Frequency and Correlates of Mild Cognitive Impairment in Myasthenia Gravis

Iacono, Salvatore; Stefano, Vincenzo Di; Costa, Vanessa; Schirò, Giuseppe; Lupica, Antonino; Maggio, Bruna; Norata, Davide; Pignolo, Antonia; Brighina, Filippo; Monastero, Roberto

doi:10.3390/brainsci13020170

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…However, some MG patients experience CNS symptoms in intermediate and advanced stages, including depression, anxiety disorders, headaches, dysautonomia, sleep disorders, and epilepsy [ 46 , 47 ]. These CNS symptoms could be partially attributed to drug side effects (specifically, intravenous immunoglobulin, ravulizumab, and pyridostigmine) [ 48 – 50 ]. There are also cases where these symptoms arise from unknown factors, which require careful consideration.…”

Section: Discussionmentioning

confidence: 99%

Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model

Hao,

Su,

et al. 2024

J Neuroinflammation

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Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood–brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/β-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain–blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/β-catenin pathway. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model

Hao,

Su,

et al. 2024

J Neuroinflammation

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“…Comorbidities may arise from the same pathogenetic mechanisms underlying MG (e.g., autoantibodies) or they may be caused by MG treatment (e.g., iatrogenic), ageing and other factors. Recently, mild cognitive impairment and behavioral alterations (i.e., depression, sleep disturbances) have been shown to be common in patients with MG wherein they were associated with higher disease severity and disability [ 79 ]. Apart from autoimmune diseases, gut dysbiosis (e.g., lower presence of Firmicutes and an increase in Bacteroidetes ) has been linked to cognitive impairment and psychiatric diseases [ 80 ].…”

Section: Clinical and Therapeutics Implicationsmentioning

confidence: 99%

The Role of Human Microbiota in Myasthenia Gravis: A Narrative Review

Schirò

Iacono

Balistreri

2023

Neurology International

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Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by fluctuating weakness of the skeletal muscles. Although antibodies against the neuromuscular junction components are recognized, the MG pathogenesis remains unclear, even if with a well-known multifactorial character. However, the perturbations of human microbiota have been recently suggested to contribute to MG pathogenesis and clinical course. Accordingly, some products derived from commensal flora have been demonstrated to have anti-inflammatory effects, while other have been shown to possess pro-inflammatory properties. In addition, patients with MG when compared with age-matched controls showed a distinctive composition in the oral and gut microbiota, with a typical increase in Streptococcus and Bacteroides and a reduction in Clostridia as well as short-chain fatty acid reduction. Moreover, restoring the gut microbiota perturbation has been evidenced after the administration of probiotics followed by an improvement of symptoms in MG cases. To highlight the role of the oral and gut microbiota in MG pathogenesis and clinical course, here, the current evidence has been summarized and reviewed.

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“…The results of recent studies indicate a high occurrence of mild cognitive impairment (MCI) with a complex amnestic cognitive profile in MG. Visuoconstructive/visuospatial skills, followed by verbal short-and long-term memory and selective and divided attention, were observed to be the most frequently affected domains. However, the exact underlying processes responsible for this condition are still being studied [31,32].…”

Section: Introductionmentioning

confidence: 99%

Depression: A Contributing Factor to the Clinical Course in Myasthenia Gravis Patients

Mihalache,

Vilciu,

Petrescu

et al. 2023

Medicina

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Background and Objectives: The association between myasthenia gravis (MG) and depression is intricate and characterized by bidirectional causality. In this regard, MG can be a contributing factor to depression and, conversely, depression may worsen the symptoms of MG. This study aimed to identify any differences in the progression of the disease among patients with MG who were also diagnosed with depression as compared to those without depression. Our hypothesis focused on the theory that patients with more severe MG symptoms may have a higher likelihood of suffering depression at the same time. Materials and Methods: One hundred twenty-two male and female patients (N = 122) aged over 18 with a confirmed diagnosis of autoimmune MG who were admitted to the Neurology II department of Myasthenia Gravis, Clinical Institute Fundeni in Bucharest between January 2019 and December 2020, were included in the study. Patients were assessed at baseline and after six months. The psychiatric assessment of the patients included the Hamilton Depression Rating Scale-17 items (HAM-D), and neurological status was determined with two outcome measures: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Life (MG-ADL). The patients were divided into two distinct groups as follows: group MG w/dep, which comprised 49 MG patients diagnosed with depressive disorder who were also currently receiving antidepressant medication, and group MG w/o dep, which consisted of 73 patients who did not have depression. Results: In our study, 40.16% of the myasthenia gravis (MG) patients exhibited a comorbid diagnosis of depression. Among the MG patients receiving antidepressant treatment, baseline assessments revealed a mean MG-ADL score of 7.73 (SD = 5.05), an average QMG score of 18.40 (SD = 8.61), and a mean Ham-D score of 21.53 (SD = 7.49). After a six-month period, a statistically significant decrease was observed in the MG-ADL (2.92, SD = 1.82), QMG (7.15, SD = 4.46), and Ham-D scores (11.16, SD = 7.49) (p < 0.0001). These results suggest a significant correlation between MG severity and elevated HAM-D depression scores. Regarding the MG treatment in the group with depression, at baseline, the mean dose of oral corticosteroids was 45.10 mg (SD = 16.60). Regarding the treatment with pyridostigmine, patients with depression and undergoing antidepressant treatment remained with an increased need for pyridostigmine, 144.49 mg (SD = 51.84), compared to those in the group without depression, 107.67 mg (SD = 55.64, p < 0.001). Conclusions: Our investigation confirms that the occurrence of depressive symptoms is significantly widespread among individuals diagnosed with MG. Disease severity, along with younger age and higher doses of cortisone, is a significant factor associated with depression in patients with MG. Substantial reductions in MG-ADL and QMG scores were observed within each group after six months, highlighting the effectiveness of MG management. The findings suggest that addressing depressive symptoms in MG patients, in addition to standard MG management, can lead to improved clinical outcomes.

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Frequency and Correlates of Mild Cognitive Impairment in Myasthenia Gravis

Cited by 5 publications

References 44 publications

Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model

Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model

The Role of Human Microbiota in Myasthenia Gravis: A Narrative Review

Depression: A Contributing Factor to the Clinical Course in Myasthenia Gravis Patients

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