Use of functional MRI to guide decisions in a clinical stroke trial.

Background and purposeAn investigational trial examined safety and efficacy of targeted subthreshold cortical stimulation in patients with chronic stroke. The anatomical location for the target, hand motor area, varies across subjects, and so was localized with functional MRI (fMRI). This report describes the experience of incorporating standardized fMRI into a multisite stroke trial.MethodsAt 3 enrollment centers, patients moved (0.25 Hz) the affected hand during fMRI. Hand motor function was localized at a fourth center guiding intervention for those randomized to stimulation.ResultsThe fMRI results were available within 24 hours. Across 12 patients, activation site variability was substantial (12, 23, and 11 mm in x, y, and z directions), exceeding stimulating electrode dimensions.ConclusionsUse of fMRI to guide decision-making in a clinical stroke trial is feasible

Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes

Objective: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints. Methods: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-betal, Fibroblast growth factor-2 and Plate let-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff(R)-11), in culture or in nude mice. Human native menisci were assessed as reference. Results: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9 were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation. Conclusions: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights rese

Predicting functional gains in a stroke trial.

A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment.Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains.Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment.Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention

Outcomes following therapeutic intervention of post-traumatic vasospasm: A systematic review and meta-analysis

Background: Vasospasm occurrence following traumatic brain injury may impact neurologic and functional recovery of patients, yet treatment of post-traumatic vasospasm (PTV) has not been well documented. This systematic review and meta-analysis aims to assess the current evidence regarding favorable outcome as measured by Glasgow Outcome Scale (GOS) scores following treatment of PTV. Methods: A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality; occurrence of PTV; rate of favorable outcome following each treatment modality; and follow-up duration. Treatments evaluated were calcium channel blockers (CCBs), endovascular intervention, and dopamine-induced hypertension. Outcomes were compared via the random-effects analysis. Results: Fourteen studies with 1885 PTV patients were quantitatively analyzed: 982 patients who received tailored therapeutic intervention and 903 patients who did not receive tailored therapy. For patients undergoing treatment, the rate of favorable outcome was 57.3 % (500/872 patients; 95 % CI 54.1 – 60.6 %) following administration of CCBs, 94.1 % (16/17 patients; 95 % CI 82.9 – 100.0 %) following endovascular intervention, and 54.8 % (51/93 patients; 95 % CI 44.7 – 65.0 %) following dopamine-induced hypertension. Of note, the endovascular group had the highest rate of favorable outcome but was also the smallest sample size (n = 17). Patients who received tailored therapeutic intervention for PTV had a higher rate of favorable outcome than patients who did not receive tailored therapy: 57.7 % (567/982 patients; 95 % CI 54.1 – 60.8 %) versus 52.0 % (470/903 patients; 95 % CI 48.8 – 55.3 %), respectively. Conclusions: The available data suggests that tailored therapeutic intervention of PTV results in a favorable outcome. While endovascular intervention of PTV had the highest rate of favorable outcome, both CCB administration and dopamine-induced hypertension had similar lower rates of favorable outcome.12 month embargo; first published 11 July 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Outcomes following therapeutic intervention of post-traumatic vasospasm: A systematic review and meta-analysis.

BACKGROUND: Vasospasm occurrence following traumatic brain injury may impact neurologic and functional recovery of patients, yet treatment of post-traumatic vasospasm (PTV) has not been well documented. This systematic review and meta-analysis aims to assess the current evidence regarding favorable outcome as measured by Glasgow Outcome Scale (GOS) scores following treatment of PTV. METHODS: A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality; occurrence of PTV; rate of favorable outcome following each treatment modality; and follow-up duration. Treatments evaluated were calcium channel blockers (CCBs), endovascular intervention, and dopamine-induced hypertension. Outcomes were compared via the random-effects analysis. RESULTS: Fourteen studies with 1885 PTV patients were quantitatively analyzed: 982 patients who received tailored therapeutic intervention and 903 patients who did not receive tailored therapy. For patients undergoing treatment, the rate of favorable outcome was 57.3 % (500/872 patients; 95 % CI 54.1 - 60.6 %) following administration of CCBs, 94.1 % (16/17 patients; 95 % CI 82.9 - 100.0 %) following endovascular intervention, and 54.8 % (51/93 patients; 95 % CI 44.7 - 65.0 %) following dopamine-induced hypertension. Of note, the endovascular group had the highest rate of favorable outcome but was also the smallest sample size (n = 17). Patients who received tailored therapeutic intervention for PTV had a higher rate of favorable outcome than patients who did not receive tailored therapy: 57.7 % (567/982 patients; 95 % CI 54.1 - 60.8 %) versus 52.0 % (470/903 patients; 95 % CI 48.8 - 55.3 %), respectively. CONCLUSIONS: The available data suggests that tailored therapeutic intervention of PTV results in a favorable outcome. While endovascular intervention of PTV had the highest rate of favorable outcome, both CCB administration and dopamine-induced hypertension had similar lower rates of favorable outcome

Current management and surgical outcomes of medically intractable epilepsy

Epilepsy is one of the most common neurologic disorders in the world. While anti-epileptic drugs (AEDs) are the mainstay of treatment in most cases, as many as one-third of patients will have a refractory form of disease indicating the need for a neurosurgical evaluation. Ever since the first half of the twentieth century, surgery has been a major treatment option for epilepsy, but the last 10-15 years in particular has seen several major advances. As shown in relatively recent studies, resection is more effective for medically intractable epilepsy (MIE) than AED treatment alone, which is why most clinicians now endorse a neurosurgical consultation after approximately two failed regimens of AEDs, ultimately leading to decreased healthcare costs and increased quality of life. Temporal lobe epilepsy (TLE) is the most common form of MIE and comprises about 80% of epilepsy surgeries with the majority of patients gaining complete seizure-freedom. As the number of procedures and different approaches continues to grow, temporal lobectomy remains consistently focused on resection of mesial structures such as the amygdala, hippocampus, and parahippocampal gyrus while preserving as much of the neocortex as possible resulting in optimum seizure control with minimal neurological deficits. MIE originating outside the temporal lobe is also effectively treated with resection. Though not as successful as TLE surgery because of their frequent proximity to eloquent brain structures and more diffuse pathology, epileptogenic foci located extratemporally also benefit from resection. Favorable seizure outcome in each of these procedures has heavily relied on pre-operative imaging, especially since the massive surge in MRI technology just over 20 years ago. However, in the absence of visible lesions on MRI, recent improvements in secondary imaging modalities such as fluorodeoxyglucose positron emission computed tomography (FDG-PET) and single-photon emission computed tomography (SPECT) have lead to progressively better long-term seizure outcomes by increasing the neurosurgeon\u27s visualization of supposed non-lesional foci. Additionally, being historically viewed as a drastic surgical intervention for MIE, hemispherectomy has been extensively used quite successfully for diffuse epilepsies often found in pediatric patients. Although total anatomic hemispherectomy is not utilized as commonly today, it has given rise to current disconnective techniques such as hemispherotomy. Therefore, severe forms of hemispheric developmental epilepsy can now be surgically treated while substantially decreasing the amount of potential long-term complications resulting from cavitation of the brain following anatomical hemispherectomy. Despite the rapid pace at which we are gaining further knowledge about epilepsy and its surgical treatment, there remains a sizeable underutilization of such procedures. By reviewing the recent literature on resective treatment of MIE, we provide a recent up-date on epilepsy surgery while focusing on historical perspectives, techniques, prognostic indicators, outcomes, and complications associated with several different types of procedures