On the recovery of disorders of consciousness under intrathecal baclofen administration for severe spasticity—An observational study

Abstract Background Occasionally, patients show dramatic recovery from disorders of consciousness (DOC) under intrathecal baclofen (ITB), an established treatment option for severe supraspinal spasticity. Anecdotal explanations for ITB‐related recovery of cognition include modulation of afferent impulses at the spinal level, thereby reducing spasticity‐related proprioceptive information overload within cortico–thalamo–cortical connections. Objective In this retrospective patient chart analysis, we assessed whether a reduction in spasticity would be associated with an increase in Coma Recovery Scale revised (CRS‐R) scores in a larger sample of patients than previously published. Methods From a hospital‐based ITB treatment register, we extracted data from 26 patients with DOC and severe supraspinal spasticity who improved by >2 points on the Coma Recovery Scale revised (CRS‐R) within 6 months after ITB treatment initiation. We assessed Modified Ashworth scale (MAS) scores and CRS‐R scores on admission (PRE) and 3 and 6 months after initiation of ITB treatment (3M, 6M). We performed correlation analysis of the scores and their respective changes (PRE to 3M, 3M to 6M). We also correlated the time from acute event until ITB initiation to CRS‐R scores at 3M and 6M. Results ITB led to significant improvement in spasticity based on MAS scores, which did not correlate to the improvements seen in CRS‐R total and subscale scores. Daily ITB dose did neither correlate to MAS scores nor to CRS‐total scores in the whole patient group, but after 3 months, ITB dose correlated to some CRS‐R subscale scores in some patient subgroups. Time until ITB treatment did not correlate to CRS‐R scores later on. Conclusions Our data confirm that ITB may exert beneficial effects in selected DOC patients with respect to improved cognitive functions, which, however, do not correlate to its antispastic effect. The lack of correlation between time to ITB and CRS‐R outcome, but significant CRS‐R improvements following pump implantation, renders spontaneous remissions unlikely and leaves room for alternative pharmacological mechanisms

Therapeutic potential of adipose-derived stromal cells in age-related osteoporosis

Adipose-derived stromal cells (ASCs) are increasingly being used for orthopedic-based tissue engineering approaches due to their ability to readily undergo osteogenic differentiation. In the present study, we used in vitro and in vivo approaches to evaluate the use of ASCs as a treatment strategy for age-related osteoporosis. Molecular, histological and micro-computed tomography (micro-CT) based approaches confirmed that ASCs isolated from 18-week-old osteoporotic senescence-accelerated mice (SAMP6) were capable of undergoing osteogenesis when cultured in either silk fibroin (SF) scaffolds or scaffold-free microtissues (ASC-MT). A single intratibial injection of CM-Dil-labeled isogeneic ASCs or ASC-MT into SAMP6 recipients significantly improved trabecular bone quality after 6 weeks in comparison to untreated contralateral bones, as determined by micro-CT. Injected ASCs could be observed in paraffin wax bone sections at 24 h and 6 weeks post treatment and induced a significant increase in several molecular markers of bone turnover. Furthermore, a significant improvement in the osteogenic potential of osteoporotic patient-derived human bone marrow stromal cells (BMSCs) was observed when differentiated in conditioned culture media harvested from osteoporotic patient-derived human ASCs. These findings therefore support the use of ASCs as an autologous cell-based approach for the treatment of osteoporosi