Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data in SCI. TDA also revealed that perioperative hypertension predicted long-term recovery better than any tested drug after thoracic SCI in rats. TDA-based data-driven discovery has great potential application for decision-support for basic research and clinical problems such as outcome assessment, neurocritical care, treatment planning and rapid, precision-diagnosis.

Efforts to understand spinal cord injury (SCI) and other complex neurotrauma disorders at the pre-clinical level have shown progress in recent years. However, successful translation of basic research into clinical practice has been slow, partly because of the large, heterogeneous data sets involved. In this sense, translational neurological research represents a "big data" problem. In an effort to expedite translation of pre-clinical knowledge into standards of patient care for SCI, we describe the development of a novel database for translational neurotrauma research known as Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI). We present demographics, descriptive statistics, and translational syndromic outcomes derived from our ongoing efforts to build a multi-center, multi-species pre-clinical database for SCI models. We leveraged archived surgical records, postoperative care logs, behavioral outcome measures, and histopathology from approximately 3000 mice, rats, and monkeys from pre-clinical SCI studies published between 1993 and 2013. The majority of animals in the database have measures collected for health monitoring, such as weight loss/gain, heart rate, blood pressure, postoperative monitoring of bladder function and drug/fluid administration, behavioral outcome measures of locomotion, and tissue sparing postmortem. Attempts to align these variables with currently accepted common data elements highlighted the need for more translational outcomes to be identified as clinical endpoints for therapeutic testing. Last, we use syndromic analysis to identify conserved biological mechanisms of recovery after cervical SCI between rats and monkeys that will allow for more-efficient testing of therapeutics that will need to be translated toward future clinical trials.

No abstract

OBJECTIVE With the recent evolution of endovascular therapies, objective evaluation of the efficacy of clip ligation for cerebral aneurysms should be performed. This study was undertaken to evaluate the durability of microsurgical clip ligation, identify risk factors for recurrence, and assess the need for long-term follow-up imaging. METHODS A retrospective review of medical records identified 616 consecutive patients (156 male and 460 female patients; mean age 48.4 ± 12.4 years; range 6-90 years) who underwent microsurgical clip ligation and follow-up imaging at least 1 year after discharge between 1990 and 2010 at our institution. Of a total of 926 aneurysms in 616 patients, 758 aneurysms were microsurgically clip-ligated. At presentation, 431 of these aneurysms were ruptured and 327 aneurysms were unruptured. All patients underwent postoperative baseline imaging within the 1st month of their operation. A logistic regression analysis was performed to identify which variables are more likely to predict recurrence. RESULTS Late follow-up angiographic imaging was obtained at a mean of 7.2 ± 4.7 years postdischarge (median 5.7 years; range 1-23 years). Of the 699 clipped aneurysms without residua, late follow-up angiography revealed only 1 (0.14%) recurrent aneurysm. Of the 59 residual aneurysms that remained after initial clip ligation on early postoperative imaging, 8 (13.6%) demonstrated growth. All of these aneurysms required treatment. None of the recurrences were due to broken or delayed displacement of clips. A total of 111 patients presented with multiple aneurysms. De novo aneurysm formation occurred in 8 (0.97%) patients, all of whom initially presented with multiple aneurysms. CONCLUSIONS This study provides additional evidence to support the long-term efficacy of aneurysm clip ligation. The chance of aneurysm recurrence after complete clip ligation is very small. However, there is a regrowth risk of 1.83% per year for aneurysm remnants after incomplete clip ligation. These findings support the necessity for continued followup, late angiographic imaging, and the potential need for further intervention of incompletely ligated aneurysms. Furthermore, completely clip-ligated aneurysms may not require additional surveillance imaging unless multiple aneurysms were evident at presentation.