SummaryWe have reported previously that naive T cells from relapsing-remitting multiple sclerosis (RRMS) patients have T cell receptor (TCR) repertoire shifts, but the basis of these TCR repertoire shifts was uncertain. Here, we questioned whether RRMS patients have altered naive CD4 and CD8 T cell homeostasis by studying homeostatic proliferation and thymic production in RRMS patients and healthy controls. We measured thymic production by quantifying signal joint T cell receptor excision circles (sjTRECs). Both naive T subsets from controls showed an age-associated decrease in sjTRECs, i.e. evidence of progressive thymic involution, but we detected no age-associated decrease in sjTRECs in RRMS patients. Instead, naive CD8 T cells from patients had lower sjTRECs ( P = = = = 0·012) and higher Ki-67 proliferation levels ( P = = = = 0·04) than controls. Naive CD4 T cell sjTRECs did not differ between patients and controls. However, in RRMS these sjTRECs correlated strongly with CD31, a marker expressed by newly generated CD4 T cells but not by naive CD4 T cells that have undergone homeostatic proliferation. HLA-DR2 positivity correlated negatively with naive CD4 T cell CD31 expression in RRMS ( P = = = = 0·002). We conclude in RRMS that naive T subsets have homeostatic abnormalities due probably to peripheral (non-thymic) mechanisms. These abnormalities could have relevance for MS pathogenesis, as naive T cell changes may precede MS onset.

Background: Neurogenic lower urinary tract dysfunction (NULTD) is common in patients with multiple sclerosis (MS); nevertheless, it is often underestimated, underdiagnosed, and undertreated due to patients' sense of shame, variability of symptoms, as well as lack of communication between neurologists and urologists, despite the availability of several guidelines based on scientific evidence and expert opinion. Objective: This study was conducted to develop an easy-to-perform algorithm for diagnosing neurogenic lower urinary tract disease in patients with MS for daily neurological and urological routine, including the identification of red flags. Methods: In consensus group meetings, interprofessional experts (neurologists, urologists, neurourologists, nurses, nurse practitioners, occupational therapists, physical therapists as well as representatives of national MS centers, self-care groups, social care, residential care, and health-aid-providers) developed a diagnostic algorithm to detect NULTD in patients with MS. Subsequently, the group evaluated the algorithm in 121 patients with MS using micturition diary, post-void residual volume, uroflowmetry, and urodynamic studies. Statistical analysis was conducted on the basis of logistic regression models to compare patients with normal and abnormal urodynamic examinations. Differentiation was performed using selected diagnostic parameters as well as standard performance measures for binary classifiers to assess prognostic quality. Results: The following four parameters allowed to diagnose NLUTD in patients with MS: post-void residual urine volume, rate of urinary tract infections during the past 6 months, micturition frequency, and incontinence. According to statistical analysis, the following thresholds could be defined: post-void residual volume (PVR) ≥70 mL (Odds Ratio (OR) = 1.24; 95% CI:[1.07,1.62]), urinary tract infection (UTI) rate -none in 6 months (OR = 2.03; 95% CI:[1.04,6.68]), and micturition frequency >13/day, standardized on 2000 mL urine

Background: Multiple sclerosis patients often develop neurogenic lower urinary tract dysfunction with a potential risk of upper urinary tract damage. Diagnostic tools are urodynamics, bladder diary, uroflowmetry, and post-void residual, but recommendations for their use are controversial. Objective: We aimed to identify clinical parameters indicative of neurogenic lower urinary tract dysfunction in multiple sclerosis patients. Methods: 207 patients were prospectively assessed independent of the presence of lower urinary tract symptoms. We analyzed Expanded Disability Status Scale scores, uroflowmetry, post-void residual, rate of urinary tract infections, standardized voiding frequency, and voided volume in correlation with urodynamic findings. Results: We found a significant correlation between post-void residual (odds ratio (OR) 4.17, confidence interval (CI) 1.20–22.46), urinary tract infection rate (OR 3.91, CI 1.13–21.0), voided volume (OR 4.53, CI 1.85–11.99), increased standardized voiding frequency (OR 7.40, CI 2.15–39.66), and urodynamic findings indicative of neurogenic lower urinary tract dysfunction. Expanded Disability Status Scale shows no correlation. Those parameters (except post-void residual) are also associated with reduced bladder compliance, as potential risk for kidney damage. Conclusion: Therefore, bladder diary and urinary tract infection rate should be routinely assessed to identify patients who require urodynamics.