Early Surgery for Traumatic Spinal Cord Injury: Where Are We Now?

Study Design: Narrative review. Objective: There is a strong biological rationale to perform early decompression after traumatic spinal cord injury (SCI). With an enlarging clinical evidence base, most spine surgeons internationally now favor early decompression for the majority of SCI patients; however, a number of pertinent questions remain surrounding this therapy. Methods: A narrative review evaluating the status of early surgery for SCI. In particular, we addressed the following questions: (1) Which patients stand to benefit most from early surgery? 2) What is the most appropriate time threshold defining early surgery? Results: Although heterogeneity exists, the evidence generally seems to support early surgery. While the best evidence exists for cervical SCI, there is insufficient data to support a differential effect for early surgery depending on neurological level or injury severity. When comparing thresholds to define early versus late surgery-including a later threshold (48-72 hours), an earlier threshold (24 hours), and an ultra-early threshold (8-12 hours)-the 2 earlier time points seem to be associated with the greatest potential for improved outcomes. However, existing prehospital and hospital logistics pose barriers to early surgery in a significant proportion of patients. An overview of recommendations from the recent AOSpine guidelines is provided. Conclusion: In spite of increasing acceptance of early surgery post SCI, further research is needed to (1) identify subgroups of patients who stand to derive particular benefit-in particular to develop more evidence-based approaches for central cord syndrome and (2) investigate the efficacy and feasibility of ultra-early surgery targeting more aggressive timelines

Occupational Disruption: The Influence of the COVID-19 Pandemic on the Behavioral Inflexibility and Anxiety of Autistic Children

Background: The COVID-19 pandemic caused unprecedented changes to the lives of many. The aim of this paper was to understand how the COVID-19 pandemic impacted behavioral inflexibility (BI) and anxiety among autistic children and how autistic children and their families have adapted to COVID-19-related routine changes. Methods: This sequential mixed-method study included two phases. During the first phase, parents of autistic children (N = 48) completed an online survey consisting of the Behavioral Inflexibility Scale (BIS) and the Parent-Rated Anxiety Scale – Autism Spectrum Disorder (PRAS-ASD). During the second phase, a subset of parents (parents of adolescents, N = 11) was invited to participate in a virtual focus-group. Results: The parents reported a wide range of BI during the pandemic (BIS M = 2.03, SD = 1.02, range = 0.21 – 3.86). Child BI was a significant predictor of anxiety (t[40] = 5.56, p \u3c .0001). From the focus groups, 155 codes were organized into four themes, two of which are discussed in this paper: child client factors that have changed during the pandemic and changes to family routines. Conclusions: In this preliminary study, the parents identified problematic BI and anxiety among their autistic children. The outcomes of this small-scale study indicate that some of the changes to routines brought about by the pandemic may be helpful for autistic children after the pandemic restrictions have ended. We provide a unique perspective on how to leverage occupational changes that resulted from the COVID-19 pandemic to aid autistics during non-pandemic times

A thermally stable {FeNO}(8) complex: properties and biological reactivity of reduced MNO systems

Reduced nitrogen oxide ligands such as NO−/HNO or nitroxyl participate in chemistry distinct from nitric oxide (NO). Nitroxyl has been proposed to form at heme centers to generate the Enemark–Feltham designated {FeNO}8 system. The synthesis of a thermally stable {FeNO}8 species namely, [Co(Cp*)2][Fe(LN4)(NO)] (3), housed in a heme-like ligand platform has been achieved by reduction of the corresponding {FeNO}7 complex, [Fe(LN4)(NO)] (1), with decamethylcobaltocene [Co(Cp*)2] in toluene. This complex readily reacts with metMb, resulting in formation of MbNO via reductive nitrosylation by the coordinated HNO/NO−, which can be inhibited with GSH. These results suggest that 3 could serve as a potential HNO therapeutic. Spectroscopic, theoretical, and structural comparisons are made to 1 and the {CoNO}8 complex, [Co(LN4)(NO)] (2), an isoelectronic analogue of 3

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

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 p<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 (p<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.NIHR Welcome Trus

Efficacy and safety of methylprednisolone sodium succinate in acute spinal cord injury: a systematic review

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies ere critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system. Results: The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment. Conclusion: Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI

A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy

Occupational Disruption: The Influence of the COVID-19 Pandemic on the Behavioral Inflexibility and Anxiety of Autistic Children

Background: The COVID-19 pandemic caused unprecedented changes to the lives of many. The aim of this paper was to understand how the COVID-19 pandemic impacted behavioral inflexibility (BI) and anxiety among autistic children and how autistic children and their families have adapted to COVID-19-related routine changes. Methods: This sequential mixed-method study included two phases. During the first phase, parents of autistic children (N = 48) completed an online survey consisting of the Behavioral Inflexibility Scale (BIS) and the Parent-Rated Anxiety Scale – Autism Spectrum Disorder (PRAS-ASD). During the second phase, a subset of parents (parents of adolescents, N = 11) was invited to participate in a virtual focus-group. Results: The parents reported a wide range of BI during the pandemic (BIS M = 2.03, SD = 1.02, range = 0.21 – 3.86). Child BI was a significant predictor of anxiety (t[40] = 5.56, p < .0001). From the focus groups, 155 codes were organized into four themes, two of which are discussed in this paper: child client factors that have changed during the pandemic and changes to family routines. Conclusions: In this preliminary study, the parents identified problematic BI and anxiety among their autistic children. The outcomes of this small-scale study indicate that some of the changes to routines brought about by the pandemic may be helpful for autistic children after the pandemic restrictions have ended. We provide a unique perspective on how to leverage occupational changes that resulted from the COVID-19 pandemic to aid autistics during non-pandemic times

Neurologic improvement after thoracic, thoracolumbar, and lumbar spinal cord (conus medullaris) injuries

Study Design. Retrospective. Objective. With approximately 10,000 new spinal cord injury (SCI) patients in the United States each year, predicting public health outcomes is an important public health concern. Combining all regions of the spine in SCI trials may be misleading if the lumbar and sacral regions (conus) have a neurologic improvement at different rates than the thoracic or thoracolumbar spinal cord. Summary of Background Data. Over a 10-year period between January 1995 to 2005, 1746 consecutive spinal injured patients were seen, evaluated, and treated through a level 1 trauma referral center. A retrospective analysis was performed on 150 patients meeting the criteria of T4 to S5 injury, excluding gunshot wounds. One-year follow-up data were available on 95 of these patients. Methods. Contingency table analyses (chi-squared statistics) and multivariate logistic regression. Variables of interest included level of injury, initial American Spinal Injury Association (ASIA), age, race, and etiology. Results. A total of 92.9% of lumbar (conus) patients neurologically improved one ASIA level or more compared with 22.4% of thoracic or thoracolumbar spinal cord-injured patients. Only 7.7% of ASIA A patients showed neurologic improvement, compared with 95.2% of ASIA D patients; ASIA B patients demonstrated a 66.7% improvement rate, whereas ASIA C had a 84.6% improvement rate. When the two effects were considered jointly in a multivariate analysis, ASIA A and thoracic/thoracolumbar patients had only a 4.1% rate of improvement, compared with 96% for lumbar (conus) and incomplete patients (ASIA B-D) and 66.7% to 72.2% for the rest of the patients. All of these relationships were significant to P \u3c 0.001 (chi-square test). There was no link to age or gender, and race and etiology were secondary to region and severity of injury. Conclusion. Thoracic (T4-T9) SCIs have the least potential for neurologic improvement. Thoracolumbar (T10-T12) and lumbar (conus) spinal cord have a greater neurologic improvement rate, which might be related to a greater proportion of lower motor neurons. Thus, defining the exact region of injury and potential for neurologic improvement should be considered in future clinical trial design. Combining all anatomic regions of the spine in SCI trials may be misleading if different regions have neurologic improvement at different rates. Over a ten-year period, 95 complete thoracic/thoracolumbar SCI patients had only a 4.1% rate of neurologic improvement, compared with 96.0% for incomplete lumbar (conus) patients and 66.7% to 72.2% for all others

The role of electrical stimulation for rehabilitation and regeneration after spinal cord injury

Electrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications. Furthermore, this paper addresses the potential future of the technology

Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review

BACKGROUND: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation. AIM: To determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics. DESIGN: A systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed. REVIEW SOURCES: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration. RESULTS: The systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites. CONCLUSIONS: We estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years