Evaluation of the Safety and Efficacy of the Therapeutic Potential of Adipose-Derived Stem Cells Injected in the Cerebral Ischemic Penumbra.

INTRODUCTION: Stroke represents an attractive target for cell therapy. Although different types of cells have been employed in animal models with variable results, the human adipose-derived stem cells (hASCs) have demonstrated favorable characteristics in the treatment of diseases with inflammatory substrate, but experience in their intracerebral administration is lacking. The purpose of this study is to evaluate the effect and safety of the intracerebral application of hASCs in a stroke model. METHODS: A first group of Athymic Nude mice after stroke received a stereotactic injection of hASCs at a concentration of 4 × 104/µL at the penumbra area, a second group without stroke received the same cell concentration, and a third group had only stroke and no cells. After 7, 15, and 30 days, the animals underwent fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging; subsequently, they were sacrificed for histological evaluation (HuNu, GFAP, IBA-1, Ki67, DCX) of the penumbra area and ipsilateral subventricular zone (iSVZ). RESULTS: The in vitro studies found no alterations in the molecular karyotype, clonogenic capacity, and expression of 62 kDa transcription factor and telomerase. Animals implanted with cells showed no adverse events. The implanted cells showed no evidence of proliferation or differentiation. However, there was an increase of capillaries, less astrocytes and microglia, and increased bromodeoxyuridine and doublecortin-positive cells in the iSVZ and in the vicinity of ischemic injury. CONCLUSIONS: These results suggest that hASCs in the implanted dose modulate inflammation, promote endogenous neurogenesis, and do not proliferate or migrate in the brain. These data confirm the safety of cell therapy with hASCs.

Foot drop after percutaneous treatment with radiopaque gelified ethanol (Discogel®).

Sciatica due to a lumbar disc herniation is a frequent symptom, between 13% and 40% of the general population will experience an episode of sciatica during their lives. Different techniques exist to treat this condition. Among them the percutaneous intradiscal Discogel®. In all the series of patients reviewed treated with Discogel®, so far, there is not any case reported with disc extrusion and significant neurological damage. We present a case of a foot drop, caused by a disc herniation after percutaneous treatment with Discogel®. We hypothesize that the pathogenic mechanism would be the increased intradiscal volume and pressure post-puncture and annulus fibrosus damage, which could produce the disc extrusion. The extrusion of Discogel® material is possible. To the best of our knowledge, this is the first reported case of this complication with this product.

Are We Ready for Cell Therapy to Treat Stroke?

Clinical trials of cell therapies that target stroke started at the beginning of this century and they have experienced a significant boost in recent years as a result of promising data from basic research studies. The increase in the information available has paved the way to carry out more innovative and varied human studies. Efforts have focused on the search for a safe and effective treatment to stimulate neuro-regeneration in the brain and to reduce the sequelae of stroke in patients. Therefore, this review aims to evaluate the clinical trials using cell therapy to treat stroke published to date and assess their limitations. From 2000 to date, most of the published clinical trials have focused on phases I or II, and the vast majority of them demonstrate that stem cells are essentially safe to use when administered by different routes, with transient and mild adverse events that do not generally have severe consequences for health. In general, there is considerable variation in the trials in terms of statistical design, sample size, the cells used, the routes of administration, and the functional assessments (both at baseline and follow-up), making it difficult to compare the studies. From this general description, possibly the experimental protocol is the main element to improve in future studies. Establishing an adequate experimental and statistical design will be essential to obtain favorable and reliable results when conducting phase III clinical trials. Thus, it is necessary to standardize the criteria used in these clinical trials in order to aid comparison. Shortly, cell therapy will be a key approach in the treatment of stroke if adequate and comprehensive levels of recovery are to be achieved.

Decompressive craniectomy in traumatic brain injury: The intensivist's point of view.

OBJETIVE: To perform a score with early clinical and radiological findings after a TBI that identifies the patients who in their subsequent evolution are going to undergo DC. METHOD: Observational study of a retrospective cohort of patients who, after a TBI, enter the Neurocritical Section of the Intensive Care Unit of our hospital for a period of 5 years (2014-2018). Detection of clinical and radiological criteria and generation of all possible models with significant, clinically relevant and easy to detect early variables. Selection of the one with the lowest Bayesian Information Criterion and Akaike Information Criterion values for the creation of the score. Calibration and internal validation of the score using the Hosmer-Lemeshow and a bootstrapping analysis with 1000 re-samples respectively. RESULTS: 37 DC were performed in 153 patients who were admitted after a TBI. The resulting final model included Cerebral Midline Deviation, GCS and Ventricular Collapse with an Area under ROC Curve: 0.84 (95% IC 0.78-0.91) and Hosmer-Lemeshow p=0.71. The developed score detected well those patients who were going to need an early DC (first 24h) after a TBI (2.5±0.5) but not those who would need it in a later stage of their disease (1.7±0.8). However, it seems to advice us about the patients who, although not requiring an early DC are likely to need it later in their evolution (DC after 24h vs. do not require DC, 1.7±0.8 vs. 1±0.7; p=0.002). CONCLUSION: We have developed a prognostic score using early clinical-radiological criteria that, in our environment, detects with good sensitivity and specificity those patients who, after a TBI, will require a DC.

Decompressive craniectomy in traumatic brain injury: the intensivist's point of view. / Craniectomías descompresivas en el traumatismo craneoencefálico: la visión del intensivista.

OBJETIVE: To perform a score with early clinical and radiological findings after a TBI that identifies the patients who in their subsequent evolution are going to undergo DC. METHOD: Observational study of a retrospective cohort of patients who, after a TBI, enter the Neurocritical Section of the Intensive Care Unit of our hospital for a period of 5 years (2014-2018). Detection of clinical and radiological criteria and generation of all possible models with significant, clinically relevant and easy to detect early variables. Selection of the one with the lowest Bayesian Information Criterion and Akaike Information Criterion values for the creation of the score. Calibration and internal validation of the score using the Hosmer-Lemeshow and a bootstrapping analysis with 1,000 re-samples respectively. RESULTS: 37 DC were performed in 153 patients who were admitted after a TBI. The resulting final model included Cerebral Midline Deviation, GCS and Ventricular Collapse with an Area under ROC Curve: 0.84 (95% IC 0.78-0.91) and Hosmer-Lemeshow p=0.71. The developed score detected well those patients who were going to need an early DC (first 24hours) after a TBI (2.5±0.5) but not those who would need it in a later stage of their disease (1.7±0.8). However, it seems to advice us about the patients who, although not requiring an early DC are likely to need it later in their evolution (DC after 24hours vs do not require DC, 1.7±0.8 vs 1±0.7; p=0.002). CONCLUSION: We have developed a prognostic score using early clinical-radiological criteria that, in our environment, detects with good sensitivity and specificity those patients who, after a TBI, will require a DC.