Neurological symptoms might be associated with a Covid-19 infection. There are frequent reports in the last weeks. The neurological symptoms range from harmless side effects of a viral infection to meningoencephalitis and acute haemorrhagic necrotizing encephalopathy. Our patient reported burning headache and paresthesia as the initial symptoms mainly without other signs of viral infection like cough or fever. Such an initial neurological presentation seems to be rare. Most cases have neurological symptoms which can be expected after severe systemic viral infections like fever associated headache. Many COVID-19 patients with mild disease are at home and the further course is unknown. Our case shows, that neurological symptoms can be the first manifestation of an COVID-19 disease. While restricted paraesthesia has been reported in SARS-CoV-2 infections, hemisymptoms have not been described as initial symptoms.

Osteopontin (OPN) is a secreted phosphoprotein shown to function in wound healing, inflammation, and tumor progression. Expression of OPN is often co-localized with members of the matrix metalloproteinase (MMP) family. We report that OPN is a novel substrate for two MMPs, MMP-3 (stromelysin-1) and MMP-7 (matrilysin). Three cleavage sites were identified for MMP-3 in human OPN, and two of those sites were also cleaved by MMP-7. These include hydrolysis of the human Gly Osteopontin (OPN)1 is an arginine-glycine-aspartic acid (RGD)-containing glycoprotein that interacts with integrins and CD44 as major receptors. OPN has been shown to be multifunctional, with activities in cell migration, cell survival, inhibition of calcification, regulation of immune cell function, and control of tumor cell phenotype (1-4). Targeting of the gene encoding OPN, spp1, has revealed that while OPN is not necessary for normal embryonic development, fertility, and health under pathogen-free conditions (5, 6), loss of the protein has significant consequences in several models of injury/disease as diverse as renal injury, viral and bacterial infection, bone remodeling, and tumor growth (7-12). The fact that no other proteins seem to share a redundant activity with OPN under these conditions suggests that OPN has a unique functional role during tissue injury and stress. Interestingly, several members of the matrix metalloproteinase (MMP) family are also induced during injury/disease processes in patterns overlapping that of OPN (13). In particular, we have found that during squamous cell carcinoma progression, OPN and MMP-3 expression correspond both in a temporal and cell-specific fashion (9, 14). We have also identified overlapping expression patterns of OPN and MMP-3 in the stroma during skin incisional wound healing (5) and OPN and MMP-7 during involution of the postpartum uterus (15).OPN is known to be a substrate for proteolytic cleavage by the proteases thrombin (16, 17) and enterokinase (18). Thrombin cleavage of OPN (Arg 168 -Ser 169 in humans, Arg 153 -Ser 154 in rats) is of interest, since hydrolysis of this peptide bond reveals a binding site for the integrins ␣ 9 ␤ 1 (19) and ␣ 4 ␤ 1 (20), SV-VYGLR, not present in the full-length molecule (16). In addition, functional properties of thrombin-cleaved OPN differ from the intact protein (21-24), demonstrating that proteolytic cleavage is one mechanism of regulating the bioactivity of OPN.In the present study, we have identified and characterized novel cleavage sites in OPN for two members of the MMP family, MMP-3 and MMP-7. Furthermore, we show that lower molecular weight forms of OPN corresponding to predicted MMP cleavage fragments are present in cell lines in vitro and in tissues in vivo. Biological assays demonstrate that the MMPcleaved OPN has increased activity in promoting both cell adhesion and migration compared with full-length OPN. In addition, using inhibitory reagents, we have determined that the same receptors that interact with OPN also mediate interaction of MMP-c...

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Intervertebral disc herniation is a major cause of low back pain and sciatica. Spontaneous resorption of herniated disc (HD) is frequently detected by magnetic resonance imaging (MRI). Marked infiltration by macrophages and neo-vascuIarizatiol1~tioii are observed upon histogical exainiiiatioii of HD.

The incidence of meniscal tear associated with ACL injury is higher in chronic cases; the number of medial meniscal tears is particularly high, many of which require meniscectomy. Early ACL reconstruction is recommended also for the prevention of secondary meniscal tear.

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Intervertebral disc herniation (HD) is one of the most common orthopaedic conditions. MRI analysis of H D has revealed a spontaneous resorption mechanism related with neo-vascularization. It appears that the interaction of activated macrophages with disc tissues leads to the generation of inflammatory cytokines. Moreover, inflammatory cytokines such as tumor necrosis factor-a (TNF-a) is required for the induction of angiogenesis inducing factors such as vascular endothelial growth factor (VEGF) or matrix degrading enzymes such as MMP-3, MMP-7 and plasmin. We hypothesized that these molecules play a crucial role during spontaneous H D resorption. In this study, we have examined the sequential expression of these molecules using a co-culture system which is composed of the interaction of activated macrophages and disc tissues as a model of the acute response of inflammation occurred in HD. We have also considered the mechanism of activating latent MMPs during H D resorption process. Current our results indicate that upregulation of both TNF-cl mRNA and protein expressions occur first in the inflammation induced by HD. VEGF upregulation follows the increased level of TNF-a expression. Both plasmin and MMP-3 are upregulated at later time points. We also demonstrate that both TNF-a and VEGF induce upregulated expression of urokinase-type plasminogen activator (u-PA). Our previous work has demonstrated that TNF-(r could upregulate the expression of VEGF, MMP-3 and MMP-7 in the co-culture system. It has been reported that plasmin could affect to activate latent MMPs. Based on these findings, we suggest that TNF-a acts as the initiator of inflammation following contact between macrophages and disc chondrocytes and that plasmin and u-PA play a crucial role in activation of MMPs. We propose a spontaneous H D resorption cascade. Further understanding of the resorption process may provide future novel therapies for HD.