Spinal Cord Research Articles

The presence of oligoclonal bands predicts conversion to multiple sclerosis in isolated myelitis

Acute transverse myelitis (ATM) is a disease characterized by inflammation of the spinal cord and may have various causes. In the context of this work, the distinction between isolated ATM and initial manifestation of autoimmune-mediated diseases of the central nervous system such as multiple sclerosis (MS) is crucial. Hence, the aim of this work was to identify predictive factors associated with the conversion to definite MS in a collective of individuals after their initial episode of isolated ATM (no initial identified cause). In this retrospective data analysis from the Vienna MS Database, all patients from Jan. 1, 1999, to Dec. 31, 2019, with a diagnosis of isolated ATM (according to the criteria of the Transverse Myelitis Consortium Working Group) who underwent lumbar puncture were extracted. Electronic medical records were reviewed on the availability of clinical data including therapy and follow-up, laboratory results including cerebrospinal fluid (CSF) analysis, evoked potentials (EP) as well as magnetic resonance imaging data. Among 42 patients with the diagnosis of isolated ATM, 12 (29%) were subsequently diagnosed with MS over a median follow-up period of 7.7 years. Univariately, MS converters were younger (32 years [25–39] vs. 42 years [31–50], p = 0.032), had a lower CSF/serum albumin ratio (29 [24–35] vs 37 [27–52], p = 0.037), lower CSF total protein (4.5 [2.8–4.8] vs. 5.5 [3.4–8.5], p = 0.023) and a higher proportion of CSF-specific oligoclonal bands (OCB; 83% vs. 30%, p = 0.002). In the multivariate regression analysis, the presence of CSF-specific OCB emerged as the sole predictive factor of subsequent MS diagnosis (OR: 14.42, 95% CI 1.39 to 149.48, p = 0.03). In a collective of 42 patients with isolated ATM and an MS conversion rate of nearly 30%, the only but highly predictive factor were CSF-specific OCB. This emphasizes the significance of conducting timely CSF analysis in such patients and underscores the need for tailored monitoring and follow-up strategies in this specific group.

Addressing bladder and bowel challenges in dutch multiple sclerosis patients: Symptom prevalence and patient referral pathways.

Nerve damage and/or spinal cord injury in individuals with multiple sclerosis (MS) may result in the development of bladder and bowel problems. We wanted to gain insight into two issues: the prevalence of bladder and bowel problems among individuals with MS and the referral pathways for these problems to various physicians treating patients with MS. In the autumn of 2021, we undertook a nationwide cross-sectional study. We used a comprehensive questionnaire comprising 63 questions covering aspects such as MS diagnosis, disease progression, bladder and bowel issues, and consultations with healthcare professionals. Individuals with MS were invited to participate through social media or by direct mail. The study included 1,082 validated respondents (81.5% female) with an average age of 53.3 years at participation, and an average age of 38.3 years at MS-diagnosis. Among the respondents, 91% experienced bladder problems while 73% indicated they had bowel problems. Within these respective groups, 42% and 47% were not aware of the connection between these issues and MS. Bladder and bowel related complaints disrupted daily life for 45% and 28% of the respondents, respectively. The patients consulted various healthcare providers for their complaints. Most respondents expressed dissatisfaction with the time it took to resolve their problems and 9% of those with bladder complaints and 60% of those with bowel complaints had not yet found a satisfactory solution. In the Netherlands, bladder and bowel symptoms in individuals with MS are highly prevalent and have a considerable impact on quality of life. Lack of awareness of these symptoms frequently leads to inadequate recognition, both by the patient and healthcare professional. Patients often consult various healthcare professionals for these complaints, which can potentially result in suboptimal treatment due to a lack of specialized expertise.

A central and peripheral dual neuromodulation strategy in pain management of zoster-associated pain.

Spinal cord stimulation (SCS) has shown effectiveness in relieving zoster-associated pain (ZAP), but some patients still experience moderate or severe pain after SCS treatment. This study aims to evaluate the impact of SCS combined with dorsal root ganglion (DRG) pulsed radiofrequency (PRF) as a dual neuromodulation strategy on the prognosis of ZAP. The clinical records of patients diagnosed with ZAP who underwent SCS (SCS group) or SCS combined with PRF (SCS + PRF group) at The Third Xiangya Hospital, Central South University, were retrospectively analyzed to compare the effectiveness of the two treatment approaches for ZAP. Outcome measures included changes in Visual Analog Scale (VAS) scores before and after neuromodulation treatment, response rates, and incidence of progression to postherpetic neuralgia (PHN).13 SCS patients and 15 SCS + PRF patients were analyzed. Admission VAS scores were similar (P = 0.934). Upon discharge, no significant differences in VAS or response rates were observed (P > 0.05). However, at 6-month follow-up, the SCS + PRF group had lower VAS scores (1.53 ± 1.06 vs. 3.23 ± 1.50, P < 0.001) and a lower proportion of residual moderate pain (P = 0.041). None in the SCS + PRF group progressed to PHN in the acute/subacute phases, differing significantly from the SCS group (P = 0.038).Therefore, SCS combined with DRG PRF is feasible and effective in the treatment of ZAP. This dual neuromodulation strategy may be a more appropriate regimen for the treatment of ZAP.

Clinical signs, diagnostic imaging, histopathology and outcome in a dog with meningoencephalomyelitis of unknown origin and concurrent involvement of the cauda equina and left sciatic nerve

AbstractA 3‐year‐old, female, neutered toy poodle dog was presented with generalised tremors, neck pain and obtundation. Neurological examination revealed a multifocal localisation (brainstem and cervical spinal cord). Magnetic resonance imaging findings and cerebrospinal fluid tap were consistent with meningoencephalomyelitis of unknown origin. After immunosuppressive treatment, the dog improved, but while tapering experienced two relapses. During the second relapse, clinical presentation revealed multifocal clinical signs affecting the brainstem, the lumbosacral spinal cord and the left sciatic nerve. Magnetic resonance imagings of the brain, lumbosacral spinal cord and the left sciatic nerve, cerebrospinal fluid analysis and histopathology of the left sciatic nerve confirmed a recurrence of a meningoencephalomyelitis of unknown origin involving the central nervous system and the peripheral nervous system. Immunosuppressive treatment was re‐instituted, with improvement of clinical signs. At 1‐year follow‐up, the dog remains clinically stable with no treatment.

Falcarindiol improves functional recovery and alleviates neuroinflammation after spinal cord injury by inhibiting STAT/MAPK signaling pathways

Spinal cord injury (SCI) is a devastating trauma in the central nervous system (CNS), leading to motor and sensory impairment. Neuroinflammation is one of the critical contributors to the progression of secondary injury. Falcarindiol has been reported to efficaciously mitigate lipopolysaccharide (LPS)-mediated inflammation in RAW 264.7 cells. The role of falcarindiol in SCI recovery remains unclear. In this present study, traumatic SCI mice models and LPS-stimulated murine microglia cell line (BV2 cells) were performed to explore the pharmacological effects and the underlying mechanisms of falcarindiol in improving SCI repair with detection of motor function recovery, morphological changes, numbers of survival neurons and protein expression levels of inflammation or apoptosis-related proteins. Our study found that falcarindiol intervention could promote motor function recovery and reduce spinal cord tissue damage in mice following SCI. Mechanistically, falcarindiol intervention suppressed apoptosis-driven neuronal cell death and mitigated inflammatory reactions following SCI. Additionally, falcarindiol inhibited the activation of signal transducer and activator of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in vivo and in vitro. This suppression of STAT and MAPK activation by falcarindiol was reversed by STAT3 agonist Colivelin TFA and MAPK agonist C16-PAF in BV2 cells, respectively. Moreover, the study further demonstrated that the anti-inflammation role of falcarindiol was obstructed by Colivelin TFA but not by C16-PAF in LPS-stimulated BV2 cells, suggesting that falcarindiol may efficaciously ameliorate neuroinflammation through inhibiting the activation of STAT signaling pathway following SCI. Collectively, our study indicates that falcarindiol may be a novel drug candidate for the treatment and management of SCI.

Urban-Rural Disparities in Community Participation after Spinal Cord Injury in Ontario.

Personal, social, and environmental factors may influence self-efficacy and social reintegration among people living with spinal cord injury or disease (SCI/D) in urban and rural areas. Novel data collection methods have the potential to characterize community participation (CP) in diverse settings. The objectives were (1) to describe and compare self-reported community participation (Reintegration to Normal Living Index (RNLI) and Moorong Self-Efficacy Scale (MSES)) levels of individuals with SCI/D living in urban or rural Ontario, Canada; and (2) to determine the accuracy of an artificial intelligence (AI) optical mark recognition tool for extracting data from CP surveys conducted among participants after transitioning from inpatient rehabilitation to home and residing in the community. We partnered with SCI Ontario staff to collect MSES and RNLI survey data from adults with motor complete (e.g., AIS A-B) and incomplete (AIS C-D) SCI/D living in urban or rural Ontario, Canada, between January and October 2022. The Rurality Index of Ontario (RIO) from the postal code determined urban or rural residency. Optical mark recognition (OMR) software was used for survey data extraction. A Research Associate validated the extracted survey responses. Descriptive statistics, correlation analysis, and non-parametric statistics were used to describe the participants, their impairments, and their reported CP levels across urban and rural settings. Eighty-five individuals with SCI/D (mean age 53.7 years, 36.5% female) completed the survey. Most of the participants resided in major urban areas (69.4%) and had traumatic injuries (64.7%). The mean total MSES score for Ontarians with SCI/D was 87.96 (95% confidence interval [CI]: 84.45, 91.47), while the mean total RNLI score for the same individuals was 75.61 (95% CI: 71.85, 79.37). Among the MSES domains, the lowest score was observed in response to sexual satisfaction (mean: 4.012, 95% CI: 3.527, 4.497), while the lowest RNLI domain item score was associated with the ability to travel out of town (mean: 5.965, 95% CI: 5.252, 6.678). Individuals with incomplete injuries in rural areas reported lower MSES and RNLI scores than those with complete motor injuries, whereas no significant differences were found in MSES and RNLI scores among urban residents based on impairment. These findings suggest that, depending on the environmental context (e.g., rural vs. urban areas), AIS categories may influence the perception of CP among people living with SCI/D. The OMR tool had 97.4% accuracy in extracting data from the surveys. The CP (MSES and RNLI) scores reported by individuals with SCI/D differ based on their living setting. In rural Ontario, individuals with greater functional ability reported lower CP than their counterparts living in urban settings. Although CP remains a challenge, the needs of individuals with motor incomplete SCI/D and heterogeneous levels of mobility residing in rural areas require exploration and targeted interventions. The OMR tool facilitates accurate data extraction from surveys across settings.

The Ambivalent Role of miRNA-21 in Trauma and Acute Organ Injury

Since their initial recognition, miRNAs have been the subject of rising scientific interest. Especially in recent years, miRNAs have been recognized to play an important role in the mediation of various diseases, and further, their potential as biomarkers was recognized. Rising attention has also been given to miRNA-21, which has proven to play an ambivalent role as a biomarker. Responding to the demand for biomarkers in the trauma field, the present review summarizes the contrary roles of miRNA-21 in acute organ damage after trauma with a specific focus on the role of miRNA-21 in traumatic brain injury, spinal cord injury, cardiac damage, lung injury, and bone injury. This review is based on a PubMed literature search including the terms “miRNA-21” and “trauma”, “miRNA-21” and “severe injury”, and “miRNA-21” and “acute lung respiratory distress syndrome”. The present summary makes it clear that miRNA-21 has both beneficial and detrimental effects in various acute organ injuries, which precludes its utility as a biomarker but makes it intriguing for mechanistic investigations in the trauma field.

Apelin regulates mitochondrial dynamics by inhibiting Mst1-JNK-Drp1 signaling pathway to reduce neuronal apoptosis after spinal cord injury

In the secondary injury stage of spinal cord injury, mitochondrial dysfunction leads to decreased ATP production, increased ROS production, and activation of the mitochondria-mediated apoptosis signaling pathway. This ultimately intensifies neuronal death and promotes the progression of the injury. Apelin, a peptide produced by the APLN gene, has demonstrated promise in the treatment of spinal cord injury. The aim of this study was to investigate how Apelin protects neurons after spinal cord injury by influencing the mitochondrial dynamics. The results showed that Apelin has the ability to reduce mitochondrial fission, enhance the mitochondrial membrane potential, improve antioxidant capacity, facilitate the clearance of excess ROS, and ultimately decrease apoptosis in PC12 cells. Moreover, Apelin is overexpressed in neurons in the damaged part of the spinal cord, contributing to reduce mitochondrial fission, improve antioxidant capacity, increase ATP production, decrease apoptosis, promote spinal cord morphological repair, maintain the number of nissl bodies, and enhance signal transduction in the descending spinal cord pathway. Apelin exerts its protective effect by inhibiting the Mst1-JNK-Drp1 signaling pathway. In summary, our study further improved the effect of Apelin in the treatment of spinal cord injury, revealed the mechanism of Apelin in protecting damaged neurons after spinal cord injury by maintaining mitochondrial homeostasis, and provided a new therapeutic mechanism for Apelin in spinal cord injury.

Shh signaling directs dorsal ventral patterning in the regenerating X. tropicalis spinal cord.

Tissue development and regeneration rely on the deployment of embryonic signals to drive progenitor activity and thus generate complex cell diversity and organization. One such signal is Sonic Hedgehog (Shh), which establishes the dorsal-ventral (D/V) axis of the spinal cord during embryogenesis. However, the existence of this D/V axis and its dependence on Shh signaling during regeneration varies by species. Here we investigate the function of Shh signaling in patterning the D/V axis during spinal cord regeneration in Xenopus tropicalis tadpoles. We find that neural progenitor markers Msx1/2, Nkx6.1, and Nkx2.2 are confined to dorsal, intermediate and ventral spatial domains, respectively, in both the uninjured and regenerating spinal cord. These domains are altered by perturbation of Shh signaling. Additionally, we find that these D/V domains are more sensitive to Shh perturbation during regeneration than uninjured tissue. The renewed sensitivity of these neural progenitor cells to Shh signals represents a regeneration specific response and raises questions about how responsiveness to developmental patterning cues is regulated in mature and regenerating tissues.

Anti-nociceptive effect of STW 5-II in rodent models of stress and post-inflammatory visceral hypersensitivity

AimsVisceral hypersensitivity is a therapy-resistant hallmark of irritable bowel syndrome (IBS). Many IBS patients’ symptoms develop following an acute colitis, and most report that stress worsens symptoms. STW 5-II, a combination of six herbal extracts, is a clinically proven treatment for IBS, but the mechanism is uncertain. Here, we employ two well-characterized rodent models to test the hypothesis that STW 5-II attenuates chronic colonic hypersensitivity. Main methodsSeparate cohorts of male rats were used for each model of colonic hypersensitivity. The first model used repeated water avoidance stress (1hr/day for 10 days), while the second model used intracolonic trinitrobenzene sulfonic acid to induce a short-lived colitis followed by post-inflammatory visceral hypersensitivity. Both models used sham treatment controls. Colonic sensitivity was quantified as the number of abdominal contractions to graded pressures (20–60 mmHg) of isobaric colorectal distension (CRD). Phosphorylation of extracellular signal-regulated kinase (pERK) was assessed via immunohistochemistry in the brain, spinal cord, and dorsal root ganglion (DRG). STW 5-II (10 ml/kg, p.o.) or vehicle (p.o.) was administered for 7 days, prior to CRD and pERK expression. Key findingsRats exposed to either model developed significant colonic hypersensitivity. Both models enhanced CRD-evoked pERK in DRGs, spinal cord, and brain. STW 5-II decreased colonic hypersensitivity and reduced CRD-evoked brain, spinal, and DRG pERK. SignificanceBoth models induced colonic hypersensitivity and enhanced pERK expression. STW 5-II inhibited colonic hypersensitivity and decreased noxious neuronal activation in both models, which could explain its clinically proven efficacy in relieving visceral hypersensitivity-related symptoms in IBS.

Natural polymeric biomaterials for managing peripheral nerve injuries : a novel approach for tissue repair and reconstruction.

Peripheral nerve injury serves as a major challenge to clinicians and researchers due to the complexity and functions of peripheral nerves that play the crucial role of transmitting signals between spinal cord and other human body tissues. Biomaterials offer promising solutions for regeneration of nerve tissues owing to their biodegradability, and biocompatibility. They can be fabricated as hydrogels, scaffolds, nanofibrous matrices, and nanoparticles that can facilitate the release of therapeutic molecules to reduce inflammation and promote neuronal growth. Managing peripheral nerve injuries through natural polymeric based biomaterials represents as a novel approach for tissue repair and reconstruction in the field of regenerative medicine. This correspondence will give an insight into the different types of natural polymeric biomaterials that can be efficiently used in managing peripheral nerve injuries.

Surgical Management of Thoracic Dorsal Arachnoid Webs: A Ten-Year Single-Institution Experience

ObjectiveThoracic dorsal arachnoid webs are intradural membranes that may cause obstruction of CSF flow and spinal cord compression. While well-recognized, they are rare and there is a paucity of long-term data on their natural history and prognosis. We reviewed radiographic features, surgical indications, and pathologic specimens of patients diagnosed with focal thoracic dorsal arachnoid webs. MethodsA radiology database and surgical case logs were queried for thoracic arachnoid webs at a single hospital system for a ten-year period. A retrospective chart review was performed on identified cases. ResultsWe identified 127 patients with dorsal thoracic arachnoid webs. Arachnoid webs were radiographically classified into three morphologic types: Type 1 (54%) causing spinal cord deformity only, Type 2 (32%) producing cord deformity with myelomalacia, and Type 3 (14%) with cord deformity, myelomalacia, and syringomyelia. These arachnoid webs were commonly centered at the upper thoracic T4 segmental level. Forty-one cases (32%) required surgery, generally for thoracic myelopathy with gait instability (46%) and lower extremity numbness and pain (39%). In patients who underwent surgery, 79% experienced symptomatic improvement and 21% remained stable, after an average of 21 months follow-up evaluation. Surgical pathology revealed fibrous connective tissue (100%) with calcifications (26%) or inflammation (7%). ConclusionsThe majority in a large series of patients with dorsal arachnoid webs did not undergo surgical intervention, but those with myelomalacia and syrinx experienced radiographic and clinical deterioration without surgery. Surgery to treat symptomatic arachnoid webs results in significant clinical improvement with low surgical morbidity.

Effect of surgical resection extent on neurological prognosis of adult intradural spinal teratomas.

Intradural spinal teratomas are very rare in adults and may cause severe neurological deficits. Tumors often tightly attached to the spinal cord, making complete resection difficult. The purpose of this study was to evaluate the impact of surgical resection extent on neurologic outcomes in these patients. A retrospective study of IST patients who underwent microsurgery in our center was performed. Age, sex, symptoms, duration of symptoms, tumors size, neurologic status, extent of resection, and surgical outcome were reviewed for each patient. The Kruskal-Wallis test and multivariate logistic regression were used to assess affecting factors on neurological outcomes. A total of 26 adult patients underwent microsurgical management were studied. The mean age at surgery was 41.3 years (range 23-66 years). The mean follow-up was 109.5 months (range 17-216 months). Gross total resection (GTR) was achieved in 12 (46.2%) cases and subtotal resection (STR) in 14 (53.8%) cases. 6 patients (23.1%) had recurrence, and the mean time to recurrence (TTR) was 86.0 months (range 3-168 months) after the first surgery. No recurrence was found after the second surgery during follow-up. All tumors were pathologically confirmed as mature teratomas. In analysis of neurological outcomes, patients with shorter symptom duration (p = 0.035) and lower MMcS grade (p = 0.025) had better postoperative neurological outcomes. The neurological prognosis of STR patients was better than that of GTR patients (p = 0.041). Multivariate logistic regression confirmed that the extent of resection differences remained significant (p = 0.017). Surgical resection is optimal therapeutical management of IST and can obtain a good prognosis. STR appeared to be superior to GTR in terms of neurological improvement. Considering the characteristics of slow growth and long TTR of IST, STR may be a feasible option for highly adherent tumors.

Multimodal intraoperative neurophysiological monitoring may better predict postoperative distal upper extremities’ complex-functional outcome than spinal and muscular motor evoked potentials alone in high-cervical intramedullary spinal cord tumor surgery

ObjectiveD-wave can safely monitor the corticospinal-tract (CST)-function regarding gross-motor outcome of lower extremities, but it is still unknown whether i)D-wave can also safely monitor the gross-motor outcome of distal upper extremities in those patients undergoing high-cervical intramedullary-spinal-cord-tumor (IMSCT)-resection (enabling epidural D-wave-placement below C5) and ii)multimodal IONM can also predict fine-motor/complex hand function. MethodsWe prospectively assessed 20 patients undergoing IMSCT-surgery above the C4/5-level with multimodal IONM (D-wave/mMEPs/EMG/SSEPs). Detailed gross-/fine-motor and complex hand function was assessed pre- and postoperatively and during long-term follow-up (mean:29.5 ± 18.8 months) and correlated with IONM-findings. ResultsD-wave monitoring was without intraoperative critical changes in all patients and none had any permanent postoperative gross-motor deficits. However, D-wave did not allow to predict the occurrence of mild permanent postoperative deficits affecting fine-motor function which was the case in 8% for distal upper extremities. The complex distal upper extremities’ function assessed by Nine-Hole-Peg-Test (reflecting the complex motor/sensory interaction for hand-usability) was permanently deteriorated in 15% postoperatively and only the combination of D-wave/mMEPs/EMG/SSEPs was able to provide a viable predictive power (specificity:79%/sensitivity:43%). ConclusionsIn high-cervical IMSCT-surgery, unimpaired D-wave reliably predicts preserved gross-motor function, but fails to sufficiently cover distal upper extremities’ fine-motor/complex function. SignificanceOur study underlines the importance of multimodal IONM for fine-motor/complex hand function.

Anesthetic management of laparoscopically assisted fetoscopic surgery to correct spina bifida

Introduction. The growing incidence of intrauterine pathology in the fetus at the present stage dictates the need to develop and improve intrauterine surgical correction of defects in the fetus. Myelomeningocele (SPINA BIFIDA) is the most common and severe neural tube defect in the fetus, the severity of the neurological deficit is determined by the level of location and extent of the anomaly. By uniting doctors of various specialties (obstetricians-gynecologists, neonatologists, surgeons, anesthesiologists-resuscitators), the Clinic of the St. Petersburg State Pediatric Medical University effectively introduces methods of prenatal surgery.The objective was to demonstrate by clinical example the experience of successful fetoscopic correction of myeloneningocele to reduce maternal risks and injuries, to reduce risks aimed at protecting the tissues of the spinal cord of the fetus, as well as to reduce the need for postpartum correction of the defect in the fetus, to improve prognosis and risks of subsequent disability.Materials and methods. The article presents the first successful experience of minimally invasive laparoscopic correction of myelomeningocele in the fetus with the participation of the multidisciplinary team and the features of anesthesiological support of the method.Conclusion. Laparoscopic access, together with the optimal choice of anesthetic management in fetal surgery, allows not only to successfully correct the defect in myelomeningocele in the fetus, but also to significantly minimize and reduce the risks of injury to the mother, and also reduces the need for postpartum surgical treatment and reduce disability. Accumulation and improvement of experience, a multidisciplinary approach is the key to successful correction of intrauterine fetal pathology.

Dosing overground robotic gait training after spinal cord injury: a randomized clinical trial protocol

BackgroundRobotic exoskeletons have changed rehabilitation care available to people after spinal cord injury (SCI). Yet, the current evidence base is insufficient to identify the optimal dose and neurophysiological mechanism of robotic exoskeleton gait training (RGT) as an effective rehabilitation approach. This study will (1) examine whether the frequency of RGT after motor incomplete SCI impacts function and health outcomes, (2) analyze the neuroplastic effects of RGT dose, and (3) evaluate the safety, tolerability, and feasibility of delivering RGT.MethodsWe will enroll 144 participants with motor incomplete SCI admitted to inpatient rehabilitation within 6 months of SCI. Participants will be randomized based on injury severity and level into one of 3 RGT frequency groups (high, moderate, low) or none/usual care only. Participants will complete 24 RGT sessions and be assessed at admission and discharge to inpatient rehabilitation, post-RGT intervention, 1-month post-RGT, and 9-month post-SCI. Outcomes include Walking Index for Spinal Cord Injury-II, health outcomes (gait speed, Spinal Cord Independence Measure, pain, fatigue, spasticity, general health, quality of life, physical activity), and motor evoked potential amplitudes obtained using transcranial magnetic stimulation.DiscussionSuccessful completion of this study will provide an evidence-based intervention, specifically tailored to meet the unique needs of people with SCI, which supports walking recovery; maximizing health, function, and ultimately participation. The intervention will further support widespread clinical implementation of exoskeleton use during acute rehabilitation.Trial registrationClinicalTrials.gov NCT05218447. Registered on June 23, 2022.

Predestinative role acidic cerebrospinal fluid on the destiny of central channel in spinal cord following subarachnoid hemorrhage: an experimental study

Predestinative role acidic cerebrospinal fluid on the destiny of central channel in spinal cord following subarachnoid hemorrhage: an experimental study

High-Definition Trans-Spinal Current Stimulation Improves Balance and Somatosensory Control: A Randomised, Placebo-Controlled Trial.

To investigate and compare the effects of three different high-definition (HD) non-invasive current stimulation (NICS) protocols on the spinal cord on support balance and somatosensory abilities in healthy young people. Fifty-eight students were enrolled in this crossover study. All participants underwent application of (i) 1.5 mA anodal high-definition trans spinal direct current stimulation (HD-tsDCS), (ii) 1.5 mA cathodal HD-tsDCS, (iii) 1.5 mA high-definition trans spinal alternating current stimulation (HD-tsACS), and (iv) sham HD-tsDCS/ACS over the eighth thoracic vertebra in a randomised order. Balance (Y Balance test), deep sensitivity (Tuning Fork Test), and superficial sensitivity (Monofilament Test) of the lower limbs were tested immediately before and after each intervention. Balance ability improved significantly following anodal HD-tsDCS and HD-tsACS compared with that following sham HD-tsDCS/ACS. Similarly, deep sensitivity increased significantly with anodal HD-tsDCS and HD-tsACS compared to that with sham HD-tsDCS/ACS and cathodal HD-tsDCS. Furthermore, superficial sensitivity improved significantly following anodal HD-tsDCS compared with that after HD-tsACS and cathodal HD-tsDCS. Our data show that HD-tsNICS effectively modulates the balance and somatosensory control of the lower limbs. Several diseases are associated with illness-induced changes in the spinal network in parallel with sensorimotor disabilities. Non-invasive spinal modulation may be a favourable alternative to conventional brain applications in rehabilitation. Future studies should therefore investigate these promising approaches among cohorts of patients with disabilities.

Modulation of heteromeric glycine receptor function through high concentration clustering.

Ion channels are targeted by many drugs for treating neurological, musculoskeletal, renal and other diseases. These drugs bind to and alter the function of individual channels to achieve desired therapeutic effects. However, many ion channels function in high concentration clusters in their native environment. It is unclear if and how clustering modulates ion channel function. Human heteromeric glycine receptors (GlyRs) are the major inhibitory neurotransmitter receptors in the spinal cord and are active targets for developing chronic pain medications. We show that the α2β heteromeric GlyR assembles with the master postsynaptic scaffolding gephyrin (GPHN) into micron-sized clustered at the plasma membrane after heterologous expression. The inhibitory trans- synaptic adhesion protein neuroligin-2 (NL2) further increases both the cluster sizes and GlyR concentration. The apparent glycine affinity increases monotonically as a function of GlyR concentration but not with cluster size. We also show that ligand re-binding to adjacent GlyRs alters kinetics but not chemical equilibrium. A positively charged N- terminus sequence of the GlyR β subunit was further identified essential for glycine affinity modulation through clustering. Taken together, we propose a mechanism where clustering enhances local electrostatic potential, which in turn concentrates ions and ligands, modulating the function of GlyR. This mechanism is likely universal across ion channel clusters found ubiquitously in biology and provides new perspectives in possible pharmaceutical development.

Brown Sequard Syndrome: A Case Report

A very unusual neurological disorder known as Brown-Séquard Syndrome (BSS) may develop when the spinal cord is severed or damaged on one side. Ipsilateral motor paralysis, loss of proprioception, and a lack of pain and temperature sensitivity on the opposite side are hallmarks of this disorder's distinctive pattern of neurological impaired functions. A 45-year-old man with a history of severe injuries who acquired Brown-Séquard Syndrome is the subject of this case report.