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Background and Purpose: Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting‐state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. Methods: Ten SCI patients (SCI + NP, n = 7, and SCI − NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed‐to‐voxel analysis using PAG as the seed region and then group‐based analysis comprising three groups (SCI + NP, SCI − NP, and HC). Age and gender were considered as confounding variables. Results: Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI − NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. Conclusions: Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V. [ABSTRACT FROM AUTHOR]

Context: Spinal cord injury (SCI) is a devastating condition that results in severe disability and significant comorbidities. The complex pathophysiology of SCI repair and difficulties understanding neural regeneration are treatment challenges. Objectives: The aim of this study is to systematically review the diverse applications of various fish species as models for SCI research. Evidence Acquisition: PRISMA guidelines were used to review observational and interventional studies that utilized fish species as SCI models, published from inception to July 2023. Two independent reviewers screened and performed the data extraction. One independent reviewer assessed the risk of bias for the included studies. Results: Five thousand six hundred and thirty-three records were reviewed, and 144 met the inclusion criteria and were categorized by fish species. The majority of studies employed complete transection injuries, with the remainder being crush injuries, laser injuries, electro-ablations, and demyelination with substances. Zebrafish (Danio rerio) were most commonly utilized 102/144 (71%), primarily with larval models. Other models included Lamprey (Petromyzon marinus and Lethenteron reissued); Goldfish (Carassius auratus); European eel (Anguilla Anguilla); Knifefish (Apteronotus leptorhynchus and Apteronotus albifrons); Sailfin Molly (Poecilia latipinna); and African turquoise killifish (Nothobranchiusfurzeri). Conclusions: This systematic review highlights that fish models, particularly zebrafish, goldfish, and European eels, are important models for further defining SCI pathophysiology and regenerative processes. These models provide a less complex model to gain insights into apoptosis and glial networks. [ABSTRACT FROM AUTHOR]

Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient's physical, psychological, and social well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of magnetic resonance imaging, and the type and timing of rehabilitation. This lack of consensus has prevented the standardization of care across treatment centers and among the various disciplines that encounter patients with SCI. The objective of this guideline is to form evidence-based recommendations for these areas of controversy and outline how to best manage patients with SCI. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care and encouraging clinicians to make evidence-informed decisions.

ObjectiveTo develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome.MethodsA systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as "we recommend," whereas a weak recommendation is presented as "we suggest."ResultsConclusions from the systematic review included (1) isolated studies reported statistically significant and clinically important improvements following early decompression at 6 months and following discharge from inpatient rehabilitation; (2) in one study on acute central cord syndrome without instability, a marginally significant improvement in total motor scores was reported at 6 and 12 months in patients managed with early versus late surgery; and (3) there were no significant differences in length of acute care/rehabilitation stay or in rates of complications between treatment groups. Our recommendations were: "We suggest that early surgery be considered as a treatment option in adult patients with traumatic central cord syndrome" and "We suggest that early surgery be offered as an option for adult acute SCI patients regardless of level." Quality of evidence for both recommendations was considered low.ConclusionsThese guidelines should be implemented into clinical practice to improve outcomes in patients with acute SCI and central cord syndrome by promoting standardization of care, decreasing the heterogeneity of management strategies, and encouraging clinicians to make evidence-informed decisions.

IntroductionThe objective of this guideline is to outline the role of magnetic resonance imaging (MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury (SCI).MethodsA systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI. This review focused on longitudinal studies that controlled for baseline neurologic status. A multidisciplinary Guideline Development Group (GDG) used this information, their clinical expertise, and patient input to develop recommendations on the use of MRI for SCI patients. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest."ResultsBased on the limited available evidence and the clinical expertise of the GDG, our recommendations were: (1) "We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention, when feasible, to facilitate improved clinical decision-making" (quality of evidence, very low) and (2) "We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome" (quality of evidence, low).ConclusionsThese guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI.

IntroductionThe objective of this study is to develop evidence-based guidelines that recommend effective, safe and cost-effective thromboprophylaxis strategies in patients with spinal cord injury (SCI).MethodsA systematic review of the literature was conducted to address key questions relating to thromboprophylaxis in SCI. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest."ResultsBased on conclusions from the systematic review and expert panel opinion, the following recommendations were developed: (1) "We suggest that anticoagulant thromboprophylaxis be offered routinely to reduce the risk of thromboembolic events in the acute period after SCI;" (2) "We suggest that anticoagulant thromboprophylaxis, consisting of either subcutaneous low-molecular-weight heparin or fixed, low-dose unfractionated heparin (UFH) be offered to reduce the risk of thromboembolic events in the acute period after SCI. Given the potential for increased bleeding events with the use of adjusted-dose UFH, we suggest against this option;" (3) "We suggest commencing anticoagulant thromboprophylaxis within the first 72 hours after injury, if possible, in order to minimize the risk of venous thromboembolic complications during the period of acute hospitalization."ConclusionsThese guidelines should be implemented into clinical practice in patients with SCI to promote standardization of care, decrease heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions.

IntroductionThe objective of this study is to develop guidelines that outline the appropriate type and timing of rehabilitation in patients with acute spinal cord injury (SCI).MethodsA systematic review of the literature was conducted to address key questions related to rehabilitation in patients with acute SCI. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the type and timing of rehabilitation. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest.ResultsBased on the findings from the systematic review, our recommendations were: (1) We suggest rehabilitation be offered to patients with acute spinal cord injury when they are medically stable and can tolerate required rehabilitation intensity (no included studies; expert opinion); (2) We suggest body weight-supported treadmill training as an option for ambulation training in addition to conventional overground walking, dependent on resource availability, context, and local expertise (low evidence); (3) We suggest that individuals with acute and subacute cervical SCI be offered functional electrical stimulation as an option to improve hand and upper extremity function (low evidence); and (4) Based on the absence of any clear benefit, we suggest not offering additional training in unsupported sitting beyond what is currently incorporated in standard rehabilitation (low evidence).ConclusionsThese guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care, decreasing the heterogeneity of management strategies and encouraging clinicians to make evidence-informed decisions.

Study designGuideline development.ObjectivesThe objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy.MethodsFive systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the management of degenerative cervical myelopathy (DCM).ResultsOur recommendations were as follows: (1) "We recommend surgical intervention for patients with moderate and severe DCM." (2) "We suggest offering surgical intervention or a supervised trial of structured rehabilitation for patients with mild DCM. If initial nonoperative management is pursued, we recommend operative intervention if there is neurological deterioration and suggest operative intervention if the patient fails to improve." (3) "We suggest not offering prophylactic surgery for non-myelopathic patients with evidence of cervical cord compression without signs or symptoms of radiculopathy. We suggest that these patients be counseled as to potential risks of progression, educated about relevant signs and symptoms of myelopathy, and be followed clinically." (4) "Non-myelopathic patients with cord compression and clinical evidence of radiculopathy with or without electrophysiological confirmation are at a higher risk of developing myelopathy and should be counselled about this risk. We suggest offering either surgical intervention or nonoperative treatment consisting of close serial follow-up or a supervised trial of structured rehabilitation. In the event of myelopathic development, the patient should be managed according to the recommendations above."ConclusionsThese guidelines will promote standardization of care for patients with DCM, decrease the heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions.

IntroductionThe objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI).MethodsA systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest."ResultsThe main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) "We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI"; (2) "We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option"; and (3) "We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI."ConclusionsThese guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients.

Study Design: Retrospective Cohort Study. Objectives: To determine the ability of early vital sign abnormalities to predict functional independence in patients with SCI that required surgery. Methods: A retrospective analysis of data extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients >18 years with a diagnosis of SCI who required urgent spine surgery in Pennsylvania from 1/1/2010-12/31/2020 and had complete records available. Results: A total of 644 patients met the inclusion criteria. The mean age was 47.1 ± 14.9 years old and the mean injury severity score (ISS) was 22.3 ± 12.7 with the SCI occurring in the cervical, thoracic, and lumbar spine in 61.8%, 19.6% and 18.0%, respectively. Multivariable logistic regression analyses for predictors of functional independence at discharge showed that higher HR at the scene (OR 1.016, 95% CI 1.006-1.027, P =.002) and lower ISS score (OR.894, 95% CI.870-.920, P <.001) were significant predictors of functional independence. Similarly, higher admission HR (OR 1.015, 95% CI 1.004-1.027, P =.008) and lower ISS score (OR.880, 95% CI 0.864-.914, P <.001) were significant predictors of functional independence. Peak Youden indices showed that patients with HR at scene >70 and admission HR ≥83 were more likely to achieve functional independence. Conclusions: Early heart rate is a strong predictor of functional independence in patients with SCI. HR at scene >70 and admission HR ≥83 is associated with improved outcomes, suggesting lack of neurogenic shock. [ABSTRACT FROM AUTHOR]