Publications by authors named "Bizhan Aarabi"

144 Publications

Imaging and Electrophysiology for Degenerative Cervical Myelopathy [AO Spine RECODE DCM Research Priority Number 9].

Global Spine J 2021 Nov 19:21925682211057484. Epub 2021 Nov 19.

Department of Neurosurgery, 5506Medical College of Wisconsin, Wauwatosa, WI, USA.

Study Design: Narrative review.

Objective: The current review aimed to describe the role of existing techniques and emerging methods of imaging and electrophysiology for the management of degenerative cervical myelopathy (DCM), a common and often progressive condition that causes spinal cord dysfunction and significant morbidity globally.

Methods: A narrative review was conducted to summarize the existing literature and highlight future directions.

Results: Anatomical magnetic resonance imaging (MRI) is well established in the literature as the key imaging tool to identify spinal cord compression, disc herniation/bulging, and inbuckling of the ligamentum flavum, thus facilitating surgical planning, while radiographs and computed tomography (CT) provide complimentary information. Electrophysiology techniques are primarily used to rule out competing diagnoses. However, signal change and measures of cord compression on conventional MRI have limited utility to characterize the degree of tissue injury, which may be helpful for diagnosis, prognostication, and repeated assessments to identify deterioration. Early translational studies of quantitative imaging and electrophysiology techniques show potential of these methods to more accurately reflect changes in spinal cord microstructure and function.

Conclusion: Currently, clinical management of DCM relies heavily on anatomical MRI, with additional contributions from radiographs, CT, and electrophysiology. Novel quantitative assessments of microstructure, perfusion, and function have the potential to transform clinical practice, but require robust validation, automation, and standardization prior to uptake.
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http://dx.doi.org/10.1177/21925682211057484DOI Listing
November 2021

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.

J Clin Med 2021 Oct 18;10(20). Epub 2021 Oct 18.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada.

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 ( = 354) versus without ( = 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, = 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%), < 0.001; odds ratio (OR) = 2.09 (95% confidence interval (CI) 1.31-3.35), = 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), = 0.001) and in the AIS D or E category at the final follow-up (OR = 0.36 (95% CI 0.16-0.82), = 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), = 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.
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http://dx.doi.org/10.3390/jcm10204778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537526PMC
October 2021

The development of lived experience-centered word clouds to support research uncertainty gathering in degenerative cervical myelopathy: results from an engagement process and protocol for their evaluation, via a nested randomized controlled trial.

Trials 2021 Jun 25;22(1):415. Epub 2021 Jun 25.

Academic Neurosurgery Unit & Anne McLaren Laboratory of Regenerative Medicine, Department of Clinical Neurosurgery, University of Cambridge, Cambridge, UK.

Objectives: AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as a nested methodological study within our PSP.

Methods: An online poll asked PwCM to submit and vote on words associated with aspects of DCM. After review, a refined word list was re-polled for voting and word submission. Word clouds were generated and an implementation plan for AO Spine RECODE-DCM PSP surveys was subsequently developed.

Results: Seventy-nine terms were submitted after the first poll. Eighty-seven refined words were then re-polled (which added a further 39 words). Four word clouds were generated under the categories of diagnosis, management, long-term effects, and other. A 1:1 block randomization protocol to assess word cloud impact on the number and relevance of PSP research questions was generated.

Conclusions: We have shown it is feasible to work with PwCM to generate a tool for the AO Spine RECODE-DCM nested methodological study. Once the survey stage is completed, we will be able to evaluate the impact of the word clouds. Further research will be needed to assess the value of any impact in terms of stimulating a more creative research agenda.
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http://dx.doi.org/10.1186/s13063-021-05349-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235822PMC
June 2021

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

J Clin Pharmacol 2021 09 9;61(9):1232-1242. Epub 2021 Jul 9.

Department of Neurosurgery, Houston Methodist Research Institute, Houston, Texas, USA.

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.
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http://dx.doi.org/10.1002/jcph.1876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457124PMC
September 2021

Trajectory-Based Classification of Recovery in Sensorimotor Complete Traumatic Cervical Spinal Cord Injury.

Neurology 2021 Apr 13. Epub 2021 Apr 13.

Division of Neurosurgery and Spine Program, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Objective: To test the hypothesis that sensorimotor complete traumatic cervical spinal cord injury is a heterogenous clinical entity comprising several subpopulations that follow fundamentally different trajectories of neurologic recovery.

Methods: We analyzed demographic and injury data from 655 patients who were pooled from 4 prospective longitudinal multicenter studies. Group based trajectory modeling was applied to model neurologic recovery trajectories over the initial 12-months postinjury and to identify predictors of recovery trajectories. Neurologic outcomes included: Upper Extremity Motor Score, Total Motor Scores and AIS grade improvement.

Results: The analysis identified 3 distinct trajectories of neurologic recovery. These clinical courses included: (1) Marginal recovery trajectory: characterized by minimal or no improvement in motor strength or change in AIS grade status (remained grade A); (2) Moderate recovery trajectory: characterized by low baseline motor scores that improved approximately 13 points; or AIS conversion of one grade point; (3) Good recovery trajectory: characterized by baseline motor scores in the upper quartile that improved to near maximum values within 3 months of injury. Patients following the moderate or good recovery trajectories were of younger age, had more caudally located injuries, a higher degree of preserved motor and sensory function at baseline examination and exhibited a greater extent of motor and sensory function in the zone of partial preservation.

Conclusion: Cervical complete SCI can be classified into one of 3 distinct subpopulations with fundamentally different trajectories of neurologic recovery. This study defines unique clinical phenotypes based on potential for recovery, rather than baseline severity of injury alone. This approach may prove beneficial in clinical prognostication and in the design and interpretation of clinical trials in SCI.
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http://dx.doi.org/10.1212/WNL.0000000000012028DOI Listing
April 2021

CT of Skull Base Fractures: Classification Systems, Complications, and Management.

Radiographics 2021 May-Jun;41(3):762-782. Epub 2021 Apr 2.

From the Department of Diagnostic Radiology and Nuclear Medicine (D.D., K.C., D.G., R.E.M.), R. Adams Cowley Shock Trauma Center (D.D., B.A., A.J.N.), Department of Neurosurgery (B.A.), Division of Plastic Surgery (A.J.N.), and Department of Otorhinolaryngology-Head and Neck Surgery (D.J.E.), University of Maryland Medical Center, 22 S Greene St, Baltimore, MD 21201; Department of Radiology, Boston Medical Center, Boston University School of Medicine, Boston, Mass (O.S.); and Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD (K.C.).

As advances in prehospital and early hospital care improve survival of the head-injured patient, radiologists are increasingly charged with understanding the myriad skull base fracture management implications conferred by CT. Successfully parlaying knowledge of skull base anatomy and fracture patterns into precise actionable clinical recommendations is a challenging task. The authors aim to provide a pragmatic overview of CT for skull base fractures within the broader context of diagnostic and treatment planning algorithms. Laterobasal, frontobasal, and posterior basal fracture patterns are emphasized. CT often plays a complementary, supportive, or confirmatory role in management of skull base fractures in conjunction with results of physical examination, laboratory testing, and neurosensory evaluation. CT provides prognostic information about short- and long-term risk of cerebrospinal fluid (CSF) leak, encephalocele, meningitis, facial nerve paralysis, hearing and vision loss, cholesteatoma, vascular injuries, and various cranial nerve palsies and syndromes. The radiologist should leverage understanding of specific strengths and limitations of CT to anticipate next steps in the skull base fracture management plan. Additional imaging is warranted to clarify ambiguity (particularly for potential sources of CSF leak); in other cases, clinical and CT criteria alone are sufficient to determine the need for intervention and the choice of surgical approach. The radiologist should be able to envision stepping into a multidisciplinary planning discussion and engaging neurotologists, neuro-ophthalmologists, neurosurgeons, neurointerventionalists, and facial reconstructive surgeons to help synthesize an optimal management plan after reviewing the skull base CT findings at hand. RSNA, 2021.
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http://dx.doi.org/10.1148/rg.2021200189DOI Listing
November 2021

Efficacy of Early (≤ 24 Hours), Late (25-72 Hours), and Delayed (>72 Hours) Surgery with Magnetic Resonance Imaging-Confirmed Decompression in American Spinal Injury Association Impairment Scale Grades C and D Acute Traumatic Central Cord Syndrome Caused by Spinal Stenosis.

J Neurotrauma 2021 Aug 6;38(15):2073-2083. Epub 2021 Apr 6.

Department of Neurosurgery and University of Maryland School of Medicine, Baltimore, Maryland, USA.

The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. During a 19-year period, 101 patients with ATCCS, admission ASIA Impairment Scale (AIS) grades C and D, and an admission AMS of ≤95 were surgically decompressed. Twenty-four of 101 patients had an AIS grade C injury. Eighty-two patients were males, the mean age of patients was 57.9 years, and 69 patients had had a fall. AMS at admission was 68.3 (standard deviation [SD] 23.4); upper extremities (UE) 28.6 (SD 14.7), and lower extremities (LE) 41.0 (SD 12.7). AMS at the latest follow-up was 93.1 (SD 12.8), UE 45.4 (SD 7.6), and LE 47.9 (SD 6.6). Mean number of stenotic segments was 2.8, mean canal compromise was 38.6% (SD 8.7%), and mean intramedullary lesion length (IMLL) was 23 mm (SD 11). Thirty-six of 101 patients had decompression within 24 h, 38 patients had decompression between 25 and 72 h, and 27 patients had decompression >72 h after injury. Demographics, etiology, AMS, AIS grade, morphometry, lesion length, surgical technique, steroid protocol, and follow-up AMS were not statistically different between groups treated at different times. We analyzed the effect size of timing of decompression categorically and in a continuous fashion. There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21;  = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.
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http://dx.doi.org/10.1089/neu.2021.0040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309437PMC
August 2021

A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury.

J Neurotrauma 2021 Aug 1;38(15):2065-2072. Epub 2021 Mar 1.

BioAxone BioSciences, Inc, Boston, Massachusetts, USA.

Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. The study enrolled patients 14-75 years of age with acute traumatic cervical SCIs, C4-C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72 h after injury. Patients were randomized 1:1 with stratification by age (<30 vs. ≥30 years) and AIS grade (A vs. B with sacral pinprick preservation vs. B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetics and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after ∼33% of patients were enrolled. The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.
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http://dx.doi.org/10.1089/neu.2020.7096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309435PMC
August 2021

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

Lancet Neurol 2021 02 21;20(2):117-126. Epub 2020 Dec 21.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/S1474-4422(20)30406-3DOI Listing
February 2021

Trends in Demographics and Markers of Injury Severity in Traumatic Cervical Spinal Cord Injury.

J Neurotrauma 2021 03 8;38(6):756-764. Epub 2021 Jan 8.

R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Over the past four decades, there have been progressive changes in the epidemiology of traumatic spinal cord injury (tSCI). We assessed trends in demographic and injury-related variables in traumatic cervical spinal cord injury (tCSCI) patients over an 18-year period at a single Level I trauma center. We included all magnetic resonance imaging-confirmed tCSCI patients ≥15 years of age for years 2001-2018. Among 1420 patients, 78.3% were male with a mean age 51.5 years. Etiology included falls (46.9%), motor vehicle collisions (MVCs; 34.2%), and sports injuries (10.9%). Median American Spinal Injury Association (ASIA) Motor Score (AMS) was 44, complete tCSCI was noted in 29.6% of patients, fracture dislocations were noted in 44.7%, and median intramedullary lesion length (IMLL) was 30.8 mm (complete injuries 56.3 mm and incomplete injuries 27.4 mm). Over the study period, mean age and proportion of falls increased ( < 0.001) whereas proportion attributable to MVCs and sports injuries decreased ( < 0.001). Incomplete injuries, AMS, and the proportion of patients with no fracture dislocations increased whereas complete injuries decreased significantly. IMLL declined ( = 0.17) and proportion with hematomyelia did not change significantly. In adjusted regression models, increase in age and decreases in prevalence of MVC mechanism and complete injuries over time remained statistically significant. Changes in demographic and injury-related characteristics of tCSCI patients over time may help explain the observed improvement in outcomes. Further, improved clinical outcomes and drop in IMLL may reflect improvements in initial risk assessment and pre-hospital management, advances in healthcare delivery, and preventive measures including public education.
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http://dx.doi.org/10.1089/neu.2020.7415DOI Listing
March 2021

The Effect of Elevated Mean Arterial Blood Pressure in Cervical Traumatic Spinal Cord Injury with Hemorrhagic Contusion.

World Neurosurg 2020 12 2;144:e405-e413. Epub 2020 Sep 2.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA; Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, Maryland, USA.

Objective: Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied.

Methods: A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months.

Results: A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm. Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87-0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99-1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination.

Conclusion: The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.
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http://dx.doi.org/10.1016/j.wneu.2020.08.163DOI Listing
December 2020

Surgical Management of Thoracolumbar Burst Fractures: Surgical Decision-making Using the AOSpine Thoracolumbar Injury Classification Score and Thoracolumbar Injury Classification and Severity Score.

Clin Spine Surg 2021 02;34(1):4-13

Rothman Institute, Philadelphia, PA.

The management of thoracolumbar burst fractures is controversial with no universally accepted treatment algorithm. Several classification and scoring systems have been developed to assist in surgical decision-making. The most widely accepted are the Thoracolumbar Injury Classification and Severity Score (TLICS) and AOSpine Thoracolumbar Injury Classification Score (TL AOSIS) with both systems designed to provide a simple objective scoring criteria to guide the surgical or nonsurgical management of complex injury patterns. When used in the evaluation and treatment of thoracolumbar burst fractures, both of these systems result in safe and consistent patient care. However, there are important differences between the 2 systems, specifically in the evaluation of the complete burst fractures (AOSIS A4) and patients with transient neurological deficits (AOSIS N1). In these circumstances, the AOSpine system may more accurately capture and characterize injury severity, providing the most refined guidance for optimal treatment. With respect to surgical approach, these systems provide a framework for decision-making based on patient neurology and the status of the posterior tension band. Here we propose an operative treatment algorithm based on these fracture characteristics as well as the level of injury.
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http://dx.doi.org/10.1097/BSD.0000000000001038DOI Listing
February 2021

The Use of Magnetic Resonance Imaging by Spine Surgeons in Management of Spinal Trauma Across AO Regions-Results of AO Spine Survey.

World Neurosurg 2020 05 4;137:e389-e394. Epub 2020 Feb 4.

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address:

Objective: To determine use of magnetic resonance imaging (MRI) for management of spinal trauma as a function of the availability of an MRI scanner across AO regions.

Methods: A survey regarding MRI availability and/or accessibility was conducted across 6 global AO regions. Questions were formulated to 1) evaluate availability of an MRI scanner and 2) whether the availability of an MRI scanner influenced time taken to image patients with spinal trauma. Pairwise comparison of responses among AO regions was performed.

Results: The survey was sent to 5.813 AO Spine members and 561 completed surveys were obtained (Africa, 3%; Asia Pacific, 22.1%; Europe, 30.8%; Latin America, 25.7%; Middle East, 9.4%; and North America, 8.9%). On availability of MRI for spinal trauma, 31.9% reported that MRI was readily available at all times, 51.3% noted 24-hour availability, but more difficult to obtain during nighttime, and 8.7% reported not having an MRI at their hospital. On time taken to obtain scans if MRI is readily available, 32.4% responded that imaging was obtained within 1 hour, whereas 39.9% stated between 1 and 4 hours. On time taken to obtain scans when MRI is least available, 7% responded that imaging was completed within 1 hour whereas 31.4% stated between 1 and 4 hours. Responses from Latin America significantly differed (P < 0.05) from all other AO regions except Africa.

Conclusions: MRI use varies across AO regions, with clinical decision making on obtaining MRI in spinal trauma being influenced heavily by the availability of an MRI scanner.
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http://dx.doi.org/10.1016/j.wneu.2020.01.200DOI Listing
May 2020

Personalising pain control with spinal cord stimulation.

Authors:
Bizhan Aarabi

Lancet Neurol 2020 02 20;19(2):103-104. Epub 2019 Dec 20.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address:

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http://dx.doi.org/10.1016/S1474-4422(19)30484-3DOI Listing
February 2020

Recovery priorities in degenerative cervical myelopathy: a cross-sectional survey of an international, online community of patients.

BMJ Open 2019 10 10;9(10):e031486. Epub 2019 Oct 10.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

Objectives: To establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM).

Design: A cross-sectional, observational study.

Setting: Patients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity.

Participants: 481 individuals suffering from DCM completed the online survey fully.

Main Outcome Measures: Functional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain (Visual Analogue Scale) and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains (arm and hand function, walking, upper body/trunk function, sexual function, elimination of pain, sensation and bladder/bowel function) in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significance <0.05.

Results: Of 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment (<0.005) who prioritised walking, even among patients with lower pain scores.

Conclusions: This is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs.
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http://dx.doi.org/10.1136/bmjopen-2019-031486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797315PMC
October 2019

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.

Crit Care Med 2019 11;47(11):e854-e862

Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.

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.
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http://dx.doi.org/10.1097/CCM.0000000000003937DOI Listing
November 2019

Iodine-based Dual-Energy CT of Traumatic Hemorrhagic Contusions: Relationship to In-Hospital Mortality and Short-term Outcome.

Radiology 2019 09 30;292(3):730-738. Epub 2019 Jul 30.

From the Departments of Diagnostic Radiology and Nuclear Medicine (U.K.B., K.S., D.D., T.P., G.L., T.R.F.), Neurosurgery (B.A., G.S., M.S.), Neurology, R. Adams Cowley Shock Trauma Center (Y.G.P.), Epidemiology and Public Health (Y.L.), University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201; and University of Maryland School of Medicine, Baltimore, Md (M.R., S.T.).

BackgroundTraumatic hemorrhagic contusions are associated with iodine leak; however, quantification of leakage and its importance to outcome is unclear.PurposeTo identify iodine-based dual-energy CT variables that correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.Materials and MethodsIn this retrospective study, consecutive patients with contusions from May 2016 through January 2017 were analyzed. Two radiologists evaluated CT variables from unenhanced admission head CT and follow-up head dual-energy CT scans obtained after contrast material-enhanced whole-body CT. The outcomes evaluated were in-hospital mortality, Rancho Los Amigos scale (RLAS) score, and disability rating scale (DRS) score. Logistic regression and linear regression were used to develop prediction models for categorical and continuous outcomes, respectively.ResultsThe study included 65 patients (median age, 48 years; interquartile range, 25-65.5 years); 50 were men. Dual-energy CT variables that correlated with mortality, RLAS score, and DRS score were iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusion. The single-energy CT variable that correlated with mortality, RLAS score, and DRS score was hematoma volume at follow-up CT. Multiple logistic regression analysis after inclusion of clinical variables identified two predictors that enabled determination of mortality: postresuscitation Glasgow coma scale (P-GCS) (adjusted odds ratio, 0.42; 95% confidence interval [CI]: 0.2, 0.86; = 0.01) and iodine quantity in pseudohematoma (adjusted odds ratio, 1.4 per milligram; 95% CI: 1.02 per milligram, 1.9 per milligram; = 0.03), with a mean area under the receiver operating characteristic curve of 0.96 ± 0.05 (standard error). For RLAS, the predictors were P-GCS (mean coefficient, 0.32 ± 0.06; < .001) and iodine quantity in contusion (mean coefficient, -0.04 per milligram ± 0.02; 0.01). Predictors for DRS were P-GCS (mean coefficient, -1.15 ± 0.27; < .001), age (mean coefficient, 0.13 per year ± 0.04; .002), and iodine quantity in contusion (mean coefficient, 0.19 per milligram ± 0.07; .02).ConclusionIodine-based dual-energy CT variables correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.© RSNA, 2019See also the editorial by Talbott and Hess in this issue.
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http://dx.doi.org/10.1148/radiol.2019190078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705608PMC
September 2019

Survival following Self-Inflicted Gunshots to the Face.

Plast Reconstr Surg 2019 08;144(2):415-422

From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins Hospital; the Department of Surgery, the Division of Plastic and Reconstructive Surgery, and the Department of Neurosurgery, University of Maryland School of Medicine; and the Division of Plastic, Reconstructive, and Maxillofacial Surgery, R Adams Cowley Shock Trauma Center.

Background: Self-inflicted gunshot wounds involving the face are highly morbid. However, there is a paucity of objective estimates of mortality. This study aims to provide prognostic guidance to clinicians that encounter this uncommon injury.

Methods: A retrospective review of patients presenting to R Adams Cowley Shock Trauma Center (a Level I trauma center) with self-inflicted gunshot wounds to the face from 2007 to 2016. Isolated gunshot wounds to the calvaria or neck were excluded. The data were analyzed to determine predictors of survival.

Results: Of the 69 patients that met inclusion criteria, 90 percent were male and 80 percent were Caucasian, with an age range of 21 to 85 years. The most frequently seen injury patterns showed submental (57 percent), intraoral (22 percent), and temporal (12 percent) entry sites. Fewer than half (41 percent) of the cohort sustained penetrative brain injury. Overall, there were 18 deaths (overall mortality, 26 percent), 17 of which were secondary to brain injury. Independent predictors of death included penetrative brain injury (OR, 17; p < 0.0001) and age. Mortality was 17 percent among patients younger than 65 years, compared with 73 percent for those aged 65 years or older (p = 0.0001). Gastrostomy placement was independently associated with 25 percent reduction in length of hospitalization (p = 0.0003).

Conclusions: Despite tremendous morbidity, the overwhelming majority of patients who present with facial self-inflicted gunshot wounds will survive, especially if they are young and have no penetrative brain injury. These findings should help guide clinical decisions for this devastating injury.

Clinical Question/level Of Evidence: Risk, III.
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http://dx.doi.org/10.1097/PRS.0000000000005842DOI Listing
August 2019

Efficacy of Ultra-Early (< 12 h), Early (12-24 h), and Late (>24-138.5 h) Surgery with Magnetic Resonance Imaging-Confirmed Decompression in American Spinal Injury Association Impairment Scale Grades A, B, and C Cervical Spinal Cord Injury.

J Neurotrauma 2020 02 1;37(3):448-457. Epub 2019 Aug 1.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland.

In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12-24 h), and 15 underwent decompressive surgery late (> 24-138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients ( = 0.009) and those with fracture dislocations ( = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score ( = 0.0004) and pre-operative IMLL ( = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively ( = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862-0.957;  < 0.001). We conclude that in patients with post-operative MRI confirmation of complete decompression following cervical TSCI, pre-operative IMLL, not the timing of surgery, determines long-term neurological outcome.
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http://dx.doi.org/10.1089/neu.2019.6606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978784PMC
February 2020

AOSpine Subaxial Cervical Spine Injury Classification System: The Relationship Between Injury Morphology, Admission Injury Severity, and Long-Term Neurologic Outcome.

World Neurosurg 2019 Oct 21;130:e368-e374. Epub 2019 Jun 21.

Department of Neurosurgery, R. Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, Maryland, USA; Department of Trauma Critical Care, R. Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, Maryland, USA.

Objective: The AOSpine Subaxial Cervical Spine Injury Classification System was introduced to improve communication, clinical management, and research. Here, the system was studied in relation to injury severity along with admission and long term neurologic follow-up.

Methods: A retrospective study was performed in subaxial cervical spine injury patients. Morphology was classified using the AOSpine Subaxial Cervical Spine Injury Classification System. Six major morphology subtypes were selected for analysis. The American Spinal Injury Association (ASIA) motor and Abbreviated Injury Severity (AIS) scores were recorded at admission and at follow-up >6 months. Admission intramedullary lesion length (IMLL) on MRI was recorded.

Results: In all, 82 patients met criteria for analysis. The mean follow-up time was 11 months (range, 6-33 months). The were 36 patients with morphology subtypes A0, 4 with A1/A2, 9 with A3/A4, 8 with B2, 11 with B3, and 14 with C. The A1/2 subtype had the least severe injuries on admission. The C and A3/A4 subtypes had the most severe injuries. The subtype C had the lowest ASIA Motor Score (AMS) and second highest percentage of complete injuries. A3/A4 patients had the highest percentage of complete injuries on admission. At follow-up, A3/A4 patients had the lowest AMS, and 33% of patients continued to have complete injuries. C subtype injuries all converted to AIS incomplete injuries on follow-up (P = 0.04). IMLL was found to be significantly different compared across multiple morphologic subtypes. Surgical management for each morphology subtype was reported.

Conclusion: The AOSpine Subaxial Cervical Spine Injury Classification System successfully associated injury morphology with IMLL along with admission and long-term neurologic function and recovery.
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http://dx.doi.org/10.1016/j.wneu.2019.06.092DOI Listing
October 2019

Comparison of Acute Diffusion Tensor Imaging and Conventional Magnetic Resonance Parameters in Predicting Long-Term Outcome after Blunt Cervical Spinal Cord Injury.

J Neurotrauma 2020 02 2;37(3):458-465. Epub 2019 Aug 2.

R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland.

This prospective longitudinal study compares the ability of conventional and diffusion tensor imaging (DTI) parameters made at the cervical spinal cord injury (CSCI) site to predict long-term neurological and functional outcomes. Twenty patients with CSCI, with follow-up at 6 or 12 months, and 15 control volunteers were included. Conventional magnetic resonance imaging (MRI) and DTI parameters were measured on admission and follow-up studies. Stepwise regression analysis was performed to find relevant parameters (normalized DTI values, conventional MRI measurements, hemorrhagic contusion [HC] or non-HC [NHC]) that correlated with three primary outcome measures: patient International Standards for Neurological Classification of Spinal Cord Injury total motor score (ISNCSCI-TMS), ability to walk, and expected recovery of upper limb motor scores (ER-ULMS) at 6 or 12 months. Univariate analysis showed HC ( < 0.0001 to 0.0098), lesion length on follow-up MRI ( < 0.0001 to 0.019), mean diffusivity ( = 0.01 to 0.045), and axial diffusivity ( = 0.004 to 0.023) predicted all three primary outcomes. Conspicuity of HC was significantly better on axial susceptibility-weighted imaging (SWI) compared with T2* images ( = 0.0009). A negative correlation existed between HC volumes on sagittal SWI images and follow-up ISNCSCI-TMS (  = 0.02). The regression model identified NHC as the best predictor of the ability to walk (sensitivity = 88.9%; specificity = 100%; positive predictive value = 100%; negative predictive value = 91%;  < 0.0001) and lesion length on follow-up MRI as the best predictor of ER-ULMS (β coefficient = 0.12, standard error [SE] = 0.07; R = 0.64;  = 0.0002). Finally, NHC (β coefficient = 24.2, SE = 3.7;  < 0.0001) and lesion length on initial MRI (β coefficient = 0.78, SE = 0.2;  = 0.002) were the best predictors of ISNCSCI-TMS (R = 0.83;  < 0.0001). Our study demonstrates HC and follow-up lesion length are potential neuroimaging biomarkers in predicting long-term neurological and functional outcome following blunt CSCI.
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http://dx.doi.org/10.1089/neu.2019.6394DOI Listing
February 2020

RE-CODE DCM (search Objectives and ommon ata lements for egenerative ervical yelopathy): A Consensus Process to Improve Research Efficiency in DCM, Through Establishment of a Standardized Dataset for Clinical Research and the Definition of the Research Priorities.

Global Spine J 2019 May 8;9(1 Suppl):65S-76S. Epub 2019 May 8.

Academic Neurosurgery Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Study Design: Mixed-method consensus process.

Objectives: Degenerative cervical myelopathy (DCM) is a common and disabling condition that arises when mechanical stress damages the spinal cord as a result of degenerative changes in the surrounding spinal structures. RECODE-DCM (search Objectives and ommon ata lements for egenerative ervical yelopathy) aims to improve efficient use of health care resources within the field of DCM by using a multi-stakeholder partnership to define the DCM research priorities, to develop a minimum dataset for DCM clinical studies, and confirm a definition of DCM.

Methods: This requires a multi-stakeholder partnership and multiple parallel consensus development processes. It will be conducted via 4 phases, adhering to the guidance set out by the COMET (Core Outcomes in Effectiveness Trials) and JLA (James Lind Alliance) initiatives. Phase 1 will consist of preliminary work to inform online Delphi processes (Phase 2) and a consensus meeting (Phase 3). Following the findings of the consensus meeting, a synthesis of relevant measurement instruments will be compiled and assessed as per the COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) criteria, to allow recommendations to be made on how to measure agreed data points. Phase 4 will monitor and promote the use of eventual recommendations.

Conclusions: RECODE-DCM sets out to establish for the first time an index term, minimum dataset, and research priorities together. Our aim is to reduce waste of health care resources in the future by using patient priorities to inform the scope of future DCM research activities. The consistent use of a standard dataset in DCM clinical studies, audit, and clinical surveillance will facilitate pooled analysis of future data and, ultimately, a deeper understanding of DCM.
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http://dx.doi.org/10.1177/2192568219832855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512197PMC
May 2019

AOSpine Global Survey: International Trends in Utilization of Magnetic Resonance Imaging/Computed Tomography for Spinal Trauma and Spinal Cord Injury across AO Regions.

J Neurotrauma 2019 12 21;36(24):3323-3331. Epub 2019 Jun 21.

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin.

The aim of this study was to determine the current trends in magnetic resonance imaging (MRI)/computed tomography (CT) utilization for spine trauma in various clinical scenarios. We conducted a survey across six AO regions and preformed pair-wise comparisons between responses obtained from different AO regions. The survey was sent to 5813 surgeons and had a 9.6% response rate with the majority being orthopedic followed by neurosurgeons. In a neurologically intact patient, the predominant imaging modality for all AO regions was CT. For patients with spinal cord injury (SCI), the predominant choice for all AO regions was CT + MRI + x-ray except North America, which was CT + MRI; pair-wise comparisons revealed significant differences involving LATAM (Latin America) versus (Asia-Pacific [APAC], Europe [EU], and Middle East [MEA]) and APAC versus (LATAM and North America [NA]). In a patient with incomplete SCI (ISCI) who presented within 4 h and had CT, the predominant choice for all AO regions was "forgo MRI and proceed to operating room (OR)." Similar to ISCI, in a patient with complete SCI, the predominant option for all AO regions was the same as ISCI, but the range was lower. Pair-wise comparisons noted significant differences between MEA and APAC, with both exhibiting differences compare to NA, LATAM, and EU for complete and ISCI. Most AO regions obtained post-operative MRI only if there was a new deficit. In summary, decisions about the use of a particular imaging modality across AO regions appears to be influenced by the neurological status of the patient upon admission and the presence of neurological deficits post-surgery. Type of residency training and fellowship training did not have an influence on choosing the appropriate imaging modality for both intact and impaired patients. Further study is needed to determine whether accessibility to MRI would change surgeons' attitude toward obtaining MRI in patients with SCI.
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http://dx.doi.org/10.1089/neu.2019.6464DOI Listing
December 2019

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

J Neurotrauma 2019 11 17;36(21):3044-3050. Epub 2019 Jun 17.

Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.

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%;  = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%;  < 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.
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http://dx.doi.org/10.1089/neu.2018.6245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791472PMC
November 2019

Extent of Spinal Cord Decompression in Motor Complete (American Spinal Injury Association Impairment Scale Grades A and B) Traumatic Spinal Cord Injury Patients: Post-Operative Magnetic Resonance Imaging Analysis of Standard Operative Approaches.

J Neurotrauma 2019 03 9;36(6):862-876. Epub 2018 Oct 9.

5 Walter Reed National Military Medical Center, Bethesda, Maryland.

Although decompressive surgery following traumatic spinal cord injury (TSCI) is recommended, adequate surgical decompression is rarely verified via imaging. We utilized magnetic resonance imaging (MRI) to analyze the rate of spinal cord decompression after surgery. Pre-operative (within 8 h of injury) and post-operative (within 48 h of injury) MRI images of 184 motor complete patients (American Spinal Injury Association Impairment Scale [AIS] grade A = 119, AIS grade B = 65) were reviewed to verify spinal cord decompression. Decompression was defined as the presence of a patent subarachnoid space around a swollen spinal cord. Of the 184 patients, 100 (54.3%) underwent anterior cervical discectomy and fusion (ACDF), and 53 of them also underwent laminectomy. Of the 184 patients, 55 (29.9%) underwent anterior cervical corpectomy and fusion (ACCF), with (26 patients) or without (29 patients) laminectomy. Twenty-nine patients (16%) underwent stand-alone laminectomy. Decompression was verified in 121 patients (66%). The rates of decompression in patients who underwent ACDF and ACCF without laminectomy were 46.8% and 58.6%, respectively. Among these patients, performing a laminectomy increased the rate of decompression (72% and 73.1% of patients, respectively). Twenty-five of 29 (86.2%) patients who underwent a stand-alone laminectomy were found to be successfully decompressed. The rates of decompression among patients who underwent laminectomy at one, two, three, four, or five levels were 58.3%, 68%, 78%, 80%, and 100%, respectively (p < 0.001). In multi-variate logistic regression analysis, only laminectomy was significantly associated with successful decompression (odds ratio 4.85; 95% confidence interval 2.2-10.6; p < 0.001). In motor complete TSCI patients, performing a laminectomy significantly increased the rate of successful spinal cord decompression, independent of whether anterior surgery was performed.
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http://dx.doi.org/10.1089/neu.2018.5834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484360PMC
March 2019

Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury.

J Neurotrauma 2019 03 19;36(6):891-902. Epub 2018 Oct 19.

1 Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.

Human neural stem cell transplantation (HuCNS-SC) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. In Cohort I (n = 6) dose escalation from 15,000,000 to 40,000,000 cells was performed to determine the optimum dose. In Cohort II an additional six participants were transplanted at target dose (40,000,000) and compared with four untreated controls. Within the transplant group, there were nine American Spinal Injury Association Impairment Scale (AIS) B and three AIS A participants with a median age at transplant of 28 years with an average time to transplant post-injury of 1 year. Immunosuppression was continued for 6 months post-transplant, and immunosuppressive blood levels of tacrolimus were achieved and well tolerated. At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.
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http://dx.doi.org/10.1089/neu.2018.5843DOI Listing
March 2019

Response to Cadotte et al. (doi: 10.1089/neu.2018.5903): What Has Been Learned from Magnetic Resonance Imaging Examination of the Injured Human Spinal Cord: A Canadian Perspective.

J Neurotrauma 2019 04 12;36(8):1386-1387. Epub 2018 Dec 12.

3 Department of Neurosurgery, University of Maryland Medical Center, Baltimore, Maryland.

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http://dx.doi.org/10.1089/neu.2018.6135DOI Listing
April 2019

Sulfonylurea Receptor 1, Transient Receptor Potential Cation Channel Subfamily M Member 4, and KIR6.2:Role in Hemorrhagic Progression of Contusion.

J Neurotrauma 2019 04 4;36(7):1060-1079. Epub 2018 Oct 4.

1 Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland.

In severe traumatic brain injury (TBI), contusions often are worsened by contusion expansion or hemorrhagic progression of contusion (HPC), which may double the original contusion volume and worsen outcome. In humans and rodents with contusion-TBI, sulfonylurea receptor 1 (SUR1) is upregulated in microvessels and astrocytes, and in rodent models, blockade of SUR1 with glibenclamide reduces HPC. SUR1 does not function by itself, but must co-assemble with either KIR6.2 or transient receptor potential cation channel subfamily M member 4 (TRPM4) to form K (SUR1-KIR6.2) or SUR1-TRPM4 channels, with the two having opposite effects on membrane potential. Both KIR6.2 and TRPM4 are reportedly upregulated in TBI, especially in astrocytes, but the identity and function of SUR1-regulated channels post-TBI is unknown. Here, we analyzed human and rat brain tissues after contusion-TBI to characterize SUR1, TRPM4, and KIR6.2 expression, and in the rat model, to examine the effects on HPC of inhibiting expression of the three subunits using intravenous antisense oligodeoxynucleotides (AS-ODN). Glial fibrillary acidic protein (GFAP) immunoreactivity was used to operationally define core versus penumbral tissues. In humans and rats, GFAP-negative core tissues contained microvessels that expressed SUR1 and TRPM4, whereas GFAP-positive penumbral tissues contained astrocytes that expressed all three subunits. Förster resonance energy transfer imaging demonstrated SUR1-TRPM4 heteromers in endothelium, and SUR1-TRPM4 and SUR1-KIR6.2 heteromers in astrocytes. In rats, glibenclamide as well as AS-ODN targeting SUR1 and TRPM4, but not KIR6.2, reduced HPC at 24 h post-TBI. Our findings demonstrate upregulation of SUR1-TRPM4 and K after contusion-TBI, identify SUR1-TRPM4 as the primary molecular mechanism that accounts for HPC, and indicate that SUR1-TRPM4 is a crucial target of glibenclamide.
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http://dx.doi.org/10.1089/neu.2018.5986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446209PMC
April 2019

Natural History, Predictors of Outcome, and Effects of Treatment in Thoracic Spinal Cord Injury: A Multi-Center Cohort Study from the North American Clinical Trials Network.

J Neurotrauma 2018 11 7;35(21):2554-2560. Epub 2018 Jun 7.

8 Division of Neurosurgery, Toronto Western Hospital, University of Toronto , Toronto, Ontario, Canada .

The course, treatment response, and recovery potential after acute traumatic spinal cord injury (SCI) have been shown to differ depending on the neurological level of injury. There are limited data focused on thoracic-level injuries, however. A cohort of 86 patients from the prospectively maintained North American Clinical Trials Network SCI registry were identified and studied to characterize the patterns of neurological recovery and to determine rates of acute hospital death and pulmonary complications. Regression analyses were used to examine the relationship between timing of surgery and administration of methylprednisolone on neurologic and clinical outcomes. Neurological conversion (≥1 American Spinal Injury Association Impairment Scale [AIS] grade improvement) was poorest for AIS grade A patients; 14.3% converted at last available follow-up (mean eight months). While rates of conversion were more optimistic for AIS-B patients (54.5%) and AIS C injuries (77.8%) at the same time point, none of the AIS grade D patients converted to AIS E. At last available follow-up (mean eight months), the magnitudes of lower motor extremity score (LEMS) change were highest for AIS C injuries (21.9 points), then AIS B (17.7 points), AIS D (16.4 points), and finally AIS A (2.5 points) (p < 0.05). Early surgical intervention (<24 h post-injury) was independently associated with an additional seven points in motor recovery and a 60% decreased incidence of pulmonary events (p < 0.05). Methylprednisolone administration was not an independent predictor of neurological outcome or pulmonary complications. Evaluation of this cohort obtained from a modern multi-center SCI registry provides an update on the natural history, acute death, and incidence of pulmonary complications after traumatic thoracic SCI. Although small sample size limited the extent of analyses possible, early surgical treatment was associated with significantly larger motor recovery and lower rates of pulmonary complications.
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http://dx.doi.org/10.1089/neu.2017.5535DOI Listing
November 2018
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