Search Results (342)

Background: multiple sclerosis (MS) presentation varies depending on the location and severity of the lesions affecting different areas of the spinal cord and brain. Extensive research has focused on specific systems to detect the disease in its various stages. The objective of this study was to investigate the concentration of the soluble scavenger receptor for haptoglobin–haemoglobin complex (Hb-Hp), sCD163, which is mostly expressed by monocytes and protects tissues from oxidative damage, in patients with MS. Methods: enzyme-Linked Immunosorbent Assay (ELISA) analysis was conducted in plasma samples collected from twenty-three relapsing–remitting MS (RRMS) subjects treated with teriflunomide and ten healthy control subjects (HCs). Results: the study results showed no differences between RRMS subjects and HCs in the concentration of CD163. A significantly higher concentration of sCD163 in RRMS was found in men in comparison to women (p = 0.038, Cohen d = 0.97). Conclusions: a significant correlation between disease activity, estimated using plasma-soluble CD163 (sCD163) and clinical assessment of the Expanded Disability Status Scale (EDSS) (p = 0.021), was detected in female patients with RRMS. Full article

Spinal cord injury (SCI) profoundly affects motor–sensory functions, reducing mobility and quality of life. Robotic exoskeletons offer a promising solution to support gait training, improve mobility, and prevent secondary complications. Existing research predominantly focuses on complete SCI, with limited exploration of long-term effects and tailored training for incomplete SCI. This study investigates device-based outcomes of personalized exoskeleton gait training in 33 individuals with incomplete SCI, with different lesion levels: cervical, thoracic, and lumbar. Participants underwent up to 39 sessions of gait training with a commercially available lower limb exoskeleton. Session parameters, including duration, intensity, and modality, were tailored to each individual’s clinical needs as determined by a medical team. Analysis focused on endurance, performance on the device, and patient-reported outcomes related to walking fluidity, safety, and satisfaction. Results showed overall improvement in endurance and performance, with the most significant gains observed in participants with thoracic-level injuries. All participants reported increased perceived safety, walking fluidity, and high satisfaction with the training. These findings support the potential of personalized exoskeleton training to enhance outcomes and experiences for individuals with incomplete SCI. The difference in improvement between lesion levels highlights the need for customized approaches to address the diverse clinical conditions within this population. Full article

Background and Clinical Significance: Spinal arachnoid cysts are rare lesions that may become symptomatic through progressive spinal cord compression. We present a complex case of a thoracic extradural SAC in a 17-year-old male, managed through a stepwise, multidisciplinary approach. Case Presentation: The patient presented with progressive lower limb weakness, right knee paresthesia, and urinary hesitancy following physical exertion. MRI revealed a large posterior extradural SAC extending from T2–T3 to T8, with associated spinal cord compression. Initial management involved T8 laminectomy and cyst fenestration under intraoperative neurophysiological monitoring, with partial clinical improvement. However, early recurrence with pseudomeningocele formation prompted a second surgery, including external CSF drainage. Persistent cerebrospinal fluid (CSF) leakage led to targeted epidural blood patching, followed by temporary stabilization. Due to continued cyst enlargement and spinal cord compression, definitive surgical repair was undertaken: fistula clipping at T3 and embolization with platinum coils inside the cystic cavity, combined with a new blood patch. This novel technique resulted in radiological improvement and clinical stabilization. Conclusions: This case highlights the diagnostic and therapeutic challenges of managing symptomatic extradural SACs, particularly in young patients. Our experience underscores the utility of a staged approach involving surgical decompression, neuroimaging-guided interventions, and definitive dural repair. The combination of fistula clipping and coil embolization may offer a promising strategy for refractory cases, potentially reducing recurrence and preserving neurological function. Full article

Background: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety. Purpose: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement thresholds and assess the role of baseline shift correction adaptative planning in improving treatment delivery efficiency. Methods: Twelve patients underwent two MRI sessions on the MRL. The optimal registration structure was identified, and intrafraction motion was assessed to calculate delivery efficiency. Baseline shift (BLS) simulations were applied for five cases that showed significant motion and suboptimal delivery efficiency, and the dosimetric impact of the BLS was evaluated. The simulated BLS-based plan adaptation was implemented via a segment aperture morphing adapt-to-position workflow. Results: The most stable registration structure was the spinal canal plus three adjacent vertebrae. Cine imaging revealed average intrafraction motion (95th to 5th percentiles) of 0.8 ± 0.5 mm in the right-left (RL) direction, 0.9 ± 0.6 mm in the anterior–posterior (AP) direction, and 0.7 ± 0.5 mm in the SI direction. Simulated BLS improved delivery efficiency to >80% in all but one case, with a ±1 mm displacement threshold tolerance. While target coverage remained consistent after BLS simulation, the spinal cord dose increased by 7–60%, exceeding the 14 Gy constraint in three of the five simulated cases. Conclusions: Cine imaging and BLS can enhance delivery efficiency in spine SBRT but may increase spinal cord dose. These findings underscore the need for careful patient selection, advanced motion management, and patient-specific BLS protocols. Full article

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection after SCI, with their therapeutic potential validated in clinical trials demonstrating safe and feasible transplantation in humans. Although SC transplantation has shown promising results, challenges remain, including modest graft survival, limited host integration, and restricted migration that collectively contribute to constrain efficacy. To address these limitations, biomaterial scaffolds have been explored as synergistic platforms to enhance SC delivery and function. When combined with natural or synthetic biomaterials such as hydrogels, nanofiber scaffolds, or ECM-mimetic matrices, SCs demonstrate improved survival, retention, spatial distribution, and regenerative activity. The intrinsic regenerative properties of SCs, first demonstrated in models of peripheral nerve injury, make them particularly well-suited for neural repair of the central nervous system (CNS) compared to other cell types and their effectiveness can be enhanced synergistically when combined with biomaterials. These constructs not only provide structural support but also modulate the lesion microenvironment, enhance axon growth and improve SC integration with host tissue. Combinatorial approaches incorporating biomaterials with SCs are emerging as next-generation strategies to optimize repair for clinical translation. This review focuses on current progress in SC-based therapies combined with biomaterials, highlighting key preclinical advances, clinical translation efforts, and the path forward toward effective regenerative interventions for SCI. Full article

In this report of two cases, we describe two patients with spinal involvement of gout. The first case involved a 67-year-old female who presented to the emergency department with a one-week history of weakness in both the upper and lower limbs, despite no prior history of gout. Cervical spine MRI revealed spinal cord compression at the C4 level from a posterior lesion. During surgery, chalky white deposits consistent with gouty tophi were observed in the ligamentum flavum within the epidural space at C4. These intraoperative findings correlated with elevated serum uric acid levels. The second case concerned a 68-year-old male who presented with a five-day history of right lower limb pain along with bilateral knee discomfort. Radiologic and laboratory evaluations revealed elevated inflammatory markers, negatively birefringent crystals in knee joint aspirate, spondylodiscitis at the L5-S1 level, and a right-sided synovial cyst at the T10–T11 level causing spinal cord compression. Following the initiation of anti-gout therapy, the patient experienced significant clinical improvement, normalization of inflammatory markers, and radiologic resolution of the thoracic synovial cyst. Full article

Spinal cord injury (SCI) is a major disability that, to this day, does not have a permanent cure. The spinal cord extends caudally through the body structure of the vertebral column and is part of the central nervous system (CNS). The spinal cord enables neural communication and motor coordination, so injuries can disrupt sensation, movement, and autonomic functions. Mechanical and traumatic damage to the spinal cord causes lesions to the nerves, resulting in the disruption of relayed messages to the extremities. Various forms of treatment for the spinal cord include functional electrical stimulation (FES), epidural electrical stimulation (EES), ‘SMART’ devices, exoskeleton and robotic systems, transcranial magnetic stimulation, and neuroprostheses using AI for the brain–computer interface. This research is going to analyse and review these current treatment methods for spinal cord injury and identify the current gaps and limitations in these, such as long-term biocompatibility, wireless adaptability, cost, regulatory barriers, and risk of surgery. Future advancements should work on implementing wireless data logging with AI algorithms to increase SCI device adaptability, as well as maintaining regulatory and health system integration. Full article

Background/Objectives: Spinal cord injuries (SCIs) are among the most debilitating conditions and are a leading cause of disability in young people. This study aimed to analyze the causes of SCIs, assess injury severity using the AIS scale, and evaluate complications during rehabilitation in a hospital setting. Methods: The study involved 176 individuals with SCI, including 142 with a traumatic SCI (TSCI) and 34 with a non-traumatic SCI (NTSCI), rehabilitated at various times post-injury. The data on injury causes, paresis type, complications, wheelchair use, gender, age, and treatment methods were collected. The injury severity was assessed using the AIS. Results: A significant gender difference was found between the TSCI and NTSCI groups (85.2% male vs. 61.8% male). TSCI individuals were also younger. The causes of TSCI were traffic accidents, falls from height, and diving, while the causes for NTSCI included spinal ischemia, tumors, degenerative disc disease, and inflammation. TSCI individuals had more AIS A lesions (52.8% vs. 26.5%) and more cervical injuries (53.5% vs. 14.7%), whereas NTSCI individuals had more AIS C lesions (38.2% vs. 18.3%) and thoracic damage (58.8% vs. 35.2%). TSCI patients were more often treated surgically (95.7% vs. 61.8%) and used wheelchairs (88% vs. 55.9%). No significant differences were found in terms of complications between the groups, though TSCI individuals underwent more chronic rehabilitation. Conclusions: Our research shows that there are significant differences between TSCI and NTSCI both in terms of the level of damage and the severity of damage to neural structures (AIS scales), and thus significant differences in the patients’ functioning in later life for both groups of individuals. Full article

(1) Background: Multiple sclerosis (MS) is a biologically highly heterogeneous disease and has poor predictability at diagnosis. Moreover, robust data indicate that early disease activity strongly correlates with future disability. Therefore, there is a need for strong and reliable biomarkers from diagnosis to characterize and identify patients who require highly effective disease-modifying treatments (DMTs). Several biomarkers are promising, particularly neurofilament light chains (NFLs), but the relevance of others is less consolidated. (2) Methods: We evaluated a panel of axonal damage and inflammatory biomarkers in cerebrospinal fluid (CSF) and matched serum obtained from a cohort of 60 newly diagnosed MS patients. Disability at diagnosis, negative prognostic factors, and the initial DMT prescribed were carefully recorded. (3) Results: We observed correlations between different axonal biomarkers: CSF and serum NFL versus CSF total tau; and between the inflammatory marker osteopontin (OPN) and axonal biomarkers CSF p-Tau, CSF total tau, and serum NFL. CSF and serum NFL and total tau, as well as CSF OPN, positively correlated with EDSS at diagnosis. Moreover, CSF and serum NFL levels were increased in patients with gadolinium-enhancing lesions (p = 0.01 and p = 0.04, respectively) and in those treated with highly effective DMT (p = 0.049). Furthermore, CSF OPN and both CSF and serum NFL levels significantly differentiated patients based on EDSS, with a combined ROC AUC of 0.88. We calculated and internally validated biomarker (in particular serum NFL) thresholds that significantly identified patients with higher disability. Finally, CSF OPN levels and dissemination in the spinal cord were significant predictors of EDSS at diagnosis. (4) Conclusions: These preliminary exploratory data confirm the pathological interconnection between inflammation and axonal damage from early disease stages, contributing to early disability. Follow-up data, such as longitudinal disability scores, repeated serum measurements, a healthy control group, and external validation of our results, are needed. We suggest that combining several fluid biomarkers may improve the clinical characterization of patients. Full article

Machupo virus (MACV), a member of the Arenaviridae family and causative agent of Bolivian hemorrhagic fever, results in lethality rates of 25–35% in humans. Mice lacking the signal transducer and activator of transcription 1 (STAT-1^−/−) have previously been shown to succumb to MACV infection within 7–8 days via the intraperitoneal route. Despite these reports, we observed partial lethality in STAT-1^−/− mice following challenge with wild-type MACV. Serial sampling studies to evaluate the temporal progression of infection and pathologic changes after challenge revealed a two-phase disease course. The first phase was characterized by viral load and pathological lesions in the spleen, liver, and kidney followed by a second, lethal phase, defined by high viral titers and inflammation in the brain and spinal cord resulting in neurological manifestations and subsequent mortality. Tissue adaptation in the brains of challenged STAT-1^−/− mice resulted in a fully lethal model in STAT-1^−/− mice (mouse-adapted; maMACV). A similar two-phase disease course was observed following maMACV challenge, but more rapid dissemination of the virus to the brain and overall pathology in this region was observed. The outcome of these studies is a lethal small rodent model of MACV that recapitulates many aspects of human disease. Full article

Background: Enteroviruses, members of the Picornaviridae family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute spinal cord dysfunction, leading to neurological deficits below the level of the lesion. Case report: We report a case series of eight pediatric patients admitted over a three-month period, June to August 2024. All patients presented with ataxia and/or other neurological symptoms, alongside abnormal cerebrospinal fluid (CSF) findings. Although ataxia is commonly associated with cerebellitis, magnetic resonance imaging (MRI) in this cohort revealed findings consistent with TM. Notably, all patients demonstrated similar MRI abnormalities. The onset of symptoms occurred over a short time during an enterovirus epidemic. Enteroviral RNA was detected, or the virus was isolated in seven patients, while one patient had a close epidemiological link to the virus. All patients achieved full recovery following immunomodulatory therapy. Conclusions: This case series underscores that ataxia may be an atypical symptom associated with TM. Furthermore, there was a notable distinction between the clinical presentation and neuroradiological findings. Immunomodulatory therapy with immunoglobulins and corticosteroids has been shown to be effective and safe, supporting the hypothesis of an immune-mediated pathogenesis in these patients. Full article

Secondary Progressive Multiple Sclerosis (SPMS) represents a challenging phase of multiple sclerosis, marked by gradual neurological decline and reduced inflammatory activity. In recent years, magnetic resonance imaging (MRI) has become essential for characterizing the neurodegenerative changes underlying SPMS, including white and gray matter damage, brain atrophy, slowly expanding lesions, and iron rim lesions. This narrative review aims to synthesize the current knowledge on established and emerging MRI biomarkers relevant to SPMS, with a particular focus on their diagnostic, prognostic, and therapeutic implications. This review discusses key themes, such as the shift from inflammatory to neurodegenerative mechanisms, the role of advanced imaging techniques, and the limitations of conventional MRI in detecting smoldering disease. In doing so, it identifies current gaps in evidence, including the need for standardized imaging protocols and large-scale longitudinal studies. A clearer understanding and application of MRI biomarkers may facilitate earlier diagnosis, more tailored treatment strategies, and improved outcomes in patients with SPMS. Full article

Spasticity is a common complication after spinal cord injury (SCI) that significantly diminishes quality of life and complicates daily management. As a hallmark of upper motor neuron lesions, spasticity emerges through a complex post-injury process involving the resolution of spinal shock, an imbalance between excitatory and inhibitory signaling, and maladaptive neuronal plasticity, leading to hyperreflexia and chronic spasticity. Severe spasticity frequently results in pain, sleep disturbances, and marked functional impairments. This review systematically integrates motor neuron alterations with corresponding muscle manifestations, providing a comprehensive analysis of the brain–spinal cord–muscle pathway in spasticity pathogenesis. Through an in-depth analysis of the pathological and physiological changes in motor neurons post-SCI, this review offers a novel perspective that unveils the intrinsic mechanisms underlying spasticity formation, thereby establishing a robust theoretical foundation for developing targeted therapeutic strategies. Full article

Background and Clinical Significance: The coexistence of spinal hemangiomas and dural arteriovenous fistula (SDAVF) is uncommon. Unclear imaging and progressive neurological impairment require early surgical management. Case Presentation: A 76-year-old woman presented with progressive thoracolumbar pain and worsening bladder dysfunction. Magnetic resonance imaging (MRI) of the thoracic spine revealed a round-shape expansive lesion at T11 with spinal cord edema and homogeneous contrast enhancement. Despite a chronic presentation, the subacute progression of bladder dysfunction and spinal cord edema warranted timely intervention. Intraoperatively, a vascular malformation resembling a dural arteriovenous fistula (SDAVF), unrecognized at pre-operative imaging, was found in association, and histological examination confirmed the diagnosis of hemangioma. The mechanism of coexistence remains unclear, although venous hypertension due to fistula could induce vascular malformations. Conclusions: This case emphasizes the importance of thorough imaging, timely intervention and intraoperative assessment in patients presenting with a suspicion of spinal hemangioma; it may also provide awareness of potentially associated concurrent lesions such as SDAVFs, unrecognized at pre-operative imaging, and technical insights during surgery. Full article

In the adult central nervous system (CNS), myelin regeneration primarily occurs through the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes. In men, declining testosterone levels accelerate the progression of multiple sclerosis (MS), while in women, menopause worsens MS-related disability. We previously demonstrated that functional testes and testosterone are required for the spontaneous remyelination of a focal lysolecithin (LPC)-induced demyelinating lesion in the spinal cords of male mice. Testosterone-dependent myelin repair was dependent on the induction of the chemokine receptor CXCR4 in astrocytes that repopulated the lesion and on cooperation between androgen-receptor signaling and CXCR4 signaling. In the present study, we investigated whether ovaries and estradiol have a comparable key role in female mice. Ovariectomy prevents, the appearance of astrocytes, while treatment with estradiol enhances astrocyte numbers and promotes remyelination by oligodendrocytes within the LPC-demyelinated lesion. Unlike testosterone, estradiol did not induce CXCR4 expression, and its effects remained unaffected by the CXCR4 inhibitor AMD3100. As was seen with testosterone treatment, the presence of astrocytes and myelinating oligodendrocytes within the LPC lesion of estradiol-treated females prevented the incursion of Schwann cells. These findings highlight estradiol’s crucial role in CNS remyelination in females, providing a strong rationale for estrogen-replacement therapy in estrogen-deficient and menopausal women with MS. Full article