Spinal Cord Lesions Research Articles

Spinal cord MRI activity in multiple sclerosis: Predictive value for relapses and impact on treatment decisions

IntroductionEmerging evidence suggests the prognostic value of spinal cord (SC) pathology in multiple sclerosis (MS). However, the 2021 MAGNIMS-CMSC-NAIMS guidelines don't recommend routine SC MRI for disease monitoring. This study investigates the frequency of new asymptomatic and isolated SC lesions, exploring their potential to predict clinical activity and guide treatment decisions. MethodsWe enrolled relapsing-remitting MS (RRMS) patients who underwent brain and SC MRI at baseline and after 12 months. New, enlarged, or gadolinium-enhanced (Gd+) lesions on MRI were considered disease activity markers. Clinical relapses and treatment changes observed 3 months after the 12-month MRI were analyzed using regression analysis, evaluating their association with worsening SC findings. ResultsA total of 201 RRMS patients (56 males, 27.9%, mean age 42.5 ± 12.1 years, mean EDSS 2.7 ± 1.9) were included. Isolated worsening of T2 lesion burden in the SC occurred in 16 patients (8%), and 12 (6%) had Gd + lesions. Among patients without brain MRI activity (n = 138), regression analysis revealed a significant association between new Gd + SC lesions and clinical relapses within 3 months of the 12-month MRI (p = 0.024). Worsening SC findings (p = 0.021) and SC lesion enhancement (p = 0.046) emerged as key factors influencing disease-modifying therapy changes within 3 months in these patients. Notably, even without clinical symptoms, worsening SC findings significantly predicted treatment changes (p = 0.003). ConclusionOur findings highlight the independent value of SC MRI findings in MS monitoring. Importantly, isolated and asymptomatic SC worsening significantly impacted treatment decisions.

Contributions of CSF interleukin-6 elevation to the pathogenesis of myelin oligodendrocyte glycoprotein antibody–associated disease

Background: Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is a rare neuroinflammatory disorder characterized by acute episodes of central nervous system (CNS) demyelination. Previous studies have reported elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) of MOGAD patients. Objective: We examined if CSF IL-6 level increase is associated with clinical parameters in MOGAD. Methods: IL-6 levels were measured using 44 CSF samples during the acute phase and 6 samples during recovery from 34 MOGAD patients, as well as 65 CSF samples from 45 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4Ab + NMOSD), 107 samples from 76 multiple sclerosis patients, and 45 samples from neurodegenerative disease patients. Associations between IL-6 levels and clinical parameters in MOGAD were also evaluated. Results: CSF IL-6 levels were significantly comparably elevated during acute-phase in MOGAD and AQP4Ab + NMOSD, but declined following the acute phase. Among MOGAD patients, CSF IL-6 level was significantly correlated with CSF cell count, greater in patients with brain lesions than spinal cord lesions, and higher in CSF than serum, suggesting that excessive IL-6 is produced predominantly in CNS. Neurological recovery was tended to be poorer in MOGAD patients with higher CSF IL-6 level. Conclusion: CSF IL-6 may play important roles in the pathogenesis of MOGAD, especially in CNS inflammation.

A Case of Heat Stroke with Presumed Spinal Cord Lesions

A Case of Heat Stroke with Presumed Spinal Cord Lesions

Clinical characteristics of ultra-longitudinally extensive transverse myelitis in a Peruvian cohort

IntroductionUltra-longitudinally extensive transverse myelitis (uLETM) is defined as an inflammatory lesion involving 10 or more spinal cord segments. The aim of our study is to describe the clinical and radiological features of this atypical form of myelitis. MethodsWe conducted a descriptive cross-sectional study of clinical data from 57 patients older than 18 years diagnosed with longitudinally extensive transverse myelitis. Nineteen cases were classified as uLETM. ResultsTwelve of the 19 patients were women, age ranged between 18 and 76 years, and the main aetiology was neuromyelitis optica spectrum disorder (8 patients), followed by anti-MOG antibody myelitis (3 patients). The main region involved was at cervical-thoracic spinal cord. Two patients presented complete spinal cord lesion. ConclusionsOur results are consistent with previous reports suggesting that neuromyelitis optica spectrum disorder remains the main aetiology in uLETM; however, anti-MOG antibodies should be considered within the differential diagnosis.

MR Imaging Features of Critical Spinal Demyelinating Lesions Associated with Progressive Motor Impairment.

Progressive MS is typically heralded by a myelopathic pattern of asymmetric progressive motor weakness. Focal individual "critical" demyelinating spinal cord lesions anatomically associated with progressive motor impairment may be a compelling explanation for this clinical presentation as described in progressive solitary sclerosis (single CNS demyelinating lesion), progressive demyelination with highly restricted MR imaging lesion burden (2-5 total CNS demyelinating lesions; progressive paucisclerotic MS), and progressive, exclusively unilateral hemi- or monoparetic MS (>5 CNS demyelinating progressive unilateral hemi- or monoparetic MS [PUHMS] lesions). Critical demyelinating lesions appear strikingly similar across these cohorts, and we describe their specific spinal cord MR imaging characteristics. We performed a retrospective, observational MR imaging study comparing spinal cord critical demyelinating lesions anatomically associated with progressive motor impairment with any additional "noncritical" (not anatomically associated with progressive motor impairment) spinal cord demyelinating lesions. All spinal cord MR images (302 cervical and 91 thoracic) were reviewed by an experienced neuroradiologist with final radiologic assessment on the most recent MR imaging. Anatomic association with clinical progressive motor impairment was confirmed independently by MS subspecialists. Ninety-one individuals (PUHMS, 37 [41%], progressive paucisclerosis 35 [38%], progressive solitary sclerosis 19 [21%]) with 91 critical and 98 noncritical spinal cord MR imaging demyelinating lesions were evaluated. MR imaging characteristics that favored critical spinal cord demyelinating lesions over noncritical lesions included moderate-to-severe, focal, lesion-associated spinal cord atrophy: 41/91 (45%) versus 0/98 (0%) (OR, 161.91; 9.43 to >999.9); lateral column axial location (OR, 10.43; 3.88-28.07); central region (OR, 3.23; 1.78-5.88); ventral column (OR, 2.98; 1.55-5.72); and larger lesion size of the axial width (OR, 2.01;1.49-2.72), transverse axial size (OR, 1.66; 1.36-2.01), or lesion area (OR, 1.14; 1.08-1.2). Multiple regression analysis revealed focal atrophy and lateral axial location as having the strongest association with critical demyelinating lesions. Focal, lesion-associated atrophy, lateral column axial location, and larger lesion size are spinal cord MR imaging characteristics of critical demyelinating lesions. The presence of critical demyelinating lesions should be sought as these features may be associated with the development of progressive motor impairment in MS.

Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model

In chronic stages of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalitis (EAE), connexin (Cx)43 gap junction channel proteins are overexpressed because of astrogliosis. To elucidate the role of increased Cx43, the central nervous system (CNS)-permeable Cx blocker INI-0602 was therapeutically administered. C57BL6 mice with chronic EAE initiated by MOG35-55 received INI-0602 (40 mg/kg) or saline intraperitoneally every other day from days post-immunization (dpi) 17–50. Primary astroglia were employed to observe calcein efflux responses. In INI-0602-treated mice, EAE clinical signs improved significantly in the chronic phase, with reduced demyelination and decreased CD3+ T cells, Iba-1+ and F4/80+ microglia/macrophages, and C3+GFAP+ reactive astroglia infiltration in spinal cord lesions. Flow cytometry analysis of CD4+ T cells from CNS tissues revealed significantly reduced Th17 and Th17/Th1 cells (dpi 24) and Th1 cells (dpi 50). Multiplex array of cerebrospinal fluid showed significantly suppressed IL-6 and significantly increased IL-10 on dpi 24 in INI-0602-treated mice, and significantly suppressed IFN-γ and MCP-1 on dpi 50 in the same group. In vitro INI-0602 treatment inhibited ATP-induced calcium propagations of Cx43+/+ astroglial cells to similar levels of those of Cx43−/− cells. Astroglial Cx43 hemichannels represent a novel therapeutic target for chronic EAE and MS.

Clinico-radiologic Spectrum and Outcome of Pediatric Acquired Demyelinating Disorders of Central Nervous System: A Retrospective Indian Tertiary Care Hospital Cohort.

Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied. Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS (n = 27), ADEM (n = 16), NMOSD (n = 13), MS (n = 1), and MOGAD (n = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p = 0.004), spinal cord (p = 0.01), and cerebellar lesions (p = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% (n = 64) had good recovery, 8.6% (n = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed. The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.

Anatomical damages in the spinal nerve roots and the spinal cord after brachial plexus injury: descriptive study from a cohort of consecutive patients who underwent DREZ-lesioning for pain-practical implications.

Systematic descriptions of anatomical damage after brachial plexus injury (BPI) at the intradural level have been scarcely reported in detail. However, considering these damages, not only in the spinal nerve roots but also in the spinal cord itself, is crucial in determining the appropriate surgical approach to restore upper limb function and address refractory pain. Therefore, the authors present a descriptive study focusing on intradural findings observed during microsurgical DREZ-lesioning. This study enrolled 19 consecutive patients under the same protocol. Microsurgical observation through exposure of C4 to Th1 medullary segments allowed to describe the lesions in spinal nerve roots, meninges, and spinal cord. Electrical stimulation of the ventral roots checked the muscle responses. Extensive damage was observed among the 114 explored roots (six roots per patient), with only 21 (18.4%) ventral (VR) and 17 (14.9%) dorsal (DR) roots retaining all rootlets intact. Damage distribution varied, with the most frequent impairments in C6 VRs (18 patients) and the least in Th1 VRs (14 patients), while in all the 19 patients for the C6 DRs (the most frequently impaired) and in 14 patients for Th1 DRs (the less impaired). C4 roots were found damaged in 12 patients. Total or partial avulsions affected 63.3% and 69.8% of DRs and VRs, respectively, while 15.8% and 14.0% of the 114 DRs and VRs were atrophic, maintaining muscle responses to stimulation in half of those VRs. Pseudomeningoceles were present in 11 patients but absent in 46% of avulsed roots. Adhesive arachnoiditis was noted in 12 patients, and dorsal horn parenchymal alterations in 10. Knowledge of intradural lesions post-BPI helps in guiding surgical indications for repair and functional neurosurgery for pain control.

Factors associated with symptomatic urinary tract infection in persons with spinal cord lesions who perform clean intermittent catheterization with single-use catheters.

To investigate factors associated with symptomatic urinary tract infection (sUTI) in persons with chronic spinal cord lesion (SCL) who were using single-use catheters for intermittent self-catheterization (ISC). Among respondents to an internet survey on the burden of illness on persons with SCL who were considered to be able to perform ISC, 111 persons using single-use catheters were included to examine factors associated with self-reported sUTI by univariate as well as multivariable analysis. The incidence of sUTI was significantly higher in males than in females (56.9% vs. 31.6%, p = .011), persons with stocks of antibiotics than those without it (82.9% vs. 28.6%, p < .011), and persons with more frequent bleeding during catheterization than those with less frequent bleeding (100% vs. 46.5%, p = .036). The incidence did not significantly differ between respective groups when various variables were evaluated by other characteristics of the participants, adherence to ISC procedures, and complications. On multivariable analysis, male gender and stocks of antibiotics were significant independent factors for sUTI. Male gender and stocks of antibiotics were associated with sUTI in persons with SCL who were performing ISC with single-use catheters.

Real-World Experience and Complications with Intermittent Balloon Catheters : A Predictor Analysis

Intermittent balloon catheterization with a reusable and temporary balloon catheter that could be implanted and removed by the patient was developed in Japan in 1995. Although the intermittent balloon catheter has the potential to improve the patient's quality of life (QOL), appropriate information and guidelines are needed to prevent complications such as hematuria and urinary tract infection. This study aimed to assess the real-world practice, complications, and problems associated with the use of intermittent balloon catheters and provide useful information for future medical care. We conducted a questionnaire survey on patients with spinal cord lesions who currently use or have used intermittent balloon catheters in the past. Seventy-six patients with spinal cord lesions who visited Kanagawa Rehabilitation Hospital from August 2020 to March 2021 and gave consent for participating in this study were included. QOL scores before and after intermittent balloon catheter use showed significant improvement after use. Forty-six of the 76 (61.3%) patients had complications. Overall complications were significantly associated with male sex and possibly linked to non-traumatic spinal cord lesions.

Galectin-3 absence alters lymphocytes populations dynamics behavior and promotes functional recovery after spinal cord injury in mice

Spinal cord injury (SCI) results from various mechanisms that damage the nervous tissue and the blood-brain barrier, leading to sensory and motor function loss below the injury site. Unfortunately, current therapeutic approaches for SCI have limited efficacy in improving patients outcomes. Galectin-3, a protein whose expression increases after SCI, influences the neuroinflammatory response by favoring pro-inflammatory M1 macrophages and microglia, while inhibiting pro-regenerative M2 macrophages and microglia, which are crucial for inflammation resolution and tissue regeneration. Previous studies with Galectin-3 knock-out mice demonstrated enhanced motor recovery after SCI. The M1/M2 balance is strongly influenced by the predominant lymphocytic profiles (Th1, Th2, T Reg, Th17) and cytokines and chemokines released at the lesion site. The present study aimed to investigate how the absence of galectin-3 impacts the adaptive immune system cell population dynamics in various lymphoid spaces following a low thoracic spinal cord compression injury (T9-T10) using a 30 g vascular clip for one minute. It also aimed to assess its influence on the functional outcome in wild-type (WT)and Galectin-3 knock-out (GALNEG) mice. Histological analysis with hematoxylin-eosin and Luxol Fast Blue staining revealed that WT and GALNEG animals exhibit similar spinal cord morphology. The absence of galectin-3 does not affect the common neuroanatomy shared between the groups prompting us to analyze outcomes between both groups. Following our crush model, both groups lost motor and sensory functions below the lesion level. During a 42-day period, GALNEG mice demonstrated superior locomotor recovery in the Basso Mouse Scale (BMS) gait analysis and enhanced motor coordination performance in the ladder rung walk test (LRW) compared to WT mice. GALNEG mice also exhibited better sensory recovery, and their electrophysiological parameters suggested a higher number of functional axons with faster nerve conduction. Seven days after injury, flow cytometry of thymus, spleen, and blood revealed an increased number of T Reg and Th2 cells, accompanied by a decrease in Th1 and Th17 cells in GALNEG mice. Immunohistochemistry conducted on the same day exhibited an increased number of Th2 and T Reg cells around the GALNEG's spinal cord lesion site. At 42-day dpi immunohistochemistry analyses displayed reduced astrogliosis and greater axon preservation in GALNEG's spinal cord seem as a reduction of GFAP immunostaining and an increase in NFH immunostaining, respectively. In conclusion, GALNEG mice exhibited better functional recovery attributed to the milder pro-inflammatory influence, compensated by a higher quantity of T Reg and Th2 cells. These findings suggest that galectin-3 plays a crucial role in the immune response after spinal cord injury and could be a potential target for clinical therapeutic interventions.

Overview of Brown-Sequard Syndrome.

A neurologic syndrome called Brown-Séquard syndrome is brought on by spinal cord hemisection. On the side of the body, ipsilateral to the lesion, it presents as weakness or paralysis, proprioceptive abnormalities, and loss of pain and temperature perception. Brown-Séquard syndrome is an incomplete spinal cord syndrome with a range of severity in its clinical presentation.&#x0D; One of the most intricate and fascinating areas of the nervous system to study is the spinal cord. Its overwhelming clinical presentation, development problems, lesions, and intricate connections call for a deeper comprehension of its anatomical and physiological makeup.&#x0D; Like the brain, the extremely fragile and sensitive spinal cord is well-protected by the robust bony cage comprising the vertebral arch and vertebral bodies. Together, they create the spinal hollow, or long spinal column, which houses the spinal cord. Millions of neurons reside in the spinal cord, and their bundled fibers run as ascending or descending tracts. Thirty-one pairs of spinal nerves, primarily supplying the trunk and limbs, emerge from the spinal cord. These are mixed spinal nerves with a motor component that assists in controlling the trunk and voluntary muscles in all limbs. Additionally, they have a sensory component that aids in taking in the sensory data from these regions. Therefore, for a better understanding of the clinical presentation and its pathology in any spinal cord lesion, it is imperative to grasp the fundamentals of anatomy.&#x0D; In this short review, we have discussed the symptoms, management, and prevention of brown syndrome.

A case of thoracic epidural angiolipoma with intracranial hypertension

AbstractSpinal cord tumors sometimes present with intracranial hypertension and can be difficult to diagnose at the initial presentation without symptoms due to spinal cord compression. Here, we report a case of a patient with thoracic epidural angiolipoma complicated by increased intracranial pressure and normal protein levels in cerebrospinal fluid (CSF). His neurological symptoms improved immediately after partial removal of the core part of epidural angiolipoma. Spinal cord lesions should be ruled out in cases with intracranial hypertension, even if the CSF protein levels are normal.

Lymphomatoid Granulomatosis: A Rare Lymphoproliferative Disorder on the Differential Diagnosis for Brain and Spinal Cord Lesions (P4-5.027)

Lymphomatoid Granulomatosis: A Rare Lymphoproliferative Disorder on the Differential Diagnosis for Brain and Spinal Cord Lesions (P4-5.027)

Diffusion tensor imaging in differentiation of spinal cord lesions

Background Spinal lesions sometimes remain insufficiently visualized by ‘conventional’ magnetic resonance imaging techniques; indeed very often the lesions seen on T2 weighted images do not completely display the effects of pathology on the long tracts. Diffusion imaging, which enables the imaging of molecular water motion, has been applied recently to spinal cord diseases Aim The purpose of this study was to assess the role of Diffusion tensor imaging in in differentiation between different spinal cord lesions Patients &amp; methods This prospective study included 30 patients with myelopathy symptoms. All patients were subjected to full history taking, clinical examination, magnetic resonance imaging and diffusion tensor imaging MRI. Results The mean FA values at the site of the lesion was significantly lower than the normal appearing spinal cord in inflammation/demyelination, compressive myelopathy and traumatic spinal cord injury groups while the mean apparent diffusion coefficient values at the site of the lesions was significantly higher than the normal appearing spinal cord in inflammation/demyelination group. FA was sensitive than apparent diffusion coefficient in the detection of the spinal cord abnormalities with a sensitivity of 90% versus 60% respectively. Conclusion Diffusion tensor imaging with its quantitative indices is a non-invasive tool that is used in functional assessment of normal and pathologic spinal cord white matter, giving detailed information about different pathology and helping early management.

Spinal cord involvement in progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging.

Clinical characteristics and MRI features of autoimmune glial fibrillary acidic protein astrocytopathy: a case series of 34 patients.

To analyze the clinical and imaging characteristics of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Forty-three patients diagnosed with GFAP-A between March 2017 and July 2023 were retrospectively recruited. The clinical characteristics and magnetic resonance imaging (MRI) features were collected. Twenty-one patients (61.8%) had a fever and 16 (47.1%) had a headache. Five patients (14.7%) had coexisting neural autoantibodies and one patient (2.9%) had a coexisting neoplasm. The most common presentation was meningoencephalomyelitis (13/34, 38.3%), followed by meningoencephalitis (12/34, 35.3%). The other clinical manifestations included blurred visions (5/34, 14.7%) and peripheral nervous system involvement (4/34, 11.8%). Twenty-six patients (76.5%) had elevated nucleated cell count, predominantly lymphocytes (15/15, 100%), and 27 (79.4%) had elevated protein levels of cerebrospinal fluid. One-half (50%) of the patients presented with hyponatremia. A majority of the patients (30/33, 90.9%) exhibited abnormal hyperintense lesions on T2WI, which were often located in juxtacortical white matter (18/33, 54.5%), followed by periventricular white matter (16/33, 48.5%), basal ganglia (15/ 33, 45.5%), brainstem (11/33, 33.3%), and thalamic lesions (9/33, 27.3%). Twenty-four patients (72.7%) had abnormal brain enhancement, with supratentorial leptomeningeal enhancement being the most frequent enhancement pattern (15/33, 45.5%), followed by linear perivascular radial enhancement (14/33, 42.4%). Nineteen patients (70.4%) had hyperintense intramedullary spinal cord lesions, with long segments (15/27, 55.6%) and transverse lesions (14/27, 51.9%) being the most frequent lesions. Most cases were sensitive to immunotherapy, such as glucocorticoids, intravenous immunoglobulin, and tacrolimus, with three patients (8.8%) experiencing relapses. Patients with brainstem lesions had higher onset modified Rankin scale scores and were more prone to intensive care unit admissions. Linear perivascular radial enhancement was positively associated with poor prognosis (p < 0.05). GFAP-A presented with meningoencephalomyelitis and meningoencephalitis. The brain lesions were often located in juxtacortical white matter, periventricular white matter, basal ganglia, brainstem, and thalamus. Long segments and transverse were the most frequent spine lesions. Leptomeningeal enhancement was the most frequent enhancement pattern, followed by linear perivascular radial enhancement, which may provide new insight into the differential diagnosis of GFAP-A.

A Case Report on Transverse Myelitis

Scrub typhus is known to cause central nervous system involvement, which can show as meningitis or meningoencephalitis. However, relatively few reports of acute transverse myelitis (ATM), a spinal cord lesion, have been linked to scrub typhus. Patients with a spinal lesion and scrub typhus have neurologic symptoms such as dysuria and sensory and motor impairment. Here, we report on an uncommon instance of ATM linked to scrub typhus. The diagnosis of ATM linked with scrub typhus was made based on the patient’s clinical features, cerebral fluid cytology, Orientia tsutsugamushi serum antibody titer, and several magnetic resonance imaging scans.

Radiologically isolated syndromes: to treat or not to treat?

The widespread use of magnetic resonance imaging (MRI) has led to increased detection of individuals exhibiting asymptomatic brain and spinal cord lesions suggestive of multiple sclerosis (MS), defined as "radiologically isolated syndrome" (RIS). Specific criteria have been proposed and updated over time to identify individuals with RIS. Moreover, a younger age, the presence of infratentorial, spinal cord or gadolinium-enhancing lesions, as well as of cerebrospinal fluid-specific oligoclonal bands have been recognized as relevant risk factors for the occurrence of a first clinical event. Recent randomized controlled trials conducted in individuals with RIS have shown that dimethyl fumarate and teriflunomide significantly reduce the occurrence of clinical events in this population. These findings support the notion that early treatment initiation may positively influence the prognosis of these patients. However, several aspects should be taken into account before treating individuals with RIS in the real-world clinical setting, including an accurate identification of individuals with RIS to avoid misdiagnosis, a precise stratification of their risk of experiencing a first clinical event and further data supporting favorable balance between benefits and risks, even in the long term. This commentary provides an overview of the latest updates in RIS diagnosis, prognosis, and emerging treatment evidence.

Neurological recovery and neurogenesis by curcumin sustained-release system cross-linked with an acellular spinal cord scaffold in rat spinal cord injury: Targeting NLRP3 inflammasome pathway.

In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.