There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.

Introduction: Higher cortical activity has been observed in people with multiple sclerosis (pwMS) during walking and dual-tasking. However, further studies in overground walking and considering pre-frontal cortex (PFC) sub-areas are necessary. Objectives: To investigate PFC activity during a cognitive-motor dual-task (DT) and its single component tasks, in combination with behavioral outcomes in pwMS. Methods: Fifteen pwMS (EDSS 3.5 [2-5.5], 42 ± 11 years) and 16 healthy controls (HC, 45.2 ± 13.2 years) performed 3 conditions: single motor-walking (SWT), single cognitive – subtracting sevens (SCT), and a DT. Meters walked and the number of correct answers were obtained from which, respectively, the motor (mDTC) and cognitive (cDTC) DT costs were calculated. A functional Near-Infrared Spectroscopy covering the frontopolar and dorsolateral PFC (DLPFC) areas was used to concentration of relative oxyhemoglobin (ΔHbO2) and deoxyhemoglobin (ΔHHb) in the PFC. A repeated 2-way ANOVA (group × conditions) was used to compare ΔHbO2/ΔHHb and behavioral outcomes. Results: PwMS walked shorter distances ( P < .002) and answered fewer correct numbers ( P < .03) than HC in all conditions, while cDTC and mDTC were similar between groups. PwMS presented higher ΔHbO2 in the frontopolar area than HC in the SWT ( P < .001). HC increased ΔHbO2 in frontopolar during the SCT ( P < .029) and DT ( P < .037) compared with the SWT. Conclusion: Higher frontopolar activity in pwMS compared to HC in the SWT suggests reduced gait automaticity. Furthermore, it seems that only HC increased neural activity in the frontopolar in the SCT and DT, which might suggest a limit of cognitive resources to respond to DT in pwMS.

Background: Gait characteristics and their changes during the 6-minute walking test (6MWT) in people with multiple sclerosis (pwMS) have been described in the literature, which one may refer to as walking fatigability in the body function level of the International Classification of Functioning, Disability, and Health. However, whether these metrics are reliable is unknown. Objective: To investigate the between-day reliability of the gait characteristics and their changes in pwMS and healthy controls (HCs). Methods: Forty-nine pwMS (EDSS 4.82 ± 1.22 and 54.7 ± 9.36 years) and 23 HCs (50.6 ± 6.1 years) performed the 6MWT, as fast as possible but safely while wearing Inertial Measurement Units. Gait characteristics were measured in the pace, rhythm, variability, asymmetry, kinematics, coordination, and postural control domains and were obtained in intervals of 1 minute during the 6MWT. In addition, gait characteristics change in the last minute compared with the first minute were calculated for all gait variables using a fatigability index (ie, distance walking index). The intraclass correlation coefficient (ICC), Bland–Altman Plots, and Standard error of measurement were applied to investigate reliability. Results: Reliability of gait characteristics, minute-by-minute, and for their changes (ie, using the fatigability index) ranged from poor to excellent (pwMS: ICC 0.46-0.96; HC: ICC 0.09-0.97 and pwMS: ICC 0-0.72; HC: ICC 0-0.77, respectively). Conclusion: Besides coordination, at least 1 variable of each gait domain showed an ICC of moderate or good reliability for gait characteristics changes in both pwMS and HC. These metrics can be incorporated into future clinical trials and research on walking fatigability. Clinical Trial Registration: NCT05412043.