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Search Results (390)

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Keywords = spinal cord lesions

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16 pages, 9732 KB  
Article
Cryopreserved Mucosal Olfactory Ensheathing Cells Promote Functional Recovery After Dorsal Root Injury
by Kamile Minkelyte, Daqing Li, Ying Li and Ahmed Ibrahim
Cells 2026, 15(10), 944; https://doi.org/10.3390/cells15100944 - 20 May 2026
Viewed by 120
Abstract
Olfactory ensheathing cell (OEC) transplantation has been widely shown to support axonal regeneration, remyelination, and functional recovery after central nervous system injury; however, autologous approaches are limited by low cell yields from patient biopsies, which may be insufficient for large spinal cord lesions. [...] Read more.
Olfactory ensheathing cell (OEC) transplantation has been widely shown to support axonal regeneration, remyelination, and functional recovery after central nervous system injury; however, autologous approaches are limited by low cell yields from patient biopsies, which may be insufficient for large spinal cord lesions. This study evaluated whether cryopreservation could provide a scalable alternative by preserving the therapeutic potential of mucosa-derived OECs. Using a rat dorsal root injury model, cryopreserved mucosa-derived OECs (CmOECs) were thawed and assessed for viability, phenotype, and efficacy following transplantation. Although total viable cell yield was reduced compared with primary cultures, the relative proportion of OECs remained stable, and cells retained characteristic morphology and marker expression in vitro. In vivo, transplantation of CmOECs resulted in significant functional recovery in climbing and forepaw fault tasks compared with injured controls, with outcomes comparable to primary mucosal OEC transplantation. Immunohistochemical analysis confirmed the survival and integration of transplanted cells at the dorsal root entry zone, alongside evidence of axonal regeneration and astrocytic remodeling. These findings demonstrate that mucosa-derived OECs retain therapeutic efficacy following cryopreservation and support the development of standardized OEC biobanks as a scalable strategy for spinal cord repair. Full article
(This article belongs to the Collection Cell Biology of Spinal Cord Injury and Repair)
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17 pages, 444 KB  
Review
Restless Legs Syndrome and Neurological Comorbidities: A Narrative Review
by Kyrillos Ghattas, Helen Hernandez, Yongwoon Huh, Zhanna Fast and Zhikui Wei
J. Clin. Med. 2026, 15(10), 3725; https://doi.org/10.3390/jcm15103725 - 12 May 2026
Viewed by 322
Abstract
Restless legs syndrome (RLS) is a common yet underrecognized neurological disorder characterized by uncomfortable sensations and an irresistible urge to move he legs, typically following a circadian pattern. RLS frequently co-occurs with various other neurological diseases, raising questions about shared mechanisms and clinical [...] Read more.
Restless legs syndrome (RLS) is a common yet underrecognized neurological disorder characterized by uncomfortable sensations and an irresistible urge to move he legs, typically following a circadian pattern. RLS frequently co-occurs with various other neurological diseases, raising questions about shared mechanisms and clinical consequences. This review synthesizes evidence on the prevalence, outcomes, and pathophysiology of RLS in various neurological disorders, including Parkinson’s disease, multiple sclerosis, migraine, dementia, stroke, epilepsy, and peripheral neuropathy. In Parkinson’s disease, RLS is linked to disease progression and dopaminergic therapy. In stroke and multiple sclerosis, RLS is associated with structural lesions at specific locations, such as the pons or spinal cord. In epilepsy, RLS is associated with refractory or nocturnal seizures. In neuropathies, disruption of small sensory fibers may contribute to RLS symptoms. In dementia, RLS adds diagnostic complexity. Overlapping mechanisms between RLS and its neurological comorbidities include altered sensorimotor processing, brainstem and spinal circuitry, and sleep/arousal regulation. RLS in neurological conditions often worsens sleep quality, mood, and fatigue, and contributes to reduced quality of life and worse outcomes. Future research should prioritize longitudinal designs, standardized diagnostic approaches, and mechanistically driven studies to clarify relationships between RLS and these neurological comorbidities. Full article
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14 pages, 1239 KB  
Review
Multimodal Management of Spinal Cord Hemangioblastomas: A Comprehensive Review
by Francisco Alfredo Call-Orellana, Juan Pablo Zuluaga-Garcia, Maria Alejandra Sierra, Mariana Zuluaga-Garcia, Esteban Ramirez-Ferrer and Alejandro Bugarini
Therapeutics 2026, 3(2), 12; https://doi.org/10.3390/therapeutics3020012 - 12 May 2026
Viewed by 169
Abstract
Spinal cord hemangioblastomas are rare, benign, and highly vascular tumors that occur sporadically or in association with von Hippel–Lindau disease. Despite their histological benignity, they often cause significant morbidity due to progressive neurological deficits, syrinx formation, and recurrence in the von Hippel-Lindau population. [...] Read more.
Spinal cord hemangioblastomas are rare, benign, and highly vascular tumors that occur sporadically or in association with von Hippel–Lindau disease. Despite their histological benignity, they often cause significant morbidity due to progressive neurological deficits, syrinx formation, and recurrence in the von Hippel-Lindau population. We performed a comprehensive review of the literature by searching PubMed, EMBASE, and Scopus for studies published in English on spinal cord hemangioblastomas. Eligible studies included original research, case series, and case reports with explicit clinical outcomes or management strategies for pathologically or radiographically confirmed SCHb. Gross total resection is feasible in most cases, leading to durable tumor control and favorable neurological outcomes. Preoperative embolization has been employed selectively to reduce intraoperative bleeding. Radiotherapy, particularly stereotactic radiosurgery, has shown promising local control for surgically inaccessible or recurrent lesions, while conventional external beam approaches provide less consistent results. Anti-angiogenic agents have demonstrated anecdotal benefit, and the HIF-2α inhibitor belzutifan represents the first systemic therapy approved by the FDA for VHL-associated hemangioblastomas. The management of SCHb requires an individualized, multimodal strategy. Microsurgery remains the cornerstone of treatment; radiotherapy and pharmacotherapy are valuable adjuncts for specific clinical scenarios. Further prospective studies are needed to optimize patient selection and integration of these therapies. Full article
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12 pages, 1794 KB  
Case Report
Steroid Refractory and Plasma Exchange Partially Responsive Longitudinally Extensive Transverse Myelitis Due to Tumor Necrosis Factor-Alpha (Etanercept): A Case Report
by Jelena Stojsavljevic, Rafael R. Perez, Emilia Petcu, Celestine Odenigbo, Cristian Madrid, Igor Dumic and Charles W. Nordstrom
Clin. Pract. 2026, 16(5), 86; https://doi.org/10.3390/clinpract16050086 - 29 Apr 2026
Viewed by 364
Abstract
Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis [...] Read more.
Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted. Full article
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9 pages, 1213 KB  
Case Report
Spinal Epidural Empyema Associated with Bite Wounds in an Indian Crested Porcupine (Hystrix indica)
by Avital Levy, Ruthie Shviro, Shira Gonen, Nitzan Adam, David Eshar, Orit Chai and Hagar Merav Shamir
Vet. Sci. 2026, 13(5), 432; https://doi.org/10.3390/vetsci13050432 - 28 Apr 2026
Viewed by 333
Abstract
Spinal epidural empyema (SEE) is an uncommon but potentially severe cause of spinal cord compression and neurological dysfunction in veterinary patients. Bite wounds involving the vertebral column may result in deep tissue contamination, paraspinal abscessation, and secondary epidural infection; however, such injuries are [...] Read more.
Spinal epidural empyema (SEE) is an uncommon but potentially severe cause of spinal cord compression and neurological dysfunction in veterinary patients. Bite wounds involving the vertebral column may result in deep tissue contamination, paraspinal abscessation, and secondary epidural infection; however, such injuries are poorly described in wildlife species. We report a case of SEE associated with chronically infected bite wounds in an adult Indian crested porcupine (Hystrix indica) with paraplegia. Physical and neurological examinations revealed exudative paravertebral wounds, paraplegia with preserved nociception, and findings consistent with a thoracolumbar spinal cord lesion. Survey radiography and contrast myelography demonstrated an extradural compressive lesion at L1–L2. Surgical exploration revealed a purulent tract extending from the skin and paraspinal tissues into the vertebral canal, and a left L1–L2 hemilaminectomy was performed with drainage, debridement, lavage, and Penrose drain placement. Staphylococcus aureus was isolated from the abscess, and antimicrobial therapy was adjusted based on susceptibility testing. Postoperative management included physiotherapy and environmental modifications to support ambulation. The porcupine regained ambulation within 4 days after surgery and was released back into the wild approximately 50 days postoperatively with normal gait and tail-rattling behaviour. This case highlights bite-wound-associated SEE as an important differential diagnosis in porcupines presenting with paraplegia and draining paraspinal wounds and suggests that surgical decompression combined with prolonged culture-guided antimicrobial therapy and environmental modifications may result in a favourable outcome. Full article
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15 pages, 480 KB  
Article
Clinical Outcomes and Patterns of Neurological Toxicity After Stereotactic Body Radiotherapy Reirradiation (reSBRT) of Spine Metastases Previously Treated with SBRT
by Ahmed N. Elguindy, Eric R. Cochran, Khaled N. Dibs, Katelyn Fernando, Mark Addington, Eugene Yap, Robyn Handschuh, Dominic J. DiCostanzo, Daniel Schneider, Brian Park, James B. Elder, Russell Lonser, Daniel Boulter, Eric C. Bourekas, David J. Konieczkowski, Sasha Beyer, Simeng Zhu, Raj Singh, Raju Raval, John C. Grecula, Arnab Chakravarti, Joshua D. Palmer and Dukagjin M. Blakajadd Show full author list remove Hide full author list
Cancers 2026, 18(8), 1301; https://doi.org/10.3390/cancers18081301 - 20 Apr 2026
Viewed by 558
Abstract
Background/Objectives: Stereotactic body radiation therapy (SBRT) provides improved pain response and local control for spinal metastases. However, management of local failure after initial SBRT is challenging. We report institutional outcomes, dosimetry, and toxicity for reSBRT following SBRT. Methods: We retrospectively reviewed 61 lesions [...] Read more.
Background/Objectives: Stereotactic body radiation therapy (SBRT) provides improved pain response and local control for spinal metastases. However, management of local failure after initial SBRT is challenging. We report institutional outcomes, dosimetry, and toxicity for reSBRT following SBRT. Methods: We retrospectively reviewed 61 lesions (55 patients) treated with reSBRT after prior SBRT. Both SBRT courses delivered a median dose of 27 Gy. Patients underwent clinical and radiological evaluation every three months. Toxicity was graded using CTCAE v5.0. Dosimetric parameters for the spinal cord (SC), cauda equina (CE), planning organ-at-risk volumes (PRV), and thecal sac were converted to equivalent dose in 2 Gy fractions (EQD2) using the linear–quadratic model (α/β = 2). Results: Median follow-up was 10.3 months. Forty lesions (65%) were cervicothoracic and 21 (35%) were lumbosacral. One- and two-year overall survival (OS) were 45% and 29%, respectively, and one- and two-year local control (LC) were 89% and 88%, respectively. Gastrointestinal primary tumors were associated with inferior LC (HR 2.41, 95% CI 1.11–5.23, p = 0.026). Fifteen patients (27%) reported myelitis/neuropathic symptoms during follow-up; four (7%) developed new post-radiation myelitis or neuropathy (RMN) without radiologic progression. Five patients (9%) developed vertebral compression fractures (VCF). Cumulative EQD2 was not significantly associated with RMN (p = 0.344); all affected patients had thecal sac EQD2 > 95.5 Gy and relevant nerve roots EQD2 > 108 Gy. Conclusions: ReSBRT provided a favorable LC with acceptable toxicity. High cumulative dose to the thecal sac and nerve roots may contribute to neurologic toxicity as peripheral nerve injury. Full article
(This article belongs to the Special Issue New Approaches in Radiotherapy for Cancer)
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85 pages, 11594 KB  
Review
The Dual Role of Connexins in Stroke, Neurotrauma, Neurodegenerative and Psychiatric Disorders: A Global Systematic Review
by Stanislav Rodkin, Mitkhat Gasanov, Alexander Tushev, Elena Belousova, Yulia Gordeeva, Chizaram Nwosu and Anastasia Tolmacheva
Molecules 2026, 31(8), 1341; https://doi.org/10.3390/molecules31081341 - 19 Apr 2026
Viewed by 817
Abstract
Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue [...] Read more.
Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article
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31 pages, 1407 KB  
Review
Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs
by Valentina Ciampana, Eleonora Virgilio, Loredana Paciolla, Sofia Asaro, Alessandro Franceschini, Muralidharan Thavamani, Letizia Mazzini, Cristoforo Comi, Nadia Barizzone, Sandra D’Alfonso and Domizia Vecchio
Int. J. Mol. Sci. 2026, 27(8), 3583; https://doi.org/10.3390/ijms27083583 - 17 Apr 2026
Viewed by 456
Abstract
Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease characterized by marked clinical heterogeneity. While the genetic architecture underlying disease susceptibility is well established, the role of genetic factors in shaping disease prognosis remains clearly defined. In this structured narrative review, we [...] Read more.
Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease characterized by marked clinical heterogeneity. While the genetic architecture underlying disease susceptibility is well established, the role of genetic factors in shaping disease prognosis remains clearly defined. In this structured narrative review, we examine available evidence on genetic contribution to key MS prognostic domains. This includes clinical outcomes, such as age at onset, relapse rate, disability progression, neurological sequelae, and cognitive impairment. We also consider radiological measures like brain and spinal cord lesion burden, gadolinium-enhancing lesions, and atrophy, as well as laboratory biomarkers, such as oligoclonal bands and Immunoglobulin G (IgG) index. Overall, current evidence suggests that genetic influences on prognosis are modest and highly heterogeneous. Only a limited number of associations—primarily from genome-wide association studies (GWAS)—have shown consistent replication, whereas many reported findings come from small candidate-gene studies and remain unconfirmed. Among these, the largest GWAS on age-related Multiple Sclerosis Severity Score (MSSS) identified a locus in the DYSF–ZNF638 region reaching genome-wide significance. The strongest evidence from GWAS relates to relapse rate, magnetic resonance imaging (MRI) measures (e.g., thalamic atrophy) and intrathecal IgG synthesis, the latter also reaching genome-wide significance. Interpretation of genotype–phenotype associations is further limited by small sample sizes, limited replication, heterogeneity in study design with the predominance of candidate-gene approaches, variability in outcome definitions, treatment exposure, and population ancestry. These limitations currently preclude the routine use of genetic markers for prognostic stratification in clinical practice. Larger studies and collaborative genetic consortia efforts are needed to improve statistical power and reproducibility. Additionally, emerging epigenetic studies may provide valuable insights into prognosis and disease management. Understanding which genetic factors can predict diverse MS courses could enhance patient management and enable personalized treatment approaches. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
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26 pages, 5002 KB  
Article
Propentofylline and Interleukin-4 Modulate Lesion-Associated Myeloid Responses and Improve Functional Recovery After Spinal Cord Injury
by Mousumi Ghosh, Amir-Hossein Bayat, Keeley S. Garvey, Tolani Oshinusi, Thomas De Leon, Jacqueline Sagen and Damien D. Pearse
Cells 2026, 15(7), 625; https://doi.org/10.3390/cells15070625 - 31 Mar 2026
Viewed by 632
Abstract
Spinal cord injury (SCI) triggers a secondary injury cascade characterized by persistent innate immune activation, chronic neuroinflammation, and progressive tissue loss that limits functional recovery. Here, we evaluated a systemic combination treatment using propentofylline (PPF), a glial modulator, together with interleukin-4 (IL-4), a [...] Read more.
Spinal cord injury (SCI) triggers a secondary injury cascade characterized by persistent innate immune activation, chronic neuroinflammation, and progressive tissue loss that limits functional recovery. Here, we evaluated a systemic combination treatment using propentofylline (PPF), a glial modulator, together with interleukin-4 (IL-4), a cytokine associated with repair-related myeloid responses. In vitro, PPF enhanced IL-4-dependent induction of arginase-1 (ARG1) in TNFα-primed BV2 microglia. In vivo, adult Fischer rats of both sexes received vehicle, PPF, IL-4, or combined PPF + IL-4 beginning within 1 h after moderate T8 contusive SCI and continuing daily for 14 days. Locomotor recovery was assessed longitudinally for 8 weeks, followed by histological and immunohistochemical analyses. Combined PPF + IL-4 treatment produced the greatest improvement in gross and skilled locomotor recovery compared with vehicle, or either monotherapy. At 8 weeks post-SCI, the combined therapy aligned with a reduction in chronic lesion-associated p-p38 MAPK, decreased pP65 NFkB (RelA) activation, increased expression of reparative factors ARG1 and CD206, as well as reduced lesion cavitation and trends toward greater gray and white matter preservation. Stratification of functional data by sex showed BBB improvements with combined PPF + IL-4 in both males and females after SCI. Together, these findings show that combined systemic PPF and IL-4 treatment was associated with improved functional recovery, reduced lesion cavitation, and changes in lesion-associated molecular and histological endpoints after SCI, supporting further preclinical investigation. Full article
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13 pages, 4073 KB  
Case Report
Nine-Year Follow-Up of Gamma Knife Surgery for Hemangioblastomas in von Hippel–Lindau Disease: Illustrating the Challenge of Distinguishing Radiosurgical Effect from Natural Tumor Quiescence
by Rusli Muljadi, Lutfi Hendriansyah, Patricia Diana Prasetiyo and Gilbert Sterling Octavius
Radiation 2026, 6(1), 11; https://doi.org/10.3390/radiation6010011 - 17 Mar 2026
Viewed by 550
Abstract
Background/Objectives: Hemangioblastomas are rare, benign, highly vascular tumors of the central nervous system, frequently associated with von Hippel–Lindau (vHL) disease. Case Presentation: We report a 16-year-old female with vHL presenting with recurrent headaches, abdominal distension, and ocular discomfort. Imaging revealed hemangioblastomas in the [...] Read more.
Background/Objectives: Hemangioblastomas are rare, benign, highly vascular tumors of the central nervous system, frequently associated with von Hippel–Lindau (vHL) disease. Case Presentation: We report a 16-year-old female with vHL presenting with recurrent headaches, abdominal distension, and ocular discomfort. Imaging revealed hemangioblastomas in the fourth ventricle and retrobulbar space, alongside multiple pancreatic cysts. The patient underwent three sessions of Gamma Knife Surgery (GKS) with initial tumor regression and symptom relief. However, long-term follow-up demonstrated progressive disease, with new lesions in the cerebellum, spinal cord, and orbit, including cystic transformation. Histopathology confirmed the reticular variant of hemangioblastoma. Despite further radiosurgical and surgical recommendations, the patient and family opted for conservative management, with lesions remaining radiographically stable over nine years. Conclusions: This case demonstrates that Gamma Knife Surgery may provide temporary local disease control for selected solid hemangioblastomas in von Hippel–Lindau disease but does not alter the underlying disease course. Long-term radiographic stability should be interpreted cautiously, as hemangioblastomas exhibit saltatory growth patterns that make it difficult to distinguish treatment effect from natural tumor quiescence. These findings emphasize that radiosurgery should be regarded as a disease-control strategy rather than curative therapy, underscoring the importance of individualized management, multidisciplinary decision-making, and prolonged surveillance. Full article
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17 pages, 354 KB  
Review
Early Prognostic Factors in Multiple Sclerosis: Clinical and Therapeutic Implications
by Katarzyna Maciejowska-Szydło and Przemysław Puz
Medicina 2026, 62(3), 475; https://doi.org/10.3390/medicina62030475 - 2 Mar 2026
Viewed by 903
Abstract
Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective [...] Read more.
Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective treatments. Objective: The aim of this review was to synthesize current data on prognostic factors in multiple sclerosis, with particular emphasis on their significance in the early stages of the disease and potential clinical implications. Methods: A narrative systematic review of the literature was conducted, including observational studies, cohort studies, meta-analyses, and systematic reviews on the natural course of MS, prognostic factors, and clinical, neuroimaging, and laboratory biomarkers. We comprehensively reviewed PubMed and Scopus databases, focusing on English-language publications. Study selection prioritized longitudinal studies and meta-analyses with clear outcome definitions and sufficient follow-up. Formal quality scoring was not applied due to the narrative design of the review. Results: Key adverse prognostic factors include older age at onset, polysymptomatic onset, high relapse activity in the first years, incomplete remission after relapses, and the primary progressive form. Magnetic resonance imaging features, including the number and location of T2 lesions, contrast activity, the presence of spinal cord lesions, PRLs and SELs, and severe brain atrophy, also have significant predictive value. Increasing importance is being attached to laboratory biomarkers, such as oligoclonal bands, light neurofilaments, free kappa light chains, and GFAP. Conclusions: An integrated assessment of clinical, neuroimaging, and laboratory factors enables more effective risk stratification in patients with newly diagnosed MS. Early identification of an unfavorable prognostic profile may provide a basis for individualizing treatment and considering the use of highly effective therapies early in the course of the disease. Full article
(This article belongs to the Section Neurology)
13 pages, 668 KB  
Article
Spinal Cord Stimulation for Non-Reconstructable Chronic Limb-Threatening Ischemia: A Real-World, Multidisciplinary, Single-Center Experience
by Naoufel Ouerchefani, Edward Goldberg and Pascal Desgranges
J. Clin. Med. 2026, 15(5), 1760; https://doi.org/10.3390/jcm15051760 - 26 Feb 2026
Viewed by 542
Abstract
Background/Objectives: Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by ischemic rest pain or ulcer necrosis. In Europe, spinal cord stimulation (SCS) can be offered to CLTI patients with chronic pain to improve mobility and prolong limb [...] Read more.
Background/Objectives: Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by ischemic rest pain or ulcer necrosis. In Europe, spinal cord stimulation (SCS) can be offered to CLTI patients with chronic pain to improve mobility and prolong limb preservation. We evaluated the long-term, real-world outcomes of SCS therapy in patients with CLTI. Methods: In this observational study, medical chart review data from consecutive CLTI patients treated with SCS were analyzed. Results: Fifty-three patients (56.6% Fontaine Stage III, 39.6% Fontaine Stage IV, 3.8% Fontaine Stage IIb) had a single-stage SCS implant procedure between 2013 and 2022. Two years after SCS therapy activation, claudication pain intensity had significantly improved; the overall numerical rating scale pain score decreased from 9.4 ± 0.9 at baseline to 3.7 ± 3.2 (p < 0.0001). In addition, walking distance increased by more than 350 m (from 70 ± 87 to 429 ± 320 m, p < 0.0001), and pre-existing skin lesions stabilized in ten patients (63%). The probability of limb survival in Fontaine’s stage IIb/III and Fontaine’s stage IV patients at 12 months was 90% and 70%, respectively (log-rank p-value = 0.04). Finally, significant associations were found between the occurrence of an amputation after SCS and Fontaine Stage (p = 0.01), active smoking (p = 0.02), hypertension (p = 0.04), and prior minor amputation (p = 0.02). No major complications were reported. Conclusions: Our real-world experience suggests that SCS for CLTI patients provides significant and durable improvements in ischemic pain and functional outcomes. SCS may also help reduce the natural risk of major amputation, especially when implemented at early CLTI stages. Full article
(This article belongs to the Section Vascular Medicine)
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14 pages, 1044 KB  
Case Report
Spinal Cord Toxoplasmosis: Mapping the Journey of a Rare Entity Through a Case Report and Review of the Literature
by Sara Kamel Rey, Hessameldin Iranmanesh, Maya Hites, Sophie Elands and Sophie Henrard
Microorganisms 2026, 14(3), 535; https://doi.org/10.3390/microorganisms14030535 - 26 Feb 2026
Viewed by 800
Abstract
Toxoplasmosis remains the most frequent cause of cerebral lesions in patients with acquired immunodeficiency syndrome (AIDS), especially in those not receiving prophylaxis. Medullary involvement, although rare, can cause irreversible neurological damage. When associated with fever in the returning traveler, the etiological diagnosis of [...] Read more.
Toxoplasmosis remains the most frequent cause of cerebral lesions in patients with acquired immunodeficiency syndrome (AIDS), especially in those not receiving prophylaxis. Medullary involvement, although rare, can cause irreversible neurological damage. When associated with fever in the returning traveler, the etiological diagnosis of spinal cord lesions can be challenging due to the wide range of diagnostic possibilities. We report a unique case of spinal cord toxoplasmosis associated with Salmonella non-typhi bacteremia after a trip to Cameroon, revealing an advanced human immunodeficiency virus (HIV) infection in an otherwise healthy adult male. We also conducted a comprehensive review of reported spinal cord toxoplasmosis cases between the years 2000 and 2025 in both immunocompromised and immunocompetent patients. In our review, paraparesis, sensory loss, and urinary retention were the most frequent clinical presentations (52.17%; 56.52% and 47.84%, respectively), and the majority of the patients had concomitant cerebral lesions (78.26%). Diagnosis remains a challenge, with 48.0% of the reported cases diagnosed through histological detection of the parasite in central nervous system (CNS) tissue. Sulfadiazine–pyrimethamine with additional folinic acid and trimethoprim-sulfamethoxazole (TMP-SMX) remains the treatment of choice for treating cerebral toxoplasmosis in people living with HIV (PLHIV), with no particular recommendation regarding patients with spinal cord involvement. In the reviewed cases, neurological sequelae occurred in 52.2% of patients, and mortality was as high as 30.4%. Full article
(This article belongs to the Section Medical Microbiology)
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32 pages, 3842 KB  
Article
Hyaluronic Acid Profhilo® Alleviates Skin Inflammation and Spinal Neuroimmune Alterations in a Mouse Model of Atopic Dermatitis
by Gabriel Siquier-Dameto, Javier Gimeno-Beltrán, Gilberto Bellia, Andrea Giori, Pere Boadas-Vaello and Enrique Verdú
Medicina 2026, 62(2), 405; https://doi.org/10.3390/medicina62020405 - 20 Feb 2026
Viewed by 2354
Abstract
Background and Objectives: Hyaluronic acid (HA) is extensively used in dermo-aesthetic medicine for its hydrating and tissue-repairing properties. Beyond cosmetic use, HA has shown therapeutic effects in inflammatory skin diseases such as seborrheic, radiation-induced, and atopic dermatitis (AD). However, HA-based aesthetic formulations [...] Read more.
Background and Objectives: Hyaluronic acid (HA) is extensively used in dermo-aesthetic medicine for its hydrating and tissue-repairing properties. Beyond cosmetic use, HA has shown therapeutic effects in inflammatory skin diseases such as seborrheic, radiation-induced, and atopic dermatitis (AD). However, HA-based aesthetic formulations such as Profhilo®, a hybrid complex of high- and low-molecular weight HA, have not been tested in immunologically driven models of AD. This study aimed to investigate the therapeutic effects of intradermal Profhilo® injections in a recently developed ovalbumin (OVA)-induced murine model of AD. Specific objectives included assessing changes in skin inflammation, pain sensitivity, and spinal cord pathology. Materials and Methods: Twenty-eight adult female ICR-CD1 mice were sensitized and exposed to OVA via intraperitoneal, subcutaneous, and topical routes over 49 days to induce AD-like lesions. Control animals received saline. On day 50, mice were subdivided into four groups receiving intradermal injections of Profhilo® or saline. Skin inflammation was evaluated using the SCORAD index on days 49 and 57, and nociceptive responses were measured using the plantar thermal hyperalgesia test. On day 57, dorsal skin and thoracic spinal cord samples were collected for histological and immunohistochemical analysis, including assessments of epidermal and dermal thickness, mast cell density, collagen content, CGRP immunoreactivity, and microglial activation. Results: OVA-treated mice developed significant skin inflammation (p < 0.0001) and thermal hyperalgesia. Intradermal HA injection significantly reduced SCORAD scores (p < 0.01) and mast cell density (p < 0.05) while increasing dermal thickness (p < 0.05). In the spinal cord, HA treatment reduced CGRP immunoreactivity and microglial activation (p < 0.01 and p < 0.05, respectively), especially in OVA-treated animals. Conclusions: Intradermal Profhilo® alleviated both cutaneous inflammation and neurogenic pain in an OVA-induced AD model. These findings suggest that HA not only improves local skin pathology but also modulates central neuroimmune responses, supporting its therapeutic potential for inflammatory skin conditions involving peripheral and central sensitization. Full article
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10 pages, 7207 KB  
Case Report
Primary Non-Germinal Center-Type Large B-Cell Lymphoma Involving the Thoracic Epidural Space, Cauda Equina, and Filum Terminal: Diagnosis and Treatment Using Biportal Endoscopic Spine Surgery—A Case Report and Literature Review
by Nan-Fu Chen and Chien-Yu Ou
Reports 2026, 9(1), 61; https://doi.org/10.3390/reports9010061 - 13 Feb 2026
Viewed by 612
Abstract
Background and Clinical Significance: We report a rare case of a 66-year-old male with malignant non-germinal center-type large B-cell lymphoma involving the thoracic epidural, cauda equina, and filum terminal simultaneously. Case Presentation: The patient complained of back pain, rapid progressive numbness, [...] Read more.
Background and Clinical Significance: We report a rare case of a 66-year-old male with malignant non-germinal center-type large B-cell lymphoma involving the thoracic epidural, cauda equina, and filum terminal simultaneously. Case Presentation: The patient complained of back pain, rapid progressive numbness, and motor palsy in both legs in one month. Neurological examination revealed grade 2 muscle power in both lower limbs, hypesthesia below the T8 dermatome, and bladder and bowel dysfunctions. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural lesion extending from the T7 to T9 level, with severe spinal cord compression. Additionally, it revealed enlargement of the cauda equina occupying the extradural space from the L1-S1 level. The lesion appeared isointense on T1, mildly hyperintense on T2-weighted images, and exhibited homogeneous enhancement on post-contrast images. To relieve the patient’s spinal cord compression as soon as possible and allow the patient to recover quickly after surgery, we performed unilateral biportal endoscopy (UBE) to completely remove the T7-9 epidural lesion. The immunohistochemical assessment confirmed a histological diagnosis of diffuse large B-cell lymphoma, a non-germinal center type. The patient received radiotherapy to the thoracic and lumbosacral areas (50 Gy) and chemotherapy with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) after surgery. Follow-up positron emission tomography (PET) scan and MRI performed 4 months after surgery revealed complete remission of the lesion. The patient was able to walk using a walker after therapy. Conclusions: UBE is a favorable option for selected patients requiring immediate chemotherapy or radiotherapy owing to its reduced tissue trauma compared to traditional open surgery. Full article
(This article belongs to the Section Surgery)
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