A review of vascular endothelial growth factor and its potential to improve functional outcomes following spinal cord injury.

Spinal cord injuries (SCI) are traumatic events with limited treatment options. Following injury, the lesion site experiences a drastic change to both its structure and vasculature which reduces its ability for tissue regeneration. Despite the lack of clinical options, researchers are investigating therapies to induce neuronal regeneration. Cell-based therapies have long been assessed in the context of SCI to promote neuronal protection and repair. Vascular endothelial growth factor (VEGF) not only demonstrates this ability, but also demonstrates angiogenic potential to promote blood vessel formation. While there have been numerous animal studies investigating VEGF, further research is still warranted to pinpoint its role following SCI. This review aims to discuss the literature surrounding the role of VEGF following SCI and its potential in promoting functional recovery.

Systems neuroimmunology: a review of multiomics methodologies to characterize neuroimmunological interactions in spinal and cranial diseases.

Neuroimmunology plays a critical role in our understanding of the pathophysiological processes that underlie a variety of diseases treated by neurosurgeons, including degenerative disc disease (DDD), glioblastoma (GBM), aneurysmal subarachnoid hemorrhage (aSAH), and others. Compared with traditional methods in neuroimmunology, which study one pathway or gene at a time, emerging multiomics methodologies allow for holistic interrogation of multiple immune-signaling pathways to test hypotheses and the effects of therapeutics at a systems level. In this review, the authors summarize key concepts for gathering and analyzing multiomics data so that neurosurgeons can contribute to the emerging field of systems neuroimmunology. Additionally, they describe 3 use cases, based on original research published by their group and others, that utilize transcriptomic, metabolomic, and proteomic analyses to study immune-signaling pathways in DDD, aSAH, and GBM. Through these use cases, techniques for performing machine learning and network-based analyses to generate new clinical insights from multiomics data are shared. The authors hope that neurosurgeons might use this review as a summary of common tools and principles in systems immunology to better engage in creating the immunotherapies of tomorrow.

Clinical characteristics and management differences for grade II and III spinal meningiomas.

PURPOSE: The majority of spinal meningiomas are grade I tumors, as defined by World Health Organization (WHO) classification making atypical (grade II) or anaplastic (grade III) tumors extremely rare lesions to encounter in clinical practice. Here, we present our institutional experience of management of grade II and III spinal meningiomas. METHODS: Following IRB approval, we queried all available institutional electronic medical records for patients undergoing surgical resection of pathology-proven spinal meningiomas, with further review of patients with grade II and III. Variables of interest included age, sex, histological type, tumor size, symptoms at baseline, treatment characteristics, symptom resolution at the last follow-up, recurrence, NF-2 status, concurrent intracranial meningioma, and mortality. Kaplan Meier curves were constructed to study time to progression/recurrence. RESULTS: A total of 188 patients undergoing surgical resection of spinal meningioma between 1988 and 2018 were identified. Among those, 172 (91.5%) patients had grade I meningioma and 16 (8.5%) patients had high grade meningiomas [grade II (15) and III (1)]. Over a median (IQR) follow-up of 8.0 years (5.1-13.0), mortality and recurrence rates were 18.8% (n = 3) and 47.1% (n = 8), respectively. In univariate analysis, adjuvant radiotherapy and thoracic segment involvement were associated with lower rates of recurrence while male sex was associated with a higher rate of recurrence. CONCLUSIONS: Results showed variations in clinical outcomes for patients with high grade spinal meningiomas, especially the recurrence. Adjuvant radiotherapy and thoracic segment involvement was associated with lower rates of recurrence while recurrence ocurred at a higher rate in males.

Early and sustained improvements in motor function in rats after infusion of allogeneic umbilical cord-derived mesenchymal stem cells following spinal cord injury.

STUDY DESIGN: Animal study. OBJECTIVES: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have recently been shown to hold great therapeutic potential for spinal cord injury (SCI). However, majority of the studies have been done using human cells transplanted into the rat with immunosuppression; this may not represent the outcomes that occur in humans. Herein, we present the therapeutic effect of using rat UC-MSCs (rUC-MSC) without immunosuppression in a rat model of SCI. SETTING: Mayo Clinic, Rochester, MN, USA. METHODS: Twelve female rats were randomly divided into two groups, control, and rUC-MSC group, and then subjected to a T9 moderate contusion SCI. Next, 2 × 106 rUC-MSCs or ringer-lactate solution were injected through the tail vein at 7 days post injury. Rats were assessed for 14 weeks by an open-field Basso, Beattie, and Bresnahan (BBB) motor score as well as postmortem quantification of axonal sparing/regeneration, cavity volume, and glial scar. RESULTS: Animals treated with rUC-MSCs were found to have early and sustained motor improvement (BBB score of 14.6 ± 1.9 compared to 10.1 ± 1.7 in the control group) at 14 weeks post injury (mean difference: 4.55, 95% CI: 2.04 to 7.06; p value < 0.001). Total cavity volume in the injury epicenter was significantly reduced in the rUC-MSC group; control: 33.0% ± 2.1, rUC-MSC: 25.3% ± 3.8 (mean difference: -7.7% (95% CI: -12.3 to -2.98); p value < 0.05). In addition, spinal cords from rats treated with rUC-MSCs were found to have a significantly greater number of myelinated axons, decreased astrogliosis, and reduced glial scar formation compared to control rats. CONCLUSIONS: Our study indicates that intravenous injection of allogenic UC-MSCs without immunosuppression exert beneficial effects in subacute SCI and thus could be a useful therapy to improve the functional capacity among patients with SCI.

Dural sac shrinkage signs on magnetic resonance imaging at the thoracic level in spontaneous intracranial hypotension-its clinical significance.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. METHODS: Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. RESULTS: The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913-0.931). CONCLUSIONS: Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.

Improved 3-year survival rates for glioblastoma multiforme are associated with trends in treatment: analysis of the national cancer database from 2004 to 2013.

PURPOSE: Glioblastoma multiforme (GBM) is a common and aggressive malignancy associated with poor prognosis. Characteristics and treatment of long-term survivors are of particular interest in efforts to improve outcomes. Therefore, the objective of this study was to examine trends and prognostic factors for 3-year survival from a national database. METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with cranial GBM from 2004 to 2013 and with 3-year follow-up. Trends in 3-year and overall survival, patient characteristics, tumor properties, and treatment modalities were examined. Multivariable logistic regression was utilized to investigate the association of these factors with 3-year survival. Predictor importance analysis was conducted using a metric defined as Wald χ2 penalized by degrees of freedom. RESULTS: A total of 88,919 GBM patients with 3-year follow-up were identified. Overall, 8757 (9.8%) patients survived ≥ 3 years. Three-year survival significantly improved from 8.0 to 10.5% (p < 0.001) from 2004 to 2013. Trimodal treatment administration also significantly increased from 38.7 to 55.9% (p < 0.001). During this span, patients increasingly presented as older (p = 0.040), without private insurance (p < 0.001), and with a higher comorbidity index (p < 0.001). On multivariable regression, factors such as trimodal treatment (p < 0.001), younger age (p < 0.001), and MGMT methylation (p < 0.001) were significantly associated with increased odds of 3-year survival. Predictor importance analysis indicated that MGMT methylation, age, and treatment modality were the most significant relative determinants of 3-year survival. CONCLUSION: These findings illustrate an improved 3-year survival rate for GBM patients from 2004 to 2013 with a concurrent increase in trimodal treatment administration despite more adverse patient presenting characteristics.

Variation in management of spinal gliobastoma multiforme: results from a national cancer registry.

PURPOSE: Primary glioblastoma of the spinal cord (spinal GBM) is a rare central nervous system tumor, relative to its cranial counterpart (cranial GBM). Our current knowledge of spinal GBM epidemiology, tumor characteristics and treatment are insufficient and mostly based on single-institution case series. METHODS: All patients diagnosed with grade-4 GBM from 2004 to 2014 were queried from the National Cancer Database. Chi square analysis was used to compare presenting characteristics while Kaplan-Meier and Cox regression analyses were employed for survival analyses. RESULTS: Total 103,496 patients with cranial GBM and 190 patients with spinal GBM were analyzed. Median survival for spinal GBM was found to be higher compared to cranial GBM (p = 0.07). Spinal GBM patients had significant better survival in 18 to 65 years age group than < 18 years and > 65 years age group (p = 0.003). Overall survival time for 95 spinal GBM patients with available treatment data was not statistically different among the four treatment modalities (radiation with or without chemotherapy, surgery alone, surgery with adjuvant therapy, and palliative therapy; p = 0.28).On multivariable analysis, < 18 years age group was associated with improved survival (HR 0.50, 95% CI 0.23-1.00, p = 0.046), while tumor extension was associated with poor survival (HR 2.71, 95% CI 1.04-6.22, p = 0.041). Interestingly surgery with adjuvant therapy was unable to show increase survival compared to other treatment modalities. CONCLUSIONS: Our study adds to the growing literature on spinal GBM with a focus on comparative trends with cranial GBM and outcomes with different treatment modalities.

Trends in the utilization of radiotherapy for spinal meningiomas: insights from the 2004-2015 National Cancer Database.

OBJECTIVERecent studies have reported on the utility of radiosurgery for local control and symptom relief in spinal meningioma. The authors sought to evaluate national utilization trends in radiotherapy (including radiosurgery), investigate possible factors associated with its use in patients with spinal meningioma, and its impact on survival for atypical tumors.METHODSUsing the ICD-O-3 topographical codes C70.1, C72.0, and C72.1 and histological codes 9530-9535 and 9537-9539, the authors queried the National Cancer Database for patients in whom spinal meningioma had been diagnosed between 2004 and 2015. Patients who had undergone radiation in addition to surgery and those who had received radiation as the only treatment were analyzed for factors associated with each treatment.RESULTSFrom among 10,458 patients with spinal meningioma in the database, the authors found a total of 268 patients who had received any type of radiation. The patients were divided into two main groups for the analysis of radiation alone (137 [51.1%]) and radiation plus surgery (131 [48.9%]). An age > 69 years (p < 0.001), male sex (p = 0.03), and tumor size 5 to < 6 cm (p < 0.001) were found to be associated with significantly higher odds of receiving radiation alone, whereas a Charlson-Deyo Comorbidity Index ≥ 2 (p = 0.01) was associated with significantly lower odds of receiving radiation alone. Moreover, a larger tumor size (2 to < 3 cm, p = 0.01; 3 to < 4 cm, p < 0.001; 4 to < 5 cm, p < 0.001; 5 to < 6 cm, p < 0.001; and ≥ 6 cm, p < 0.001; reference = 1 to < 2 cm), as well as borderline (p < 0.001) and malignant (p < 0.001) tumors were found to be associated with increased odds of undergoing radiation in addition to surgery. Receiving adjuvant radiation conferred a significant reduction in overall mortality among patients with borderline or malignant spinal meningiomas (HR 2.12, 95% CI 1.02-4.1, p = 0.02).CONCLUSIONSThe current analysis of cases from a national cancer database revealed a small increase in the use of radiation for the management of spinal meningioma without a significant increase in overall survival. Larger tumor size and borderline or malignant behavior were found to be associated with increased radiation use. Data in the present analysis failed to show an overall survival benefit in utilizing adjuvant radiation for atypical tumors.

Changes in quality of life in patients with acromegaly after surgical remission - A prospective study using SF-36 questionnaire.

Patients with acromegaly have a compromised quality of life (QOL). Modern surgical techniques have improved the surgical cure rate. However, there are no prospective studies reporting postoperative changes in QOL among patients cured solely by surgery. The aim of the present study was to determine the effect of surgery on QOL using the 36-item short form health survey (SF-36) questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS). Included in this prospective cohort were 41 patients with acromegaly who underwent surgery alone and achieved postoperative normalization of insulin-like growth factor-1. All participants completed the SF-36 preoperatively and 1 year postoperatively. Preoperatively, RCS and 4 subscale scores (role physical, social functioning, role emotional, mental health) were below the set standards for the normal population. Postoperatively, the PCS and RCS scores did not change significantly, but the MCS score improved significantly (from 48.1 ± 11.3 to 51.7 ± 8.9, p=0.03). Further we compared the QOL of 26 patients whose nadir GH level was < 0.4 µg/L during postoperative oral glucose tolerance testing (complete remission group) with that of 15 patients whose nadir GH level was ≥ 0.4 µg/L (partial remission group). There were no significant differences between these groups in terms of PCS, MCS, RCS, or any subscale scores. In conclusion, surgical remission mostly improved the participants' mental condition. There was no difference in QOL between patients who achieved the new remission criteria and those who did not.

Long-term outcome after endovascular treatment of cavernous sinus dural arteriovenous fistula and a literature review.

BACKGROUND: The long-term efficacy of endovascular treatment (EVT) for cavernous sinus dural arteriovenous fistulae (CS-dAVF) was assessed with a special focus on residual shunts after initial EVT. PATIENTS AND METHODS: This retrospective survey included 50 patients who had undergone EVT and were followed for 1 month or longer (median follow-up 56 months). RESULTS: Common preoperative symptoms were chemosis (78%), extra-ocular motor palsy (72%), exophthalmos (66%), and tinnitus (26%). CS-dAVF were addressed by transvenous embolization (tVE, n = 48), tVE only was used in 43 instances and tVE plus transarterial embolization (tAE) in five. Two patients underwent tAE only. Procedure-related morbidity (brainstem infarction) was recorded in one patient (2%) and transient symptom exacerbation (paradoxical worsening) in 12 patients (24%). Postoperative digital subtraction angiography showed no major retrograde shunt or cortical venous reflux in any of the 50 patients. Anterograde or minor retrograde residual shunt was observed in 17 patients (34%); three of these underwent additional tVE and four had Gamma Knife surgery. The shunt flow disappeared in all 17 patients 12.6 ± 13.4 (mean ± SD) months after initial EVT. At the latest follow-up, 65.7 ± 52.6 months after the initial operation, no shunt flow was observed in any of the 50 patients. None had remaining or newly developed chemosis or tinnitus on follow-up. The rate of persistent cavernous sinus symptoms at the latest follow-up was higher in patients with than without post-procedural paradoxical worsening (5/12, 41.7% vs. 2/38, 5.3%, p = 0.0059 by Fisher's exact test). CONCLUSIONS: Long-term follow-up showed that EVT, especially tVE, is an efficient and safe treatment for CS-dAVF. It resulted in the eventual disappearance of shunt flow. Residual shunt without major retrograde flow or cortical venous reflux can be monitored without additional treatment.

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 µ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older.

To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated. From 1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima- and Hiroshima University hospitals in Japan. Ten (1.1%) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients. The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2-3 on American Society of Anesthesiologists' Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered. Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients' general condition is well preserved and pituitary hormonal deficiency is adequately replaced.

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Patients of idiopathic normal-pressure hydrocephalus have small dural sac in cervical and upper thoracic levels: A supposed causal association.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder presenting a triad including dementia and ventricular enlargement. The mechanism causing excessive cerebrospinal fluid (CSF) accumulation in the ventricles in iNPH is poorly understood. We hypothesized that the age-related degradation of the spinal shock-absorbing system composed of a spinal dural sac (SDS) and surrounding soft tissue, preventing ventricular enlargement caused by wide CSF pulsation driven by heartbeats, may be involved in the ventricular enlargement observed in iNPH. Methods: Sixty-four patients with iNPH in their seventies who underwent a lumboperitoneal shunt and a control group of 79 people in the same age group who underwent brain check-ups were included in the study. We compared the sizes of the cervical and upper parts of the thoracic SDS using magnetic resonance imaging between the two groups. Results: The anterior-posterior distances of the dural sac at C5 were shorter in patients with iNPH of both sexes than those in the control group (P = 0.0008 in men and P = 0.0047 in women). The number of disc levels with disappeared CSF space surrounding the cervical cord was more in iNPH (P = 0.0176 and P = 0.0003). The midsagittal area of the upper part of the spinal sac, C2-Th4, was smaller in iNPH (P = 0.0057 and P = 0.0290). Conclusion: Narrowing of the cervical dural sac and midsagittal area in the upper part of the SDS in patients with iNPH may reflect the degradation of the shock-absorbing mechanism for CSF pressure pulsations, which may cause iNPH or at least aggravate iNPH by other unknown causes.

Prediction Model for Neurogenic Bladder Recovery One Year After Traumatic Spinal Cord Injury.

INTRODUCTION: Neurogenic bladder is a common complication after spinal cord injury (SCI) that carries substantial burdens on the inflicted individual. The objective of this study is to build a prediction model for neurogenic bladder recovery 1 year after traumatic SCI. METHODS: We queried the National Spinal Cord Injury Model Systems database for patients with traumatic SCI who had neurogenic bladder at the time of injury. The primary outcome of interest was the complete recovery of bladder function at 1 year. Multiple imputations were performed to generate replacement values for missing data, and the final imputed data were used for our analysis. A multivariable odds logistic regression model was developed for complete bladder recovery at 1 year. RESULTS: We identified a total of 2515 patients with abnormal bladder function at baseline who had an annual follow-up. A total of 417 patients (16.6%) recovered bladder function in 1 year. Predictors of complete bladder recovery included the following baseline parameters: sacral sensation, American Spinal Injury Association (ASIA) impairment score, bowel function at baseline, voluntary sphincter contraction, anal sensation, S1 motor scores, and the number of days in the rehabilitation facility. The model performed with a discriminative capacity of 90.5%. CONCLUSIONS: We developed a prediction model for the probability of complete bladder recovery 1 year after SCI. The model performed with a high discriminative capacity. This prediction model demonstrates potential utility in the counseling, research allocation, and management of individuals with SCI.

Dissecting aneurysm of the anterior inferior cerebellar artery in the internal auditory canal presenting with deafness without hemorrhage: A case report and literature review.

Background: Anterior inferior cerebellar artery (AICA) aneurysms in the internal auditory canal (IAC) are rare. We have reported a case of dissecting AICA aneurysm in the IAC presenting initially with the eighth nerve palsy followed by the seventh nerve palsy without hemorrhage. Case Description: A 68-year-old woman presented with a sudden onset of vertigo accompanied by deafness and tinnitus on the right side that was preceded by intermittent right retroauricular pain 2 weeks before. Audiogram showed severe sensorineural hearing loss. Computed tomography and magnetic resonance imaging (MRI) indicated absence of prior subarachnoid hemorrhage. Magnetic resonance angiogram (MRA) suggested a tiny aneurysm at the fundus of the IAC accompanied with thinning of the lateral pontine segment of the AICA. Conservative treatment led to moderate improvement of the symptoms. However, the patient developed the right retroauricular pain again, followed by the right facial paralysis 5 months later but still without signs of hemorrhage on MRI. Digital subtraction angiogram showed dissecting aneurysm in the IAC. The patient was managed with oral steroids and direct intervention was avoided due to a risk of ischemia supposed by large area irrigated by the AICA. Follow-up MRA 18 months after the first presentation showed improvement in the narrowing of the AICA proximal to the aneurysm. The patient was functionally independent despite right-sided hearing loss and slight facial paresis. Conclusion: This report warns physicians that a dissecting AICA aneurysm without subarachnoid hemorrhage may cause eighth and seventh nerve palsy.

The Role of Alginate Hydrogels as a Potential Treatment Modality for Spinal Cord Injury: A Comprehensive Review of the Literature.

OBJECTIVE: To comprehensively characterize the utilization of alginate hydrogels as an alternative treatment modality for spinal cord injury (SCI). METHODS: An extensive review of the published literature on studies using alginate hydrogels to treat SCI was performed. The review of the literature was performed using electronic databases such as PubMed, EMBASE, and OVID MEDLINE electronic databases. The keywords used were "alginate," "spinal cord injury," "biomaterial," and "hydrogel." RESULTS: In the literature, we identified a total of 555 rat models that were treated with alginate scaffolds for regenerative biomarkers. Alginate hydrogels were found to be efficient and promising substrates for tissue engineering, drug delivery, neural regeneration, and cellbased therapies for SCI repair. With its ability to act as a pro-regenerative and antidegenerative agent, the alginate hydrogel has the potential to improve clinical outcomes. CONCLUSION: The emerging developments of alginate hydrogels as treatment modalities may support current and future tissue regenerative strategies for SCI.

Dural sac shrinkage signs on spinal magnetic resonance imaging indicate overdrainage after lumboperitoneal shunt for idiopathic normal pressure hydrocephalus.

Background: We previously found the usefulness of dural sac shrinkage signs (DSSSs), which are the anterior shift of the spinal cord and dura mater behind the cord, detected by magnetic resonance imaging (MRI) at the thoracic level for the diagnosis of spontaneous intracranial hypotension (IH). This is a retrospective survey on the usefulness of DSSSs for the early detection of iatrogenic IH caused by overdrainage through a lumboperitoneal shunt (LPS) for patients with idiopathic normal pressure hydrocephalus (INPH). Methods: Forty-five INPH patients had an LPS using a pressure programmable valve equipped with an anti-siphon device. Results: Nine patients complained of orthostatic headache after the LPS, indicating IH due to overdrainage, which persisted for more than a week in three patients and 2-7days in six patients. The headache was transient/ nonorthostatic in ten patients and absent in 26 patients. The DSSSs and accompanying enlargement of the venous plexus were observed in all three patients with prolonged orthostatic headaches. Only the anterior shift of the dura mater was observed in 1 (4%) among 25 patients who had short-term orthostatic headache, transient/ nonorthostatic headache, or absent headache, and underwent spinal MRI. A patient with prolonged severe orthostatic headache with both DSSSs eventually developed intracranial subdural effusion and underwent tandem valve surgery, which provided a quick improvement of symptoms. The DSSSs on thoracic MRI also disappeared promptly. Conclusion: DSSSs may serve as objective signs for the diagnosis of IH due to overdrainage through an LPS for INPH.

Time-to-enrollment in clinical trials investigating neurological recovery in chronic spinal cord injury: observations from a systematic review and ClinicalTrials.gov database.

Currently, large numbers of clinical trials are performed to investigate different forms of experimental therapy for patients suffering from chronic spinal cord injury (SCI). However, for the enrollment process, there are different views on how the time period between injury and interventions should be determined. Herein, we sought to evaluate the impact of time-to-enrollment in chronic SCI clinical trials. A data set comprising 957 clinical studies from clinicalTrials.gov was downloaded and analyzed focusing on the eligibility criteria for post-injury time-to-enrollment. We also aggregated individual patient data from nine clinical trials of regenerative interventions for chronic SCI selected by a systematic literature search from 1990 to 2018. Characteristics of the studies were assessed and compared by dividing into three groups based on time-to-enrollment (group 1 ≤ 12 months, group 2 = 12-23 months and group 3 ≥ 24 months). In ClinicalTrials.gov registry, 445 trials were identified for chronic SCI where 87% (385) were unrestricted in the maximum post-injury time for trial eligibility. From systematic literature search, nine studies and 156 patients (group 1 = 30, group 2 = 55 and group 3 = 71) were included. The range of time-to-enrollment was 0.5 to 321 months in those studies. We also observed various degrees of motor and sensory improvement in between three time-to-enrollment groups. Our results indicate that enrolling wide ranges of time-to-enrollment in a group may present imprecise outcomes. Clinical trial designs should consider appropriate post-injury time frames to evaluate therapeutic benefit.

Characteristics of completed clinical trials for spinal cord injury from 1999 to 2020.

Numerous clinical trials are being conducted in the field of spinal cord injury (SCI). These trials are typically registered on ClinicalTrials.gov. The objective of this study was to identify the characteristics of the completed SCI trials and characterize the potential factors associated with publication. ClinicalTrials.gov database was queried for all the completed trials on patients with SCI. Baseline characteristics of the completed trials were assessed. The publication status of these trials was identified using PubMed or Google Scholar. The secondary and primary outcomes reported in the publication were then compared to the outcomes registered in ClinicalTrial.gov. Multivariable logistic regression analysis was performed to determine the characteristics associated with publication status and time to publication. A total of 457 of 1,061 trials on SCI were completed. Of those, 60% were ultimately published. Trials that had received funding from sources besides the NIH, private industries, or the federal government were more likely to remain unpublished. The median time to publish was three years, with larger trials taking a longer time. The median sample size for completed trials was 30. Assessment of mismatch rates in primary outcomes of published data to registered outcomes was 8.9%. In SCI trials, outcomes registered on ClinicalTrial.gov often matched published results. Additionally, sample size and funding source play a significant role in the publication rate of these trials. Published data represents a reliable source for clinicians, researchers, and patients; efforts to curb publication bias and reporting bias are paramount for implementing evidence-based practices and ensure proper scientific conduct.