Spinal Cord Research Articles

TMOD-31. SINGLE-CELL PROFILING AND CHARACTERIZATION OF PATIENT-DERIVED XENOGRAFT GLIOBLASTOMA MODEL IN HUMANIZED MICE

Abstract Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, and the current standard therapy has limited efficacy. To develop effective therapies, it is desirable to develop an animal model that can replicate the tumor heterogeneity and immune microenvironment of human GBM. Here, we describe a novel GBM mouse model established with a patient-derived xenograft (PDX) in humanized mice harboring a nearly complete human immune environment. Humanized mice were generated by engrafting human CD34+ hematopoietic stem cells from umbilical cord blood into immunocompromised mice (NSG, NSG-SGM3, and NOG-EXL) after myeloablation. NSG-SGM3 is a triple transgenic mouse encoding human IL3, GM-CSF, and SCF on the NSG strain background. NOG-EXL is a NOG strain with human IL3 and GM-CSF expression. These cytokines foster the development of the human myeloid lineage and its differentiation. NSG-SGM3 and NOG-EXL were superior in immune cell reproducibility, especially myeloid cells. Radioresistant PDX GBM cells established after repeated irradiation were injected into the forebrain of humanized mice and the same immunocompromised mice without humanization. Human PDX GBM cells formed aggressive tumors with similar growth speed in the humanized mice compared to non-humanized mice; however, their dissemination to the spinal cord was significantly suppressed in humanized mice, suggesting that human immune cells impact the spinal dissemination of GBM cells. Single-cell RNA sequencing analysis revealed infiltration of human CD4+ T, CD8+ T, NK cells, and macrophages, as well as infiltration of regulatory T and exhausted CD8+ cells into the brain tumor, reflecting the immunosuppressive landscape of recurrent human GBM. Furthermore, we found that tumor heterogeneity was increased in humanized mice compared to non-humanized mice. There was a notable rise in neural progenitor-like cell populations, indicating tumor adaptation to immune pressures. This novel GBM-PDX humanized mouse model might be highly beneficial for analyzing the interaction between human tumor cells and human immune cells, and evaluating the effect of immunotherapies.

Progress in treatment of pathological neuropathic pain after spinal cord injury

Pathological neuropathic pain is a common complication following spinal cord injury. Due to its high incidence, prolonged duration, tenacity, and limited therapeutic efficacy, it has garnered increasing attention from both basic researchers and clinicians. The pathogenesis of neuropathic pain after spinal cord injury is multifaceted, involving factors such as structural and functional alterations of the central nervous system, pain signal transduction, and inflammatory effects, posing significant challenges to clinical management. Currently, drugs commonly employed in treating spinal cord injury induced neuropathic pain include analgesics, anticonvulsants, antidepressants, and antiepileptics. However, a subset of patients often experiences suboptimal therapeutic responses or severe adverse reactions. Therefore, emerging treatments are emphasizing a combination of pharmacological and non-pharmacological approaches to enhance neuropathic pain management. We provide a comprehensive review of past literature, which aims to aim both the mechanisms and clinical interventions for pathological neuropathic pain following spinal cord injury, offering novel insights for basic science research and clinical practice in spinal cord injury treatment.

Clinical features and rehabilitation outcome after surgical treatment of spinal meningioma.

Retrospective analysis of clinical routine data. Spinal meningioma is a common type of benign spinal tumor. Surgical removal is the standard therapeutic approach. While surgery is generally associated with excellent outcomes, little is known about the rehabilitation outcome of patients with postoperative deficits. Therefore, we aim to describe the clinical features and rehabilitation outcomes of patients after surgical removal of spinal meningioma. Region of Swabia, Bavaria, Germany. We conducted a retrospective analysis of patients with spinal meningioma who underwent a rehabilitation program for patients with non-traumatic spinal cord injury at our department over the past five years. In addition to routine data, we focussed on analysing the Barthel Index, SCIM III score, and ASIA impairment scale before and after rehabilitation. 15 patients were included in the analysis. While most of them only had a few restrictions relevant to activities of daily living, some had severely limited walking ability. The predominant clinical feature was incomplete paraplegia with or without neurogenic bladder and bowel affection. The Barthel Index and SCIM III score demonstrated positive changes in the majority of cases, while alterations in the ASIA impairment scale were observed in a minority. Considering the results of outcome parameters, rehabilitation treatment appears effective for these patients. Nonetheless, further studies with larger patient cohorts are necessary to confirm these findings.

Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.

CNSC-66. STRUCTURAL AND ELECTROPHYSIOLOGICAL CONNECTIVITY IN GLIOBLASTOMA IS MEDIATED BY TUMOR AND IMMUNE DERIVED CYTOKINES

Abstract BACKGROUND In glioblastomas (GBM), the pleiotropic cytokine interleukin-6 (IL-6) upregulates PD-L1 expression. This results in local immunosuppression favorable to tumor progression, and may account for the limited efficacy of immune checkpoint inhibition. Additionally, IL-6 increases synaptogenesis during development, and contributes to neuronal network remodeling following focal brain or spinal cord injury. Therefore, the aim was to determine whether IL-6 contributes to GBM-induced circuit remodeling from a structural and electrophysiological perspective. METHODS In magnetoencephalography (MEG)-based intratumoral regions of High- (HFC) and Low-Functional Connectivity (LFC) from GBM patients, the expression of IL-6 and GAP43 was compared using bulk and single-cell RNA sequencing and immunofluorescence staining in biological replicates (n=44). In mouse postnatal cortical neurons and primary patient-derived GBM cell cocultures, the expression of Ki67, GAP43, tumor connectivity and neuronal activity were monitored after exogenous application of recombinant human IL-6 (rIL-6) or microglial depletion using PLX5622. Results. IL-6 and GAP43 were overexpressed in HFC compared to LFC regions. In neuron-GBM cocultures, the tumour proliferation index was significantly increased by rIL-6 and decreased by PLX5622. Morphologically, the number of microtubes per tumor cell was significantly increased by rIL-6 and decreased by PLX5622. The expression of GAP43 was inconstantly increased by rIL-6, suggesting the regulation of other pathways involved in tumour microtube formation. Multielectrode array recordings showed a significant increase or decrease in the neuronal activity, following the addition of rIL-6 or microglial depletion, respectively. CONCLUSIONS IL-6-signaling increases proliferation, structural and electrophysiological connectivity in gliomas and may contribute to neuronal network hyper-excitability and synchrony. Microglial depletion provided opposite effects. Additional experiments are mandatory to determine whether the effects of IL-6 on GBM cells depend on the presence of microglial cells or not. These data will be critical to design new therapeutic options, likely to improve the oncological and functional outcomes of patients treated for GBM.

Intramedullary Spinal Cord Abscess in an Adult Patient: A Case Report

Intramedullary Spinal Cord Abscess in an Adult Patient: A Case Report

Electrospun gelatin/hyaluronic acid nanofibers as a platform for uric acid delivery to neural tissue.

Uric acid (UA) is an antioxidant that has been reported to be a neuroprotective compound for injuries and diseases, and specifically, diseases of the central nervous system. However, uric acid is highly insoluble in aqueous solutions, and high levels in the serum lead to gout, which limits its use in humans. Here, we develop a novel drug delivery platform that will release uric acid in a sustained manner for application to neural tissue. We demonstrate that one-step incorporation of UA into an electrospun gelatin/hyaluronic acid nanofiber mat results in controlled release of UA in culture medium. Taking a unique approach, we made solutions of 12% gelatin and 1% hyaluronic acid in a formic acid solvent and added UA for production of nanofiber mats. We then dehydrothermally crosslinked the mats and tested for release of UA into physiological cell culture medium. To test whether the mats have any detrimental effects on healthy nervous system tissue, we cultured spinal cord explants on the mats extended and assessed extensions from the explants. We observed that comparable numbers and lengths of dendrites are extended from the spinal cord tissue, regardless of the amount UA content in the mats. Our results suggest that electrospun gelatin/hyaluronic acid nanofibers can be used as a platform for sustained uric acid delivery to neural tissue without detrimental effects.

Suppurative Meningitis in the Infectious Diseases Clinic - Etiology, Clinic, Laboratory, Course and Outcome

Suppurative meningitis is a bacterial infection of the meninges, which are the protective membranes for the brain and spinal cord, resulting in inflammation[1]. Bacterial meningitis is most commonly caused by Streptococcus pneumoniae and Neisseria meningitidis and continues to pose a major public health threat. The morbidity and mortality of meningitis depend on the uncontrolled inflammatory response of the infected person or host [2]. The purpose of this paper is to present the epidemiological, clinical and laboratory features of cases with bacterial meningitis treated at the Infectious Diseases Clinic within the studied period January 2021 – December 2022. To present the impact of the COVID-19 pandemic on the number of cases treated at the Infectious Diseases Clinic in Prishtina, Kosovo. The total number of patients with bacterial meningitis who received treatment at the Infectious Diseases Clinic during the period from January 2021 to December 2022 was 66. The number of cases was much higher in 2022 compared to 2021.

Outcomes for Degenerative Cervical Myelopathy Following Implementation of the AO Spine International Guidelines: A Single-Centre Service Evaluation.

Degenerative cervical myelopathy (DCM) is a syndrome of symptomatic cervical spinal cord compression due to degenerative spinal changes. Until recently there was no formal consensus on exactly which patients are suitable for surgical or conservative management. The AO Spine international guidelines were introduced to address this issue, based on the best available current evidence. However, their implementation into routine clinical practice has not yet been reported. The objective was to evaluate surgical outcomes following the implementation of the AO Spine guidelines at our spinal neurosurgical centre. A service evaluation was conducted using data collected from electronic healthcare records for 259 patients, with outcomes of interest including change in mJOA score and complications. Data from 193 patients were included in the final analysis. There was a mean improvement of the mJOA score by 1.53 points, 1.44 point and 1.92 points at post-operative intervals of 3months (P < .001), 6months (P < .001) and 12months (P < .001). The percentage (number) of patients whose increase in mJOA score was greater than or equal to the minimal clinically importance difference (MCID) was 41% (44/107), 34% (33/96) and 43% (49/114) at these respective time intervals. Intraoperative complications occurred in 28 patients (11.7%). No association was found between BMI and postoperative change in mJOA score. Our results are comparable to those from best practice data and suggest adherence to international guidelines provides a service that promotes meaningful recovery for patients with DCM. Therefore, our results offer support for implementation of the AO Spine international guidelines in clinical practice.

Corticosteroid Effect in Acute Spinal Cord Injury in the Rural Area

Spinal cord injuries (SCI) are devastating traumatic events in the lives of patients, often resulting in severe and/or permanent neurologic disabilities. Nearly half a million people are living permanently disabled in the United States due to traumatic SCI and 12,000–15,000 patients per year incur new injuries. A 78-year-old male patient came to the emergency room with a history of falling from a height with a pelvic position below exposed to trees 30 hours before admission, found weakness in the lower limbs, unable to urinate since yesterday. On radiologic examination, a burst fracture was found in the collumna of the 1st lumbar vertebra. The patient could not be examined for MRI due to limitations and unavailability of equipment at the hospital. The patient was given high dose of Methylprednisolone treatment for 3 days and there was no motoric improvement in the patient. Acute spinal cord injury is a very dangerous disease because it can cause patients both psychological and non psychological disorders. In areas that are left behind and do not have very good facilities and medical personnel to carry out this treatment. There is no treatment option other than using corticosteroids. However, the effect of corticosteroids still needs to be further developed and researched.

Predictors of Early Mortality After Traumatic Spinal Cord Injury in South Africa.

Retrospective cohort study. To identify predictors for early mortality following traumatic spinal cord injury (TSCI), as recognition of factors associated with early mortality is essential for public resource allocation and optimized acute care. Retrospective Analysis of SCI patients admitted to the acute SCI ward from 2003 to 2022 was performed. Days elapsing from the date of injury to date of death established the survival time. Early mortality was defined as survival time ≤ 365days. Multivariable logistic regression was used in modeling of early death following TSCI with age, gender, neurologic deficit, type of neurologic injury, ventilation status, and count of complications as covariates. Simple logistic regression indicated a significant association of early mortality with the number of complications (P < .0001), neurological deficit (P < .0001), complete neurological injury (P < .0001), ventilation status (P < .0001), and age group (P < .0003). After adjusting for other covariates, complete neurological injury (OR: 1.75, P < .0001), ventilation (OR: 2.80, P < .0001), and Age group (over 60 OR: 17.71, P < .0001) were significantly associated with early mortality. The multivariable model showed a good overall fit (Hosmer-Lemeshow P = .315; AUC 0.85). Predictors of early mortality after TSCI are high complete spinal cord injury, age, number of complications, and the need for ventilation. Identification of high-risk patients is crucial to rationalize and improve acute care to potentially reduce mortality rates.

Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction

Multiple sclerosis (MS) is an autoimmune disease mediated by T helper cells, which is characterized by neuroinflammation, axonal or neuronal loss, demyelination, and astrocytic gliosis. Histone deacetylase inhibitors (HDACis) are noted for their roles in easing inflammatory conditions and suppressing the immune response. Panobinostat, an HDACi, is now being used in treating multiple myeloma. Nevertheless, the effect of panobinostat on autoimmune diseases remains largely unclear. Thus, our research endeavored to determine if the administration of panobinostat could prevent experimental autoimmune encephalomyelitis (EAE) in mice, one of the most commonly used animal models of MS, and further explored the underlying mechanisms. The EAE mice were generated and then administered continuously with panobinostat at a dosage of 30 mg/kg for 16 days. The results indicated that panobinostat markedly alleviated the clinical symptoms of EAE mice, inhibiting demyelination and loss of oligodendrocytes in the central nervous system (CNS). Moreover, panobinostat decreased inflammation and the activation of microglia and astrocytes in the spinal cords of EAE mice. Mechanistically, treatment with panobinosat significantly suppressed M1 microglial polarization by blocking the activation of toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (MyD88)/interferon regulatory factor 5 (IRF5) pathway. Additionally, panobinostat inhibited mitochondrial dysfunction and reduced oxidative stress in the spinal cords of EAE mice. In conclusion, our findings reveal that panobinostat significantly ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting oxidative stress-linked neuroinflammation and mitochondrial dysfunction.

Differential target multiplexed spinal cord stimulation in patients with Persistent Spinal Pain Syndrome Type II: a study protocol for a 12-month multicentre cohort study (DETECT)

IntroductionDifferential target multiplexed spinal cord stimulation (DTM SCS) is a new stimulation paradigm for chronic pain management with the aim of modulating glial cells and neurons in order to rebalance...

Chitosan-Modified Hydrogel Microsphere Encapsulating Zinc-Doped Bioactive Glasses for Spinal Cord Injury Repair by Suppressing Inflammation and Promoting Angiogenesis.

Spinal cord injury (SCI) is a common nerve injury caused by external force, resulting in sensory and motor impairments. Previous studies demonstrated that inhibiting the neuroinflammation promoted SCI repair. However, these approaches are low efficient, and lack targeting specificity, and even require repeated and high doses of systemic administration. To address such issues, in the present study, chitosan-modified hydrogel microspheres encapsulating with zinc-doped bioactive glasses (CS-MG@Zn/BGs) is constructed for targeted repair of SCI. In vitro, the CS-MG@Zn/BGs effectively inhibited the acute inflammatory response initiated by microglia and promoted angiogenic activities. In vivo, CS-MG@Zn/BGs targeted the injured site, and attenuated neuroinflammation by inhibiting microglia infiltration and modulating microglia polarization toward M2 type. Furthermore, it facilitated vascular reconstruction, neuronal differentiation, axonal regeneration and remyelination at the injured site, and thereby promoted motor function recovery of SCI mice. The in vitro and in vivo results implied that CS-MG@Zn/BGs may be a promising alternative for the rehabilitation of SCI.

Surgically managed traumatic spinal cord injury in Singapore: a descriptive study across two level one trauma centres

Study designCase SeriesObjectivesTo provide an updated understanding of the incidence of surgically managed Traumatic Spinal Cord Injury (TSCI) in Singapore and to identify factors affecting discharge disposition.SettingPatients were identified from two level one trauma centres in Singapore.MethodsAll patients who underwent surgical management for acute TSCI between January 2020 to December 2021 were included. Demographics, injury details, peri-operative condition, hospital length of stay (LOS) and discharge disposition were evaluated. The overall characteristics of TSCI were summarised using descriptive statistics. The difference between discharge destinations was compared using chi-square test or t test. Variables with p values < 0.3 were selected for multivariable analysis.ResultsForty-four patients were included. Median age was 65. The most common SCI aetiology was fall from standing height or less (54.6%). Accidents involving personal mobility devices, bicycles and motor vehicles made up the next largest group (20.5%). Thirty-nine cases (88.6%) involved the cervical region. There were two cases of inpatient mortality. Twenty-one patients (50%) were discharged home, 21 (50%) were discharged to a community hospital (CH) or nursing home (NH). The median LOS in an acute hospital was 41 days. Multivariable logistic regression analysis revealed that functional independence measure (FIM) score on discharge was an independent factor that influenced discharge disposition (p = 0.037).ConclusionA public health focus on falls prevention, the development of geriatric spinal rehabilitation programs, and the consideration of a national registry are recommended for the comprehensive management of TSCI in Singapore.

The therapeutic potential of Apigenin in amyotrophic lateral sclerosis through ALDH1A2/Nrf2/ARE signaling

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss leading to muscle weakness and atrophy. Apigenin (APG), known for its antioxidant properties, holds potential as a therapeutic compound in ALS.MethodsWe used the Tg(SOD1*G93A)1Gur/J transgenic mouse model of ALS to investigate the therapeutic effects of APG. Key measured included motor function via the ALSTDI score, molecular markers of oxidative stress (OS) and apoptosis in spinal cord tissues. Techniques used included pathological, Western blotting, flow cytometry, and qRT-PCR to assess the effect of ALDH1A2.ResultsAPG treatment attenuated weight loss and improved motor function scores in ALS mice compared to untreated ALS models. Molecular analyses revealed a significant upregulation of ALDH1A2 in APG-treated groups, along with a reduction in markers of OS and apoptosis. In vitro studies in NSC34 cells further confirmed the protective effects of APG against SOD1*G93A mutation-induced cytotoxicity. In addition, suppression of ALDH1A2 by shRNA exacerbated disease markers that were ameliorated by APG treatment.ConclusionsOur results suggest that APG attenuates the progression of ALS pathology by regulating OS and apoptosis through ALDH1A2. These results support further investigation of APG as a potential therapeutic agent for the treatment of ALS.Graphical

Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats. Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated. Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group. Conclusions: These results indicate SEMA’s neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects.

Bioactive Peptide Hydrogel Scaffold with High Fluidity, Thermosensitivity, and Neurotropism in 3D Spatial Structure for Promoted Repair of Spinal Cord Injury.

Spinal cord injury (SCI) has been considered a clinically challenging disease that is characterized by local disturbance of the microenvironment, which inhibits post-injury neural regeneration. The simulation of a microenvironment conducive to the regeneration of spinal cord is beneficial for SCI repair. In this study, bioactive composite hydrogels are developed that mimic the regenerative microenvironment of spinal cord for enhanced SCI repair. The fabricated composite hydrogels (CRP) based on chitosan (CS), RADA16 nanofibers, and nerve-promoted peptide (PPFLMLLKGSTR) exhibit excellent injectability, superior biodegradability and biocompatibility. In addition, the CRP hydrogels can formquickly (a few minutes) by mixing three components at human body temperature, showing high potential as a biomimetic matrix for in situ repair of SCI. The in vitro studies demonstrate that the CRP hydrogels can not only promote the proliferation and migration of bone marrow mesenchymal stem cells but also induce the proliferation and differentiation of neural stem cells (NSCs) into neurons. Meanwhile, the hydrogels reveal the efficiency of protecting neurons and promoting axonal growth. Furthermore, the in vivo tests prove that the CRP hydrogels can reduce post-SCI inflammatory responses, inhibit reactive astrocyte over-proliferation, and promote the migration, proliferation, and differentiation of endogenous NSCs, which agree well with the in vitro results. The pre-clinical test demonstrates that the CRP hydrogels restore the motor function in completely transected spinal cord rats, and the SCI repair mechanism may involve the activation of the PI3K/AKT/mTOR pathway. It is believed that the strategies shown in this work will be valuable for the design and synthesis of novel hydrogels for biomedical and tissue engineering applications.

Transoral Atlantoaxial Reduction Plate (TARP) Technique for the Treatment of Irreducible Atlantoaxial Dislocation (IAAD) Caused by Old Odontoid Fracture.

Retrospective case series study. This study aimed to evaluate the clinical efficacy of TARP technique for treating IAAD caused by old odontoid fracture and assess the outcomes of patients who underwent TARP technique over 2years of follow-up. Between January 2005 and September 2017, 56 patients with IAAD caused by old odontoid fractures were treated with TARP technique. Patients' clinical, radiological, and surgical data were retrospectively analyzed. Radiological parameters included the atlantodental interval (ADI) and the space available for the spinal cord (SAC) were measured. Occipitocervical pain levels and neurologic status were evaluated with Visual Analog Scale (VAS) and Japanese Orthopaedic Association (JOA) score respectively. Degree of cervical dysfunction was assessed by Neck Disability Index (NDI). Fusion status was evaluated by images during the follow-ups. Surgeries for 56 cases were performed successfully with no injury to the spinal cord, nerve, or blood vessels. All patients achieved satisfactory reduction and fixation. Clinical symptomatic relief was obtained in all cases (100%). Patients were followed up for an average of 33.9 ± 9.6 months (ranged 24-60 months). Improvements in the postoperative ADI, SAC, VAS, JOA score and NDI were significant (P < .05). Besides, Bone fusion was observed in all patients. No hardware failure or re-dislocation occurred during the follow-up period. TARP technique is an effective procedure for the treatment of IAAD caused by old odontoid fracture, which can achieve complete release, satisfactory decompression, reduction and fixation, and reliable bone fusion through a single transoral approach.

Presentation and physical therapy management using a neuroplasticity approach for patients with hypermobility-related upper cervical instability: a brief report

BackgroundUpper cervical instability (UCI) is a potentially disabling complication of the connective tissue disorders hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (hEDS/HSD). UCI can impact various neurological structures, including the brainstem, spinal cord, cranial nerves, and blood supply to and from the brain, resulting in complex neurological signs and symptoms in this population. The current study was an observational study applying recent expert consensus recommendations for physical therapy assessment and management of patients with UCI associated with hEDS/HSD.MethodsThis was a retrospective observational study describing how the clinical decision-making model was used to screen, examine, and treat three patients with highly irritable hEDS/HSD-related UCI, resulting in complex neurological presentation. The treatment used a neuroplasticity approach, including proprioception and motor control training emphasizing patient education and biofeedback. Outcome measures tracked progress.ResultsAll patients started with significant disability associated with UCI. One patient returned to full function with intermittent flares that he was able to manage. The second patient continued to have mild-moderate irritability but returned to parenting responsibilities and full-time work. The third patient required cervical fusion and remained disabled but was better able to minimize flares. The number of initial red and yellow flags was associated with the final outcomes, suggesting that the decision-making model might be useful for predicting patient prognosis.ConclusionThis brief report applies recent recommendations for safely evaluating and managing hypermobility-related UCI and provides a first step in experimental studies to test both the assessment and physical therapy treatment approaches.