Minimal Neurological Disability Research Articles

Deciphering the shift from benign to active relapsing-remitting multiple sclerosis: Insights into T regulatory cell dysfunction and apoptosis regulation

BackgroundRelapsing-remitting multiple sclerosis (RRMS), a common demyelinating disease among young adults, follows a benign course in 10–15% of cases, where patients experience minimal neurological disability for a decade following disease onset. However, there is potential for these benign cases to transition into a clinically active, relapsing state. ObjectiveTo elucidate the biological mechanisms underlying the transition from benign to active RRMS using gene expression analysis. MethodsWe employed complementary-DNA microarrays to examine peripheral-blood gene expression patterns in patients with benign MS, defined as having a disease duration exceeding 10 years and an Expanded Disability Status Scale (EDSS) score of ≤3.0. We compared the gene expression pattern between patients who switched to active disease (Switching BMS) with those who maintained a benign state (Permanent-BMS) during an additional 5-year follow-up. ResultsWe identified two primary mechanisms linked to the transition from benign MS to clinically active disease. The first involves the suppression of regulatory T cell activity, and the second pertains to the dysfunction of nuclear receptor 4 A family-dependent apoptosis. These mechanisms collectively contribute to an augmented autoimmune response and increased disease activity. ConclusionsThe intricate gene regulatory networks that operate in switching-BMS are related to suppression of immune tolerance and aberrant apoptosis. These findings may lead to new therapeutic targets to prevent the escalation to active disease.

Disease associations of excessive daytime sleepiness in multiple sclerosis: A prospective study.

Excessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood. We prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders. A total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction. There is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted.

Exercise-induced changes in gait kinematics in multiple sclerosis with minimal neurological disability

BackgroundExercise-induced gait deterioration is a frequently encountered symptom that limits ambulation throughout the clinical course, becoming more prominent with increasing neurological disability in people with MS (pwMS). ObjectiveWe attempted to objectively document exercise-induced gait changes in pwMS with minimal neurological disability and stable disease. MethodsGait kinematics and spatio-temporal parameters were recorded using 3D motion analysis before and after a 20-minute treadmill walk (Group A, n=15)/run (Group B, n=15) at a self-selected speed in pwMS and compared with healthy controls (n=15). ResultsGait analysis revealed a significant decrease in peak ankle dorsiflexion in swing of the most affected leg, post-exercise task, in both Group A (EDSS 2.5-3.5) and Group B (EDSS 1-2.5) and not in healthy controls. Fourteen out of 30 MS participants showed an exercise-induced gait deterioration, based on minimal detectable change. Pre-exercise gait parameters in Group A showed a significantly higher peak dorsiflexion in swing with shorter step length and higher cadence, whereas Group B was comparable to healthy controls. ConclusionThe detection of exercise-induced gait deterioration (foot drop) in pwMS with minimal neurological disability and stable disease indicates the potential of gait kinematics, before and after an exercise task, to monitor subtle neurological deficits from an early stage of MS.

18F-FDG uptakes in leptomeningeal metastases from carcinoma of the breast on a positron emission tomography/computerized tomography study

Leptomeningeal metastases (LM) are most commonly observed in hematological malignancies. With prolonged survival in solid tumors, an increased frequency of metastases is noted in these tumors too. Early diagnosis, when the patient has minimal neurological disability, is associated with prolonged survival and improved functional outcome although the therapy is palliative. The diagnosis of LM is difficult, and the demonstration of tumor cells in the cerebrospinal fluid remains the gold standard. This can also be done by definitive neuroimaging. MRI is routinely used in this aspect. We discuss here a case where 18F-FDG PET/CT (Fluoro-de-oxy glucose positron emission tomography/computerized tomography) study helped us in the diagnosis of LM. Whole-body PET/CT imaging could be a useful tool in identifying the possibility of metastases of breast carcinoma in the usual sites and the not-so-usual sites of metastases.