10 patients were able to discontinue steroids and an improvement was seen on QMG and other quality of life measures. There is also a number of case reports that suggest a benefit in treatment refractory patients (51)(52)(53)(54). Side-effects of tacrolimus include hypertension, headache, tremor, renal impairment, new-onset diabetes mellitus, diarrhea, malignancy (e.g., lymphoma and dermatologic), and increased risk of infection.…”

Section: Immunosuppressive Therapymentioning

confidence: 99%

Management of Juvenile Myasthenia Gravis

2020

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Juvenile Myasthenia Gravis (JMG) is a rare disorder, defined as myasthenia gravis in children younger than 18 years of age. While clinical phenotypes are similar to adults, there are a number of caveats that influence management: broader differential diagnoses; higher rates of spontaneous remission; and the need to initiate appropriate treatment early, to avoid the long-term physical and psychosocial morbidity. Current practice is taken from treatment guidelines for adult MG or individual experience, with considerable variability seen across centers. We discuss our approach to treating JMG, in a large specialist JMG service, and review currently available evidence and highlight potential areas for future research. First-line treatment of generalized JMG is symptomatic management with pyridostigmine, but early use of immunosuppression, where good control is not achieved is important. Oral prednisolone is used as first-line immunosuppression with appropriate prevention and monitoring of side effects. Second-line therapies including azathioprine and mycophenolate may be considered where there is: no response to steroids, inability to wean to a reasonable minimum effective dose or if side-effects are intolerable. Management of ocular JMG is similar, but requires close involvement of ophthalmology in young children to prevent amblyopia. Muscle-specific tyrosine kinase (MuSK)-JMG show a poorer response to pyridostigmine and anecdotal evidence suggests that rituximab should be considered as second-line immunosuppression. Thymectomy is indicated in any patient with a thymoma, and consideration should be given in acetylcholine receptor (AChR) positive JMG allowing time for spontaneous remission. The benefit is less clear in ocular JMG and is not advised in MuSK-JMG. Children experiencing a myasthenic crisis require urgent hospital admission with access to the intensive care unit. PLEX is preferred over IVIG due to rapid onset of action, but this needs to be balanced with feasibility in very young children. Key questions remain in the management of JMG: when to initiate both first- and second-line treatments, choosing between steroid-sparing agents, and determining the optimal dose and treatment duration. We feel that given the rarity of this disease, the establishment of national registries and collaboration across groups will be needed to address these issues and facilitate future drug trials in JMG.

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Section: Immunosuppressive Therapymentioning

confidence: 99%

Management of Juvenile Myasthenia Gravis

2020

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“…[35][36][37][38] Moreover, some authors have identified clustered AChR-Abs that might have low affinity when conventional laboratory methods are employed. 9,39 Finally, although antibodies against muscle proteins such as titin and ryanodine may be used as markers of disease severity and the presence of thymoma, they play no role in the pathogenesis of MG. 32 In conclusion, in the study population, triple-SN MG showed a female predominance, and the most frequent initial symptoms were ptosis, diplopia, and generalized weakness. The majority of patients presented mild symptoms and had adequate responses to treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with possible MG were selected based on clinical findings, among these, we included patients who fulfilled clinical (fluctuating muscle weakness with fatigue), electrophysiological (repetitive nerve stimulation -RNS-with an abnormal decrement of compound muscle action potential greater than 10%) 10 or laboratory (detection of serum autoantibodies against AChR, MuSK or LRP4) diagnostic criteria for MG. Patients who satisfied both clinical and electrophysiological criteria but lacked antibodies against AChR, MuSK, and LRP4 were categorized as having triple-SN MG. 8,9 We excluded patients who did not have a serum antibody dosage performed, who did not undergo clinical follow-up, and those who had genetic analysis confirming other neuromuscular disorders (e.g., congenital myasthenic syndrome) conducted using a target next-generation sequencing (NGS) panel.…”

Section: Methodsmentioning

confidence: 99%

“…2,6,7 Even so, there are MG cases without autoantibodies against AChR, MuSK, or LRP4, that are called triple-seronegative (triple-SN) MG. 8 It can be speculated that the lack of autoantibody reactivity in these patients is due to the low sensitivity of the available tests or the presence of antigens not yet identified. 8,9 However, few studies have characterized individuals with triple-SN MG, and, to the best of our knowledge, there are none with Brazilian patients. This study aims to describe patients with triple-SN MG followed up in a tertiary care hospital in southern Brazil and compare them between groups with different serological profiles.…”

Section: Introductionmentioning

confidence: 99%

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Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics

Rodrigues,

Kay,

Ducci

et al. 2024

Arq Neuropsiquiatr

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Background Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG. Objective This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG. Methods This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile. Results The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment. Conclusion Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.

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“…CaN can be a potential use as a therapeutic approach to treat HD. A 5-year follow-up study report based on seronegative myasthenia gravis, a disease occurs in an absence of a seropositive status for anti-acetylcholine receptor (AChR) antibodies, describes a case of juvenile triple-seronegative myasthenia gravis that was successfully managed with tacrolimus therapy [13]. Briefly, tacrolimus is widely used in organ transplantation and autoimmune diseases such as myasthenia gravis, inflammatory myopathy, ulcerative colitis, and lupus nephritis [14].…”

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confidence: 99%

Effects of tacrolimus on c-fos in hippocampus and memory performances in streptozotocin model of Alzheimer’s disease of rats

Köylü¹,

Altunkaynak²,

Delibaş³

2021

Turk J Med Sci

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IntroductionAlzheimer's disease (AD), the most common dementia in older population is a progressive neurodegenerative age-related disease. The frequency of this disease is 0.1% between 60 and 65 ages and increases logarithmically up to 48% over age of 85. Considering that, by 2050, 25% of the world's population will be over 65; AD will be the most important health problem on the top [1]. There is no promising cure yet in fact the main factor that lies under the mechanism to cause the defects is not even known for certain. However, we know that the most important defect of this disease is the debates which appears as a form of amyloid beta (Aβ) plaque accumulation [2]. These plaques later become a slayer for the neuron itself. It is not accurate to label the pathway either as apoptosis or as necrosis, which is another fact to discuss [3]. However, it is certain that significant amount of neuron dies through this process. Another known defect is the tau neurofibrillary tangles, which occur between the neurons and in later on interrupts the communication between each of them. Without communication and nutrition, neurons begin to die and soon cell reduction happens. As time progresses more the Aβ plaques accumulate more debits surrounds the brain. Patients usually die of aspiration pneumonia about 9 years after disease onset [4].Different drugs are used for AD treatment, but they can only slow the decline of the diseases' progression. A class of a pharmacotherapy which contains cholinesterase Background/aim: Calcineurin, an inhibitor of calcium dependent phosphatase is highly presented in a brain of an Alzheimer's disease. Aging brain gets more sensitive to hyperactivation of calcineurin, and this event causes tau neurofibrillary plaque accumulation, which is one of the outcomes of this disease. The regions of hippocampus are much effected from the results of this process. Our hypothesis is that a calcineurin inhibitor, tacrolimus, could prevent the accumulation and the decrease of the neuronal cells. Therefore, this immunosuppressive drug could be a candidate for an early treatment of Alzheimer disease. Materials and methods:Fifteen male Wistar albino rats were divided to three groups; control, Alzheimer, and Alzheimer+Tacrolimus. The Alzheimer group received an injection of streptozotocin intracerebroventricularly for the purpose of modelling the disease via generating free radicals leading a cognitive impairment. Alzheimer+Tacrolimus group first received an oral drug, a calcineurin inhibitor for 10 days afterwards prepared for the model as same as the Alzheimer group received. Finally, all groups performed the Morris water maze test for four days then sacrificed. For the aim of counting neurons in the hippocampus stereological methods, as well as for an evaluation of cellular response to stress in dentate gyrus, a c-Fos immunohistochemistry was performed.Results: According to the probe trial of Morris water maze test, the latency time was dramatically higher at both Alzheimer and Alzheimer+Tacrolimus group (p < 0....

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A 5-Year Follow-Up of Triple-Seronegative Myasthenia Gravis Successfully Treated with Tacrolimus Therapy

Cited by 4 publications

References 13 publications

Management of Juvenile Myasthenia Gravis

Management of Juvenile Myasthenia Gravis

Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics

Effects of tacrolimus on c-fos in hippocampus and memory performances in streptozotocin model of Alzheimer’s disease of rats

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