Long-Term Efficacy and Safety of Chronic Globus Pallidus Internus Stimulation in Different Types of Primary Dystonia

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) offers a very promising therapy for medically intractable dystonia. However, little is known about the long-term benefit and safety of this procedure. We therefore performed a retrospective long-term analysis of 18 patients (age 12-78 years) suffering from primary generalized (9), segmental (6) or focal (3) dystonia (minimum follow-up: 36 months). Methods: Outcome was assessed using the Burke-Fahn-Marsden (BFM) scores (generalized dystonia) and the Tsui score (focal/segmental dystonia). Follow-up ranged between 37 and 90 months (mean 60 months). Results: Patients with generalized dystonia showed a mean improvement in the BFM movement score of 39.4% (range 0 68.8%), 42.5% (range -16.0 to 81.3%) and 46.8% (range-2.7 to 83.1%) at the 3- and 12-month, and long-term follow-up, respectively. In focal/ segmental dystonia, the mean reduction in the Tsui score was 36.8% (range 0-100%), 65.1% (range 16.7-100%) and 59.8% (range 16.7-100%) at the 3- and 12-month, and long-term follow-up, respectively. Local infections were noted in 2 patients and hardware problems (electrode dislocation and breakage of the extension cable) in 1 patient. Conclusion: Our data showed Gpi-DBS to offer a very effective and safe therapy for different kinds of primary dystonia, with a significant long-term benefit in the majority of cases. Copyright (c) 2008 S. Karger AG, Base

Cardiac adaptations to 60 day head-down-tilt bed rest deconditioning. Findings from the AGBRESA study

Aims: Reduced physical activity increases the risk of heart failure; however, non-invasive methodologies detecting subclinical changes in myocardial function are not available. We hypothesized that myocardial, left ventricular, systolic strain measurements could capture subtle abnormalities in myocardial function secondary to physical inactivity. Methods and results: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (eight women) were submitted to 60 day strict -6° head-down-tilt bed rest. Participants were assigned to three groups of eight subjects: a control group, continuous artificial gravity training on a short-arm centrifuge (30 min/day), or intermittent centrifugation (6 × 5 min/day). We assessed cardiac morphology, function, strain, and haemodynamics by cardiac magnetic resonance imaging (MRI) and echocardiography. We observed no differences between groups and, therefore, conducted a pooled analysis. Consistent with deconditioning, resting heart rate (∆8.3 ± 6.3 b.p.m., P < 0.0001), orthostatic heart rate responses (∆22.8 ± 19.7 b.p.m., P < 0.0001), and diastolic blood pressure (∆8.8 ± 6.6 mmHg, P < 0.0001) increased, whereas cardiac output (∆-0.56 ± 0.94 L/min, P = 0.0096) decreased during bed rest. Left ventricular mass index obtained by MRI did not change. Echocardiographic left ventricular, systolic, global longitudinal strain (∆1.8 ± 1.83%, P < 0.0001) decreased, whereas left ventricular, systolic, global MRI circumferential strain increased not significantly (∆-0.68 ± 1.85%, P = 0.0843). MRI values rapidly returned to baseline during recovery. Conclusion: Prolonged head-down-tilt bed rest provokes changes in cardiac function, particularly strain measurements, that appear functional rather than mediated through cardiac remodelling. Thus, strain measurements are of limited utility in assessing influences of physical deconditioning or exercise interventions on cardiac function

Nose to back: compatibility of nasal chondrocytes with environmental conditions mimicking a degenerated intervertebral disc

Nasal chondrocytes (NCs) have gained increased recognition for cartilage tissue regeneration. To assess NCs as a source for cell therapy treatment of intervertebral disc (IVD) degeneration, tissue-forming properties of NCs under physiological conditions mimicking the degenerated IVD were compared to those of mesenchymal stromal cells (MSCs) and articular chondrocytes (ACs), two cell sources presently used in clinical trials. Cells were cultured in a combination of low glucose, hypoxia, acidity and inflammation for 28 d. Depending on the conditions, cells were either cultured in the absence of instructive growth factors or underwent chondrogenic instructional priming by addition of transforming growth factor β1 (TGFβ1) for the first 7 d. Histology, immunohistochemistry, biochemistry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses demonstrated limited cell maintenance and accumulation of cartilaginous extracellular matrix for MSCs in IVD conditions. ACs maintained a steady accumulation of glycosaminoglycans (GAGs) throughout all non-acidic conditions, with and without priming, but could not synthesise type II collagen (Col2). NCs accumulated both GAGs and Col2 in all non-acidic conditions, independent of priming, whereas MSCs strongly diminished their GAG and Col2 accumulation in an inflamed environment. Supplementation with inflammatory cytokines or an acidic environment affected NCs to a lower extent than ACs or MSCs. The data, overall indicating that in an inflamed IVD environment NCs were superior to ACs and MSCs, encourage further assessment of NCs for treatment of degenerative disc disease

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part IV: deep brain stimulation

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients

Iodine-125 brachytherapy for brain tumours - a review

Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells.

Translational research in bone tissue engineering is essential for “bench to bedside” patient benefit. However, the ideal combination of stem cells and biomaterial scaffolds for bone repair/regeneration is still unclear. The aim of this study is to investigate the osteogenic capacity of a combination of poly(DL-lactic acid) (PDLLA) porous foams containing 5 wt% and 40 wt% of Bioglass particles with human adipose-derived stem cells (ADSCs) in vitro and in vivo. Live/dead fluorescent markers, confocal microscopy and scanning electron microscopy showed that PDLLA/Bioglass porous scaffolds supported ADSC attachment, growth and osteogenic differentiation, as confirmed by enhanced alkaline phosphatase (ALP) activity. Higher Bioglass content of the PDLLA foams increased ALP activity compared with the PDLLA only group. Extracellular matrix deposition after 8 weeks in the in vitro cultures was evident by Alcian blue/Sirius red staining. In vivo bone formation was assessed by using scaffold/ADSC constructs in diffusion chambers transplanted intraperitoneally into nude mice and recovered after 8 weeks. Histological and immunohistochemical assays indicated significant new bone formation in the 40 wt% and 5 wt% Bioglass constructs compared with the PDLLA only group. Thus, the combination of a well-developed biodegradable bioactive porous PDLLA/Bioglass composite scaffold with a high-potential stem cell source (human ADSCs) could be a promising approach for bone regeneration in a clinical setting

Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue

Grafts generated by cultivation of progenitor cells from the stromal vascular fraction of human adipose tissue have been proven to have osteogenic and vasculogenic properties in vivo. However, in vitro manufacture of such implants is challenged by complex, impractical and expensive processes, and requires implantation in a separate surgery. This study investigates the feasibility of an intraoperative approach to engineer cell-based bone grafts with tissue harvest, cell isolation, cell seeding onto a scaffold and subsequent implantation within a few hours. Freshly isolated adipose tissue cells from a total of 11 donors, containing variable fractions of mesenchymal and endothelial progenitors, were embedded at different densities in a fibrin hydrogel, which was wrapped around bone substitute materials based on beta-tricalcium phosphate (ChronOS), hydroxyapatite (Engipore), or acellular xenograft (Bio-Oss). The resulting constructs, generated within 3 hours from biopsy harvest, were immediately implanted ectopically in nude mice and analysed after eight weeks. All explants contained blood vessels formed by human endothelial cells, functionally connected to the recipient's vasculature. Human origin cells were also found within osteoid structures, positively immunostained for bone sialoprotein and osteocalcin. However, even with the highest loaded cell densities, no frank bone tissue was detected, independently of the material used. These results provide a proof-of-principle that an intraoperative engineering of autologous cell-based vasculogenic bone substitutes is feasible, but highlight that - in the absence of in vitro commitment--additional cues (e.g., low dose of osteogenic factors or orthotopic environmental conditions) are likely needed to support complete osteoblastic cell differentiation and bone tissue generation