Quantitative physical performance tests can effectively detect Degenerative Cervical Myelopathy: A systematic review and meta-analysis.

PURPOSE: This review aimed to identify effective physical performance tests (PPT) as clinical outcome indicators for detecting and monitoring degenerative cervical myelopathy (DCM). METHODS: A comprehensive literature search was performed on seven electronic databases on the effectiveness in detection and monitoring of DCM by PPT. All included studies were reviewed and undergone quality assessments on the risk-of-bias by Newcastle-Ottawa Scale and were pooled by random-effect analysis with level of significance at 0.05. Homogeneity among studies was assessed by I2-statistics and effect of PPT was confirmed by Cohen's d effect size and confidence intervals. RESULTS: Totally, 3111 articles were retrieved, and 19 studies were included for review and meta-analysis. There were 13 studies investigating PPT regarding the upper limbs and 12 studies regarding the lower limbs. Performance in 10-second-Grip-and-Release Test (G&R) and 9-Hole-Peg Test (9HPT) was studied in 10 and 3 articles, respectively, while 10-second-Stepping Test (SST), 30-meter-Walking Test (30MWT) and Foot-Tapping Test (FTT) for lower limbs were studied in 5, 4, and 3 articles correspondingly. Only 1 study utilized the Triangle-Stepping Test. High-quality study with fair risk-of-bias was revealed from Newcastle-Ottawa scale. Large effect size facilitated detection and monitoring in DCM was unveiling for G&R, 9HPT, SST, and 30MWT. FTT, while also effective, was hindered by a high-degree heterogeneity in the meta-analysis. CONCLUSION: Effective PPT including G&R, 9HPT, SST, 30MWT, and FTT was identified for disease detection and monitoring in DCM.

Oral Zoledronic acid bisphosphonate for the treatment of chronic low back pain with associated Modic changes: A pilot randomized controlled trial.

To assess the safety and efficacy of oral 50 mg Zoledronic acid (ZA) bisphosphate once-a-week for 6-weeks to placebo among patients with chronic low back pain (cLBP) and Modic changes (MC) on MRI. A parallel, double-blinded randomized controlled study was performed at a single center, consisted of 25 subjects with cLBP and MC that received ZA (n = 13) or placebo (n = 12). Evaluation was at baseline, 2-weeks, 4-weeks, 3-months and 6-months for assessment of LBP/leg pain intensity, disability (Oswestry-Disability-Index: ODI), health-related quality-of-life (RAND-36), and mental component summary scores (MCS). Type 2 MC at baseline (56%) were prevalent. In the ZA group, LBP intensity was lower at 4-weeks in comparison to placebo (5.1 ± 1.9 vs. 6.9 ± 1.8, p = 0.038) (minimal clinically important difference [MCID] = 1.5). LBP intensity reduced at 4-weeks and 3-months in the ZA-treated group in comparison to baseline. Although there was no difference in ODI, subscale RAND-36 metrics for physical function (p = 0.038), energy/fatigue (p = 0.040) and pain (p = 0.003) were improved at 3-months compared to placebo, with moderate significant difference for pain at 6-months (p = 0.051). Correlated MCS scores to baseline also improved at 3-months (p = 0.035) and 6-months (p = 0.028) by 6.9 and 6.8, respectively, (MCID = 3.8). A reduction in MC endplate affected area at 6-month follow-up was noted in the ZA group (-0.67 ± 0.69 cm2 ), while in the placebo group no change in size was observed (0.0 ± 0.15; p = 0.041). Three subjects withdrew from the study and no long-lasting adverse events. Oral ZA was a safe and effective treatment that reduced MC volume, improved LBP symptoms and quality-of-life measures in cLBP subjects with MCs.

Derivation of Fate-Committed Schwann Cells from Bone Marrow Stromal Cells of Adult Rats.

Our goal is to derive phenotypically stable Schwann cells from bone marrow stromal cells (BMSCs) for use in transplantation studies of central/peripheral nerve injuries. With the adult rat as model, here we describe steps that foster (1) expansion of the BMSC subpopulation of neural progenitors as neurosphere cells, (2) differentiation of the progenitors into Schwann cell-like cells in adherent culture supplemented with soluble factors, and (3) cell-intrinsic switch of Schwann cell-like cells to the Schwann cell fate following co-culture with sensory neurons purified from dorsal root ganglia. The derived Schwann cells retain marker expression despite withdrawal of supplements and neuronal cues, survive passaging and cryopreservation, and, importantly, show functional capacity for myelination.

Bone marrow-derived Schwann cells achieve fate commitment--a prerequisite for remyelination therapy.

Schwann cell transplantation improves post-traumatic nerve regeneration in both PNS and CNS but sufficient numbers of immunocompatible cells are required for clinical application. Currently, Schwann cell-like cells derived from the bone marrow lack fate commitment and revert to a fibroblast-like phenotype upon withdrawal of differentiation-inducing factors. In recapitulation of embryonic events leading to Schwann cell maturation, we hypothesize that the Schwann cell-like cells acquire the switch to fate commitment through contact-dependent cues from incipient neurons of the developing dorsal root ganglia. To address this, Schwann cell-like cells derived from adult rat bone marrow were cocultured with neurons purified from embryonic dorsal root ganglia. A cell-intrinsic switch to the Schwann cell fate was achieved consistently and the cell progeny maintained expression of the markers S100 beta, p75(NTR) , GFAP, P0 and Sox 10 even without exogenous differentiation-inducing factors or neurons. In vitro formation of MBP-positive segments under myelinating conditions by the cell progeny was comparable to that by sciatic nerve-derived Schwann cells. Controls in which Schwann cell-like cells were barred from direct contact with neurons in coculture reverted to SMA/CD90-expressing myofibroblasts. We demonstrate therefore for the first time fate commitment among bone marrow-derived Schwann cells. The therapeutic potential of these cells may be tested in future transplantation studies. (206 words).