Search Results (2,945)

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B mutations, characterized by hepatic copper accumulation and multisystem involvement. Several rare inherited and acquired conditions can closely mimic WD, posing diagnostic challenges and the risk of inappropriate therapy. By examining neuroimaging patterns and distinguishing between diagnostic criteria, this narrative review provides a comprehensive synthesis of WD-mimicking disorders, emphasizing their molecular mechanisms, clinical phenotypes, and biochemical features. WD-mimicking disorders encompass ATP7A-related neurodegenerations (Menkes disease, occipital horn syndrome, X-linked distal hereditary motor neuropathy), MEDNIK syndrome, Huppke–Brendel syndrome, aceruloplasminemia, congenital disorders of glycosylation, primary familial intrahepatic cholestasis type 3, and acquired copper deficiency syndromes. Mechanisms include systemic copper deficiency, impaired intracellular trafficking, defective ceruloplasmin biosynthesis, secondary hepatic copper accumulation, and abnormal glycosylation. Clinical features range from neurodevelopmental delay, movement disorders, and hepatic dysfunction to dermatologic, hematologic, and connective-tissue abnormalities. Biochemical profiles may overlap with WD, particularly low serum ceruloplasmin and total copper, altered urinary copper excretion, and elevated hepatic copper in some disorders. Neuroimaging and genetic testing provide critical discriminative value. Management is largely supportive, with disease-specific therapies available in selected conditions, such as subcutaneous copper in Menkes disease or monosaccharide supplementation in certain congenital disorders of glycosylation subtypes. Accurate differentiation between WD and WD-mimicking disorders requires careful integration of clinical, biochemical, imaging, and molecular data. Recognition of distinctive features and understanding underlying pathophysiology are essential to avoid misdiagnosis and inappropriate anti-copper therapy, optimize management, and improve patient outcomes. Full article

Pediatric-onset neuromuscular diseases (NMDs) represent a clinically and genetically heterogeneous group of rare disorders, often posing significant diagnostic challenges due to overlapping phenotypes. Next-generation sequencing (NGS), particularly whole-exome sequencing (WES), has transformed the diagnostic landscape; however, its clinical utility varies across phenotypic subgroups. We conducted a combined retrospective–prospective cohort study that included 100 pediatric patients with suspected neuromuscular disorders evaluated at a tertiary referral center between 2015 and 2025. Patients were stratified into seven clinically defined diagnostic categories prior to genetic testing. NGS-based diagnostics (primarily WES) were performed following initial clinical and targeted evaluations. Diagnostic yield and predictors of a positive genetic result were analyzed using univariate and multivariable statistical approaches. A molecular diagnosis was established in 71% of patients, including 64% with pathogenic/likely pathogenic variants and 7% with clinically consistent variants of uncertain significance. Diagnostic yield varied significantly across disease categories (p < 0.001), reaching near-complete rates in well-defined phenotypes such as congenital myasthenic syndromes, neuropathies, and metabolic myopathies, while markedly lower yield was observed in unclassified cases (38.2%). Multivariable logistic regression identified disease group as the only independent predictor of diagnostic success (B = −0.436, p = 0.001). Frequently implicated genes included DMD, RYR1, and LAMA2, reflecting a predominance of structural and excitation–contraction coupling defects. NGS demonstrates high diagnostic utility in pediatric neuromuscular disorders, particularly when applied in a phenotype-driven framework. Diagnostic performance is strongly influenced by the degree of clinical definition prior to testing, highlighting the continued importance of expert phenotyping in the genomic era. Full article

Retinal ganglion cell (RGC) degeneration underlies glaucomatous optic neuropathy and remains a leading cause of irreversible vision loss worldwide. Although elevated intraocular pressure (IOP) is the primary modifiable risk factor, RGC death reflects converging mechanisms including mechanical stress, vascular insufficiency, metabolic dysfunction, and neuroinflammation. We conducted a PRISMA-guided systematic review with PICOS-defined eligibility criteria, searching PubMed, Cochrane Library, ScienceDirect, Scopus, Google Scholar, and ProQuest for studies through January 2026 on RGC degeneration and neuroprotective or regenerative therapies in glaucoma. Included studies supported OCT-based structural assessment and imaging biomarkers as essential tools for early detection, risk stratification, and monitoring of progression and treatment response. Continued RGC loss despite IOP control in many patients highlights the need for mechanism-based interventions; neuroprotective strategies targeting excitotoxicity, oxidative stress, mitochondrial dysfunction, and neurotrophic insufficiency are emerging, while stem cell and gene-based regenerative therapies remain under active investigation. Integrating molecular insights with advanced imaging and biomarker-guided endpoints may enable earlier, more individualized intervention and help explain progression despite adequate pressure control. Full article

Background: Recent studies strongly suggest that low intracranial pressure (ICP) may be involved in the pathogenesis of glaucomatous optic neuropathy. As retinal ganglion cells (RGCs) are highly susceptible to mitochondrial dysfunction, mitochondrial injury may be associated with optic neuropathy related to reduced ICP. In this study, aquaporin-1 (AQP1)-null mice were used to investigate whether reduced ICP is associated with alterations in mitochondrial structure and the release of optic atrophy type 1 (OPA1) and cytochrome c from mitochondria. Methods: Intraocular pressure (IOP) and ICP were measured in AQP1-null mice, and mitochondrial structural changes were examined using transmission electron microscopy (TEM). Total OPA1 and cytochrome c protein levels were evaluated using immunocytochemistry and Western blotting. Cytosolic and mitochondrial fractions were extracted from retinal tissues, and the subcellular distribution of OPA1 and cytochrome c was further analyzed by Western blotting. Bax and Bcl-2 expression levels were also detected. Results: TEM revealed mitochondrial fission, matrix swelling, and abnormal cristae depletion in the retinas of 1-, 3-, and 6-month-old AQP1-null mice. Morphometric quantification further confirmed significantly reduced mitochondrial length across all age groups and increased mitochondrial width at 1 and 6 months in AQP1-null mice compared with wild-type controls. Decreased retinal OPA1 immunoreactivity and protein expression were observed across all age groups of AQP1-null mice compared with age-matched C57BL/6 control mice. Subcellular fractionation showed increased mitochondrial release of OPA1 (at 3 and 6 months) and cytochrome c (at 1, 3, and 6 months) in the retinas of AQP1-null mice. Altered Bax expression was also detected in the retinas of AQP1-null mice with reduced ICP at all examined ages. Conclusions: Mitochondrial ultrastructural abnormalities, including fission and cristae depletion, altered OPA1 distribution, increased mitochondrial release of OPA1 and cytochrome c, and upregulated Bax expression were observed in the retinas of AQP1-null mice with reduced ICP. These concurrent changes indicate a close association between reduced ICP and retinal mitochondrial dysfunction. Maintaining mitochondrial integrity may therefore serve as a potential protective strategy against optic nerve degeneration in patients with chronic low ICP. Full article

Background: Guillain–Barré syndrome (GBS) is an autoimmune peripheral neuropathy that can lead to paralysis and respiratory failure. In addition to infections, several drugs have been suggested as potential triggers of GBS. This study investigated drug-associated GBS using a spontaneous adverse event reporting database through disproportionality analysis for signal detection and time-to-onset analysis. Methods: The Japanese Adverse Drug Event Report (JADER) database was analyzed to assess more than 4000 drugs for potential associations with GBS. Signal detection was performed using reporting odds ratios, Fisher’s exact test, and total report counts. For vaccines and immune checkpoint inhibitors, time-to-onset patterns were further evaluated using Weibull distribution analysis. Results: Disproportionality signals suggesting potential associations with GBS were identified for 45 drugs, including vaccines, immune checkpoint inhibitors, tumor necrosis factor-α inhibitors, other anticancer drugs, antifungal agents, and interferons. Reports following vaccination were most frequently observed within 1–3 weeks after administration of coronavirus disease 2019 (COVID-19), influenza, and pneumococcal vaccines, and within 1–3 months after human papillomavirus 2-valent vaccination, with a gradual decrease thereafter. Reports following immune checkpoint inhibitor use were most frequently observed 1–3 months after nivolumab, ipilimumab, and pembrolizumab administration, whereas atezolizumab showed a peak in reporting within 1–3 weeks. In contrast to vaccine-related reports, no clear temporal trend in reporting was observed. Conclusions: Drugs that modulate immune function, including vaccines and immune checkpoint inhibitors, may be associated with reported GBS events. Vaccine-related reports showed an early concentration in time to onset, whereas immune checkpoint inhibitor-related reports did not demonstrate a clear temporal pattern. These findings should be interpreted as hypothesis-generating and warrant further investigation. Full article

Orbital apex syndrome (OAS) is characterized by optic neuropathy and ophthalmoplegia and is generally associated with poor visual prognosis. The aim of this study was to describe patients with acute OAS who demonstrated substantial recovery of visual function and ocular motility. We retrospectively reviewed the medical records of patients treated for OAS at a tertiary medical center between 2019 and 2024 whose condition ultimately proved reversible. Data on demographics, clinical findings, imaging, management, and follow-up were collected. Six patients (three female, three male; age range 14–87 years) were included and followed for a median follow-up of 7 months (range 2–31). All presented with reduced vision and ophthalmoplegia of varying severity. Underlying etiologies included inflammatory disease (n = 2), lymphoma, infection, blunt trauma, and post-surgical OAS of undetermined etiology (n = 1 each). Treatment was directed at the underlying cause. Visual acuity ranged from 20/30 to hand motion (HM) at presentation and 20/15 to 20/60 at the final visit. Improvement in vision and ocular motility occurred after a median time to clinical improvement of 2.37 months (range 0.25–5 months). Near-complete recovery of ocular motility was observed in all patients, with only one retaining mild abduction limitation. These findings highlight a subset of OAS cases with favorable outcomes and emphasize the importance of early diagnosis and etiology-directed management. Full article

Monoclonal gammopathies of clinical significance (MGCSs) are entities in which a small hematological clone produces a monoclonal immunoglobulin capable of causing organ damage. Neurological involvement remains difficult to diagnose and treat, especially in the context of incidental monoclonal gammopathy of undetermined significance (MGUS)–peripheral neuropathy (PN) associations. We conducted a single-center retrospective study at Fundeni Clinical Institute, Bucharest, from January 2015 to December 2025. The reference population included 300 patients with MGUS. The diagnosis of MGNS was established clinically and/or electrophysiologically, with the exclusion of alternative causes of neuropathy. In total, 35 patients with MGNS were identified (prevalence 11.7%). Neuropathy was more common in IgM MGUS (36.7%) compared to IgG (15%), IgA (14.3%), or light chain MGUS (16.7%), with an increased risk for IgM (OR 3.27, p < 0.001). A total of 88.5% of patients received hematological treatment; neurological response was noted in the majority of treated patients. Mortality was 14.3%, and median OS was not reached. Our findings confirm the dissociation between low clonal load and the severity of organ involvement. IgM MGUS is associated with a significantly increased risk of neuropathy, supporting the need for systematic screening for MGUS in patients with PN and for a multidisciplinary approach. Full article

Background/Objectives: The objective was to evaluate whether surgical timing (daytime vs. nighttime) influences intraoperative and postoperative outcomes in pediatric supracondylar humerus fractures. Methods: A retrospective observational cohort study was conducted at a tertiary center. Pediatric patients aged ≤14 years who underwent surgery for supracondylar humerus fractures between January 2010 and December 2022 were included. Fractures were classified according to the Gartland system. Patients with open fractures, associated neurovascular injury, compartment syndrome, or incomplete follow-up were excluded. Primary outcomes included need for open reduction, reoperation, neuropathy, and loss of joint mobility. Patients were grouped according to the time of surgery: daytime (08:00–22:00) or nighttime (22:00–08:00). Stratified analyses were performed based on fracture severity. Results: Eighty-six patients were included: 56 underwent daytime surgery and 30 underwent nighttime surgery. Groups were comparable in age, sex, and fracture severity. Nighttime surgery was associated with a significantly higher rate of open reduction (33.3% vs. 10.7%, p = 0.023; RR = 3.11). Reoperation (16.6% vs. 5.4%, p = 0.121) and postoperative neuropathy (23.3% vs. 8.9%, p = 0.131) were more frequent in the nighttime group, although these differences were not statistically significant. In complex fractures (Gartland III–IV), nighttime surgery was associated with a significantly higher reoperation rate (20.8% vs. 2.6%, p = 0.026). Conclusions: Nighttime surgery was associated with higher rates of open reduction and reoperation, particularly in complex supracondylar humerus fractures. However, given the retrospective design and limited sample size, these findings may be influenced by residual confounding and should be interpreted as exploratory. Full article

Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden vision loss, yet no effective therapy exists to preserve retinal ganglion cells (RGCs) after ischemic injury. Nostoc commune (NC), an edible cyanobacterium with established antioxidant and anti-inflammatory activities, has emerged as a potential functional bioresource with relevance to ocular health. Here, we investigated the therapeutic effects of a crude aqueous extract of NC using a rodent model of anterior ischemic optic neuropathy (rAION). NC treatment significantly improved RGC survival, reduced apoptosis, attenuated macrophage and microglial activation (ED-1, Iba1), suppressed proinflammatory cytokine expression (IL-6), enhanced the reparative marker Ym1+2, and preserved optic-nerve myelination. Functionally, NC administration restored visual signaling as demonstrated by improved Flash Visual Evoked Potential amplitudes. Immunoblot analysis showed increased phosphorylation of PI3K/AKT/mTOR/p70S6K signaling components in retinal tissue following NC treatment. Proteomic profiling further demonstrated that NC extract comprises a coordinated repertoire of phycobiliproteins, antioxidant enzymes, and stress-response proteins that may collectively contribute to its biological effects. Together, these findings suggest that Nostoc commune extract may serve as a promising functional food-derived candidate for protecting RGCs and preserving visual function following ischemic optic neuropathy. Further studies are required to identify its active constituents, optimize formulation strategies, and evaluate its translational potential. Full article

Background/Objectives: The co-occurrence of diabetic peripheral neuropathy and depression increases the symptom burden and risk of long-term complications. Methods: This cross-sectional study enrolled 131 patients with type 1 (age: 58.47 years; duration of diabetes: 35.61 years) and type 2 diabetes (age: 63.60 years; duration of diabetes: 11.49 years). All patients underwent assessment of socioeconomic status and evaluation using the Hospital Anxiety and Depression Scale, the Mental Component Score of the Short Form Healthy Survey Questionnaire, neuropathy disability score, nerve conduction studies, corneal confocal microscopy and intraepidermal nerve fibre density (IENFD) assessment. Results: The prevalence of foot pain (45% vs. 23.9%, p = 0.019), tingling (56.7% vs. 32.9%, p = 0.013), weakness (35% vs. 9.9%, p < 0.001), ataxia (40% vs. 16.9%, p = 0.001), and upper limb symptoms (45% vs. 19.7%, p = 0.001) were statistically significantly higher, while cold perception threshold (22.50 ± 8.47 vs. 26.34 ± 3.08, p = 0.007), corneal nerve fibre density (20.49 ± 7.55 vs. 24.16 ± 5.68, p = 0.002) and length (20.06 ± 6.98 vs. 22.95 ± 6.22, p = 0.014) were statistically significantly lower, but no differences in nerve conduction studies or IENFD were observed in patients with depression compared to patients without depression. Furthermore, patients with depression were from a lower socioeconomic class (51.7% vs. 21.1%, p < 0.001), had lower educational attainment (37.9% vs. 12.9%, p < 0.001), had lower income < £37,000 (29.3% vs. 11.4%, p = 0.010) and lived in areas of high deprivation (62.1% vs. 31.4%, p < 0.001). Conclusions: Comorbid depression in people with diabetes was linked to increased socioeconomic deprivation and a greater prevalence of neuropathic symptoms and small fibre pathology. Full article

Syphilitic panuveitis is a severe and diagnostically highly challenging manifestation of ocular syphilis. Its predominant posterior-segment involvement and its tendency to mimic noninfectious or viral uveitis may delay etiologic recognition and increase the risk of permanent vision loss. Rhegmatogenous retinal detachment (RRD) is a rare but vision-threatening complication that likely reflects advanced, inflammation-induced disruption of the vitreoretinal interface. A narrative literature review was conducted using the PubMed, Scopus, and Web of Science databases (January 2000 to 10 September 2025). Studies addressing the clinical presentation, imaging findings, pathophysiology, and management of syphilitic panuveitis and associated rhegmatogenous retinal detachment were analyzed. Infectious mimickers were also presented, with particular emphasis on West Nile virus (WNV). Evidence was synthesized qualitatively. Posterior uveitis and panuveitis are one of the most common ocular manifestations of syphilis. Posterior segment involvement in ocular syphilis is frequently bilateral, typically presenting with dense vitritis, retinal vasculitis, and optic neuropathy. RRD is a rare presenting complication, most often developing in areas of prior inflammatory retinitis and arising due to retinal necrosis, persistent vitreoretinal traction, and early proliferative vitreoretinopathy, which increases surgical complexity and may limit functional recovery. HIV coinfection often modifies disease severity. In relevant endemic or seasonal settings, WNV-associated ocular inflammation represents an important diagnostic pitfall. Syphilitic panuveitis should be considered early in patients presenting with unexplained posterior uveitis or panuveitis. Routine testing for syphilis and HIV in the uveitic laboratory palette, together with targeted evaluation for infectious mimickers, is essential to reduce diagnostic delay and avoid inappropriate immunosuppression. RRD should be recognized as a marker of advanced, inflammation-induced vitreoretinal interface damage requiring timely antimicrobial therapy and early involvement of vitreoretinal surgery. Full article

Background: Diabetic foot ulcers (DFUs) and lower extremity amputations are major contributors to morbidity and mortality in individuals with diabetes. Among patients undergoing active cancer treatment, the risks are compounded by immunosuppression, peripheral neuropathy, and vascular complications. Even minor foot infections or wounds in these patients can necessitate the suspension of cancer therapy, with potentially lifethreatening consequences. This study evaluated the impaqt of integrating symptom-focused patient education with coordinated podiatric care to reduce DFUs and amputations in this highrisk population with concurrent cancer and diabetes. Methods: A five-year retrospective review was conducted at a National Cancer Institute (NCl)designated comprehensive cancer center as part of the Novel Limb Preservation Initiative. The cohort included patients with Type II diabetes undergoing treatment for prostate, breast, colorectal, lymphoma, leukemia, thyroid, or lung cancers. Patients were assigned targeted educational modules based on self-reported diabetic foot symptoms. Podiatric care was individualized according to each patient's signs and symptoms, including routine diabetic foot examinations and close, timely monitoring when indicated. Results: The intervention yielded a DFU incidence of 2. 8% and an amputation rate of 0. 43%, both lower than national benchmarks. Enhanced patient engagement through diabetic foot symptom-focused education and earlier detection of foot complications-including diabetic foot ssues that may appear minor to laypersons-contributed to these improved outcomes. Conclusion: Integrating diabetic foot symptom-focused education with proactive podiatric monitoring significantly reduced DFUs and amputations in this high-risk population. This model, developed under the Novel Limb Preservation Initiative, offers a scalable strategy for broader implementation, particularly in high-risk communities, including Hispanic, African American, low socioeconomic, and rural populations across the United States. Full article

Background: Corneal sensitivity is a key indicator of ocular surface health. This prospective, cross-sectional study evaluated agreement between corneal sensitivity thresholds obtained from equivalent stimulus settings on a contemporary, enhanced dual-temperature non-contact corneal aesthesiometer (NCCA) and a previously validated (standard) device. Methods: Central corneal sensitivity thresholds were measured in the right eyes of healthy participants using both devices. Participants with previous ocular surgery, laser treatment, trauma, contact lens wear, diabetes, or peripheral neuropathy were excluded. Sensitivity thresholds were determined using a forced-response, double-staircase protocol. Inter-device agreement was assessed using Bland–Altman analysis, and consistency was assessed using intraclass correlation coefficients. Results: Median corneal sensitivity thresholds in 51 healthy participants (32 female, 19 male; mean age: 33 ± 14 years) did not differ between enhanced (0.23 [0.18 to 0.38]) and standard (0.25 [0.15 to 0.35]) NCCA instruments (p = 0.73). Bland–Altman analysis demonstrated moderate inter-device agreement, with a mean difference of −0.01 mbar (95% limits of agreement: −0.41 to 0.39 mbar). Linear regression analysis identified greater measurement discrepancies at higher thresholds (p < 0.05), indicating greater variability in individuals with reduced corneal sensitivity. Conclusions: The enhanced NCCA yields reliable corneal sensitivity measures for a room-temperature stimulus and acceptable agreement with the existing (standard) model. Full article

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