The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral immunoreaction in the form of oligoclonal bands (OCB) is crucial in the diagnostic workup. To date, the impact of the 2010 McDonald criteria on the prevalence of OCB has not been investigated. We retrospectively evaluated data of 325 patients with a clinical relapse suggestive of demyelination that were treated in a German university hospital between 2010 and 2015. One hundred thirty-six patients (42%) were diagnosed with MS and 189 patients with CIS when the criteria of 2010 were applied. The criteria of 2005 allowed only 70 patients (22%) to be designated as MS. In contrast, the prevalence of OCB was marginal affected in MS patients with 96% for the criteria of 2010 and 98.5% for the criteria of 2005. In conclusion, OCB are prevalent in most MS patients and reflect the chronic inflammatory nature of the disease. We recommend CSF examination to exclude alternative diagnoses and reevaluation of the diagnosis MS in patients with negative OCB.

While the revised McDonald criteria of 2010 allow for the diagnosis of multiple sclerosis (MS) in an earlier stage, there is still a need to identify the risk factors for conversion to MS in patients with clinically isolated syndrome (CIS). Since the latest McDonald criteria were established, the prognostic role of cerebrospinal fluid (CSF) and visual evoked potentials (VEP) in CIS patients is still poorly defined. We conducted a monocentric investigation including patients with CIS in the time from 2010 to 2015. Follow-ups of 120 patients revealed that 42% converted to MS. CIS patients with positive oligoclonal bands (OCB) were more than twice as likely to convert to MS as OCB negative patients (hazard ratio = 2.6). The probability to develop MS was even higher when a quantitative intrathecal IgG synthesis was detected (hazard ratio = 3.8). In patients with OCB, VEP did not add further information concerning the conversion rate to MS. In patients with optic neuritis and negative OCB, a significantly higher rate converted to MS when VEP were delayed. In conclusion, the detection of an intrathecal IgG synthesis increases the conversion probability to MS. Pathological VEP can help to predict the conversion rate to MS in patients with optic neuritis without an intrathecal IgG synthesis.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron (MN) disease characterized by progressive MN loss and muscular atrophy resulting in rapidly progressive paralysis and respiratory failure. Human mesenchymal stem/stromal cell (hMSC)-based therapy has been suggested to prolong MN survival via secretion of growth factors and modulation of cytokines/chemokines. We investigated the effects of hMSCs and a hMSC-conditioned medium (CM) on Cu/Zn superoxidase dismutase 1^G93A (SOD1^G93A) transgenic primary MNs. We found that co-culture of hMSCs and MNs resulted in slightly higher MN numbers, but did not protect against staurosporine (STS)-induced toxicity, implying marginal direct trophic effects of hMSCs. Aiming to elucidate the crosstalk between hMSCs and MNs in vitro, we found high levels of vascular endothelial growth factor (VEGF) and C-X3-C motif chemokine 1 (CX3CL1) in the hMSC secretome. Co-culture of hMSCs and MNs resulted in altered gene expression of growth factors and cytokines/chemokines in both MNs and hMSCs. hMSCs showed upregulation of CX3CL1 and its receptor CX3CR1 and downregulation of interleukin-1 β (IL1β) and interleukin-8 (IL8) when co-cultured with SOD1^G93A MNs. MNs, on the other hand, showed upregulation of growth factors as well as CX3CR1 upon hMSC co-culture. Our results indicate that hMSCs only provide moderate trophic support to MNs by growth factor gene regulation and may mediate anti-inflammatory responses through the CX3CL1/CX3CR1 axis, but also increase expression of pro-inflammatory cytokines, which limits their therapeutic potential.