Trans-segmental imaging in the spinal cord of behaving mice

Spinal cord circuits play crucial roles in transmitting and gating cutaneous somatosensory modalities, such as pain, but the underlying activity patterns within and across spinal segments in behaving mice have remained elusive. To enable such measurements, we developed a wearable widefield macroscope with a 7.9 mm2 field of view, subcellular lateral resolution, 2.7 mm working distance, and <10 g overall weight. We show that highly localized painful mechanical stimuli evoke widespread, coordinated astrocyte excitation across multiple spinal segments.

Implications of Age, Gender and Lumbar Disc Level on Symptomatic Herniated Nucleus Pulposus

Background: A herniated-disc inside the spinal column is a condition applying displacement of nucleus pulposus from intervertebral space causing back pain. Objective: To analyse the association of age, gender and lumbar disc level with herniated nucleus pulposus. Study Design: Retrospective study Place and Duration of Study: Department of Neurosurgery, Shaikh Zayed Hospital, Lahore from 1st January 2011 to 31st January 2020. Methodology: One hundred and twenty patients to investigate association of herniated nucleus pulposus with age, gender and lumbar disc level were enrolled. Patient’s demographic, clinical and radiological assessments were completed for categorizing their condition and level of lumbar disc involvement. Results: There were 72.5% males and 27.5% females with a mean age of 48.6±1.26 years. The study revealed that 72.5% nucleus pulposus herniation cases were within the age group of 51-70 years. L5-S1 is more susceptible to nucleus pulposus herniation (62.5%) followed by L4-L5 (34.2%), L3-L4 (2.5%) and L1-L2 (0.8%). Conclusion: Elderly population with >51 years in males is highly prone for nucleus pulposus herniation with L5-S1 to be most affected lumbar spinal segments. Key words: Nucleus pulposus herniation, Vertebral column level, Lumbar disc level

Acetabular cup position differs in spinopelvic mobility types: a prospective observational study of primary total hip arthroplasty patients

Introduction Spinopelvic mobility was identified as a contributing factor for total hip arthroplasty (THA) instability. The influence of spinopelvic function on acetabular cup positioning has not yet been sufficiently investigated in a prospective setting. Therefore, our study aimed (1) to assess cup inclination and anteversion in standing and sitting based on spinopelvic mobility, (2) to identify correlations between cup position and spinopelvic function, (3) and to determine the influence of the individual spinal segments, spinal sagittal balance, and spinopelvic characteristics on the mobility groups. Materials and methods A prospective study assessing 197 THA patients was conducted with stereoradiography in standing and sitting position postoperatively. Two independent investigators determined cup anteversion and inclination, C7-Sagittal vertical axis, cervical lordosis (CL), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope, pelvic tilt (PT), anteinclination (AI), and pelvic femoral angle (PFA). Spinopelvic mobility is defined based on ∆PT = PTstanding − PTsitting as ∆PT < 10° stiff, ∆PT ≥ 10–30° normal, and ∆PT > 30° hypermobile. Pearson coefficient represented correlations between the cup position and spinopelvic parameters. Results Significant differences were demonstrated for cup anteversion (stiff/hypermobile 29.3°/40.1°; p < 0.000) and inclination (stiff/hypermobile 43.5°/60.2°; p < 0.000) in sitting, but not in standing position. ∆ (standing/sitting) of the cup anteversion (stiff/neutral/hypermobile 5.8°/12.4°/19.9°; p < 0.000) and inclination (stiff/neutral/hypermobile 2.3°/11.2°/18.8°; p < 0.000) revealed significant differences between the mobility groups. The acetabular cup position in sitting, was correlated with lumbar flexibility (∆LL) and spinopelvic mobility. Significant differences were detected between the mobility types and acetabular orientation (AI sit:stiff/hypermobile 47.6°/65.4°; p < 0.000) and hip motion (∆PFA:stiff/hypermobile 65.8°/37.3°; p < 0.000). Assessment of the spinal segments highlighted the role of lumbar flexibility (∆LL:stiff/hypermobile 9.9°/36.2°; p < 0.000) in the spinopelvic complex. Conclusion The significantly different acetabular cup positions in sitting and in the ∆ between standing and sitting and the significantly altered spinopelvic characteristics in terms of stiff and hypermobile spinopelvic mobility underlined the consideration for preoperative functional radiological assessment. Identifying the patients with altered spinopelvic mechanics due to a standardized screening algorithm is necessary to provide safe acetabular cup positioning. The proximal spinal segments appeared not to be involved in the spinopelvic function.

Flexible thecoscopy for extensive spinal arachnoiditis

OBJECTIVE Chronic adhesive spinal arachnoiditis (SA) is a complex disease process that results in spinal cord tethering, CSF flow blockage, intradural adhesions, spinal cord edema, and sometimes syringomyelia. When it is focal or restricted to fewer than 3 spinal segments, the disease responds well to open surgical approaches. More extensive arachnoiditis extending beyond 4 spinal segments has a much worse prognosis because of less adequate removal of adhesions and a higher propensity for postoperative scarring and retethering. Flexible neuroendoscopy can extend the longitudinal range of the surgical field with a minimalist approach. The authors present a cohort of patients with severe cervical and thoracic arachnoiditis and myelopathy who underwent flexible endoscopy to address arachnoiditis at spinal segments not exposed by open surgical intervention. These observations will inform subsequent efforts to improve the treatment of extensive arachnoiditis. METHODS Over a period of 3 years (2017–2020), 10 patients with progressive myelopathy were evaluated and treated for extensive SA. Seven patients had syringomyelia, 1 had spinal cord edema, and 2 had spinal cord distortion. Surgical intervention included 2- to 5-level thoracic laminectomy, microscopic lysis of adhesions, and then lysis of adhesions at adjacent spinal levels performed using a rigid or flexible endoscope. The mean follow-up was 5 months (range 2–15 months). Neurological function was examined using standard measures. MRI was used to assess syrinx resolution. RESULTS The mean length of syringes was 19.2 ± 10 cm, with a mean maximum diameter of 7.0 ± 2.9 mm. Patients underwent laminectomies averaging 3.7 ± 0.9 (range 2–5) levels in length followed by endoscopy, which expanded exposure by an average of another 2.4 extra segments (6.1 ± 4.0 levels total). Endoscopic dissection of extensive arachnoiditis in the dorsal subarachnoid space proceeded through a complex network of opaque arachnoidal bands and membranes bridging from the dorsal dura mater to the spinal cord. In less severely problematic areas, the arachnoid membrane was transparent and attached to the spinal cord through multifocal arachnoid adhesions bridging the subarachnoid space. The endoscope did not compress or injure the spinal cord. CONCLUSIONS Intrathecal endoscopy allowed visual assessment and safe removal of intradural adhesions beyond the laminectomy margins. Further development of this technique should improve its effectiveness in opening the subarachnoid space and untethering the spinal cord in cases of extensive chronic adhesive SA.

Biomechanical aspects of the initial stability of instrumental fixation in the treatment of subaxial cervical dislocations: an experimental study

Objective. To study the influence of thoracic inlet angle (TIA) and the fracture of the articular process on the initial strength of the fixation of the spinal segment during its anterior and circular instrumental surgical stabilization in an experiment on a model of the lower cervical spinal segment.Material and Methods. The material of the study was assembled models of C6–C7 spinal segments made using addictive technologies by 3D printing. After preliminary instrumentation, spinal segments were installed on the stand testing machine using specially manufactured equipment. A metered axial load simulating the native one was applied along the axis of the parameters SVA COG–C7 and C2–C7 SVA, which values were close to the value of 20 mm, at a rate of 1 mm/min until the shear strain was reached. The system’s resistance to displacement was measured, and the resulting load was evaluated. Four study groups were formed depending on the modeling of the T1 slope parameter, the integrity of the facets, and the type of instrumentation. Three tests were conducted in each group. The graphical curves were analyzed, and the values of the parameters of the neutral and elastic zones, the yield point, time to yield point, and the value of the applied load for the implementation of shear displacement were recorded. The data were subjected to comparative analysis.Results. In Group 1, anterior shear displacement of the C6 vertebra could not be induced in all series. In groups 2, 3, and 4 a shear displacement of ≥4 mm was noted in all series. In Group 3 where a fracture of the articular process was additionally modeled, the average value of the yield point was 423.5 ± 46.8 N. Elastic zone, the time to the onset of the yield point, the time at the end point or at a shear of C6 ≥4 mm did not differ significantly. In Group 4, a translational displacement of ≥4 mm was observed, though the average yield point was 1536.0 ± 40.0 N.Conclusion. The direction of the load applied to the fixed spinal segment, as well as the presence of damage to the articular processes, play a crucial role in maintaining resistance to shear deformation of the spinal segment during its instrumental stabilization. At high values of TIA (T1 slope) and the presence of fractures of the articular processes, the isolated anterior stabilization is less effective, circular fixation of 360° under these conditions gives a high initial stability to the spinal segment.

Exosomes Secreted by Adipose-Derived Stem Cells Following FK506 Stimulation Reduce Autophagy of Macrophages in Spine after Nerve Crush Injury

Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction.

Comparison of Sensory and Motor Innervation Between the Acupoints LR3 and LR8 in the Rat With Regional Anatomy and Neural Tract Tracing

ObjectiveThis study aimed to investigate the sensory and motor innervation of “Taichong” (LR3) and “Ququan” (LR8) in the rat and provide an insight into the neural relationship between the different acupoints in the same meridian.MethodsThe LR3 and LR8 were selected as the representative acupoints from the Liver Meridian and examined by using the techniques of regional anatomy and neural tract tracing in this study. For both acupoints, their local nerves were observed with regional anatomy, and their sensory and motor pathways were traced using neural tract tracing with single cholera toxin subunit B (CTB) and dual Alexa Fluor 594/488 conjugates with CTB (AF594/488-CTB).ResultsUsing the regional anatomy, the branches of the deep peroneal nerve and saphenous nerve were separately found under the LR3 and LR8. Using single CTB, the sensory neurons, transganglionic axon terminals, and motor neurons associated with both LR3 and LR8 were demonstrated on the dorsal root ganglia (DRG), spinal dorsal horn, Clarke’s nucleus, gracile nucleus, and spinal ventral horn corresponding to their own spinal segments and target regions, respectively. Using dual AF594/488-CTB tracing, it was shown that the sensory and motor neurons associated with LR3 were separated from that of LR8.ConclusionThis study demonstrates that LR3 and LR8 are innervated by different peripheral nerves, which originated from or terminated in their corresponding spinal segments and target regions independently through the sensory and motor pathways. These results provide an example for understanding the differential innervation between the different acupoints in the same meridian.

Natural History and Clinical Outcomes of Paravertebral Arteriovenous Shunts

Background and Purpose: Paravertebral arteriovenous shunts (PVAVSs) are rare. Whether the intradural venous system is involved in drainage may lead to differences in clinical characteristics through specific pathophysiological mechanisms. This study aims to comprehensively evaluate the natural history and clinical outcomes of PVAVSs with or without intradural drainage. Methods: Sixty-four consecutive patients with PVAVSs from 2 institutes were retrospectively reviewed. Lesions were classified as type A (n=28) if the intradural veins were involved in drainage; otherwise, they were classified as type B (n=36). The clinical course from initial presentation to the last follow-up was analyzed. Results: The patients with type A shunts were older at presentation (52.5 versus 35.5 years, P <0.0001) and more likely to have lower spinal segments affected than patients with type B PVAVSs (67.8% versus 13.9%, P =0.00006). After presentation, the deterioration rates related to gait and sphincter dysfunction were significantly higher in patients with type A than type B shunts (gait dysfunction: 71.8%/y versus 17.0%/y, P =0.0006; sphincter dysfunction: 63.7%/y versus 11.3%/y, P =0.0002). According to the angiogram at the end of the latest treatment, 79% of type A and 75% of type B PVAVSs were completely obliterated. If the lesions were partially obliterated, a significantly higher clinical deterioration rate was observed in patients with type A shunts than those with type B shunts (69.9%/y versus 3.2%/y, P =0.0253). Conclusions: Type A PVAVSs feature rapid progressive neurological deficits; therefore, early clinical intervention is necessary. For complex lesions that cannot be completely obliterated, surgical disconnection of all refluxed radicular veins is suggested.

A Review on Various Topics on the Thermal Grill Illusion

The thermal grill illusion (TGI) is a paradoxical perception of burning heat and pain resulting from the simultaneous application of interlaced warm and cold stimuli to the skin. The TGI is considered a type of chronic centralized pain and has been used to apply nociceptive stimuli without inflicting harm to human participants in the study of pain mechanisms. In addition, the TGI is an interesting phenomenon for researchers, and various topics related to the TGI have been investigated in several studies, which we will review here. According to previous studies, the TGI is generated by supraspinal interactions. To evoke the TGI, cold and warm cutaneous stimuli should be applied within the same dermatome or across dermatomes corresponding to adjacent spinal segments, and a significant difference between cold and warm temperatures is necessary. In addition, due the presence of chronic pain, genetic factors, and sexual differences, the intensity of the TGI can differ. In addition, cold noxious stimulation, topical capsaicin, analgesics, self-touch, and the presence of psychological diseases can decrease the intensity of the TGI. Because the TGI corresponds to chronic centralized pain, we believe that the findings of previous studies can be applied to future studies to identify chronic pain mechanisms and clinical practice for pain management.

Testing if Micro-CT Is Capable of Quantitating the Extent of Proteoglycan-Aggrecan Induced Axial Spondyloarthritis in Mice

ObjectiveInjections of proteoglycan aggrecan (PGA) have been reported to induce axial spondyloarthritis (ax-SpA) in BALB/c mice. It is considered to be a model for radiographic ax-SpA. However, evaluation of the extent of axial disease by histopathological assessment of every intervertebral space is labor-intensive. The objective of our paper is to test the feasibility of Micro Computed Tomography (Micro-CT) in rapidly enumerating the number of intervertebral spaces affected in each mouse.MethodsArthritis was induced in BALB/c mice by intraperitoneal injections of PGA. Involvement of several spinal segments, and selected sacroiliac and hip joints were evaluated by histopathology. The involvement of all intervertebral spaces, sacroiliac and hip joints was evaluated by Micro-CT.ResultsBALB/c mice injected with PGA developed histopathology of SpA-like axial lesions, including spondylitis, sacroiliac joint arthritis and hip joint arthritis. Micro-CT allowed us to clearly enumerate the number of lesions in each mouse.ConclusionMicro-CT allows quantitative assessment of the extent of axial involvement in PGA-induced mouse spondylitis. This can be a useful tool in assessing therapeutic interventions.