Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia giving rise to oligodendrocytes, the myelin forming cells in the central nervous system (CNS). While OPCs are highly proliferating during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated, they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar, a barrier mainly formed by reactive astrocytes, microglia, and the deposition of inhibitory extracellular matrix components. If, on one hand, glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

The aging of the population in developing and developed countries has lead to a significant increase in health burden of spinal diseases. These elderly patients often have a number of medical co-morbidities due to aging. The need for minimally invasive techniques to address spinal disorders in this elderly population group cannot be stressed enough. Minimally invasive spine surgery (MISS) has several proven benefits such as minimal muscle trauma, minimal bony resection, lesser post-operative pain, decreased infection rate and shorter hospital stay. Over the last 40 years, constant efforts are being made to develop newer techniques of spine surgery. Endoscopic spine surgery is one such subset of MISS which has all the benefits of modern MISS. Endoscopic spine surgery initially was limited only to treatment of lumbar disc herniations. With improvement in optics, endoscopes, endoscopic drills and shavers, irrigation pumps, there has been a paradigm shift. Endoscopic spine surgery can now be performed with high magnification thus allowing its application not only to lumbar spinal stenosis, but also to spinal fusion surgeries, cervical and thoracic pathology as well. There has been increasing evidence in support of these newer techniques of spine surgery. For the purpose of this review, we studied current available literature and outlined the historical evolution of endoscopic spine surgery, the various different endoscopic systems, and techniques available and the current applications of endoscopic techniques as an alternative to traditional spinal surgery.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Spinal muscular atrophy is a neuromuscular disorder caused by mutationsin both copies of the survival motor neuron gene 1 (SMN1) which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA, with much more undergoing active research. While various biomarkers have been proposed for assessing the effectiveness of SMA treatment, a universally accepted one still hasnot been identified. This study aimed to investigate whether the number of gems in cell nuclei could serve as a potential biomarker for SMA. To gain insight into whether the number of gems in cell nuclei varies based on their SMN genotype and whether the increase in gems number is associated with therapeutic response, we utilized fibroblast cell cultures obtained from a patient with SMA type II and from healthy individual. We have discovered a remarkable difference in the number of gems found in the nuclei of these cells, specifically when counting gems per 100 nuclei. Then the SMA fibroblasts were treated with antisense oligonucleotides the beneficial effects in correcting the abnormal splicing of SMN2 exon 7 have been demonstrated. It was observed that there was a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The results obtained significantly correlate with an increase of full-length SMN transcripts share. Based on our findings, it is evident that the quantity of gems can be regarded as a reliable biomarker for SMA drugs development.

Patients with degenerative diseases refer to feeling more pain during the night. However, it is unknown whether spinal nociception can be circadian and how is it controlled. We investigated whether the paw withdrawal threshold (PWT) could exhibit physiological circadian behavior as well as the contribution of the dopaminergic A11 nucleus and the spinal dopamine (DA) receptors (DRs) on the circadian PWT and the spinal clock gene transcription. Results revealed that control rats present a circadian PWT. Injecting 6-hydroxidopamine (6-OHDA) into the dopaminergic A11 nucleus reduced DA tissue content in the lumbar spinal cord, abolished the circadian PWT, induced allodynia, and reduced Period 1 and 2 (Per1 and 2), retinoid-related orphan receptor α (Rorα), Cryptochrome 1 (Cry1), and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein (Bmal) mRNA. Likewise, administration of D1-like and D2-like DR antagonists blunted circadian PWT, producing allodynia, and altered the clock genes mRNA. In contrast, administration of D1-like or D2-like DR agonists blocked 6-OHDA-induced allodynia. This study shows that the spinal cord has physiological circadian PWT, which is modulated by the descending dopaminergic A11 through differential activation of the spinal DRs. Also, A11 nuclei and spinal DRs can regulate the clock gene transcription, which can likely modulate the circadian PWT.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Background and Objectives: Although adult spinal deformity (ASD) surgery brought about the improvement of quality of life in patients, it accompanied with a high invasiveness of surgery and several complications. Specifically, mechanical complications of rod fracture, instrumentation failures, and pseudarthrosis are still unsolved issues. To better improve these problems, the oblique lateral interbody fusion at L5/S1 (OLIF51) was introduced since 2015 in my institution. The objective of this study was to compare the clinical and radiographic outcomes of anterior-posterior combined surgery for ASD between the use of OLIF51 versus transforaminal interbody fusion (TLIF) at L5/S1. Materials and Methods :A total of 117 ASD patients received anterior-posterior correction surgeries either use of OLIF51 (35 patients) or L5/S1 TLIF (82 patients). In both groups, L1-5 OLIF and minimally invasive posterior procedures of hybrid or circumferential MIS were employed. The sagittal and coronal spinal alignment and spino-pelvic parameters are recorded preoperatively and at follow-up. The quality of life parameters and visual analogue scale were evaluated as well as surgical complications at follow-up. Results: The average follow-up period was thirty months (13-84). The average fused segments were eight (4-12). The operation time and estimated blood loss were significantly smaller in OLIF51 that those in TLIF. The PI-LL mismatch, LLL, L5/S1 segmental lordosis, and L5 coronal tilt were significantly better in OLIF51 than TLIF. The complication rate was statistically equivalent between two groups. Conclusion: The introduction of OLIF51 for adult spine deformity surgery led to the decrease of operation time and estimated blood loss as well as the improvement of sagittal and coronal correction when compared to TLIF.

Finite element (FE) modeling is commonly used as a method to investigate the influence of medical devices, such as implants and screws and their effects on the biomechanical behavior of the spine. Another simulation method is a multi-body simulation (MBS), where the model is composed of several non-deformable bodies. MBS solvers generally require a very short computing time for dynamic tasks compared to an FE analysis. Considering this computational advantage, in this study, we examine whether parameters whose values are not known a priory can be determined with sufficient accuracy using MBS model. Therefore, we propose a Many-at-a-time sensitivity analysis method that allows approximating these a priory unknown parameters without requiring long simulation times. This method enables a high degree of MBS model optimization to be achieved in an iterative process. The sensitivity analysis method is applied to a simplified screw-vertebra model, consisting of an anterior anchor implant screw and vertebral body of C4. An experiment described in the literature is used as a basis for developing and assessing the potential of the method for sensitivity analysis and to validate the models action. The optimal model parameters for the MBS model were determined to be c=823224N/m for stiffness and d=488Ns/m for damping. The presented method of parameter identification can be used in studies including more complex MBS spine models or to set initial parameter values that are not available as initial values for FE models.

Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

Three types of wakefulness appeared along the vertebrate’s phylogeny and ontogeny: spinal-rhombencephalic in fish, brainstem-diencephalic in reptiles and cortical in mammals, in which the paralyzed spinal-rhombencephalic wake and the brainstem-diencephalic wake remain as REMS and NREMS The spinal-rhombencephalic and cortical types of wake are inherently anti-homeostatic. Animals must forage, reproduce, and survive to predation disregarding the environmental circumstances, hence temporarily forgetting the homeostatic regulation. After fulfilling the vital functions, the brainstem-diencephalic wake recovers the homeostatic control. The phasic signs of REMS are adaptive in immature mammals, serving for demanding heat, milk and defense to their mother. These advantages outweigh the REMS' poikilostasis in infants. The adults’ poikilostasis of REMS is harmless in thermoneutral environments but is mal-adaptive in aquatic environments in which REMS is reduced or even disappears. These exceptions explain the anomalous examples of REMS. An on-off hypothalamic switch homeostatically regulates the entrance and exit from REMS. Furthermore, the vital phasic signs of REMS depend on a second pontine proportional homeostatic control. Altogether, they regulate the expression of REMS.

The aim of the study was to assess the relationship between the shape of the anterior-posterior curvature of the spine and body composition in school-children. The study included 257 children, aged 11-12. Correct spinal curvature was established in 106 (41.08%) subjects. Other types included: decreased kyphosis and correct lordosis - 40 participants (15.50%), correct kyphosis and decreased lordosis - 24 individuals (9.30%), increased kyphosis and correct lordosis - 17 subjects (6.59%), correct kyphosis and increased lordosis - 22 children (8.53%), decreased kyphosis and decreased lordosis - 32 people (12.40%), decreased kyphosis and increased lordosis - 4 of the examined subjects (1.55%), increased kyphosis and lordosis - 13 people (5.04%). In addition, 134 (51.94%) demonstrated scoliotic posture and 8 (3.10%) scoliosis. There were significant relationships between the shape of the anterior-posterior curvatures and body composition in school-children. Those with a strong body build (predominance of mesomorphs) were generally characterised by the correct formation of these curvatures. In contrast, lean people (with the predominance of ectomorphic factors) were more likely to experience abnormalities. No correlations with body composition were observed in the group with scoliotic posture or scoliosis.

Cerebrospinal fluid contacting neurons (CSF-cNs) are a specific type of neurons located around the ventricles in the brain and the central canal in the spinal cord and have been demonstrated to be intrinsic sensory neurons in the central nervous system (CNS). One of the important channels responsible for the sensory function is polycystic kidney disease 2-like 1 (PKD2L1) channel. Most of the studies concerning the distribution and function of the PKD2L1-expressing CSF-cNs in the spinal cord have previously been performed in non-mammalian vertebrates. In the present study immunohistochemistry was performed to determine the distribution of PKD2L1-immunoreactive (IR) CSF-cNs in the spinal cords of 4 mammalian species: mouse, rat, cat, and macaque monkey. Here, we found that PKD2L1-expressing CSF-cNs were present at all levels of the spinal cord in these animal species. Although the distribution pattern was similar across these species, differences existed. Mice and rats presented a clear PKD2L1-IR cell body labeling, whereas in cats and macaques the PKD2L1-IR cell bodies were more weakly labeled. Ectopic PKD2L1-IR neurons away from the ependymal layer were observed in all the animal species although the abundance and the detailed locations varied. The apical dendritic protrusions towards the lumen of the central canal were clearly seen in all the animal species, but the sizes of protrusion bulbs were different among the species. PKD2L1-IR cell bodies/dendrites were co-expressed with doublecortin, MAP2 (microtubule-associated protein 2) and aromatic L-amino acid decarboxylase, but not with NeuN (neuronal nuclear protein), indicating their immature property and ability to synthesis monoamine transmitters. In addition, in-situ hybridization performed in rats revealed PKD2L1 mRNA expression in the cells around the central canal. Our results indicate that the intrinsic sensory neurons are conserved across non-mammalian and mammalian vertebrates, and that this may play an essential role in the regulation of motor and sensory functions as well as in the maintenance of homeostasis in the CNS.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a debilitating neuromuscular disease characterized by progressive muscular weakness and neuronal degeneration, affecting 1-2 individuals per 100,000 globally. While SBMA is relatively rare, recent studies have shown a significantly higher prevalence of the disease within the indigenous population of Western Canada compared to the general population. The disease is caused by a pathogenic expansion of polyglutamine residues in the androgen receptor protein, which acts as a key transcriptional regulator for numerous genes. SBMA has no cure, and current treatments are primarily supportive and focused on symptom management. Recently, a form of precision medicine known as antisense therapy has gained traction as a promising therapeutic option for numerous neuromuscular diseases. Antisense therapy uses small synthetic oligonucleotides to confer therapeutic benefit by acting on pathogenic mRNA molecules, serving to either degrade pathogenic mRNA transcripts or helping to modulate splicing. Recent studies have explored the suitability of antisense therapy for the treatment of SBMA, primarily focused on antisense-mediated mRNA knockdown approaches. Advancements in understanding the pathogenesis of SBMA and the development of targeted therapies offer hope for improved quality of life for individuals affected by this debilitating condition. Continued research is essential to optimize these genetic approaches, ensuring their safety and efficacy.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p<0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Background: Rod fracture (RF) is the most common cause of revision in adult spinal deformity (ASD) surgery, and various treatment strategies for preventing RF are reported in literature. This retrospective study involving 139 ASD patients (aged ≥65 years and a minimum 2-year follow-up) who underwent long-segment fixation from T10 to sacrum with pedicle subtraction osteotomy (PSO), analyzed long-term results, including radiographical parameters and the incidence of recurrent RF (re-RF), to determine the most effective revision method for preventing RF. Methods: Patients were classified into three groups according to the revision method performed for RF; simple rod replacement (SR group, n=17), lateral lumbar interbody fusion around PSO site (LLIF group, n=8), and accessory rod integration (AR group, n=22). Baseline characteristics, radiographical and clinical parameters were analyzed. Results: RF occurred in 47 patients (34%) at an average of 28 months following primary deformity correction. Re-RF occurred in six patients (13%) at an average of 37 months. Re-RF occurred most commonly in SR group (p=.048). Every re-RF in SR group occurred at the PSO site, none occurred in LLIF group, and one in AR group occurred near L4–5. After both primary deformity correction and revision surgery, spinopelvic parameters had shown favorable results and clinical outcomes had improved in all three groups, without significant intergroup differences. Conclusions: Accessory rod integration or additional LLIF around the PSO site seems to provide greater strength and stability to the previously fused segments than simple rod replacement, which demonstrates the need for additional support in revision surgery for RF after PSO.

Minimally invasive surgery for adult spinal deformities (MIS deformity surgery) utilizes MIS lumbar interbody fusion and percutaneous pedicle screw fixation (PPSF) without posterior corrective osteotomy. While MIS reduces issues associated with open deformity surgery, it has limitations in correcting sagittal imbalance. This review discusses the limitations and solutions of lateral lumbar interbody fusion (LLIF) and introduces our experience in addressing marked sagittal deformities. We reviewed the literature and incorporated our clinical experience to evaluate the efficacy of recent MIS techniques, particularly focusing on oblique lumbar interbody fusion (OLIF) at L1-5 and L5-S1. The use of higher profile and greater angle cages and the application of PPSF with curved rods and percutaneous rod compression were discussed. Advances in MIS techniques, such as OLIF, have enabled significant improvements in increasing disc height and angle. Combining these new techniques and concepts, we successfully corrected marked sagittal deformities using MIS deformity surgery. Early onset of proximal junctional kyphosis was identified as a notable complication. Although recent advancements in MIS deformity surgery have shown promise in correcting sagittal deformities, further clinical experience and data are necessary to enhance outcomes and mitigate complications such as proximal junctional kyphosis.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

Spinal muscular atrophy 5q (SMA) is the most common neuromuscular inherited disease in neonates which is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently established drugs can improve the motor functions of SMA infants when treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using real-time PCR assay with dried blood spots (DBS) was performed in Saint-Petersburg from January 2022 through November 2022. Here, 36,140 newborns were screened by GenomeX real-time PCR-based screening test, and three genotypes were determined. Homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns) and wild-type individuals (35,364 newborns) were identified. All four newborns screened positive for homozygous SMN1 deletion were confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined Saint-Petersburg spinal muscular atrophy incidence of 1 in 9,035 and SMA carrier frequency of 1 in 47. In conclusion, it can be summarized that providing both timely SMN1 information and confirmation along with SMN2 copy number as part of SMA newborn screening algorithm can significantly improve clinical follow-up, family members testing, and SMA patients' treatment.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

(1) Background: The androgen receptor (AR) is critical for mediating the effects of androgens. The polymorphic CAGn locus in exon 1 of the AR gene is associated with several diseases, including spinal and bulbar muscular atrophy (SBMA), prostate cancer, and male infertility. This study evaluated the CAGn locus in 9,000 infertile Russian men and 286 fertile men (control group); (2) Methods: The CAGn locus was analyzed using the polymorphism of lengths of amplified fragments method; (3) Results: In the infertile cohort, CAG repeats ranged from 6 to 46, with a unimodal distribution. The number of CAG repeats in infertile and fertile men was 22.15 ± 0.93 and 22.02 ± 1.36, respectively. In infertile men, variants with 16 to 29 repeats were present in 97% of alleles. A complete mutation (≥42 CAG repeats) was found in three patients, while three others had 39-41 repeats. The incidence of SBMA was 1: 3,000 infertile men. Significant differences (p<0.05) were observed between infertile and fertile men in alleles with 21, 24 and 25 repeats; (4) Conclusions: This study revealed certain differences in the CAGn polymorphic locus of the AR gene in Russian infertile and fertile men, and determined the frequency of SBMA in infertile patients.

Patients who have undergone surgery in early life may be at elevated risk for neuropathic pain in later life. The risk factors for this susceptibility are not fully understood. Here, we used a mouse chronic pain model to test the hypothesis that early exposure to general anesthetic (GA) causes cellular and molecular alterations in dorsal spinal cord (DSC) and dorsal root ganglion (DRG) that produces a predisposition to neuropathic pain via an upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 (P7) and underwent spared nerve injury at P28 which causes chronic pain. Selected groups were treated with rapamycin, an mTOR inhibitor, for eight weeks. Behavioral tests show early isoflurane exposure enhances susceptibility to chronic pain, and rapamycin treatment improves outcomes. Immunohistochemistry, Western blotting, and q-PCR indicates that isoflurane upregulates mTOR expression and neural activity in DSC and DRG. Accompanying upregulation of mTOR and rapamycin-reversible changes in chronic pain-associated markers, including N-cadherin, cAMP response element-binding protein (CREB), purinergic P2Y12 receptor, glial fibrillary acidic protein (GFAP) in DSC; and connexin 43, phospho-extracellular signal-regulated kinase (p-ERK), GFAP, Iba1 in DRG, were observed. We conclude that early GA exposure alters the development of pain circuits such that mice are subsequently more vulnerable to chronic neuropathic pain states.

This topical review describes the results of recent research into and development of silicon nitride, a ceramic material with unique properties. The outcome of this ongoing research strongly encourages the use of monolithic silicon nitride and coatings as contemporary and future biomaterial for a variety of medical applications. Crystallographic structure, synthesis and processing of monolithic structures and coatings, and examples of their medical applications are covered that relate to spinal, orthopedic and dental implants, bone grafts and scaffolds, platforms for intelligent synthetic neural circuits, antibacterial and antiviral particles and coatings, optical biosensors, and nano-photonic waveguides for sophisticated medical diagnostic devices. The examples provided show convincingly that silicon nitride is destined to become a leader to replace titanium and other entrenched biomaterials in many fields of medicine.

Background: Objectives. The objective of this study was to compare the efficacy of direct current stimulation (DCS) applied at the transcranial, suboccipital and spinal level on experimental sensory modalities and pain outcome measures in healthy subjects. The hypothesis of this study was that systematic analysis of the efficacy of DCS on modulating evoked thermal and mechanical pain modalities and mechanisms such as endogenous pain modulation in healthy individuals would reveal sensitive outcome measures help develop this technique for the control of chronic pain. Materials and Methods. Database searches were conducted up to December 2019 for randomized controlled trials that performed sham-controlled DCS of experimental sensory modalities and pain outcomes following transcranial, suboccipital and spinal locations in healthy participants. Standardized mean differences with 95% confidence intervals were calculated for sensory modalities, including random-effect metanalysis. Results: Thirty-one studies were included for analysis (647 participants). A significant decrease in pain intensity for active vs sham transcranial stimulation was identified for pain intensity (n=158; SMD=0.79; 95% CI=0.56 to 1.02), a significant increase in heat pain threshold (n=222; SMD=1.16; 95% CI=0.95 to 1.37), and a significant increase in cold pain threshold (n = 155; SMD = 0.77, 95% CI 0.53 to 1.01). No significant modulation of pressure pain threshold was identified with DCS and only a limited number of studies focused on experimental pain modulation following neuromodulation at the suboccipital or spinal level. Conclusions: These results show significant transcranial DCS neuromodulation of pain intensity and on thermal pain modalities. Future studies should focus on endogenous pain and sensory modality modulation with sham-controlled DCS applied at transcranial, suboccipital and spinal locations.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

Spinal metastatic tumors are common and often cause debilitating symptoms. Image-guided percutaneous thermal ablation (IPTA) has gained significant recognition in managing spinal column tumors due to its exceptional precision and effectiveness. Conventional guidance modalities, including computed tomography, fluoroscopy, and ultrasound, have been important in targeting spinal column tumors while minimizing harm to adjacent critical structures. This study presents a novel approach utilizing a fusion of Cone Beam Computed Tomography with Magnetic Resonance Imaging to guide percutaneous thermal ablation for four patients with secondary spinal column tumors. The visual analog scale (VAS) evaluated procedure effectiveness during an 18-month follow-up. Percutaneous vertebroplasty was performed in two cases, and a thermostat was used during all procedures. Imaging was performed using the Stealth Station navigation system Spine 8 (SSS8) and a 1.5T MRI machine. The fusion of CBCT with MRI allowed precise tumor localization and guidance for thermal ablation. Initial results indicate successful tumor ablation and symptom reduction, emphasizing the potential of CBCT-MRI fusion in spinal column tumor management. This innovative approach is promising in optimizing therapy for secondary spinal column tumors. Further studies are necessary to validate its efficacy and applicability.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

Wear simulation aims to assess wear rates and their dependence on factors like load, kinematics, temperature, and implant orientation. Despite its significance, there's a notable gap in research concerning advancements in simulator control systems and the testing of clinically relevant waveforms. This study addresses this gap by focusing on enhancing the conventional proportional-integral-derivative (PID) controller used in joint simulators through the development of a fuzzy logic-based controller. Leveraging a single-input-multiple-output (SIMO) fuzzy logic control system, the study aimed to improve displacement control, augmenting the traditional Proportional-Integral (PI) tuning approach. Implementation and evaluation of a novel Fuzzy-PI control algorithm were conducted on the Leeds spine wear simulator. The study also included testing of daily-living (DL) profiles, particularly from the hip joint, to broaden the scope of simulation scenarios. While both the conventional PI controller and the Fuzzy-PI controller met ISO tolerance criteria for the spine flexion-extension (FE) profile at 1Hz, the Fuzzy-PI controller demonstrated superior performance at higher frequencies and with DL profiles due to its real-time adaptive tuning capability. The Fuzzy-PI controller represents a significant advancement in joint wear simulation, offering improved control functionalities and a more accurate emulation of real-world physiological dynamics.

Syringomyelia can be associated with multiple etiologies. The treatment of the underlying causes is the first-line therapy, however, a direct approach to the syrinx is accepted as rescue treatment. Any direct intervention on the syrinx requires a myelotomy, posing a significant risk of iatrogenic spinal cord (SC) injury. Intraoperative neurophysiological monitoring (IONM) is crucial to detect and prevent surgically induced damage in neural SC pathways. We retrospectively reviewed the perioperative and intraoperative neurophysiological data and perioperative neurological examinations in ten cases of syringomyelia surgery. All monitored modalities remained stable throughout the surgery in six cases, correlating with no new postoperative neurological deficits. In two patients, significant transitory attenuation, or loss of motor evoked potentials (MEPs), were observed and recovered after a corrective surgical maneuver, with no new postoperative deficit. In two cases, a significant MEP decrement was noted, which lasted until the end of the surgery and was associated with postoperative weakness. A transitory train of neurotonic electromyography (EMG) discharges was reported in one case, the surgical plan was adjusted and the patient showed no postoperative deficit. The dorsal nerve roots were stimulated and identified in the seven cases where the myelotomy was performed via the dorsal root entry zone. Dorsal column mapping guided the myelotomy entry zone in four cases. In conclusion, multimodal IONM is feasible and reliable and may help prevent iatrogenic SC injury during syringomyelia surgery.

Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (ASO); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule, combination therapy