Tibial nerve stimulation in the management of primary sexual dysfunction in patients with multiple sclerosis: a pilot randomized control trial.

INTRODUCTION: Sexual dysfunction (SD) is a common symptom that affects 40-90% of patients with multiple sclerosis (MS). Previous studies have highlighted the negative impact of sexual dysfunction in the mental health status and overall quality of life in patients with MS. METHODS: The aim of this study was to examine the effects of transcutaneous tibial nerve stimulation (TTNS) in the primary SD symptoms in patients with MS. A total of 40 participants were randomized (1:1 ratio) to either TTNS or Sham group and received three 20 min sessions over the course of two months. Pre and post intervention SD was evaluated using the Multiple Sclerosis Intimacy Questionnaire (MISQ-15). RESULTS: Statistically significant improvements in the aspects of primary sexual dysfunction were observed in the TTNS group pre-post intervention (specifically erectile function (for males)/vaginal lubrication (for females) (p < .001), orgasm quality and satisfaction for both male and female patients (p < .001), sexual desire (p < .05) and bladder related symptomatology (p < .005). In the sham group pre-post intervention, the only observed improvement was in the sexual desire aspect (p < .05). Post intervention the groups significantly differed erectile function/vaginal lubrication and orgasm quality and satisfaction (p < .05). CONCLUSIONS: Our findings underline the efficacy of TTNS in improving primary SD symptoms as well as bladder problems in both male and female patients with MS. TTNS demonstrated significant improvement in the following domains: erectile function, vaginal lubrication, orgasm quality, satisfaction, bladder-related symptoms, and sexual desire.

Prevalence and epidemiology of stroke in patients with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS). OBJECTIVE: To estimate the following: (1) the pooled prevalence of all-cause stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) in MS patients; (2) the relative risk for all-cause stroke, AIS and ICH in MS patients compared to the general population; (3) associations between patient characteristics and the risk for AIS and ICH in MS patients. METHODS: Systematic review and meta-analysis of registry-based and cohort studies. RESULTS: Thirteen observational studies comprising 146,381 MS patients were included. The pooled prevalence of all-cause stroke was 2.7% (95% confidence interval [CI] 1.3-4.6%), with the relative risk of all-cause stroke being higher in MS patients compared to the general population (RR: 2.55; 95% CI 1.97-3.29). Subgroup analyses per stroke subtype revealed a pooled AIS prevalence of 2.1% (95% CI 0.8-4.1%) and a pooled ICH prevalence of 0.6% (95% CI 0.2-1.2%). Compared to the general population, patients with MS were found to harbour an increased risk for AIS (RR: 2.79; 95% CI 2.27-3.41) and ICH (RR: 2.31; 95% CI 1.04-5.11), respectively. The pooled prevalence of cardiovascular risk factors in MS patients was 11.5% (95% CI 2.9-24.7%) for dyslipidaemia, 18.2% (95% CI 5.9-35.3%) for hypertension and 5.4% (95% CI 2.1-10.2%) for diabetes. In meta-regression, age was negatively associated with AIS risk (ß = - .03, p = 0.04), with a 1-year increase in age resulting in a significant 3% (95%CI 0-5) attenuation of the risk of AIS. CONCLUSION: The findings of the present meta-analysis indicate that MS is associated with an increased risk for ischaemic and haemorrhagic stroke. Future well-designed epidemiological studies are warranted to corroborate the robustness of the present findings in the MS population.

Waist Circumference and Body Mass Index as Predictors of Disability Progression in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: While obesity has been shown to elevate the risk of developing multiple sclerosis (MS), there is a lack of strong evidence regarding its role in the disability progression and status of MS patients. Methods: This systematic review and meta-analysis aimed to provide comparative estimates of WC and BMI in patients with MS (PwMS) and to investigate potential associations between the waist circumference (WC) and body mass index (BMI) and demographic and specific MS characteristics. Adhering to PRISMA guidelines, a detailed search of the MEDLINE PubMed, Cochrane Library, and Scopus databases was conducted. Results: A total of 16 studies were included. The pooled mean WC and BMI among PwMS was estimated to be 87.27 cm (95%CI [84.07; 90.47]) and 25.73 (95%CI [25.15; 26.31]), respectively. Meta-regression models established a significant bidirectional relationship between WC and the Expanded Disability Scale (EDSS) (p < 0.001) but not between BMI and EDSS (p = 0.45). Sensitivity analyses showed no association between WC and age (p = 0.48) and a tendency between WC and disease duration (p = 0.08). Conclusions: Although WC measurements classify PwMS as normal weight, BMI measurements classify them as overweight. Therefore, WC should complement BMI evaluations in clinical practice. Additionally, our findings highlight the significant association between abdominal fat, as indicated by WC, and disease progression. Considering the heightened risk of cardiovascular comorbidity and mortality among PwMS, we recommend integrating both WC and BMI as standard anthropometric measurements in routine clinical examinations and targeted prevention strategies for PwMS.

Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience.

BACKGROUND: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. METHODS: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. RESULTS: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. CONCLUSIONS: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

Neuropsychological profiles comparison between Multiple Sclerosis patients and Multiple Sclerosis patients with overlapping features of Systemic Lupus Erythematosus.

AIM: Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) are autoimmune disorders that may lead to cognitive impairment. This study aimed to compare the neuropsychological profiles of patients with MS, and MS and coexisting SLE features. METHODS: We included a total of 90 participants, divided into 3 groups: 30 patients with clinically definite relapsing remitting MS, 30 with coexisting MS and incomplete SLE (overlap group) and 30 healthy controls (HC). All participants underwent neuropsychological assessment with the Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Selective Reminding Test (SRT). RESULTS: Both groups scored lower on the MoCA compared to the HC (p < .001). The overlap group showed the lowest performance on the SDMT and PASAT compared to the other two groups (p < .01), while the MS group scored similarly to the HC in the PASAT (p > .05). Regarding the learning rate and long-term recall, the overlap group had lower scores compared to both the MS and HC (p < .001), but it outperformed both groups in the retention efficacy score (p < .001). The MS group did not differ significantly from the HC in these memory domains (p > .05). CONCLUSION: The overlap group exhibited a broader range of impairments, including slower processing speed, decreased working memory, reduced learning rate, and long-term retrieval deficits. Their retention ability remained intact. The coexistence of MS with SLE pathology had additive impacts on cognitive function.

Interactions between fatigue and urinary quality of life in patients with Multiple Sclerosis.

INTRODUCTION: Neurogenic bladder as well as fatigue related symptoms are common in patients with Multiple Sclerosis (MS) and have a significant impact on the patients' Quality of Life (QoL). The aim of this study is to investigate the relationship between fatigue related symptomatology (FRS) and Urinary Quality of Life (UQoL). METHODS: A total of 120 consecutive MS patients were recruited from the Outpatient Clinic of Demyelinating Diseases (Second Dept. of Neurology, Attikon University Hospital Greece). Participants were then asked to complete the Modified Fatigue Impact Scale (MFIS) and the Short Form Qualiveen questionnaire. Demographic and bladder function related characteristics (incontinence, urinary frequency, use of intermittent catheterization) were collected. RESULTS: The physical and cognitive dimensions of MFIS had a moderate to high correlation with SF Qualiveen (r = 0.403, p <.000), (r = 0.329, p <.000).Multiple linear regression produced a fitted model (R2 = 0.150, F(3,111) = 5.554, p =.001) in IC use (ß = 1.086, p =.036) and the physical dimension of MFIS (ß = 0.66, p =.046) significantly predicted the SF Qualiveen score. CONCLUSION: UQoL had a moderate correlation with both physical and cognitive dimensions of fatigue. Patients with MS who experience lower levels of physical fatigue and/or manage their neurogenic bladder symptomatology (mainly with the use of intermittent catheterization) appear to have higher levels of UQoL. Due to the versatile and subjective nature of both fatigue related and neurogenic bladder symptoms, more focused studies utilizing objective evaluation tools (e.g urodynamic urine bladder study) are necessary.

Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.

This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.

Rehabilitation on cerebellar ataxic patients with multiple sclerosis: A systematic review.

Multiple Sclerosis (MS) is a chronic inflammatory, autoimmune disease of the Central Nervous System with a vast spectrum of clinical phenotypes. A major aspect of its clinical presentation is cerebellar ataxia where physiotherapy and treatment modalities play a significant role on its management. This systematic review aims to investigate the physiotherapeutic rehabilitation techniques regarding the management of cerebellar ataxia due to MS and secondary to stratify each protocol as part of a multi structural personalized rehabilitation approach based on the gravity of the symptoms. A Pubmed Medline, Scopus and Web of Science research was performed using the corresponding databases. The results were screened by the authors in pairs. In our study, six (6) non-pharmacological interventional protocols, 3 Randomized Controlled Trials and 3 pilot studies, were included with a total of 145 MS patients. Physiotherapeutic techniques, such as NDT-Bobath, robotic and visual biofeedback re-education protocols and functional rehabilitation techniques were included. In most cases cerebellar ataxic symptoms were decreased post-treatment. The overall quality of the studies included was of moderate level (level B). Rehabilitation in cerebellar ataxia due to MS should be based on multicentric studies with the scope of adjusting different types of treatments and physiotherapeutic techniques based on the severity of the symptom.

Plasma Phospho-Tau-181 as a Diagnostic Aid in Alzheimer's Disease.

Cerebrospinal fluid (CSF) biomarkers remain the gold standard for fluid-biomarker-based diagnosis of Alzheimer's disease (AD) during life. Plasma biomarkers avoid lumbar puncture and allow repeated sampling. Changes of plasma phospho-tau-181 in AD are of comparable magnitude and seem to parallel the changes in CSF, may occur in preclinical or predementia stages of the disease, and may differentiate AD from other causes of dementia with adequate accuracy. Plasma phospho-tau-181 may offer a useful alternative to CSF phospho-tau determination, but work still has to be done concerning the optimal method of determination with the highest combination of sensitivity and specificity and cost-effect parameters.

The Prevalence of Dizziness and Vertigo in COVID-19 Patients: A Systematic Review.

Clinical manifestations of COVID-19 include symptoms of vertigo and dizziness, which is rather unsurprising, since SARS-CoV-2 neurotropism may inflict a broad spectrum of neuropathic effects. The widespread nature of central and peripheral audiovestibular pathways suggests that there may be several probable pathophysiological mechanisms. The cytokine storm, CNS infiltration of the virus through ACE 2 receptors, and other systemic factors can be responsible for the significant number of COVID-19 patients reported to experience symptoms of vertigo and dizziness. In this paper, we present a systematic review of clinical studies reporting the detection of dizziness and vertigo as clinical manifestations of COVID-19 and discuss their etiopathogenesis.

Classical Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies.

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of amyloid, others with full Alzheimer Disease CSF profile (both reduced amyloid and increased phospho-tau) and some with a normal profile. Some patients may present with abnormal levels of a-synuclein. Continuous efforts will be required to establish useful CSF biomarkers for the early diagnosis of DLB. Given the heterogeneity of methods and results between studies, further validation is fundamental before conclusions can be drawn.

Rituximab and multiple sclerosis.

B lymphocytes seem to have a fundamental role in multiple sclerosis, acting as sensors, coordinators, and regulators of the immune response. Furthermore, they are important in activating T cells and they can mediate tissue injury through diverse mechanisms. Such findings have important therapeutic implications in autoimmune central nervous system diseases in a fashion similar to other autoimmune processes. The best known monoclonal antibody targeting B cells that has been used as a novel therapy for various autoimmune conditions, as well as multiple sclerosis, is rituximab. This review summarizes the available data on the role of B cell in multiple sclerosis and further reports on current knowledge on the B-cell-depleting monoclonal antibody rituximab, its mechanism of action, and its efficacy on multiple sclerosis. Data presented were categorized in 3 groups based on the nature of data presented (radiological, clinical, and immunological data). Both case-control studies and case reports were included, while table classification was in chronological order.

TGF-ß/BMPs: crucial crossroad in neural autoimmune disorders.

Transforming growth factor beta (TGF-ß) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-ß and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-ß and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role in the pathophysiology of this disorder by using references from embryonic experimental research. Available literature in the TGF/BMP signalling cascade, mostly during embryonic development of the nervous system is being reviewed. An attempt is made to further elucidate a potential role of TGF/BMP signalling in the pathophysiology of MS. During demyelination, BMP signaling, through various molecular mechanisms, directs the development of the adult neural stem cell in the astrocyte rather than the oligodendrocyte direction, therefore inhibiting the repair process. Further understanding of the above relationships could lead to the development of potentially efficient therapies for MS in the future.

Human herpesvirus 6 infection as a trigger of multiple sclerosis.

We systematically reviewed the existing evidence to determine whether a relationship exists between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) and, if so, to define the strength of that relationship. The following terms were used in searches of the Entrez-PubMed database (1966-2009): human herpes virus 6, HHV 6, demyelination, multiple sclerosis, pathogenesis, diagnosis, serology, cerebrospinal fluid, IgG antibodies, IgM antibodies, PCR, and lymphoproliferative techniques. Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high [A], intermediate [B], and low [C]) as determined by the Moore and Wolfson criteria. Overall, 25 (41%) of 61 studies, 15 (60%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of quality II-1. Limitations of the available experimental techniques and perspectives for future research are discussed. The current review supports the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.

Gender hormones: role in the pathogenesis of central nervous system disease and demyelination.

Gender hormones are associated with the evolution of Multiple Sclerosis (MS) like changes in experimental models of MS. Several clinical studies have attempted to elucidate the role of gender hormones in the evolution of the clinical spectrum of the disease. We attempt to describe the currently known data regarding such associations emphasizing the potential clinical applications in different MS scenarios i.e. pregnancy, menstruation, use of oral contraceptives and hormonal replacement therapy. Moreover we discuss relevant effects of gender hormones on immunological parameters relating to MS pathogenesis. Beneficial neuroprotective effects were noted for elevated levels of estrogens, progesterone and elevated dosages of androgens. Some of these changes may be explained by a favorable immunological shift from a Th1 to Th2 response. Further elucidation of the clinical implications of such associations is necessary.