Rapid increase in departmental scholarly activity independent of residents demonstrates reproducibility and success of intensive research initiative in neurosurgery department.

BACKGROUND: Neurological surgery remains one of the most competitive specialties with a match rate of <70%. Historically, medical student performance was gauged through the USMLE Step 1. However, with the recent exam score change, metrics such as recommendation letters, research, and clerkship grades carry increased importance. Research experiences vary greatly between institutions and medical students depend on faculty/resident mentorship in order to facilitate scholarly activity. We previously reported our 2-year intensive research initiative (IRI) in a neurosurgery program. Here we report successful implementation of the IRI in a disparate setting, a department devoid of residents, and demonstrate the IRI's reproducibility with non-resident learners. MATERIALS & METHODS: We compared retrospective data from 2007 to 2020 with the IRI's results during the 2-year study period (July 2020-July 2022). RESULTS: The IRI resulted in a rapid exponential increase in publications, with medical student led peer-reviewed publications (PRPs) increasing 1000% and pre-residency fellow (PRF) PRPs increasing by 4900%. Learner involvement on PRPs pre-IRI was 31%, increasing to 72% post-IRI implementation. CONCLUSIONS: We present the IRI's success increasing academic productivity despite utilizing only non-resident learners. Students underrepresented in medicine and those at non-tier 1 institutions receive unequal research and clinical opportunities, therefore, prioritizing and providing sufficient opportunities/mentorship is crucial in their success in matching into competitive specialties. Our IRI allows for early faculty/resident student mentorship and gives students more flexibility as it allows medical students at varying stages to participate in research with no set time frame.

The risk analysis index demonstrates superior discriminative ability in predicting extended length of stay in pituitary adenoma resection patients when compared to the 5-point modified frailty index.

Objective: To compare the predictive abilities of two frailty indices on post-operative morbidity and mortality in patients undergoing pituitary adenoma resection. Methods: The National Surgical Quality Improvement Program (NSQIP) database was used to retrospectively collect data for patients undergoing pituitary adenoma resection between 2015-2019. To compare the predictive abilities of two of the most common frailty indices, the 5-point modified frailty index (mFI-5) and the risk analysis index (RAI), receiver operating curve analysis (ROC) and area under the curve (AUC)/Cstatistic were used. Results: In our cohort of 1,454 patients, the RAI demonstrated superior discriminative ability to the mFI-5 in predicting extended length of stay (C-statistic 0.59, 95% CI 0.56-0.62 vs. C-statistic 0.51, 95% CI: 0.48-0.54, p = 0.0002). The RAI only descriptively appeared superior to mFI-5 in determining mortality (C-statistic 0.89, 95% CI 0.74-0.99 vs. Cstatistic 0.63, 95% CI 0.61-0.66, p=0.11), and NHD (C-statistic 0.68, 95% CI 0.60-0.76 vs. C-statistic 0.60, 95% CI: 0.57-0.62, p=0.15). Conclusions: Pituitary adenomas account for one of the most common brain tumors in the general population, with resection being the preferred treatment for patients with most hormone producing tumors or those causing compressive symptoms. Although pituitary adenoma resection is generally safe, patients who experience post-operative complications frequently share similar pre-operative characteristics and comorbidities. Therefore, appropriate pre-operative risk stratification is imperative for adequate patient counseling and informed consent in these patients. Here we present the first known report showing the superior discriminatory ability of the RAI in predicting eLOS when compared to the mFI-5.

Baseline labs predict adverse postoperative outcomes following metastatic brain tumor resection: Analysis of 5943 patients from a prospective surgical registry (2015-2019).

INTRODUCTION: The present study sought to evaluate the predictive accuracy of preoperative lab values (PLV) on postoperative metastatic brain tumor resection (MBTR) outcomes using data queried from a large prospective international surgical registry, representing over 700 hospitals in 11 countries. METHODS: Adult metastatic brain tumor patients (N = 5943) were queried from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database, from 2015 to 2019, using diagnostic and procedural coding. The relationship between preoperative lab values and key indicators of adverse postoperative outcomes following metastatic brain tumor resection were assessed with univariate and multivariate analyses. Adverse postoperative outcomes of interest included: 30-day mortality, Clavien-Dindo Grade IV (CDIV) complications, extended length of stay (eLOS), and discharge to non-home destination (NHD), as well as secondary outcomes: non-Clavien-Dindo Grade IV complications, unplanned reoperation, and unplanned readmission. RESULTS: Independent PLV most strongly associated with 30-day mortality were hypernatremia, increased serum creatinine, and thrombocytopenia. Significant predictors of CDIV complications were hypoalbuminemia and thrombocytopenia. eLOS was associated with hypoalbuminemia, anemia, and hyponatremia. The strongest independent predictors of NHD were anemia, hyperbilirubinemia, and hypoalbuminemia. CONCLUSION: Several pre-operative lab values independently predicted worse outcomes for metastatic brain tumor resection patients. Hypoalbuminemia, thrombocytopenia, and anemia had the strongest association with the study's adverse postoperative outcomes. These baseline lab values may be considered for preoperative risk stratification of metastatic brain tumor patients.

Superior discrimination of the Risk Analysis Index compared with the 5-item modified frailty index in 30-day outcome prediction after anterior cervical discectomy and fusion.

OBJECTIVE: The objective of this paper was to compare the predictive ability of the recalibrated Risk Analysis Index (RAI-rev) with the 5-item modified frailty index-5 (mFI-5) for postoperative outcomes of anterior cervical discectomy and fusion (ACDF). METHODS: This study was performed using data of adult (age > 18 years) ACDF patients obtained from the National Surgical Quality Improvement Program database during the years 2015-2019. Multivariate modeling and receiver operating characteristic (ROC) curve analysis, including area under the curve/C-statistic calculation with the DeLong test, were performed to evaluate the comparative discriminative ability of the RAI-rev and mFI-5 for 5 postoperative outcomes. RESULTS: Both the RAI-rev and mFI-5 were independent predictors of increased postoperative mortality and morbidity in a cohort of 61,441 ACDF patients. In the ROC analysis for 30-day mortality prediction, C-statistics indicated a significantly better performance of the RAI-rev (C-statistic = 0.855, 95% CI 0.852-0.858) compared with the mFI-5 (C-statistic = 0.684, 95% CI 0.680-0.688) (p < 0.001, DeLong test). The results were similar for postoperative ACDF morbidity, Clavien-Dindo grade IV complications, nonhome discharge, and reoperation, demonstrating the superior discriminative ability of the RAI-rev compared with the mFI-5. CONCLUSIONS: The RAI-rev demonstrates superior discrimination to the mFI-5 in predicting postoperative ACDF mortality and morbidity. To the authors' knowledge, this is the first study to document frailty as an independent risk factor for postoperative mortality after ACDF. The RAI-rev has conceptual fidelity to the frailty phenotype and may be more useful than the mFI-5 in preoperative ACDF risk stratification. Prospective validation of these findings is necessary, but patients with high RAI-rev scores may benefit from knowing that they might have an increased surgical risk for ACDF morbidity and mortality.

The 5-item modified frailty index predicts spinal osteotomy outcomes better than age in adult spinal deformity patients: an ACS - NSQIP analysis.

PURPOSE: To evaluate the utility of 5-Item Modified Frailty Index (mFI-5) as compared to chronological age in predicting outcomes of spinal osteotomy in Adult Spinal Deformity (ASD) patients. METHODS: Using Current Procedural and Terminology (CPT) codes, the American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) database was queried for adult patients undergoing spinal osteotomy from 2015 to 2019. Multivariate regression analysis was performed to evaluate the effect of baseline frailty status, measured by mFI-5 score, and chronological age on postoperative outcomes. Receiver-operating characteristic (ROC) curve analysis was performed to analyze the discriminative performance of age versus mFI-5. RESULTS: A total of 1,789 spinal osteotomy patients (median age 62 years) were included in the analysis. Among the patients assessed, 38.5% (n = 689) were pre-frail, 14.6% frail (n = 262), and 2.2% (n = 39) severely frail using the mFI-5. Based on the multivariate analysis, increasing frailty tier was associated with worsening outcomes, and higher odds ratios (OR) for poor outcomes were found for increasing frailty tiers as compared to age. Severe frailty was associated with the worst outcomes, e.g., unplanned readmission (OR 9.618, [95% CI 4.054-22.818], p < 0.001) and major complications (OR 5.172, [95% CI 2.271-11.783], p < 0.001). In the ROC curve analysis, mFI-5 score (AUC 0.838) demonstrated superior discriminative performance than age (AUC 0.601) for mortality. CONCLUSIONS: The mFI5 frailty score was found to be a better predictor than age of worse postoperative outcomes in ASD patients. Incorporating frailty in preoperative risk stratification is recommended in ASD surgery.

Comparison of the Risk Analysis Index and the modified 5-factor frailty index in predicting 30-day morbidity and mortality after spine surgery.

OBJECTIVE: Frailty's role in preoperative risk assessment in spine surgery has increased in association with the increasing size of the aging population. However, previous frailty assessment tools have significant limitations. The aim of this study was to compare the predictive ability of the Risk Analysis Index (RAI) with the 5-factor modified frailty index (mFI-5) for postoperative spine surgery morbidity and mortality. METHODS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program database for adults > 18 years who underwent spine surgery between 2015 and 2019. Multivariate modeling and receiver operating characteristic curve analysis, including area under the curve/C-statistic calculations, were performed to evaluate the comparative discriminative ability of RAI and mFI-5 on postoperative outcomes. RESULTS: In a cohort of 292,225 spine surgery patients, multivariate modeling showed that increasing RAI scores, and not increasing mFI-5 scores, were independent predictors of increased postoperative mortality for the trauma, tumor, and infection subcohorts. In the overall spine cohort, both increasing RAI and increasing mFI-5 scores were associated with increased mortality, but C-statistics indicated that the RAI (C-statistic 0.802 [95% CI 0.800-0.803], p < 0.0001, DeLong test) had superior discrimination compared with the mFI-5 (C-statistic 0.677 [95% CI 0.675-0.679], p < 0.0001, DeLong test). In subgroup analyses, the RAI had superior discriminative ability to mFI-5 for mortality in the trauma and infection groups (p < 0.001 and p = 0.039, respectively). CONCLUSIONS: The RAI demonstrates superior discrimination to the mFI-5 for predicting postoperative mortality and morbidity after spine surgery and the RAI maintains conceptual fidelity to the frailty phenotype. Patients with high RAI scores may benefit from knowing the possibility of increased surgical risk with potential spine surgery.

Preoperative Laboratory Values Are Predictive of Adverse Postoperative Outcomes in Patients Older Than 65 Years Undergoing Brain Tumor Resection: A National Surgical Quality Improvement Program Study.

OBJECTIVE: In this study, we used a large national database to assess the effect of preoperative laboratory value (PLV) derangements on postoperative outcomes in patients older than 65 years undergoing brain tumor resection. METHODS: Data was collected for patients >65 years old undergoing brain tumor resection from 2015 to 2019 (N = 10,525). Univariate and multivariate analysis were performed for 11 PLVs and 6 postoperative outcomes. RESULTS: Hypernatremia (odds ratio [OR], 4.707; 95% confidence interval [CI], 1.695-13.071; P < 0.01) and increased creatinine level (OR, 2.556; 95% CI, 1.291-5.060; P < 0.01) were the most significant predictors of 30-day mortality. The most significant predictor of Clavien-Dindo grade IV complications was increased creatinine level (OR, 1.667; 95% CI, 1.064-2.613; P < 0.05), whereas, significant predictors of major complications were hypoalbuminemia (OR, 1.426; 95% CI, 1.132-1.796; P < 0.05) and leukocytosis (OR, 1.347; 95% CI, 1.075-1.688; P < 0.05). Predictors of readmission were anemia (OR, 1.326; 95% CI, 1.047-1.680; P < 0.05) and thrombocytopenia (OR, 1.387; 95% CI, 1.037-1.856; P < 0.05), whereas, hypoalbuminemia (OR, 1.787; 95% CI, 1.280-2.495; P < 0.001) was predictive of reoperation. Increased partial thromboplastin time and hypoalbuminemia were predictors of extended length of stay (OR, 2.283, 95% CI, 1.360-3.834, P < 0.01 and OR, 1.553, 95% CI, 1.553-1.966, P < 0.001, respectively). Hypernatremia (OR, 2.115; 95% CI, 1.181-3.788; P < 0.05) and hypoalbuminemia (OR, 1.472; 95% CI, 1.239-1.748; P < 0.001) were the most significant predictors of NHD. Seven of 11 PLVs were associated with adverse postoperative outcomes. CONCLUSIONS: PLV derangements were significantly associated with adverse postoperative outcomes in patients older than 65 years undergoing brain tumor resection. The most significant predictors of adverse postoperative outcomes were hypoalbuminemia and leukocytosis.

Clinically predictive baseline labs for post-operative outcomes of brain tumors using NSQIP database.

PURPOSE: This study was performed to assess the effect of baseline Preoperative Laboratory Values (PLV) on post-operative Brain Tumor Resection (BTR) outcomes in a large national registry. METHODS: We extracted data from the National Surgical Quality Improvement Program (NSQIP) database for BTR patients 2015-2019 (n = 3 0,951). Uni- and multivariate analyses were performed for PLV and key surgical outcomes. RESULTS: The most significant PLV predictors of 30-day mortality after BTR included hypernatremia (odds ratio, OR 4.184, 95% CI, 2.384-7.343, p < 0.001), high serum creatinine (OR 2.244, 95% CI 1.502-3.352, p < 0.001), thrombocytopenia (OR 1.997, 95% CI 1.438, 2.772, p < 0.001), and leukocytosis (OR 1.635, 95% CI 1.264, 2.116, p < 0.001). The most significant predictors of Clavien IV complications were increased INR (OR 2.653, 95% CI 1.444, 4.875, p < 0.01), thrombocytopenia (OR 1.514, 95% CI 1.280, 1.792, p < 0.001), hypoalbuminemia (OR 1.480, 95% CI 1.274, 1.719, p < 0.001), and leukocytosis (OR 1.467, 95% CI 1.306, 1.647, p < 0.001). The most robust predictors of eLOS were increased INR (OR 1.941, 95% CI 1.231, 3.060, p < 0.01) and hypoalbuminemia (OR 1.993, 95% CI 1.823, 2.179, p < 0.001), and those for non-routine discharge included increased INR (OR 1.897, 95% CI 1.196, 3.008, p < 0.01) and hypernatremia (OR 1.565, 95% CI 1.217, 2.012, p < 0.001). CONCLUSIONS: Several PLV independently predicted worse outcomes in BTR patients. Baseline labs should be routinely used for the pre-operative risk stratification of these patients.

Preoperative frailty risk in deep brain stimulation patients: Risk analysis index predicts Clavien-Dindo IV complications.

OBJECTIVE: Deep brain stimulation (DBS) improves patients' quality of life in multiple movement disorders and chronic neurodegenerative diseases. There are no published studies assessing frailty's impact on DBS outcomes. We evaluated frailty's impacts on DBS outcomes, comparing discriminative thresholds of the risk analysis index (RAI) to modified frailty index-5 (mFI-5) for predicting Clavien-Dindo complications (CDIV). METHODS: Patients who underwent DBS between 2015 and 2019 in the ACS-NSQIP registry were included. We employed receiver operating characteristic (ROC) curve to examine the discriminative thresholds of RAI and mFI-5 and multivariable analyses for postoperative outcomes. Our primary outcome was CDIV, and secondary outcomes were discharge to higher-level care facility, unplanned reoperation within 30 days, in any hospital, for any procedure related to the index procedure, and extended length of stay. RESULTS: A total of 3795 patients were included. In the ROC analysis for CDIV, RAI showed superior discriminative threshold (C-statistic = 0.70, 95% CI 0.61-0.80, <0.001) than mFI-5 (C-statistic = 0.60, 95% CI 0.49-0.70, P = 0.08). On multivariable analyses, frailty stratified by RAI, had independent associations with CDIV, i.e., pre-frail 2-fold increase OR 2.04 (95% CI: 1.94-2.14) p < 0.001, and frail 39% increase OR 1.39 (95% CI: 1.27-1.53), p < 0.001. CONCLUSION: Frailty was an independent risk-factor for CDIV. The RAI had superior discriminative thresholds than mFI-5 in predicting CDIV after DBS. Our ability to identify frail patients prior to DBS presents a novel clinical opportunity for quality improvement strategies to target this specific patient population. RAI may be a useful primary frailty screening modality for potential DBS candidates.

Postprocedural Complications of External Ventricular Drains: A Meta-Analysis Evaluating the Absolute Risk of Hemorrhages, Infections, and Revisions.

BACKGROUND: External ventricular drain (EVD) insertion is often a lifesaving procedure frequently used in neurosurgical emergencies. It is routinely done at the bedside in the neurocritical care unit or in the emergency room. However, there are infectious and noninfectious complications associated with this procedure. This meta-analysis sought to evaluate the absolute risk associated with EVD hemorrhages, infections, and revisions. The secondary purpose was to identify and characterize risk factors for EVD complications. METHODS: We searched the MEDLINE (PubMed) database for "external ventricular drain," "external ventricular drain" + "complications" or "Hemorrhage" or "Infection" or "Revision" irrespective of publication year. Estimates from individual studies were combined using a random effects model, and 95% confidence intervals (CIs) were calculated with maximum likelihood specification. To investigate heterogeneity, the t2 and I2 tests were utilized. To evaluate for publication bias, a funnel plot was developed. RESULTS: There were 260 total studies screened from our PubMed literature database search, with 176 studies selected for full-text review, and all of these 176 studies were included in the meta-analysis as they met the inclusion criteria. A total of 132,128 EVD insertions were reported, with a total of 130,609 participants having at least one EVD inserted. The pooled absolute risk (risk difference) and percentage of the total variability due to true heterogeneity (I2) for hemorrhagic complication was 1236/10,203 (risk difference: -0.63; 95% CI: -0.66 to -0.60; I2: 97.8%), infectious complication was 7278/125,909 (risk difference: -0.65; 95% CI: -0.67 to -0.64; I2: 99.7%), and EVD revision was 674/4416 (risk difference: -0.58; 95% CI: -0.65 to -0.51; I2: 98.5%). On funnel plot analysis, we had a variety of symmetrical plots, and asymmetrical plots, suggesting no bias in larger studies, and the lack of positive effects/methodological quality in smaller studies. CONCLUSIONS: In conclusion, these findings provide valuable information regarding the safety of one of the most important and most common neurosurgical procedures, EVD insertion. Implementing best-practice standards is recommended in order to reduce EVD-related complications. There is a need for more in-depth research into the independent risk factors associated with these complications, as well as confirmation of these findings by well-structured prospective studies.

Advanced frailty assessment tool predicts successful awake craniotomy in a 92-year-old patient: A case report.

Background: The awake craniotomy (AC) procedure allows for safe and maximal resection of brain tumors from highly eloquent regions. However, geriatric patients are often viewed as poor candidates for AC due to age and medical comorbidities. Frailty assessments gauge physiological reserve for surgery and are valuable tools for preoperative decision-making. Here, we present a novel case illustrating how frailty scoring enabled an elderly but otherwise healthy female to undergo successful AC for tumor resection. Case Description: A 92-year-old right-handed female with history of hypertension and basal cell skin cancer presented with a 1-month history of progressive aphasia and was found to have a ring-enhancing left frontoparietal mass abutting the rolandic cortex concerning for malignant neoplasm. Frailty scoring with the recalibrated risk analysis index (RAI-C) tool revealed a score of 30 (of 81) indicating low surgical risk. The patient and family were counseled appropriately that, despite advanced chronological age, a low frailty score predicts favorable surgical outcomes. The patient underwent left-sided AC for resection of tumor and experienced immediate improvement of speech intraoperatively. After surgery, the patient was neurologically intact and had an unremarkable postoperative course with significant improvements from preoperatively baseline at follow-up. Conclusion: To the best of our knowledge, this case represents the oldest patient to undergo successful AC for brain tumor resection. Nonfrail patients over 90 years of age with the proper indications may tolerate cranial surgery. Frailty scoring is a powerful tool for preoperative risk assessment in the geriatric neurosurgery population.

Continuous Tissue Plasminogen Activator Infusion Using a Minimally Invasive Irrigating Catheter for the Treatment of Intraparenchymal Hemorrhage Within the Basal Ganglia: Case Reports.

BACKGROUND AND IMPORTANCE: Intraparenchymal hemorrhage (IPH) is a debilitating and highly morbid type of stroke with limited effective treatment modalities. Minimally invasive evacuation with tissue plasminogen activator (rt-PA) has demonstrated promise for mortality/functional improvements with adequate clot volume reduction. In this study, we report 2 cases of continuous rt-PA infusion using a closed circuit, dual lumen catheter, and irrigation system (IRRAflow) for IPH treatment. CLINICAL PRESENTATION: A 55-year-old man was admitted for acute onset left hemiparesis; he was found to have right basal ganglia IPH. He was treated with continuous rt-PA irrigation using the IRRAflow device, at a rate of 30 mL/h for 119 hours, with a total volume reduction of 87.8 mL and post-treatment volume of 1.2 mL. At 3-month follow-up, he exhibited a modified Rankin score of 4 and improved hemiparesis. A 39-year-old woman was admitted for acute onset left facial droop, left hemianopsia, and left hemiparesis; she was diagnosed with a right basal ganglia IPH. She was treated with drainage and continuous rt-PA irrigation at 30 mL/h for 24 hours, with a total hematoma volume reduction of 41 mL and with a final post-treatment volume of 9.1 mL. At 3-month follow-up, she exhibited a modified Rankin score of 3 with some improvement in left hemiparesis. CONCLUSION: Continuous rt-PA infusion using a minimally invasive catheter with saline irrigation was feasible and resulted in successful volume reduction in 2 patients with IPH. This technique is similar to the Minimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage Evacuation (MISTIE) approach but offers the potential advantages of less breaks in the sterile circuit, continuous intracranial pressure monitoring, and may provide more efficient clot lysis compared with intermittent bolusing.

Worse cranial neurosurgical outcomes predicted by increasing frailty in patients with interhospital transfer status: Analysis of 47,736 patients from the National Surgical Quality Improvement Program (NSQIP) 2015-2019.

INTRODUCTION: With limited healthcare resources and risks associated with unwarranted interhospital transfers (IHT), it is important to select patients most likely to have improved outcomes with IHT. The present study analyzed the effect of IHT and frailty on postoperative outcomes in a large database of patients who underwent cranial neurosurgical operations. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent cranial neurosurgical procedures (2015-2019, N = 47,736). Baseline demographics, clinical characteristics, and outcome variables were compared between IHT and n-IHT patients. Univariate and multivariable analyses analyzed the effect of IHT status on postoperative outcomes and the utility of frailty (modified frailty index-5 [mFI-5] stratified into "pre-frail, "frail", and "severely frail") as a preoperative risk factor. Effect sizes from regression analyses were presented as odds ratio (OR) with associated 95% confidence intervals (95% CI). RESULTS: Of 47,736 patients with cranial neurosurgical operations, 9612 (20.1%) were IHT. Patients with IHT were older, frailer, with a higher rate of functional dependence. In multivariable analysis adjusted for baseline covariates, IHT status was independent associated with 30-day mortality (OR: 2.0, 95% CI: 1.2-3.6), major complication (OR: 1.5, 95% CI: 1.1-2.1), extended hospital length of stay (eLOS) (OR: 3.8, 95% CI: 3.6-4.1), and non-routine discharge disposition (OR: 2.4, 95% CI: 1.8-3.2) (all p < 0.05). Within the IHT cohort, increasing frailty ("pre-frail", "frail", "severely frail") was independently associated with increasing odds of 30-day mortality (OR: 1.4, 1.9, 3.9), major complication (OR: 1.4, 1.9, 3.3), unplanned readmission (OR: 1.1, 1.4, 2.1), reoperation (OR: 1.3, 1.5, 1.9), eLOS (OR: 1.2, 1.3, 1.5), and non-routine discharge (OR: 1.4, 1.9, 4.4) (all p < 0.05). All levels of frailty were more strongly associated with postoperative outcomes than chronological age. CONCLUSIONS: This novel analysis suggests that patients transferred for cranial neurosurgery operations are significantly more likely to have worse postoperative health outcomes. Furthermore, the analysis suggests that frailty (as measured by mFI-5) is a powerful independent predictor of outcomes in transferred cranial neurosurgery patients. The findings support the use of frailty scoring in the pre-transfer and preoperative setting for patient counseling and risk stratification.

Corticospinal Motor Circuit Plasticity After Spinal Cord Injury: Harnessing Neuroplasticity to Improve Functional Outcomes.

Spinal cord injury (SCI) is a devastating condition that affects approximately 294,000 people in the USA and several millions worldwide. The corticospinal motor circuitry plays a major role in controlling skilled movements and in planning and coordinating movements in mammals and can be damaged by SCI. While axonal regeneration of injured fibers over long distances is scarce in the adult CNS, substantial spontaneous neural reorganization and plasticity in the spared corticospinal motor circuitry has been shown in experimental SCI models, associated with functional recovery. Beneficially harnessing this neuroplasticity of the corticospinal motor circuitry represents a highly promising therapeutic approach for improving locomotor outcomes after SCI. Several different strategies have been used to date for this purpose including neuromodulation (spinal cord/brain stimulation strategies and brain-machine interfaces), rehabilitative training (targeting activity-dependent plasticity), stem cells and biological scaffolds, neuroregenerative/neuroprotective pharmacotherapies, and light-based therapies like photodynamic therapy (PDT) and photobiomodulation (PMBT). This review provides an overview of the spontaneous reorganization and neuroplasticity in the corticospinal motor circuitry after SCI and summarizes the various therapeutic approaches used to beneficially harness this neuroplasticity for functional recovery after SCI in preclinical animal model and clinical human patients' studies.