Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder characterized by brief dystonic or dyskinetic attacks precipitated by sudden voluntary movement or arousal. Pregnancy complicated by PKD is extremely rare, and evidence guiding perinatal decision-making, especially regarding delivery mode and anesthetic management remains scarce. We report a term pregnancy in a woman with long-standing PKD managed through a multidisciplinary team involving neurology, obstetrics, anesthesiology, and neonatology. Following individualized optimization of antiseizure medications (ASMs) and intensive antenatal surveillance, the patient showed moderate symptomatic improvement during pregnancy. Given the high risk of pain, stress, or movement-triggered dystonic attacks with transient loss of voluntary motor control during labor, elective cesarean delivery was planned. Combined spinal-epidural anesthesia (CSEA) was performed to provide effective analgesia while minimizing arousal and sensory triggers. The procedure was uneventful, with no perioperative dystonic episodes. A healthy neonate was delivered with no congenital anomalies. This case demonstrates that favorable maternal and neonatal outcomes can be achieved in pregnancies complicated by PKD through individualized antiseizure medication management, multidisciplinary care, and trigger-oriented perinatal planning. The structured clinical decision-making pathway proposed in this study may provide a practical framework for managing this rare and challenging condition.
Charcot-Marie-tooth disease type 4D (CMT4D) is an early-onset, severe autosomal recessive demyelinating neuropathy, caused by mutations in the N-myc downstream-regulated gene 1 (NDRG1). Because of its rarity and predominance among specific ethnic groups, clinical knowledge remains limited. We report the case of two siblings of Romani ancestry, a 38-year-old man and a 40-year-old woman, with homozygous NM_006096.4:c.442C > T, p.(Arg148*) variant, and provide a review of the current literature.Both patients presented with severe distal-proximal sensorimotor neuropathy, muscle weakness and atrophy, generalized areflexia, and sensorineural deafness typical of CMT4D. Notably, they exhibited previously unreported features including severe dysphagia requiring PEG tube placement, bilateral vocal cord paralysis causing respiratory insufficiency necessitating non-invasive ventilation, and cognitive delay. Visual system involvement was demonstrated through abnormal visual evoked potentials with reduced P100 amplitude and absent responses, expanding the recognized phenotypic spectrum.Our systematic literature review identified 26 articles describing 72 patients with CMT4D. Twenty-two pathogenic NDRG1 variants were documented, with p.(Arg148*) being most frequent (64% of patients), predominantly in Roma populations. The median age of onset was 7 years, 96% of patients presented with lower limb involvement and all presented skeletal deformities were universal, including pes cavus (67%), claw hand (40%), and scoliosis (33%). Hearing impairment affected 61% of patients, while visual system involvement occurred in 17%.This study expands the clinical spectrum of CMT4D by documenting novel manifestations including severe bulbar dysfunction and respiratory involvement. These findings emphasize the importance of comprehensive assessment including swallowing evaluation, vocal cord examination, and pulmonary function testing in CMT4D patients, potentially impacting clinical management and prognosis.
Ofatumumab, an anti-CD20 monoclonal antibody, is a high-efficacy disease-modifying therapy for relapsing multiple sclerosis (RMS). Although pivotal trials demonstrated substantial benefits, real-world data are required to confirm treatment persistence, effectiveness, safety, and biological markers of response in routine clinical settings. This study evaluated the real-world outcomes of ofatumumab in patients treated at a specialised multiple sclerosis (MS) centre in southeastern Spain, including exploratory analyses of B cell kinetics, comorbidity burden using the Charlson Comorbidity Index (CCI), and ethnicity. A retrospective observational study was conducted in adults with MS initiating ofatumumab between December 2022 and December 2025, with ≥ 6 months of continuous therapy. Demographic, clinical, radiological, laboratory, and pharmacological data were extracted from electronic medical records. Statistical analyses encompassed Kaplan-Meier estimates. Eighty-seven patients were included (mean age 43 years; 75.9% female; 88.5% relapsing-remitting phenotype). Over a median 22-month follow-up, treatment persistence was 95.4%. Annualised relapse rate (ARR) declined from 0.48 pre-treatment to 0.03 on treatment. No evidence of disease activity (NEDA-3) was achieved in 93.1%, with no significant differences between treatment-naïve and previously treated patients. Sustained CD19+ B cell depletion was confirmed in all assessments. Immunoglobulin levels remained mostly stable. Ofatumumab was generally well tolerated: systemic injection-related reactions occurred in 29.9% and infections in 6.9%. Exploratory analyses showed no significant differences in relapse or magnetic resonance imaging outcomes by CCI category or ethnicity. In this Spanish real-world single-centre cohort, ofatumumab demonstrated high persistence, substantial suppression of inflammatory activity, and a favourable safety profile in routine clinical practice. Sustained B cell depletion aligned with clinical and radiological stability. These findings support the real-world effectiveness of ofatumumab across diverse patient profiles and complement evidence from pivotal trials. Further prospective studies with broader populations and longer follow-up are warranted to refine understanding of long-term outcomes and determinants of treatment response variability.
Differentiating epidural hematoma (EDH) from subdural hematoma (SDH) on non-contrast CT (NCCT) is clinically important but can be challenging when imaging features overlap. This study evaluated whether radiomic features combined with machine learning could improve discrimination between EDH and SDH. In this retrospective study, 175 adults with surgically confirmed EDH or SDH were analyzed. Conventional morphometric CT features and 107 radiomic features extracted from manually segmented hematomas were assessed. After LASSO-based feature selection, machine learning models were developed and evaluated using area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUCPR), and accuracy. Radiomic features showed slightly better discriminative performance than handcrafted morphometric features alone. Among the evaluated models, XGBoost achieved the best overall performance. The highest performance was obtained using the combined feature set of radiomic and morphometric variables, with an AUC of 0.75, an AUCPR of 0.70, and an accuracy of 0.74. Integrating radiomic and conventional morphometric CT features improves automated differentiation of EDH and SDH. Radiomics-assisted machine learning may serve as a useful decision-support tool in diagnostically challenging cases, although further external validation is needed before clinical implementation.
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by biallelic SMN1 variants, partially modulated by SMN2 copy number. Risdiplam, an oral SMN2 splicing modifier, has demonstrated efficacy in SMA. However, long-term adherence and persistence are key to sustaining benefit. We evaluated real-world adherence, persistence, and safety of risdiplam in a population-based cohort. This was a retrospective observational study including all genetically confirmed SMA type 1-3 patients treated with risdiplam in Spain between January 2020 and October 2025. Adherence was assessed using the proportion of days covered (PDC) from pharmacy dispensing records and the Morisky-Green questionnaire. Persistence was defined as time to permanent discontinuation or switch. Adverse events (AEs) were extracted from clinical records, and Kaplan-Meier analysis was used to estimate persistence probabilities. Fifty-three patients were included (38 adults, 15 pediatric patients); 5.7% had SMA type 1, 52.8% type 2, and 41.5% type 3. One pediatric patient with SMA type 1 was presymptomatic at treatment initiation. Median age at risdiplam initiation was 29 years (interquartile range [IQR] 17-42), and 35.8% had prior nusinersen exposure. Adherence was high: median PDC was 100% (IQR 100-100) at 12 months and throughout follow-up; all patients assessed with the Morisky-Green questionnaire (35/53, 66%) were adherent. At 12 months, 92.5% (49/53) remained on treatment (Kaplan-Meier estimate 94.3%; 95% CI 88.3-100.0). Persistence at 24 and 36 months was 87.8% and 80.1%, respectively; later estimates should be interpreted cautiously because of the limited number of patients at risk. Median treatment duration was 28.1 months. Nine patients (17.0%) discontinued treatment. Treatment-related AEs occurred in 4/53 patients (7.5%), including one pediatric case of leukocytoclastic vasculitis requiring permanent discontinuation. In this real-world population-based cohort, risdiplam showed very high adherence, favorable short- to mid-term persistence, and a favorable safety profile, supporting the feasibility of oral therapy in both pediatric and adult patients with SMA. Spinal muscular atrophy is a rare disease that leads to progressive muscle weakness and affects both children and adults. Risdiplam is an oral treatment that can be taken at home, which may be more convenient than other options that require repeated hospital visits or invasive procedures. In this study, we examined how well patients followed this treatment and how long they continued taking it in everyday clinical practice at a specialized center. We included a broad group of patients and followed them over time to better understand how the treatment performs outside clinical trials. We found that most patients took the medication consistently and continued treatment for prolonged periods. Only a small number stopped treatment, mainly due to side effects, lack of perceived benefit, or personal decisions. Overall, the treatment was well tolerated, with most side effects being mild, although one patient experienced a serious skin reaction that required discontinuation of treatment. These findings suggest that risdiplam is a practical long-term option in real-life settings, particularly because it can be taken at home. They also highlight that continuing treatment over time may reflect how patients and clinicians perceive its benefits and risks in daily practice.
Cerebral amyloid angiopathy (CAA), a cerebral small vessel disease characterized by vascular amyloid deposition, presents with heterogeneous imaging features, but the biological mechanisms underlying hemorrhagic markers remain unclear. We assessed hemorrhage patterns in CAA to determine their associations with amyloid burden and related imaging markers. Sixty-two patients with probable CAA underwent Pittsburgh compound B-positron emission tomography and structural magnetic resonance imaging. Participants were classified by dominant hemorrhagic pattern: lobar cerebral microbleed-dominant (n=31), cortical superficial siderosis-dominant (n=17), and nondominant (n=14). Global cortical amyloid burden was quantified as Pittsburgh compound B distribution volume ratio. White matter hyperintensity volume and high-degree centrum semiovale-enlarged perivascular spaces were assessed. Associations were tested using age- and sex-adjusted regression models. Global Pittsburgh compound B distribution volume ratio was significantly higher in the cerebral microbleed-dominant (1.40±0.23) and cortical superficial siderosis-dominant (1.45±0.27) groups than nondominant group (1.20±0.17; P=0.007 and P=0.006, respectively), and these associations remained independent after adjustment (odds ratio [OR], 1.8 [95% CI, 1.1-2.8]; P=0.009 and OR, 1.6 [95% CI, 1.1-2.5]; P=0.020). Compared with the nondominant group, high-degree centrum semiovale-enlarged perivascular spaces were independently associated with both cerebral microbleed-dominant (OR, 9.3 [95% CI, 1.6-52]; P=0.011) and cortical superficial siderosis-dominant (OR, 10 [95% CI, 1.6-62]; P=0.013). In the full cohort, Pittsburgh compound B distribution volume ratio was independently associated with high-degree centrum semiovale-enlarged perivascular spaces (P=0.016) and white matter hyperintensity volume (P=0.049). Findings were unchanged in sensitivity analyses, adjusting for intracerebral hemorrhage. Amyloid burden in CAA is associated with hemorrhage-dominant patterns, high-degree centrum semiovale-enlarged perivascular spaces, and greater WMH volume. These findings support a close link between vascular amyloid deposition and downstream vascular brain injury, underscoring its relevance as a therapeutic target in CAA.
To document the occurrence of radiation-induced vasculopathy as a delayed complication in the treatment of head and neck cancers. We present the case history and review the imaging findings in a 51-year-old man with a history of nasopharyngeal cancer, treated with radiotherapy 10 years prior to admission, who presented with a stroke syndrome. The pathophysiology, clinical and imaging features, and development of collateral pathways due to radiation-induced vasculopathy are discussed. The patient had occlusion of the right and left common carotid arteries, as well as of the left internal carotid artery and the right subclavian artery. The proximally occluded vessels ended in tapered "stumps". CT angiography with Maximum Intensity Projection (MIP) and 3D Volume Rendering Technique (VRT) displayed the collateralisation of the occluded arteries via the thyrocervical trunks and ascending cervical arteries. Radiation therapy for head and neck cancer is associated with a significantly increased incidence of radiation-induced vasculopathy and cerebrovascular ischaemic events. Carotid stump syndrome should be considered as a rare but serious cause of recurrent stroke and stroke-like symptoms.
Guillain-Barré syndrome (GBS) is an acute polyneuropathy with an incidence of 0.69 per 100 000 children annually. Electrophysiological variants vary geographically, with the axonal subtype more common in parts of Asia; however, pediatric data from Latin America remains limited, underscoring the need for regional studies to inform clinical management. This retrospective cohort study examined the incidence, electrophysiological variants, and clinical outcomes of children under 16 years hospitalized for GBS in an intensive care unit serving approximately 8% of the Chilean population in Santiago (2013-2023). Twenty-one patients (median age: 10 years) were included, with 11 presenting with axonal involvement and 8 with demyelinating features. Four patients required mechanical ventilation-2 in the axonal and 2 in the demyelinating group (median = 22 days, IQR = 9-43)-and 2 patients required tracheostomy. The predominance of the axonal subtype highlights critical considerations for early prognostication, critical care planning, and future inclusion in clinical trials.
Stroke disproportionately affects socioeconomically deprived populations, which leads to poor outcomes in disadvantaged groups. This study aimed to assess associations of socioeconomic status (SES) and long- and short-term functional outcome after stroke in Mongolia. A prospective, population-based incidence stroke study was performed in Ulaanbaatar, Mongolia, between 2019 and 2020. SES indicators were average household family income and highest level of education attainment. The primary outcome was an unfavorable change in functional outcome on the binary modified Rankin Scale (scores 3-6 versus 0-2) measured at 28, 90, and 365 days. Logistic regression was used to analyze the association of SES and outcomes. Generalized linear mixed-effects models were used to assess associations according to repeated measures of modified Rankin Scale over 12 months, and a mediation analysis aimed to determine the mechanism by which SES affects outcome. A total of 2205 patients (mean age, 58.0±12.8 years; 1330 [60.3%] men) were included. Patients with high-level family income were less likely to have unfavorable short-term (adjusted odds ratio, 0.36 [95% CI, 0.26-0.49]) and long-term (adjusted odds ratio, 0.41 [95% CI, 0.30-0.58]) outcomes. Patients with higher SES experience faster recovery from disability within 1 year, and patients with intracerebral hemorrhage have the slowest recovery rate among the stroke subtypes. Mediation analysis revealed that the impact of SES on functional outcome was mostly direct rather than through other mediators. Patients with higher SES exhibit a better recovery pattern up to 1 year after stroke. SES directly and significantly influenced stroke outcome.
Migraine has been linked to an increased risk of glaucoma, and our study aims to assess the temporal association between calcitonin gene-related peptide inhibitors (CGRPi) and the risks of glaucoma in individuals with migraine. This multinational retrospective cohort study included adults diagnosed with migraine who received migraine preventive medications in 2018-2024. Participants were categorized into the CGRPi group (erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant, or rimegepant) and non-CGRPi group (valproate, topiramate, flunarizine, candesartan, lisinopril, metoprolol, propranolol, nadolol, amitriptyline, and venlafaxine). Crossovers were not allowed, and the non-CGRPi group included only individuals who never used CGRPi. The CGRPi and non-CGRPi groups were propensity score matched in a 1:1 ratio and were followed for up to 3 years to monitor the occurrence of incident glaucoma. The Cox proportional hazards model was used to compare the risk of glaucoma between CGRPi and non-CGRPi users, with results reported as hazard ratios (HRs) and 95% CIs. A total of 73,644 individuals were included in the final analysis. Compared with non-CGRPi users, CGRPi users experience a lower risk of glaucoma development (HR 0.75; 95% CI 0.61-0.92) within 3 years since its first prescription. Individuals using CGRPi also exhibit a reduced risk of glaucoma compared with those using topiramate (HR 0.73; 95% CI 0.59-0.90), valproate (HR 0.54; 95% CI 0.35-0.83), propranolol (HR 0.76; 95% CI 0.59-0.98), metoprolol (HR 0.76; 95% CI 0.59-0.98), lisinopril (HR 0.49; 95% CI 0.38-0.62), amitriptyline (HR 0.69; 95% CI 0.54-0.89), and venlafaxine (HR 0.68; 95% CI 0.50-0.91). In the analysis that further classified participants based on the specific CGRPi used, only users of monoclonal antibody CGRPi show a reduced risk of glaucoma compared with non-CGRPi users (HR 0.77; 95% CI 0.61-0.98). The reduced risk of glaucoma associated with CGRPi is also observed in older adults, women, and those with chronic migraine or migraine without aura. Among adults with migraine receiving preventive treatment, systemic use of CGRPi, particularly monoclonal antibody CGRPi, is associated with a reduced risk of glaucoma compared with the use of other migraine preventive medications. This is a Class II study demonstrating that CGRPi users with migraine have a lower risk of incident glaucoma when compared with non-CGRPi users with migraine.
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Infants with severe neuromuscular disorders, presenting a birth, are often unable to move, communicate, breathe, and feed. Unlike infants with severe birth asphyxia and cerebral palsy, these neuromuscular conditions are often associated with presumed normal cognition. Supporting these very severely affected infants and maintaining life through medical intervention or re-orientating care to palliation is often debated, and decision-making can be extremely challenging. Although guidelines exist to help navigate this process (Nuffield Council of Bioethics and Royal Collage of Paediatrics guidelines) deciding what is in the child's best interest is fraught with difficulties. This article explores some of the unique issues that arise in infants with severe neuromuscular conditions and illustrates the challenges in determining best interest for these patients, using some of the cases in the legal literature and the authors personal experience.
Adherence to secondary prevention therapies after ischemic stroke or transient ischemic attack is often suboptimal, and the clinical implications of adherence patterns remain unclear. This study identified adherence trajectories to statins and antithrombotic agents and evaluated their associations with lipid control and cardiovascular outcomes. Using the Chang Gung Research Database linked to Taiwan's population claims data, we identified patients with first-ever acute ischemic stroke/transient ischemic attack between 2012 and 2018 who survived ≥1 year and initiated secondary prevention. Monthly adherence was measured by proportion of days covered and classified using group-based multitrajectory modeling. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, and myocardial infarction; secondary outcomes included individual components and all-cause death. Among 13 299 eligible patients (mean age, 65.6 years; 60.3% men), 4 adherence trajectories were identified: dual high adherence (46.7%), antithrombotic-only adherence (35.1%), early dual discontinuation (12.2%), and gradual dual decline (6.0%). Dual high adherence achieved the greatest low-density lipoprotein cholesterol reduction (-24.3%) and lowest mortality rate. Early dual discontinuation was associated with higher risks of the composite outcome (adjusted hazard ratio [aHR], 1.57 [95% CI, 1.31-1.88], recurrent ischemic stroke/systemic embolism (aHR, 1.60 [95% CI, 1.31-1.95]), myocardial infarction (aHR, 1.48 [95% CI, 1.02-2.14]), and all-cause death (aHR, 1.56 [95% CI, 1.36-1.79]). Poor adherence had greater adverse impact among patients with baseline low-density lipoprotein cholesterol ≥100 mg/dL, younger adults, and men. Adherence trajectories were strongly associated with low-density lipoprotein cholesterol and major cardiovascular outcomes. Sustained dual adherence conferred substantial protection, whereas early discontinuation markedly increased recurrent ischemic and mortality risks.
Epilepsy is one of the most common neurological disorders globally. While medications, surgical interventions, and dietary changes can be successful in controlling seizures, a subset of individuals experience refractory epilepsy and are at increased risk for sudden unexpected death in epilepsy (SUDEP). Efforts to provide a detection system using devices have been successful at identifying seizures once they start, but there are no devices or systems on the market that predict seizures. The purpose of this systematic review (PROSPERO ID: CRD42024444250) is to determine non-invasive physiologic and environmental biomarkers that can be used to forecast seizures in pediatric epilepsy patients. A systematic search of relevant literature was conducted in PubMed, Web of Science, CINAHL Ultimate, and EMBASE in August 2023. Articles were reviewed by two investigators in a two-step process. Data extraction occurred using two independent extractors to identify study characteristics, patient characteristics, and forecasting results. Evidence quality was evaluated by two investigators using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Eleven observational cohort studies were included and cardiovascular biomarkers using electrocardiogram (ECG) measurement were most commonly used. Pre-ictal anticipation algorithm times ranged from 21.8 s to 32 min, while correlational studies observed cardiovascular biomarker changes 3.59 s to 40 min before seizures. This systematic review provides a comprehensive overview of the current evidence for seizure forecasting. However, the evidence in 9/11 of reviewed studies were rated as either low or very low certainty using the GRADE tool due to methodological flaws, risk of bias, inconsistent results, and indirect or sparse evidence. There are ongoing opportunities to build on our findings, including further testing of cardiovascular biomarkers with other physiologic and environmental factors, larger sample size studies, and a precision medicine approach to tailoring algorithms and biomarker measurements to individual patients. PROSPERO (ID: CRD42024444250).
Multimodal imaging has expanded treatment for patients with acute ischemic stroke with large vessel occlusion. Blood-brain barrier (BBB) disruption measured in the ischemic core is associated with hemorrhagic transformation. However, the associations between core BBB disruption (cBBBD) and baseline clinical/imaging variables, as well as 3-month outcome, have not been explored. This is a retrospective multicenter analysis of consecutive anterior circulation patients with acute ischemic stroke with large vessel occlusion, presenting over a 4-year time period, who were transferred from a primary to a comprehensive stroke center for possible endovascular therapy, with magnetic resonance imaging that included perfusion-weighted imaging before transfer. Magnetic resonance imaging scans were processed using RAPID software to generate penumbral imaging variables. Perfusion-weighted images were processed to detect and quantify contrast leakage; cBBBD was calculated as the average of all leaky voxels in the ischemic core. Poor functional outcome was defined as a modified Rankin Scale score of >2 at 3 months. Linear regression was used except for the outcome, which used logistic regression, controlling for age, stroke severity, and baseline functional status. Out of 411 patients transferred for endovascular therapy, 291 were included in this analysis with a median age of 74 years; 49% were female patients. The median National Institutes of Health Stroke Scale score was 13, the mean core volume was 32.3 mL, and the mean cBBBD was 2.1%. 71% of patients underwent endovascular therapy. Admission National Institutes of Health Stroke Scale score (P<0.001) and glucose level (P=0.033) were independently correlated with cBBBD. All imaging variables correlated strongly with cBBBD (P<0.001). The strongest correlation was 0.50, observed between cBBBD and mismatch ratio (r2=0.254). Increasing cBBBD was independently associated with poor functional outcome (adjusted odds ratio, 1.16 [CI, 1.03-1.32]; P=0.019; n=279), indicating that for every 1% increase in cBBBD, the odds of having a poor functional outcome increase by 16%. In acute ischemic stroke with large vessel occlusion, disruption of the BBB in the core lesion is independently associated with clinical outcome. cBBBD represents a new imaging profile for acute stroke that may help guide treatments.
Chronic spine pain is linked to self-reported cognitive complaints. However, objective markers are lacking. The 90-s Continuous Visual Attention Test (CVAT) quantifies key attention subdomains: reaction time (RT, alertness), RT variability (VRT, sustained attention), omission errors (focused attention) and commission errors (impulsivity). This study aimed to identify which specific attentional subdomains, measured by the CVAT, are impaired in adults with chronic spine pain. This prospective case-control study included 84 adults with chronic lumbar/cervical pain (≥ 3 months) and 118 healthy controls. A MANCOVA tested group differences on CVAT variables, controlling for age and sex, followed by Bonferroni-corrected ANCOVAs. To isolate cognitive variability from general processing speed, the coefficient of variability (VRT/RT) was also analysed. Logistic regression assessed the predictive power of CVAT indices for pain status. The MANCOVA showed a significant group effect (Pillai's Trace = 0.46, F(4,195) = 41.43, p < 0.001). Patients exhibited impairments in all measures p < 0.001 (η2 = 0.093-0.44). The VRT deficit persisted when using VRT/RT. Logistic regression identified VRT as the strongest predictor of chronic spine pain (χ2(1) = 147.53, p < 0.001), correctly classifying 86.6% of participants. This finding remained when using VRT/RT (χ2(1) = 130.55, p < 0.001; 82.7% accuracy). Patients with chronic spine pain demonstrate attentional deficits, with sustained attention instability (VRT and VRT/RT) as the most robust marker. The CVAT detects this impairment, offering a practical tool for clinical assessment to inform treatment and monitor cognitive function in pain management. III (prospective case-control). A brief, 90-s computerized attention test provides an objective, clinic-ready screen for sustained-attention instability in spine pain patients. Identifying cognitive vulnerability at the point of care can inform perioperative counselling, driving/work-safety guidance and rehabilitation planning, and it may help monitor treatment response alongside pain metrics, offering a noninvasive, nonpharmacologic complement to standard pain assessment.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by inflammation, areas of demyelination and axonal loss called plaques, recruitment of lymphocytes and monocytes, and bursts of focal blood-brain barrier leakage. Treatment strategies for MS focus on delaying disease progression and increasing patients' quality of life. However, most therapies have inconsistent efficacies and are associated with various side effects. Recently, long non-coding RNAs have been found to play a major role in the pathogenesis and development of several diseases. Several long non-coding RNAs have been correlated with MS. We focus on the role of AFAP1-AS1 in regulating the function of M2 macrophages, one of the immune cells believed to attenuate MS. Assessing this long non-coding RNA will improve our understanding of the molecular mechanics of immune cells in MS. We observe the impact of AFAP1-AS1 silencing in M2 macrophages on essential effector and regulatory proteins like MMP9, CCL5 and CXCL10 in MS patients receiving different treatments (Fingolimod, Interferon beta-1a, Interferon beta-1b, Teriflunomide or Dimethyl fumarate). Our results reported an upstream regulatory effect of AFAP1-AS1 on MMP9, CCL5, and CXCL10 in differently treated patients. By measuring the levels of proteins upon silencing of AFAP1-AS1, it was confirmed that this lncRNA has varying effects on the expression of these proteins depending on the treatment the patient is undergoing. These data shed light on the potential role of manipulating the anti-inflammatory activity of M2 cells making it a possible therapeutic target for certain MS patients.
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Chronic total occlusion (CTO) of the internal carotid artery relies on collateral circulation, often involving retrograde ophthalmic artery (OA) flow. However, the differential vascular patterns of the retina and choroid associated with this hemodynamic alteration remain unclear. We aimed to characterize these alterations using optical coherence tomography (OCT) and OCT angiography (OCTA). This multicenter cross-sectional study enrolled patients with CTO, severe carotid artery stenosis (CAS), and controls. OA flow direction was verified by digital subtraction angiography. Swept-source OCT/OCTA was used to quantify vessel length density (VLD) in the superficial and deep vascular complexes and choroidal parameters (vascular volume [CVV] and vascular index [CVI]). A total of 216 patients with CTO (419 eyes), 192 with CAS (376 eyes), and 247 controls (467 eyes) were analyzed. Retinal VLD was significantly lower in CTO eyes than in CAS and control eyes (all p < 0.05). In contrast, choroidal parameters were relatively preserved in CTO compared with CAS (both p < 0.05). Within the CTO group, ipsilateral eyes showed reduced retinal VLD compared with contralateral eyes (both p < 0.001), without significant choroidal differences. Among ipsilateral CTO eyes, retrograde OA flow was associated with further even lower retinal VLD but significantly higher CVV and CVI compared with antegrade OA flow (all p < 0.05). Retrograde OA flow in CTO is associated with divergent ocular vascular profiles, characterized by more severe retinal microvascular loss and paradoxical choroidal vascular expansion. These findings highlight the distinct hemodynamic sensitivities of the retinal and choroidal circulations and support OCTA-derived metrics as noninvasive biomarkers for collateral-dependent perfusion.
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