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Journal of Personalized Medicine Jun 2024Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are inflammatory polyneuropathies with an autoimmune etiology. These diseases...
INTRODUCTION
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are inflammatory polyneuropathies with an autoimmune etiology. These diseases differ mainly in the timing of their course but also in certain clinical differences. Electroneurography and electromyography are crucial for fulfilling the primary (for CIDP) and secondary (for GBS) diagnostic criteria. High-resolution ultrasound (HRUS) is recognized as a complementary method in the diagnosis of CIDP and GBS.
AIM
The aim of this study was to present the neurophysiological and ultrasound findings of patients with clinically diagnosed inflammatory neuropathies (GBS and CIDP).
MATERIAL AND METHODS
We collected data from clinically confirmed patients with GBS (3 persons) and CIDP (6 persons). The neurography and high-resolution ultrasound examinations according to the UPSS scale were performed.
RESULTS
The neurography tests of GBS and CIDP patients showed mainly demyelinating lesions of the examined nerves, often with abnormal F-wave recordings. Examination using HRUS in GBS patients showed mild and regional nerve swelling with hypoechoic bundles with a predilection for proximal segments and cervical spinal nerve roots. In contrast, CIDP patients had diffused nerve swelling with hypoechoic bundles of greater severity and extent than those with GBS.
CONCLUSION
Neurophysiological tests and HRUS of peripheral nerves, plexi, and roots performed together can be very valuable, complementary diagnostic methods for the early diagnosis and effective treatment of inflammatory polyneuropathies.
PubMed: 38929824
DOI: 10.3390/jpm14060603 -
Journal of Personalized Medicine Jun 2024Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD)...
Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront.
Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments.
PubMed: 38929820
DOI: 10.3390/jpm14060599 -
Life (Basel, Switzerland) May 2024Multiple Sclerosis (MS) is a demyelinating and chronic disease with variable neurological symptoms. There are different scales that score the level of disability, but...
Multiple Sclerosis (MS) is a demyelinating and chronic disease with variable neurological symptoms. There are different scales that score the level of disability, but only few papers have taken into consideration the 5-times sit-to-stand (5STS) test and the 30 s chair stand test (30CST), which are valid and easily obtainable indicators of other neurological diseases. The aim of our research is to verify the validity, reproducibility, and responsiveness of these tests. Patients afflicted with MS were enrolled in the AISM outpatient facility. The inclusion criterion was an EDSS score less than 6.5. We performed the 5STS, 30CST, and timed 25-foot walk (T25-FW) tests and recorded EDSS scores in the first evaluation. Then, we recorded the performance after 5 days (conducted by a second blind operator to ensure test-retest reproducibility), and the last evaluation was made after 12 sessions of physiotherapy. We recruited 38 patients diagnosed with MS. The results show significant data regarding validity, reproducibility, and responsiveness for both scales. The data argue in favor of adding these tests to the relevant clinical assessments. These two tests are simple, reliable, and easy to administer, and the data confirm that they can be included in the evaluation of patients with MS.
PubMed: 38929686
DOI: 10.3390/life14060703 -
Medicina (Kaunas, Lithuania) Jun 2024: Rehabilitation is a part of the comprehensive treatment of multiple sclerosis (MS). If present, psychological reactive states limit the results of the rehabilitation....
: Rehabilitation is a part of the comprehensive treatment of multiple sclerosis (MS). If present, psychological reactive states limit the results of the rehabilitation. The objectives were to determine the impact of psychological reactive states in these patients on the functionality obtained by rehabilitation and QoL, and to determine the connection between the objective and subjective evaluation. : Based on the Hospital anxiety and depression scale, the patients were divided into a group with anxious and/or depressive reactive state and a group without the reactive state. The values of functional scores-the Berg Balance Scale (BBS) and the Expanded Disability Status Scale (EDSS), as well as the parameters of the QoL-Physical health Component Score (PCS) and the Mental health Component Score (MCS)-were determined at the beginning and at the end of the rehabilitation. : There was a statistically significant difference between the BBS, EDSS, PCS, and MCS groups at the beginning and the end of the rehabilitation in both groups. A statistically significant difference at the beginning and the end of the rehabilitation between the groups was found only in PCS and MCS. A highly statistically significant correlation between EDSS and PCS, and EDSS and MCS, was found only in the group without the reactive state. : Although rehabilitation leads to an objective improvement of functionality in patients with MS, the presence of the anxious and/or depressive reactive state limits the results of rehabilitation and leads to discrepancies in the aforementioned objective assessment and the patient's subjective experience through the evaluation of their QoL.
Topics: Humans; Multiple Sclerosis; Female; Male; Adult; Depression; Anxiety; Middle Aged; Quality of Life; Treatment Outcome; Disability Evaluation
PubMed: 38929558
DOI: 10.3390/medicina60060941 -
Medicina (Kaunas, Lithuania) May 2024: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to... (Review)
Review
: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to explore the association between inflammatory markers in saliva and PDs in MS patients, assessing the use of saliva as a non-invasive tool to monitor disease progression. : 82 publications were examined after a thorough search of scholarly databases to determine whether inflammatory markers were present in MS patients and whether they were associated with periodontal disease (PD). Quality and bias were assessed using the Newcastle-Ottawa Scale, resulting in eight articles that were thoroughly analyzed. : The results point to a strong correlation between MS and periodontal disorders, which may point to the same pathophysiological mechanism. It does, however, underscore the necessity of additional study to determine a definitive causal association. : The findings indicate a strong association between MS and PDs, likely mediated by systemic inflammatory responses detectable in saliva. The review highlights the importance of oral health in managing MS and supports the utility of saliva as a practical, non-invasive medium for monitoring systemic inflammation. Further research is necessary to confirm the causal relationships and to consider integrating salivary diagnostics into routine clinical management for MS patients.
Topics: Humans; Saliva; Multiple Sclerosis; Periodontal Diseases; Biomarkers; Inflammation
PubMed: 38929476
DOI: 10.3390/medicina60060859 -
International Journal of Molecular... Jun 2024Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how... (Review)
Review
Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.
Topics: Humans; Multiple Sclerosis; Female; Pregnancy; Computational Biology; Gene Regulatory Networks; Pregnancy Complications; Gene Expression Profiling; Signal Transduction; Gene Expression Regulation
PubMed: 38928446
DOI: 10.3390/ijms25126741 -
International Journal of Molecular... Jun 2024Multiple sclerosis (MS) onset at an advanced age is associated with a higher risk of developing progressive forms and a greater accumulation of disability for which...
Multiple sclerosis (MS) onset at an advanced age is associated with a higher risk of developing progressive forms and a greater accumulation of disability for which there are currently no effective disease-modifying treatments. Immunosenescence is associated with the production of the senescence-associated secretory phenotype (SASP), with IL-6 being one of the most prominent cytokines. IL-6 is a determinant for the development of autoimmunity and neuroinflammation and is involved in the pathogenesis of MS. Herein, we aimed to preclinically test the therapeutic inhibition of IL-6 signaling in experimental autoimmune encephalomyelitis (EAE) as a potential age-specific treatment for elderly MS patients. Young and aged mice were immunized with myelin oligodendrocyte protein (MOG) and examined daily for neurological signs. Mice were randomized and treated with anti-IL-6 antibody. Inflammatory infiltration was evaluated in the spinal cord and the peripheral immune response was studied. The blockade of IL-6 signaling did not improve the clinical course of EAE in an aging context. However, IL-6 inhibition was associated with an increase in the peripheral immunosuppressive response as follows: a higher frequency of CD4 T cells producing IL-10, and increased frequency of inhibitory immune check points PD-1 and Tim-3 on CD4 T cells and Lag-3 and Tim-3 on CD8 T cells. Our results open the window to further studies aimed to adjust the anti-IL-6 treatment conditions to tailor an effective age-specific therapy for elderly MS patients.
Topics: Encephalomyelitis, Autoimmune, Experimental; Animals; Mice; Interleukin-6; Female; CD4-Positive T-Lymphocytes; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; Multiple Sclerosis; Aging; Interleukin-10; Spinal Cord; Programmed Cell Death 1 Receptor; Signal Transduction
PubMed: 38928437
DOI: 10.3390/ijms25126732 -
International Journal of Molecular... Jun 2024The current hypothesis on the pathophysiology of multiple sclerosis (MS) suggests the involvement of both inflammatory and neurodegenerative mechanisms. Disease...
The current hypothesis on the pathophysiology of multiple sclerosis (MS) suggests the involvement of both inflammatory and neurodegenerative mechanisms. Disease Modifying Therapies (DMTs) effectively decrease relapse rates, thus reducing relapse-associated disability in people with MS. In some patients, disability progression, however, is not solely linked to new lesions and clinical relapses but can manifest independently. Progression Independent of Relapse Activity (PIRA) significantly contributes to long-term disability, stressing the urge to unveil biomarkers to forecast disease progression. Twenty-five adult patients with relapsing-remitting multiple sclerosis (RRMS) were enrolled in a cohort study, according to the latest McDonald criteria, and tested before and after high-efficacy Disease Modifying Therapies (DMTs) (6-24 months). Through Agilent microarrays, we analyzed miRNA profiles from peripheral blood mononuclear cells. Multivariate logistic and linear models with interactions were generated. Robustness was assessed by randomization tests in R. A subset of miRNAs, correlated with PIRA, and the Expanded Disability Status Scale (EDSS), was selected. To refine the patient stratification connected to the disease trajectory, we computed a robust logistic classification model derived from baseline miRNA expression to predict PIRA status (AUC = 0.971). We built an optimal multilinear model by selecting four other miRNA predictors to describe EDSS changes compared to baseline. Multivariate modeling offers a promising avenue to uncover potential biomarkers essential for accurate prediction of disability progression in early MS stages. These models can provide valuable insights into developing personalized and effective treatment strategies.
Topics: Humans; MicroRNAs; Male; Female; Adult; Disease Progression; Multiple Sclerosis, Relapsing-Remitting; Middle Aged; Biomarkers; Multiple Sclerosis; Leukocytes, Mononuclear; Cohort Studies; Recurrence; Gene Expression Profiling
PubMed: 38928049
DOI: 10.3390/ijms25126342 -
International Journal of Molecular... Jun 2024The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to... (Review)
Review
The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to play a significant role. Data from analyses of central nervous system autopsy material from patients diagnosed with multiple sclerosis, as well as from studies in the main experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), suggest the possibility of a role of oxidative stress as well. In this narrative review, we summarize the main data from studies reported on oxidative stress markers in patients diagnosed with MS and in experimental models of MS (mainly EAE), and case-control association studies on the possible association of candidate genes related to oxidative stress with risk for MS. Most studies have shown an increase in markers of oxidative stress, a decrease in antioxidant substances, or both, with cerebrospinal fluid and serum/plasma malonyl-dialdehyde being the most reliable markers. This topic requires further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls.
Topics: Humans; Oxidative Stress; Multiple Sclerosis; Biomarkers; Animals; Encephalomyelitis, Autoimmune, Experimental; Antioxidants
PubMed: 38927996
DOI: 10.3390/ijms25126289 -
Genes Jun 2024Extracellular vesicles (EVs) are "micro-shuttles" that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in... (Review)
Review
Extracellular vesicles (EVs) are "micro-shuttles" that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in both physiological and pathological conditions and are involved in intercellular communication, due to their ability to transfer proteins, lipids, and nucleic acids, and in the modulation of the immune system and neuroinflammation. Because EVs can penetrate the blood-brain barrier and move from the central nervous system to the peripheral circulation, and vice versa, recent studies have shown a substantial role for EVs in several neurological diseases, including multiple sclerosis (MS). MS is a demyelinating disease where the main event is caused by T and B cells triggering an autoimmune reaction against myelin constituents. Recent research has elucidate the potential involvement of extracellular vesicles (EVs) in the pathophysiology of MS, although, to date, their potential role both as agents and therapeutic targets in MS is not fully defined. We present in this review a summary and comprehensive examination of EVs' involvement in the pathophysiology of multiple sclerosis, exploring their potential applications as biomarkers and indicators of therapy response.
Topics: Humans; Multiple Sclerosis; Extracellular Vesicles; Biomarkers; Animals; Blood-Brain Barrier
PubMed: 38927708
DOI: 10.3390/genes15060772