Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome. Methods: Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary. Results: The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r_s = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability. Conclusions: sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.

Macular ganglion cell–inner plexiform layer (mGCIPL) is an emerging biomarker of neuroaxonal degeneration in multiple sclerosis (MS). We aimed to determine cut-off values of mGCIPL thinning for discriminating between progressing and stable patients in relapsing multiple sclerosis (RMS). This is a 3-year prospective longitudinal study on 183 RMS patients with annual optical coherence tomography. Best possible cut-off values of baseline mGCIPL and annual loss of macular ganglion cell–inner plexiform layer (aLmGCIPL) for discriminating clinically progressing (physical progression or cognitive decline) from stable patients were defined by receiver operating characteristics analysis and tested using multivariate regression models. Baseline mGCIPL thickness <77 µm was associated with an increased risk (hazard ratio: 2.7, 95% confidence interval (CI): 1.5–4.7, p < 0.001) of disability progression. An aLmGCIPL cut-off ⩾1 µm accurately identified clinically progressing patients (87% sensitivity at 90% specificity) and was a strong predictor of clinical progression (odds ratio: 18.3, 95% CI: 8.8–50.3). We present evidence that cross-sectionally measured mGCIPL thickness and annualized thinning rates of mGCIPL are able to identify clinically progressing RMS with high accuracy.

Background: The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS). Objective: To investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria. Methods: From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral-domain OCT scan obtained within 180 days. Modified DIS criteria (DIS+OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT inter-eye differences. Time to second clinical attack was the primary endpoint. Results: We analyzed 267 MS patients (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13 - 98). Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS+OCT 81.2% vs. DIS 65.6%,) and sensitivity (DIS+OCT 84.2% vs. DIS 77.9%) without lowering specificity (DIS+OCT 52.2% vs. DIS 52.2%). Fulfilling DIS+OCT criteria (≥2 of 5 DIS+OCT regions involved) indicated a similar risk of a second clinical attack (HR 3.6, CI 1.4 – 14.5) compared to a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2 – 11.8). When the analysis was conducted according to topography of the first demyelinating event, DIS+OCT criteria performed similarly in both optic neuritis and non–optic neuritis. Conclusions: Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity. Classification of Evidence: This study provides Class II evidence that adding the optic nerve as determined by optical coherence tomography (OCT) as a fifth dissemination in space (DIS) criterion to the 2017 McDonald criteria improves diagnostic accuracy.

After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68(+) cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats.

Background and purpose: There is a lack of evidence guiding discontinuation of disease‐modifying therapy (DMT) in relapsing multiple sclerosis (RMS). Thus, the objective of this study was to generate and validate a risk score for disease reactivation after DMT discontinuation in RMS.Methods: We drew a generation and validation dataset from two separate prospectively collected observational databases including RMS patients who received interferon‐β or glatiramer acetate for ≥12 months, then discontinued DMT for ≥6 months and had ≥2 years of follow‐up available. In the generation sample (n = 168), regression analysis was performed to identify clinical or magnetic resonance imaging (MRI) variables independently predicting disease reactivation after DMT discontinuation. A predictive score was calculated using the variables included in the multivariable model and applied to the validation sample (n = 98).Results: The variables included in the final model as independent predictors of disease reactivation were age at discontinuation, MRI activity at discontinuation, and duration of clinical stability (all p < 0.001). The resulting score was able to robustly identify patients at high (83%–85%), moderate (36%–38%), and low risk (7%) of disease reactivation within 5 years after DMT discontinuation in both cohorts.Conclusions: The composite VIAADISC score is a valuable tool to inform and support patients and neurologists in the process of decision making to discontinue injectable DMTs.

To examine and validate thresholds for inter-eye differences in peripapillary retinal nerve fibre (pRNFL) and ganglion cell + inner plexiform layer (GCIPL) thicknesses for identifying unilateral optic neuritis in MS. In this two-centre, cross-sectional study, optical coherence tomography was performed in 340 patients with clinically isolated syndrome (CIS) and MS. Cut-off values of inter-eye difference for identification of eyes with a history of unilateral ON were evaluated by receiver-operating characteristics analysis. For pRNFL ≥5 µm, sensitivity was 69% and specificity 68%, while for GCIPL ≥4 µm sensitivity was 67% and specificity 78%. The areas under the curve (AUC) were 0.72 (95% confidence interval: 0.64 - 0.79) for pRNFL and 0.78 (95%CI: 0.72 - 0.85) for GCIPL, indicating GCIPL as the superior model (p<0.001). When analysing only CIS patients, GCIPL inter-eye difference ≥4 µm also remained significant, while pRNFL inter-eye difference did not. Inter-eye differences of ≥4 μm for GCIPL and to a lesser degree ≥5 μm for RNFL are robust thresholds for identifying unilateral optic nerve lesions. These thresholds could be used to demonstrate previous symptomatic and possibly asymptomatic ON and might be included into a new version of the diagnostic criteria.