A unique case of pure lateral spinal cord herniation

BackgroundSpinal cord herniation (SCH) remains a challenging diagnosis for neuroradiologists and may require treatment challenging for neurosurgeons. Most cord herniations are usually found at anterior thoracic levels.Clinical presentationA 28-year-old woman presented at our department with a 7-year history of progressive myelopathy. MR analysis showed a displacement of the spinal cord in a lateral thoracic dural defect. The herniated cord was released using a microscope and the patient significantly recovered 6 months after surgery.ConclusionWe present a unique case of pure lateral SCH. In the light of reviewed literature and operative findings, the underlying pathophysiological mechanisms are discussed.     

KDM6B epigenetically regulated-interleukin-6 expression in the dorsal root ganglia and spinal dorsal horn contributes to the development and maintenance of neuropathic pain following peripheral nerve injury in male rats

The lysine specific demethylase 6B (KDM6B) has been implicated as a coregulator in the expression of proinflammatory mediators, and in the pathogenesis of inflammatory and arthritic pain. However, the role of KDM6B in neuropathic pain has yet to be studied. In the current study, the neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rats. Immunohistochemistry, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR assays were performed to investigate the underlying mechanisms. Our results showed that SNL led to a significant increase in KDM6B mRNA and protein in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn; and this increase correlated a markedly reduction in the level of H3K27me3 methylation in the same tissue. Double immunofluorescence staining revealed that the KDM6B expressed in myelinated A- and unmyelinated C-fibers in the DRG; and located in neuronal cells, astrocytes, and microglia in the dorsal horn. Behavioral data showed that SNL-induced mechanical allodynia and thermal hyperalgesia were impaired by the treatment of prior to i.t. injection of GSK-J4, a specific inhibitor of KDM6B, or KDM6B siRNA. Both microinjection of AAV2-EGFP-KDM6B shRNA in the lumbar 5 dorsal horn and sciatic nerve, separately, alleviated the neuropathic pain following SNL. The established neuropathic pain was also partially attenuated by repeat i.t. injections of GSK-J4 or KDM6B siRNA, started on day 7 after SNL. SNL also resulted in a remarkable increased expression of interleukin-6 (IL-6) in the DRG and dorsal horn. But this increase was dramatically inhibited by i.t. injection of GSK-J4 and KDM6B siRNA; and suppressed by prior to microinjection of AAV2-EGFP-KDM6B shRNA in the dorsal horn and sciatic nerve. Results of ChIP-PCR assay showed that SNL-induced enhanced binding of STAT3 with IL-6 promoter was inhibited by prior to i.t. injection of GSK-J4. Meanwhile, the level of H3K27me3 methylation was also decreased by the treatment. Together, our results indicate that SNL-induced upregulation of KDM6B via demethylating H3K27me3 facilitates the binding of STAT3 with IL-6 promoter, and subsequently mediated-increase in the expression of IL-6 in the DRG and dorsal horn contributes to the development and maintenance of neuropathic pain. Targeting KDM6B might a promising therapeutic strategy to treatment of chronic pain.     

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.     

Characterization of standing balance after incomplete spinal cord injury: Alteration in integration of sensory information in ambulatory individuals

BackgroundUp to one-third of individuals with a recent spinal cord injury (SCI) and most of the individuals with an incomplete lesion are able to regain partial balance and walking ability after the first-year post-injury. However, most individuals experience injurious falls while standing and frequent losses of balance post-rehabilitation, which can result in physical injuries and a fear of falling.Research questionControl of balance during quiet standing depends on the integration of sensory information. Since SCI causes sensory and motor impairments, understanding the underlying mechanisms of how postural control is regulated is of significant importance for targeted and guided rehabilitation post-SCI.MethodsWe characterized the impact of a variety of challenging conditions on the standing balance for eight participants with incomplete SCI with walking ability compared to twelve age-matched able-bodied individuals using a waist-mounted inertial measurement unit (IMU). We compared balance biomarkers derived from IMUs’ readouts under conditions that challenged balance by affecting somatosensory (i.e., standing on hard vs. foam surfaces) and visual (i.e., eyes open vs. closed) inputs. We performed a three-way ANOVA or a Kruskal-Wallis test to characterize changes in postural control post-SCI based on reliance on somatosensory and visual information using balance biomarkers.ResultsWe observed a reduced stability performance, an increased control demand, and a less effective active correction post-SCI in all standing conditions. Due to impaired somatosensory feedback, individuals with incomplete SCI showed a higher and lower reliance on visual and somatosensory information, respectively, for maintaining balance (p < 0.05).SignificanceUsing a single waist-mounted IMU, the proposed method could characterize standing balance in individuals with incomplete SCI compared to able-bodied participants. Having high clinical utility and sufficient resolution with discriminatory ability, our method could be used in the future to objectively evaluate the effectiveness of rehabilitative interventions on the balance performance of individuals with SCI.     

Spinal infarcts

Compared to cerebral ischaemia, the frequency of spinal cord ischaemia is rare. Spinal infarcts lead to various types of neurological deficits, usually consisting of an abrupt and complete tetra- or paraplegia. Magnetic resonance imaging is the most valuable tool to show the infarct and to rule out other causes of acute spinal cord syndromes., such as myelitis or acute compressions. Nowadays, in western countries, most spinal cord infarcts are due to aortic diseases (atherosclerosis, aneurysm, dissection) or are of iatrogenic origin (mainly aortic surgery and interventional radiology), while other causes are rare. There is no specific treatment, besides prevention of complications, treatment of the underlying cause and rehabilitation.