Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury.

OBJECTIVES: There are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome. DESIGN: Multicenter prospective registry. SETTING: Consortium of 11 university-affiliated medical centers in the North American Clinical Trials Network. PATIENTS: Eight-hundred one spinal cord injury patients enrolled by participating centers. INTERVENTIONS: Appropriate spinal cord injury treatment at individual centers. MEASUREMENTS AND MAIN RESULTS: A total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32-0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17-36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35-13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19-17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31-14.32) measured using the Spinal Cord Independence Measure subscores. CONCLUSIONS: Results from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury.

Natural history of neurological improvement following complete (AIS A) thoracic spinal cord injury across three registries to guide acute clinical trial design and interpretation.

STUDY DESIGN: Retrospective, longitudinal analysis of motor and sensory outcomes following thoracic (T2-T12) sensorimotor complete spinal cord injury (SCI) in selected patients enrolled into three SCI) registries. OBJECTIVES: To establish a modern-day international benchmark for neurological recovery following traumatic complete thoracic sensorimotor SCI in a population similar to those enrolled in acute clinical trials. SETTING: Affiliates of the North American Clinical Trial Network (NACTN), European Multicenter Study about Spinal Cord Injury (EMSCI), and the Spinal Cord Injury Model Systems (SCIMS). METHODS: Only traumatic thoracic injured patients between 2006 and 2016 meeting commonly used clinical trial inclusion/exclusion criteria such as: age 16-70, T2-T12 neurological level of injury (NLI), ASIA Impairment Scale (AIS) A, non-penetrating injury, acute neurological exam within 7 days of injury, and follow-up neurological exam at least ~ 6 months post injury, were included in this analysis. International Standards for Neurological Classification of Spinal Cord injury outcomes including AIS conversion rate, NLI, and sensory and motor scores/levels were compiled. RESULTS: A total of 170 patients were included from the three registries: 12 from NACTN, 64 from EMSCI, and 94 from SCIMS. AIS conversion rates at approximately 6 months post injury varied from 16.7% to 23.4% (21.1% weighted average). Improved conversion rates were observed in all registries for low thoracic (T10-T12) injuries when compared with high/mid thoracic (T2-T9) injuries. The NLI was generally stable and lower extremity motor score (LEMS) improvement was uncommon and usually limited to low thoracic injuries only. CONCLUSIONS: This study presents the aggregation of selected multinational natural history recovery data in thoracic AIS A patients from three SCI registries and demonstrates comparable minimal improvement of ISNCSCI-scored motor and sensory function following these injuries, whereas conversions to higher AIS grades occur at a frequency of ~20%. These data inform the development of future clinical trial protocols in this important patient population for the interpretation of the safety and potential clinical benefit of new therapies, and the potential applicability in a multinational setting. SPONSORSHIP: InVivo Therapeutics.

T cells redirected to EphA2 for the immunotherapy of glioblastoma.

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.

North American Clinical Trials Network for Spinal Cord Injury Registry: Methodology and Analysis.

The North American Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of neurosurgery departments at university affiliated hospitals with medical, nursing, and rehabilitation personnel who are skilled in the assessment, evaluation, and management of SCI. NACTN was established with the goal of consistently advancing the quality of life of people with SCI through clinical trials of new therapies that provide robust evidence of safety and effectiveness. A prospective multi-center Registry was created to collect the natural course of the acute traumatic SCI patient from time of injury to 12 months follow-up. NACTN's network of hospitals enrolls a significant number of patients, defines and adheres to standard protocols, and provides the infrastructure and highly skilled personnel to conduct trials of therapy for SCI. Registry data have been used by academic institutions and by the biotechnology and pharmaceutical sectors to create comparison datasets for Phase I clinical trials of new therapies.

Variability in Early Surgery for Acute Cervical Spinal Cord Injury Patients: An Opportunity for Enhanced Care Delivery.

Data supporting the benefits of early surgical intervention in acute spinal cord injury (SCI) is growing. For early surgery to be accomplished, understanding the causes of variabilities that effect the timing of surgery is needed to achieve this goal. The purpose of this analysis is to determine factors that affect the timing of surgery for acute cervical SCI within the North American Clinical Trials Network (NACTN) for SCI registry. Patients in the NACTN SCI registry from 2005 to 2019 with a cervical SCI, excluding acute traumatic central cord syndrome, were analyzed for time elapsed from injury to arrival to the hospital, and time to surgery. Two categories were defined: 1) Early Arrival with Early Surgery (EAES) commenced within 24 h of injury, and 2) Early Arrival but Delayed Surgery (EADS), with surgery occurring between 24 to 72 h post-injury. Patients' demographic features, initial clinical evaluation, medical comorbidities, neurological status, surgical intervention, complications, and outcome data were correlated with respect to the two arrival groups. Of the 222 acute cervical SCI patients undergoing surgery, 163 (73.4%) were EAES, and 59 (26.6%) were EADS. There was no statistical difference in arrival time between the EAES and EADS groups. There was a statistical difference in the median arrival time to surgery between the EAES group (9 h) compared with the EADS group (31 h; p < 0.05). There was no statistical difference in race, sex, age, mechanism of injury, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores, or medical comorbidities between the two groups, but the EAES group did present with a significantly lower systolic blood pressure (p < 0.05). EADS patients were more likely to present as an American Spinal Injury Association Impairment Scale (AIS) D than EAES (p < 0.05). Early surgery was statistically more likely to occur if the injury occurred over the weekend (p < 0.05). There were variations in the rates of early surgery between the eight NACTN sites within the study, ranging from 57 to 100%. Of the 114 patients with 6-month outcome data, there was no significant change between the two groups regarding AIS grade change and motor/pin prick/light touch score recovery. A trend towards improved motor scores with early surgery was not statistically significant (p = 0.21). Although there is data that surgery within 24 h of injury improves outcomes and can be performed safely, there remain variations in care outside of clinical trials. In the present study of cervical SCI, NACTN achieved its goal of early surgery in 73.4% of patients from 2005-2019 who arrived within 24 h of their injury. Variability in achieving this goal was related to severity of neurological injury, the day of the week, and the treating NACTN center. Evaluating variations within our network improves understanding of potential systemic limitations and our decision-making process to accomplish the goal of early surgery.

Mortality in ASIA Impairment Scale grade A to D Patients With Odontoid Fracture and Magnetic Resonance Imaging Evidence of Spinal Cord Injury.

Odontoid fractures are common, often presenting in the elderly after a fall and infrequently associated with traumatic spinal cord injury (tSCI). The goal of this study was to analyze predictors of mortality and neurological outcome when odontoid fractures were associated with signal change on magnetic resonance imaging (MRI) at admission. Over an 18-year period (2001-2019), 33 patients with odontoid fractures and documented tSCI on MRI were identified. Mean age was 65.3 years (standard deviation [SD] = 17.2), and 21 patients were male. The mechanism of injury was falls in 25 patients, motor vehicle accidents in 5, and other causes in 3. Mean Injury Severity Score (ISS) was 40.5 (SD = 30.2), Glasgow Coma Scale (GCS) score was 13 (SD = 3.4), and American Spinal Injury Association (ASIA) motor score (AMS) was 51.6 (SD = 42.7). ASIA Impairment Scale (AIS) grade was A, B, C, and D in 9, 2, 3, and 19 patients, respectively. Mean intramedullary lesion length was 32.3 mm (SD = 18.6). The odontoid peg was displaced ventral or dorsal in 15 patients. Twenty patients had surgical intervention: anterior odontoid screw fixation in 7 and posterior spinal fusion in 13. Eleven (33.3%) patients died in this series: withdrawal of medical care in 5; anoxic brain injury in 4; and failure of critical care management in 2. Univariate logistic regression indicated that GCS score (p < 0.014), AMS (p < 0.002), AIS grade (p < 0.002), and ISS (p < 0.009) were risk factors for mortality. Multi-variate regression analysis indicated that only AMS (p < 0.002) had a significant relationship with mortality when odontoid fracture was associated with tSCI (odds ratio, 0.963; 95% confidence interval, 0.941-0.986).

Bulbocavernosus Reflex Has No Prognostic Features During the Acute Evaluation of Spinal Cord Injuries.

The bulbocavernosus reflex (BCR) has been used during the initial evaluation of a spinal cord injury patient as a metric to determine prognosis and whether the patient is in "spinal shock." This reflex has been less utilized over the last decade, and therefore a review was performed to assess the value of BCR in patient prognosis. The North American Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that includes a prospective SCI registry. The NACTN registry data was analyzed to evaluate the prognostic implication of the BCR during the initial evaluation of a spinal cord injury patient. SCI patients were divided into those with an intact or absent BCR during their initial evaluation. Associations of participants' descriptors and neurological status on follow-up were performed, followed by associations with the presence of a BCR. A total of 769 registry patients with recorded BCRs were included in the study. The median age was 49 years (32-61 years), and the majority were male (n = 566, 77%) and white (n = 519, 73%). Among included patients, high blood pressure was the most common comorbidity (n = 230, 31%). Cervical spinal cord injury was the most common (n = 470, 76%) with fall (n = 320, 43%) being the most frequent mechanism of injury. BCR was present in 311 patients (40.4%), while 458 (59.6%) had a negative BCR within 7 days of injury or before surgery. At 6 months post-injury, 230 patients (29.9%) followed up, of which 145 had a positive BCR, while 85 had a negative BCR. The presence/absence of BCR was significantly different in patients with cervical (p = 0.0015) or thoracic SCI (p = 0.0089), or conus medullaris syndrome (p = 0.0035), and in those who were American Spinal Injury Association Impairment Scale grade A (p = 0.0313). No significant relationship was observed between BCR results and demographics, AIS grade conversion, motor score changes (p = 0.1669), and changes in pin prick (p = 0.3795) and light touch scores (p = 0.8178). In addition, cohorts were not different in surgery decision (p = 0.7762) and injury to surgery time (p = 0.0681). In our review of the NACTN spinal cord registry, the BCR did not provide prognostic utility in the acute evaluation of spinal cord injury patients. Therefore, it should not be used as a reliable marker for predicting neurological outcomes post-injury.

Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study.

BACKGROUND: Repeated periods of stimulation of the spinal cord and training increased the ability to control movement in animal models of spinal cord injury. We hypothesised that tonic epidural spinal cord stimulation can modulate spinal circuitry in human beings into a physiological state that enables sensory input from standing and stepping movements to serve as a source of neural control to undertake these tasks. METHODS: A 23-year-old man who had paraplegia from a C7-T1 subluxation as a result of a motor vehicle accident in July 2006, presented with complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. After 170 locomotor training sessions over 26 months, a 16-electrode array was surgically placed on the dura (L1-S1 cord segments) in December 2009, to allow for chronic electrical stimulation. Spinal cord stimulation was done during sessions that lasted up to 250 min. We did 29 experiments and tested several stimulation combinations and parameters with the aim of the patient achieving standing and stepping. FINDINGS: Epidural stimulation enabled the man to achieve full weight-bearing standing with assistance provided only for balance for 4·25 min. The patient achieved this standing during stimulation using parameters identified as specific for standing while providing bilateral load-bearing proprioceptive input. We also noted locomotor-like patterns when stimulation parameters were optimised for stepping. Additionally, 7 months after implantation, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation. INTERPRETATION: Task-specific training with epidural stimulation might reactivate previously silent spared neural circuits or promote plasticity. These interventions could be a viable clinical approach for functional recovery after severe paralysis. FUNDING: National Institutes of Health and Christopher and Dana Reeve Foundation.

Medulloblastoma-biology and microenvironment: a review.

Medulloblastoma (MB) is a cancer of the cerebellum and the most common primary pediatric malignancy of the central nervous system. Classified as a primitive neural ectoderm tumor; it is thought to arise from granule cell precursors in the cerebellum. The standard of care consists of surgery, chemotherapy and age-dependent radiation therapy. Despite aggressive multimodality therapy; approximately 30% of MB patients remain incurable. Moreover, for long-term survivors, the treatment related sequelae are often debilitating. Side effects include cerebellar mutism, sterility, neurocognitive deficits, and a substantial risk of developing secondary cancers. In a quest for more effective and targeted therapies, scientists have begun to investigate the biological events that not only initiate but also sustain the malignant phenotype in MB. Of particular interest is, the role of the tumor microenvironment in tumor pathogenesis. This review seeks to highlight several key processes observed in cancer biology, particularly the involvement of the tumor microenvironment, with relevant examples from MB.

Stereotaxic Atlas of the Human Lumbar-Sacral Spinal Cord.

OBJECTIVE: A Stereotaxic Atlas of the Human Lumbar-Sacral Spinal Cord has been created to provide an anatomical basis for radiologic and ultrasonic imaging and electrophysiological examination, which are used to target the placement of lumbar-sacral epidural stimulating electrodes and cellular transplantation in order to restore movement in individuals with sustained spinal cord injury or a degenerative disorder of the spinal cord. Through the availability of an atlas that exhibits axial images of the cytoarchitecture of each cord segment with a stereotaxic millimeter grid of dorsal-ventral depth from the midline dorsal surface of the cord and right-left distances from the midline of the cord, neuromodulation, and cellular therapy would undoubtedly be made not only more precise but also safer for patients. METHODS: The atlas is based upon dimension measurements and subsequent serial sectioning, staining and high-resolution digital imaging of the lumbar-sacral enlargement of 20 adult human spinal cords. RESULTS: Nissl stained cross-sections from cord segments L1-S3 illustrate the cytoarchitecture and stereotactic coordinates. CONCLUSIONS: The atlas provides an anatomical basis for radiologic and physiologic confirmation of target localization in the lumbar-sacral spinal cord.

The influence of timing of surgical decompression for acute spinal cord injury: a pooled analysis of individual patient data.

BACKGROUND: Although there is a strong biological rationale for early decompression of the injured spinal cord, the influence of the timing of surgical decompression for acute spinal cord injury (SCI) remains debated, with substantial variability in clinical practice. We aimed to objectively evaluate the effect of timing of decompressive surgery for acute SCI on long-term neurological outcomes. METHODS: We did a pooled analysis of individual patient data derived from four independent, prospective, multicentre data sources, including data from December, 1991, to March, 2017. Three of these studies had been published; of these, only one study previously specifically analysed the effect of the timing of surgical decompression. These four datasets were selected because they were among the highest quality acute SCI datasets available and contained highly granular data. Individual patient data were obtained by request from study authors. All patients who underwent decompressive surgery for acute SCI within these datasets were included. Patients were stratified into early (<24 h after spinal injury) and late (≥24 h after spinal injury) decompression groups. Neurological outcomes were assessed by American Spinal Injury Association (ASIA), or International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), examination. The primary endpoint was change in total motor score from baseline to 1 year after spinal injury. Secondary endpoints were ASIA Impairment Scale (AIS) grade and change in upper-extremity motor, lower-extremity motor, light touch, and pin prick scores after 1 year. One-stage meta-analyses were done by hierarchical mixed-effects regression adjusting for baseline score, age, mechanism of injury, AIS grade, level of injury, and administration of methylprednisolone. Effect sizes were summarised by mean difference (MD) for sensorimotor scores and common odds ratio (cOR) for AIS grade, with corresponding 95% CIs. As a secondary analysis, change in total motor score was regressed against time to surgical decompression (h) as a continuous variable, using a restricted cubic spline with adjustment for the same covariates as in the primary analysis. FINDINGS: We identified 1548 eligible patients from the four datasets. Outcome data at 1 year after spinal injury were available for 1031 patients (66·6%). Patients who underwent early surgical decompression (n=528) experienced greater recovery than patients who had late decompression surgery (n=1020) at 1 year after spinal injury; total motor scores improved by 23·7 points (95% CI 19·2-28·2) in the early surgery group versus 19·7 points (15·3-24·0) in the late surgery group (MD 4·0 points [1·7-6·3]; p=0·0006), light touch scores improved by 19·0 points (15·1-23·0) vs 14·8 points (11·2-18·4; MD 4·3 [1·6-7·0]; p=0·0021), and pin prick scores improved by 18·3 points (13·7-22·9) versus 14·2 points (9·8-18·6; MD 4·0 [1·5-6·6]; p=0·0020). Patients who had early decompression also had better AIS grades at 1 year after surgery, indicating less severe impairment, compared with patients who had late surgery (cOR 1·48 [95% CI 1·16-1·89]; p=0·0019). When time to surgical decompression was modelled as a continuous variable, there was a steep decline in change in total motor score with increasing time during the first 24-36 h after injury (p<0·0001); and after 36 h, change in total motor score plateaued. INTERPRETATION: Surgical decompression within 24 h of acute SCI is associated with improved sensorimotor recovery. The first 24-36 h after injury appears to represent a crucial time window to achieve optimal neurological recovery with decompressive surgery following acute SCI. FUNDING: None.

Spinal Cord Signal Change on Magnetic Resonance Imaging May Predict Worse Clinical In- and Outpatient Outcomes in Patients with Spinal Cord Injury: A Prospective Multicenter Study in 459 Patients.

Prognostic factors for clinical outcome after spinal cord (SC) injury (SCI) are limited but important in patient management and education. There is a lack of evidence regarding magnetic resonance imaging (MRI) and clinical outcomes in SCI patients. Therefore, we aimed to investigate whether baseline MRI features predicted the clinical course of the disease. This study is an ancillary to the prospective North American Clinical Trials Network (NACTN) registry. Patients were enrolled from 2005-2017. MRI within 72 h of injury and a minimum follow-up of one year were available for 459 patients. Patients with American Spinal Injury Association impairment scale (AIS) E were excluded. Patients were grouped into those with (n = 354) versus without (n = 105) SC signal change on MRI T2-weighted images. Logistic regression analysis adjusted for commonly known a priori confounders (age and baseline AIS). Main outcomes and measures: The primary outcome was any adverse event. Secondary outcomes were AIS at the baseline and final follow-up, length of hospital stay (LOS), and mortality. A regression model adjusted for age and baseline AIS. Patients with intrinsic SC signal change were younger (46.0 (interquartile range (IQR) 29.0 vs. 50.0 (IQR 20.5) years, p = 0.039). There were no significant differences in the other baseline variables, gender, body mass index, comorbidities, and injury location. There were more adverse events in patients with SC signal change (230 (65.0%) vs. 47 (44.8%), p < 0.001; odds ratio (OR) = 2.09 (95% confidence interval (CI) 1.31-3.35), p = 0.002). The most common adverse event was cardiopulmonary (186 (40.5%)). Patients were less likely to be in the AIS D category with SC signal change at baseline (OR = 0.45 (95% CI 0.28-0.72), p = 0.001) and in the AIS D or E category at the final follow-up (OR = 0.36 (95% CI 0.16-0.82), p = 0.015). The length of stay was longer in patients with SC signal change (13.0 (IQR 17.0) vs. 11.0 (IQR 14.0), p = 0.049). There was no difference between the groups in mortality (11 (3.2%) vs. 4 (3.9%)). MRI SC signal change may predict adverse events and overall LOS in the SCI population. If present, patients are more likely to have a worse baseline clinical presentation (i.e., AIS) and in- or outpatient clinical outcome after one year. Patients with SC signal change may benefit from earlier, more aggressive treatment strategies and need to be educated about an unfavorable prognosis.

Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent.

Riluzole, a benzothiazole sodium channel blocker that received US Food and Drug Administration approval to attenuate neurodegeneration in amyotrophic lateral sclerosis in 1995, was found to be safe and potentially efficacious in a spinal cord injury (SCI) population, as evident in a phase I clinical trial. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes can alter the pharmacokinetics of therapeutics. A 1-compartment with first-order elimination population pharmacokinetic model for riluzole incorporating time-dependent clearance and volume of distribution was developed from combined data of the phase 1 and the ongoing phase 2/3 trials. This change in therapeutic exposure may lead to a biased estimate of the exposure-response relationship when evaluating therapeutic effects. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification that preserves the required therapeutic exposure of riluzole.

Temporal variations of wall shear stress parameters in intracranial aneurysms--importance of patient-specific inflow waveforms for CFD calculations.

PURPOSE: To assess reliability of wall shear stress (WSS)calculations using computational fluid dynamics (CFD) dependent on inflow in internal carotid artery aneurysms (ICA). MATERIALS AND METHODS: Six unruptured ICA aneurysms were studied. 3D computational meshes were created from 3D digital subtraction angiographic images (Axiom Artis dBA, Siemens Medical Solutions). Transient CFD simulations(Fluent, ANSYS Inc.) were performed for two inflow conditions: (1) idealized averaged waveform from normal subjects (ID) and (2) patient-specific waveform (PS)measured with 2D phase contrast magnetic resonance imaging. Stability of calculation was assessed by comparing mean WSS (), temporal wall shear stress magnitude variation (Delta WSS), and oscillatory shear index(OSI, a measure of variation in the WSS direction) on the aneurysmal wall for both conditions. RESULTS: For all cases, mean relative difference (PS-ID) of WSS () was -15% (range -32% to 11%). Mean Delta WSS difference was -29.3% ( -100% to 67%). Mean OSI difference was 7.5% (-12% to 40%). Large variations in histograms of these parameters were noted. CONCLUSION: For accurate calculations of WSS parameters,patient-specific information on physiological flow may be necessary. Results obtained with averaged or idealized flow waveforms may have to be interpreted with caution.

The History of Neurosurgery at Houston Methodist Hospital.

The history of neurosurgery in Texas is linked with the development over the past century of the Houston Methodist Hospital (HMH) from a 30-bed hospital in downtown Houston to an academic medical center with 900 beds in the Texas Medical Center. Neurosurgery at HMH has developed to meet the needs of the Houston Metropolitan Area, which has grown from 130,000 people in 1919 to 7 million people today. Neurosurgery at HMH has had steady growth and stable leadership with Dr. James Greenwood Jr. 1936-1980, Dr. Robert Grossman 1980-2013, and Dr. Gavin Britz 2013-present, as Chiefs of the Neurosurgical Service. HMH has been affiliated with 2 medical schools: Baylor College of Medicine 1950-2003 and Weill College of Medicine Cornell University 2004-present. Neurosurgical training began at HMH with the establishment of the Baylor College of Medicine Neurosurgery Residency Program with Dr. George Ehni as Program Director 1959-1979 and Dr. Robert Grossman as Program Director 1980-2006. Training has continued in the HMH residency program from 2006 to present with Dr. David Baskin as Program Director. As of 2019, 138 neurosurgical residents have been trained at HMH. The goals of delivering responsible patient care, advancing neurosurgical knowledge, and training the next generation of practitioners and teachers of neurosurgery have remained constant and have been met and remain the mission of the department.

Changes in individual and group spatial and verbal learning characteristics after anterior temporal lobectomy.

PURPOSE: To evaluate the effects of anterior temporal lobectomy (ATL) on individual and group spatial and verbal learning and memory abilities as a function of side of surgery and seizure control outcome. METHODS: We evaluated pre- and postsurgical learning and memory abilities of 75 left-hemisphere language dominant individuals who underwent ATL (33 left, 42 right) using the 8-trial Nonverbal Selective Reminding test and the 12-trial Verbal Selective Reminding test. RESULTS: Reliable change index methods indicated that 40.5% of individuals who underwent right-ATL had a clinically significant decline in spatial memory, and 62.5% of individuals who underwent left-ATL had a significant reduction in verbal memory. Growth curve analyses indicated that both side of surgery and poor seizure outcome independently affected the learning slope in the best fitting models. Left-ATL reduced the slope, but did not affect the overall shape, of verbal learning across trials. On the other hand, poor seizure control outcome affected the slope of spatial learning regardless of the side of surgery. DISCUSSION: Results demonstrate both individual and group declines in spatial memory and learning after ATL. Results suggest that individuals who undergo right-ATL should be counseled regarding the likelihood of a decline in spatial memory and learning abilities after ATL. Results also suggest that individuals with poor seizure control after ATL should be referred for rehabilitation services given the significant declines in spatial and verbal memory that occurred in our sample regardless of side of surgery.

Five-year follow-up of unilateral posteroventral pallidotomy in Parkinson's disease.

BACKGROUND: Neurocognitive outcome research of individuals with Parkinson's disease after unilateral pallidotomy is inconsistent. Although some studies reported few cognitive changes, other investigations have more consistently shown both transient and long-term cognitive decline postoperatively. METHODS: We report the long-term motor and neurocognitive outcome 5 years post surgery for 18 patients with Parkinson's disease (12 men and 6 woman; all right-handed) who underwent right or left unilateral posteroventral pallidotomy. RESULTS: Pallidotomy patients revealed long-term motor benefits from the surgery in their "off" state and control of dopa-induced dyskinesias in their "on" state, which is consistent with previous research. We found mild declines in oral and visuomotor information processing speed, verbal recognition memory, and mental status 5 years after surgery, which differs from previous literature regarding the long-term neurocognitive outcome after pallidotomy. Differences between the right and left pallidotomy patients for both motor and cognitive skills were not found. CONCLUSION: Although deep brain stimulation is presently the treatment of choice, pallidotomy continues to be performed around the world. Consequently, although unilateral pallidotomy should be considered a treatment option for patients with Parkinson's disease who suffer from severe unilateral disabling motor symptoms or dyskinesias, the long-term neurocognitive outcome should also be considered in treatment decisions.

Intra-aneurysmal flow patterns and wall shear stresses calculated with computational flow dynamics in an anterior communicating artery aneurysm depend on knowledge of patient-specific inflow rates.

OBJECTIVE: To evaluate if knowledge of patient-specific inflow data in computational fluid dynamics simulations is required for the accurate calculation of intra-aneurysmal flow patterns and wall shear stress in an aneurysm of the anterior communicating artery (AcomA). MATERIALS AND METHODS: 3D digital subtraction angiography (3D-DSA) and phase contrast magnetic resonance (pcMRI) images were obtained in a 71-year old patient with an unruptured aneurysm of the anterior communicating artery (AcomA). A baseline computational flow dynamics simulation was performed using inflow boundary conditions measured with pcMRI. Intra-aneurysmal flow patterns, maximum, minimum and average values of wall shear stress and wall shear stress histograms were calculated. Five additional computational flow dynamics simulations were performed, in which simulated inflow from the right and left A1 segment was varied, while keeping the total inflow constant. Intra-aneurysmal flow patterns measured with pcMRI were qualitatively compared to intra-aneurysmal flow patterns derived from the simulations. RESULTS: Intra-aneurysmal flow patterns calculated in the baseline simulation were in good qualitative agreement with pcMRI measurements. Intra-aneurysmal flow patterns and wall shear stress changed considerably when inflow conditions were altered. Changes in the flow distribution between right and left A1 segments caused variations of the averaged wall shear stress as high as 43%. CONCLUSION: Intra-aneurysmal flow patterns and wall shear stress in an AcomA aneurysm calculated with computational flow dynamics depended strongly on the flow distribution between A1 segments. Patient-specific flow data measured with pcMRI obtained prior to computational flow dynamics are necessary for an accurate simulation of intra-aneurysmal flow patterns and calculation of wall shear stress in AcomA aneurysms. Further studies may indicate if wall shear stress calculated with computational flow dynamics can predict aneurysm growth and/or rupture.

Association of Pneumonia, Wound Infection, and Sepsis with Clinical Outcomes after Acute Traumatic Spinal Cord Injury.

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI.