Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study.

Diabetes is recognized as a risk factor for cognitive decline, but the underlying mechanisms remain elusive. We aimed to identify the metabolic pathways altered in diabetes-associated cognitive decline (DACD) using untargeted metabolomics. We conducted liquid chromatography-mass spectrometry-based untargeted metabolomics to profile serum metabolite levels in 100 patients with type 2 diabetes (T2D) (54 without and 46 with DACD). Multivariate statistical tools were used to identify the differentially expressed metabolites (DEMs), and enrichment and pathways analyses were used to identify the signaling pathways associated with the DEMs. The receiver operating characteristic (ROC) analysis was employed to assess the diagnostic accuracy of a set of metabolites. We identified twenty DEMs, seven up- and thirteen downregulated in the DACD vs. DM group. Chemometric analysis revealed distinct clustering between the two groups. Metabolite set enrichment analysis found significant enrichment in various metabolite sets, including galactose metabolism, arginine and unsaturated fatty acid biosynthesis, citrate cycle, fructose and mannose, alanine, aspartate, and glutamate metabolism. Pathway analysis identified six significantly altered pathways, including arginine and unsaturated fatty acid biosynthesis, and the metabolism of the citrate cycle, alanine, aspartate, glutamate, a-linolenic acid, and glycerophospholipids. Classifier models with AUC-ROC > 90% were developed using individual metabolites or a combination of individual metabolites and metabolite ratios. Our study provides evidence of perturbations in multiple metabolic pathways in patients with DACD. The distinct DEMs identified in this study hold promise as diagnostic biomarkers for DACD patients.

Rescue Stent Placement for Acute Ischemic Stroke with Large Vessel Occlusion Refractory to Mechanical Thrombectomy: A Multiethnic Middle Eastern/African/Asian Cohort.

PURPOSE: To investigate the safety and effectiveness of rescue stent placement in patients who experienced acute stroke in whom mechanical thrombectomy failed. METHODS: This was a retrospective review of a multiethnic stroke database. After stent placement, an aggressive antiplatelet protocol was followed with glycoprotein IIb/IIIa infusion. The primary outcomes were incidence of intracerebral hemorrhage (ICH), recanalization score, and favorable prognosis (modified Rankin score ≤ 2) at 90 days. A comparison was made between patients from the Middle East and North Africa (MENA) region and those from other regions. RESULTS: Fifty-five patients were included, with 87% being men. The mean age was 51.3 years (SD ±11.8); 32 patients (58%) were from South Asia, 12 (22%) from MENA, 9 (16%) from Southeast Asia, and 2 (4%) from elsewhere. Successful recanalization (modified Thrombolysis in Cerebral Infarction score = 2b/3) was achieved in 43 patients (78%), and symptomatic ICH occurred in 2 patients (4%). A favorable outcome at 90 days was seen in 26 of the 55 patients (47%). Apart from significantly older age-mean, 62.8 years (SD ±13; median, 69 years) versus 48.1 years (SD ±9.3; median, 49 years)-and coronary artery disease burden-4 (33%) versus 1 (2%) (P < .05), patients from MENA had risk factors, stroke severity, recanalization rates, ICH rates, and 90-day outcomes similar to those from South and Southeast Asia. CONCLUSION: Rescue stent placement showed good outcomes and a low risk of clinically significant bleeding in a multiethnic cohort of patients from MENA and South and Southeast Asia, similar to that in published literature.

Blood-Based Proteomic Profiling Identifies Potential Biomarker Candidates and Pathogenic Pathways in Dementia.

Dementia is a progressive and debilitating neurological disease that affects millions of people worldwide. Identifying the minimally invasive biomarkers associated with dementia that could provide insights into the disease pathogenesis, improve early diagnosis, and facilitate the development of effective treatments is pressing. Proteomic studies have emerged as a promising approach for identifying the protein biomarkers associated with dementia. This pilot study aimed to investigate the plasma proteome profile and identify a panel of various protein biomarkers for dementia. We used a high-throughput proximity extension immunoassay to quantify 1090 proteins in 122 participants (22 with dementia, 64 with mild cognitive impairment (MCI), and 36 controls with normal cognitive function). Limma-based differential expression analysis reported the dysregulation of 61 proteins in the plasma of those with dementia compared with controls, and machine learning algorithms identified 17 stable diagnostic biomarkers that differentiated individuals with AUC = 0.98 ± 0.02. There was also the dysregulation of 153 plasma proteins in individuals with dementia compared with those with MCI, and machine learning algorithms identified 8 biomarkers that classified dementia from MCI with an AUC of 0.87 ± 0.07. Moreover, multiple proteins selected in both diagnostic panels such as NEFL, IL17D, WNT9A, and PGF were negatively correlated with cognitive performance, with a correlation coefficient (r2) ≤ -0.47. Gene Ontology (GO) and pathway analysis of dementia-associated proteins implicated immune response, vascular injury, and extracellular matrix organization pathways in dementia pathogenesis. In conclusion, the combination of high-throughput proteomics and machine learning enabled us to identify a blood-based protein signature capable of potentially differentiating dementia from MCI and cognitively normal controls. Further research is required to validate these biomarkers and investigate the potential underlying mechanisms for the development of dementia.

Stroke in Airplane Passengers: A Study from a Large International Hub.

INTRODUCTION: Stroke in air travelers is being increasingly recognized. We report on stroke among passengers arriving at or transiting through a busy air travel hub. METHODS: The stroke database of the sole tertiary care center for stroke in a large busy international hub was interrogated. Demographic data of transit passengers, their stroke risk factors, stroke severity, National Institutes of Health Stroke Scale (NIHSS), acute stroke interventions, discharge status and outcome utilizing the Modified Raking scale (mRS) were retrieved and compared between passengers and non-passenger controls. RESULTS: Forty-three flight-related stroke patients were compared to 2564 non-passenger stroke patients. The mean age in the flight-related stroke group was 59.53±10.83 years, 30/43 (69.8%) were males. The stroke subtypes were ischemic in 30 (69.8%) patients, hemorrhagic in 9 (20.9%), and transient ischemic attack in 3 (7.0%), with one cerebral sinus venous thrombosis (2.3%). The mean NIHSS score was 7.79±6.44 in passengers, demonstrating moderate severity. Ten patients (23.3%) received thrombolysis, one (2.3%) received thrombectomy, and one (2.3%) received both thrombolysis and thrombectomy. Outcomes, 54.8% had a good outcome (mRS 0-2), and 45.2% had dependence/death (mRS 3-6). CONCLUSION: Air passengers with stroke were found to be older with more severe strokes and a higher probability of receiving acute stroke treatment compared to non-passengers. Increased awareness with appropriate and timely recognition and triaging of transit passengers with stroke is warranted.

Sex-Specific Differences in Short-Term and Long-Term Outcomes in Acute Stroke Patients from Qatar.

BACKGROUND: Sex differences may determine presentation, utility of treatment, rehabilitation, and occurrences of major adverse cardiovascular events (MACEs) in acute stroke (AS). OBJECTIVE: The purpose of the study was to evaluate the short-term prognosis and long-term outcomes in MACEs in Qatari nationals admitted with AS. METHODS: All AS patients admitted between January 2014 and February 2019 were included. We evaluated the preadmission modified Rankin scale (mRS) score, etiology and severity of symptoms, complications, and functional recovery at discharge and 90 days. MACEs were recorded for 5 years. RESULTS: There were 891 admissions for AS (mean age 64.0 ± 14.2 years) (male, n = 519 [mean age ± SD 62.9 ± 14.1 years]; female, n = 372 [mean age ± SD 65.6 ± 14.2 years] p = 0.005). There were no differences in the preadmission mRS and severity of symptoms as measured on National Institute of Stroke Scale. At discharge, the outcome was better (mRS 0-2) in men (57.8 vs. 46.0%), p = 0.0001. This difference persisted at the 90-day follow-up (mRS 0-2, male 69.4% vs. female 53.2%, p = 0.0001). At the 90-day follow-up, more women died (total deaths 70; women 38 [10.2%] versus men 32 [6.2%], p = 0.03). MACEs occurred in 25.6% (133/519) males and 30.9% (115/372) females over the 5-year follow-up period (odds ratio 0.77, 95% confidence interval 0.57-1.0, p = 0.83). CONCLUSIONS: Female patients have a poor short-term outcome following an AS when corrected for age and comorbidities. While our study cannot explain the reasons for the discrepancies, higher poststroke depression and social isolation in women may be important contributory factors, and requires further studies are required to confirm these findings.

Stroke Mimics: A five-year follow-up study from the Qatar Stroke Database.

BACKGROUND AND PURPOSE: Mimics comprise a third of patients presenting with an acute stroke. There is limited information on their natural history. METHODS: We evaluate long term major cardiovascular events (MACE) in stroke mimics in a prospective database from Qatar. RESULTS: Between Feb 2014 and Jan 2019, 481 patients (male: 238; female: 243) mean age 57.5 years (±18.0), with 399 (83%) medical mimics and 82 (17%) functional mimics were evaluated. Imaging revealed previous old stroke in 26.6% and small vessel disease in 5%. MACE occurred in 57 (11.9%) and there were 31 deaths (6.4%) with majority of deaths (5.6%) from cardiovascular causes. MACE was significantly higher in patients with previous stroke, p < 0.0001), coronary artery disease, p = 0.002), diabetic, p = 0.01), and hypertensive on admission, p < 0.0001. MACE were also significantly higher in patients where imaging showed a previous stroke, p = 0.006). CONCLUSION: The occurrence of MACE during follow-up suggests that patients with existing vascular disease require aggressive management of vascular risk factors.

Embolic Pattern of Stroke Associated with Cardiac Wall Motion Abnormalities; Narrowing the Embolic Stroke of Undetermined Source Category.

BACKGROUND: There is ambiguity regarding the role of left ventricle wall motion abnormalities (LVWMAs) as a potential cardioembolic source in patients, who satisfy embolic stroke of undetermined source (ESUS) criteria. METHODS AND RESULTS: We analyzed prospectively collected data in 345 acute stroke patients, 185 (53.6%) stroke with atrial fibrillation (SwAF), and 160 (46.4%) stroke with LVWMA. LVWMA were younger (P = .003), had significantly higher frequency of stroke risk factors and lower ejection fraction (P < .001). No significant difference was found between the stroke pattern in SwAF and LVWMA except focal cortical, cortical-subcortical lesions were more frequent in LVWMA (P = .002). Mean wall motion score index (WMSI) was 1.523 (range 1.05-2.71) without any correlation between the severity of WMSI and multiple strokes (P = .976). In subgroup analyses vertical basal WMSI (P = .030) and vertical mid cavity WMSI (P = .010) was significantly related to branch arterial stroke. LVWMA 94 (65%) patients were on antiplatelet/anticoagulation compared to 47 (52.4%) with atrial fibrillation (AF), with no significant difference in stroke recurrence during 4 years follow-up (P = .15). CONCLUSIONS: Patients with LVWMA who satisfy ESUS criteria, have stroke pattern on diffusion-weighted magnetic resonance imaging and risk of stroke recurrence similar to AF-related stroke despite being on appropriate antiplatelet medications. Further studies with anticoagulation therapy may be required in this group of patients to improve the high risk of recurrent stroke.

Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke: South Asian Experience.

BACKGROUND: The randomized trials showed improved outcome and reduced mortality in malignant middle cerebral artery (MMCA) undergoing Decompressive hemicraniectomy (DHC) within 48 hours of stroke onset. Despite high prevalence of stroke, especially in younger individuals, high and short-term mortality from stroke in South Asian and Middle East, there is little published data on DHC in patients with MMCA stroke. METHODS: This is a retrospective, multicenter cross-sectional study to measure outcome following DHC using the modified Rankin Scale (mRS) and dichotomized as favorable (mRS ≤ 4) or unfavorable (mRS > 4), at 3 months. RESULTS: In total, 137 patients underwent DHC. At 90 days, mortality was 16.8%; 61.3% of patients survived with an mRS of 4 or less and 38.7% had an mRS greater than 4. Age (55 years), diabetes (P = .004), hypertension (P = .021), pupillary abnormality (P = .048), uncal herniation (P = .007), temporal lobe involvement (P = .016), additional infarction (MCA + anterior cerebral artery, posterior cerebral artery) (P = .001), and infarction growth rates (P = .025) were significantly higher in patients with unfavorable prognosis in univariate analysis. Multivariate analysis showed age, additional infarction, septum pellucidum deviation greater than 1 cm, and uncal herniation to be associated with a significantly poor prognosis. Time to surgery had no impact on outcome (P = .109). CONCLUSIONS: Similar to the results of the studies from the West, DHC Improves functional outcome in predominantly South Asian patients with MMCA Stroke.

Prolonged Stay of Stroke Patients in the Emergency Department May Lead to an Increased Risk of Complications, Poor Recovery, and Increased Mortality.

BACKGROUND AND AIM: Following an acute stroke (AS), patients are at an increased risk of developing complications that may affect prognosis. With overcrowding in the emergency department (ED), patients stay longer hours to days before transfer to a proper stroke ward. The aim of this study was to evaluate the effect of increasing length of stay (LOS) in the ED on the risk of stroke-related complications. METHODS: We analyzed data from our stroke registry of patients admitted with AS during 2014. Stay in ED was divided into 2 groups: less than 8 hours and more than 8 hours. Data regarding demographics, stroke type, severity of stroke, ED (LOS) in hours, total LOS in hospital, number and types of complications, and prognosis were collected. RESULTS: Mean age was 54.8 years and 78.9% were males (total n = 894). Prior to ward admission, 265 (29.5%) patients remained in the ED for less than 8 hours and 629 (70.4%) remained for more than 8 hours. There was no significant difference in comorbidities or the severity of stroke at admission between the 2 groups. An ED LOS of less than 8 hours was associated with reduced risk of complications (14.3% versus 19.2%, P = .06), reduced LOS in hospital, better prognosis at discharge (72.5% versus 57.6% had modified Rankin Scale of ≤2, P = .001) and at 90 days (89% versus 78.8%, P = .007) and lower in-hospital mortality (1.5% versus 5.4 %, P = .004). CONCLUSION: Delays in transferring AS patients from the ED may lead to an increase in complications resulting in an increased LOS and slower recovery.

Stroke in Qatar: a decade of insights from a national registry.

BACKGROUND: Stroke is a major cause of death and disability worldwide and presents a significant burden on healthcare systems. This retrospective study aims to analyze the characteristics and outcomes of stroke patients admitted to Hamad General Hospital (HGH) stroke service in Qatar from January 2014 to July 2022. METHODS: The medical records of 15,859 patients admitted during the study period were analyzed. The data collected included patient demographics, stroke types, admission location, procedures performed, mortality rates, and other clinical characteristics. RESULTS: Of the total cohort, 70.9% were diagnosed with a stroke, and 29.1% were diagnosed with stroke mimics. Of the stroke patients, 85.3% had an ischemic stroke, and 14.7% had a hemorrhagic stroke. Male patients below 65 years old (80.2%) and of South Asian ethnicity (44.6%) were the most affected. The mortality rate was 4.6%, significantly higher for hemorrhagic stroke than ischemic stroke (12.6% vs. 3.2%). Female patients had a higher stroke-related mortality rate than male patients (6.8% vs. 4%). The thrombolysis rate was 9.5%, and the thrombectomy rate was 3.4% of the ischemic stroke cohort. The mean door-to-needle time for thrombolysis was 61.2 minutes, and the mean door-to-groin time for thrombectomy was 170 minutes. Stroke outcomes were good, with 59.3% of patients having favorable outcomes upon discharge (mRS ≤2), which improved to 68.2% 90 days after discharge. CONCLUSION: This study provides valuable insights into stroke characteristics and outcomes in Qatar. The findings suggest that stroke mortality rates are low, and favorable long-term disability outcomes are achievable. However, the study identified a higher stroke-related mortality rate among female patients and areas for improvement in thrombolysis and thrombectomy time.

Clinical diagnostic reference levels in neuroradiology based on clinical indication.

This study focuses on patient radiation exposure in interventional neuroradiology (INR) procedures, a field that has advanced significantly since its inception in the 1980s. INR employs minimally invasive techniques to treat complex cerebrovascular diseases in the head, neck, and spine. The study establishes diagnostic reference levels (DRLs) for three clinical indications (CIs): stroke (S), brain aneurysms (ANs), and brain arteriovenous malformation (AVM). Data from 209 adult patients were analyzed, and DRLs were determined in terms of various dosimetric and technical quantities. For stroke, the established DRLs median values were found to be 78 Gy cm2, 378 mGy, 118 mGy, 12 min, 442 images, and 15 runs. Similarly, DRLs for brain AN are 85 Gy cm2, 611 mGy, 95.5 mGy, 19.5, 717 images, and 26 runs. For brain AVM, the DRL's are 180 Gy cm2, 1144 mGy, 537 mGy, 36 min, 1375 images, and 31 runs. Notably, this study is unique in reporting DRLs for specific CIs within INR procedures, providing valuable insights for optimizing patient safety and radiation exposure management.

Incidence, clinical features, and outcomes of posterior circulation ischemic stroke: insights from a large multiethnic stroke database.

Background: Posterior cerebral circulation ischemic stroke (PCS) comprises up to 25% of all strokes. It is characterized by variable presentation, leading to misdiagnosis and morbidity and mortality. We aim to describe PCS in large multiethnic cohorts. Methods: A retrospective review of a large national stroke database from its inception on the 1st of January 2014 till 31 December 2020. Incidence per 100,000 adult population/year, demographics, clinical features, stroke location, and outcomes were retrieved. We divided the cohort into patients from MENA (Middle East and North Africa) and others. Results: In total, 1,571 patients were identified. The incidence of PCS was observed to be rising and ranged from 6.3 to 13.2/100,000 adult population over the study period. Men were 82.4% of the total. The mean age was 54.9 ± 12.7 years (median 54 years, IQR 46, 63). MENA patients comprised 616 (39.2%) while others were 954 (60.7%); of these, the majority (80.5%) were from South Asia. Vascular risk factors were prevalent with 1,230 (78.3%) having hypertension, 970 (61.7%) with diabetes, and 872 (55.5%) having dyslipidemia. Weakness (944, 58.8%), dizziness (801, 50.5%), and slurred speech (584, 36.2%) were the most commonly presenting symptoms. The mean National Institute of Health Stroke Score (NIHSS) score was 3.8 ± 4.6 (median 3, IQR 1, 5). The overall most frequent stroke location was the distal location (568, 36.2%). The non-MENA cohort was younger, less vascularly burdened, and had more frequent proximal stroke location (p < 0.05). Dependency or death at discharge was seen in 39.5% and was associated with increasing age, and proximal and multilocation involvement; while at 90 days it was 27.4% and was associated with age, male sex, and having a MENA nationality (p < 0.05). Conclusion: In a multiethnic cohort of posterior circulation stroke patients from the MENA region and South Asia, we noted a rising incidence over time, high prevalence of vascular risk factors, and poor outcomes in older men from the MENA region. We also uncovered considerable disparities between the MENA and non-MENA groups in stroke location and outcome. These disparities are crucial factors to consider when tailoring individualized patient care plans. Further research is needed to thoroughly investigate the underlying reasons for these variations.

An In-Depth Analysis of Medullary Strokes at a Tertiary Care Stroke Center: Incidence, Clinical and Radiological Characteristics, Etiology, Treatment, and Prognosis.

Introduction Medullary infarctions (MI) are a rare medical entity that is classified mainly as the more commonly lateral medullary infarcts (LMI) and the less common medial medullary infarcts (MMI). Lateral medullary syndrome, also known as Wallenberg syndrome, results when the medulla oblongata is affected and predominantly occurs secondary to atherosclerotic occlusion of the vertebrobasilar arteries. Previous studies have focused more on the anatomical, clinical, and topographical aspects of medullary infarcts. We describe the incidence of their presentation, radiological findings, etiology, treatment, and outcome at our comprehensive stroke center. Material and method This is a retrospective cohort study of 108 medullary stroke patients with confirmed clinical and radiological diagnoses of MI at Hamad General Hospital, Doha, between January 1, 2018 and December 31, 2020. We evaluated the electronic medical records of all stroke patients. Result During the selected period, a total of 2,912 ischemic strokes were reported. Of these, 843 (28.8%) were posterior circulation strokes. Only 108 (3.7%) patients had medullary strokes. Commonly encountered neurological features were dizziness (94.4%), limb ataxia (84.3%), dysarthria (44.4%), ipsilateral facial sensory loss (32.4%), headache (32.4%), contralateral limb sensory loss (25%), ipsilateral hemiparesis (24%), dysphagia (19.4%), and hiccups (13%). Most strokes reported were either minor (73% with National Institutes of Health Stroke Scale [NIHSS] 1-4) or moderate (26% with NIHSS 5-15). LMIs (87.9%) were the most common, followed by medial paramedian MI (10%). Twenty-five percent had extramedullary involvement, predominantly of the cerebellum (17.6%). Out of the total number of patients, 44 (40.7%) had large vessel atherosclerotic disease, followed by 41 (37.6%) whose stroke was due to small vessel disease, 15 (13.8 %) due to undetermined etiology, and 6 (5.5%) due to arterial dissection. Twenty-eight patients (25.4%) underwent 48-hour Holter monitoring, which detected atrial fibrillation in two patients (1.85%). The majority of patients (98.2%, or 106 patients) received antiplatelet therapy, while 68.5% (74 patients) received single antiplatelet therapy (SAPT), and 29.6% (32 patients) received dual antiplatelet therapy (DAPT). Noteworthy is that only 2.7% (three patients) received thrombolysis as an acute reperfusion therapy. Forty-seven percent (51 patients) were discharged home (mRS 0-2), and 51.9% (56 patients) were transferred to rehabilitation facilities. Follow-up assessments were performed at the stroke clinic for 57.4% (62) of the patients. The assessments found that 46 of the follow-up patients were functionally independent at that time (mRS 0-2). Conclusion This is the first large local study of medullary strokes to determine their frequency, presentation, etiology, treatment, and clinical outcome. Medullary strokes represent 3.7% of total ischemic strokes at our comprehensive stroke center. MI is rare and could present with a variety of neurological and non-specific symptoms that mimic common benign conditions. Prompt and early recognition with a high index of suspicion, the use of posterior NIHSS (POST-NIHSS), and urgent MRI-diffusion-weighted imaging (DWI) of the brain in acute settings can improve early diagnosis and the rate of reperfusion therapy. Further studies are needed to enable the early recognition and treatment of medullary infarcts.

Predicting 90-day prognosis for patients with stroke: a machine learning approach.

Background: Stroke is a significant global health burden and ranks as the second leading cause of death worldwide. Objective: This study aims to develop and evaluate a machine learning-based predictive tool for forecasting the 90-day prognosis of stroke patients after discharge as measured by the modified Rankin Score. Methods: The study utilized data from a large national multiethnic stroke registry comprising 15,859 adult patients diagnosed with ischemic or hemorrhagic stroke. Of these, 7,452 patients satisfied the study's inclusion criteria. Feature selection was performed using the correlation and permutation importance methods. Six classifiers, including Random Forest (RF), Classification and Regression Tree, Linear Discriminant Analysis, Support Vector Machine, and k-Nearest Neighbors, were employed for prediction. Results: The RF model demonstrated superior performance, achieving the highest accuracy (0.823) and excellent discrimination power (AUC 0.893). Notably, stroke type, hospital acquired infections, admission location, and hospital length of stay emerged as the top-ranked predictors. Conclusion: The RF model shows promise in predicting stroke prognosis, enabling personalized care plans and enhanced preventive measures for stroke patients. Prospective validation is essential to assess its real-world clinical performance and ensure successful implementation across diverse healthcare settings.

Profiling the autoantibody repertoire reveals autoantibodies associated with mild cognitive impairment and dementia.

Background: Dementia is a debilitating neurological disease affecting millions of people worldwide. The exact mechanisms underlying the initiation and progression of the disease remain to be fully defined. There is an increasing body of evidence for the role of immune dysregulation in the pathogenesis of dementia, where blood-borne autoimmune antibodies have been studied as potential markers associated with pathological mechanisms of dementia. Methods: This study included plasma from 50 cognitively normal individuals, 55 subjects with MCI (mild cognitive impairment), and 22 subjects with dementia. Autoantibody profiling for more than 1,600 antigens was performed using a high throughput microarray platform to identify differentially expressed autoantibodies in MCI and dementia. Results: The differential expression analysis identified 33 significantly altered autoantibodies in the plasma of patients with dementia compared to cognitively normal subjects, and 38 significantly altered autoantibodies in the plasma of patients with dementia compared to subjects with MCI. And 20 proteins had significantly altered autoantibody responses in MCI compared to cognitively normal individuals. Five autoantibodies were commonly dysregulated in both dementia and MCI, including anti-CAMK2A, CKS1B, ETS2, MAP4, and NUDT2. Plasma levels of anti-ODF3, E6, S100P, and ARHGDIG correlated negatively with the cognitive performance scores (MoCA) (r2 -0.56 to -0.42, value of p < 0.001). Additionally, several proteins targeted by autoantibodies dysregulated in dementia were significantly enriched in the neurotrophin signaling pathway, axon guidance, cholinergic synapse, long-term potentiation, apoptosis, glycolysis and gluconeogenesis. Conclusion: We have shown multiple dysregulated autoantibodies in the plasma of subjects with MCI and dementia. The corresponding proteins for these autoantibodies are involved in neurodegenerative pathways, suggesting a potential impact of autoimmunity on the etiology of dementia and the possible benefit for future therapeutic approaches. Further investigations are warranted to validate our findings.

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Corneal nerve loss predicts dementia in patients with mild cognitive impairment.

OBJECTIVES: This study compared the utility of corneal nerve measures with brain volumetry for predicting progression to dementia in individuals with mild cognitive impairment (MCI). METHODS: Participants with no cognitive impairment (NCI) and MCI underwent assessment of cognitive function, brain volumetry of thirteen brain structures, including the hippocampus and corneal confocal microscopy (CCM). Participants with MCI were followed up in the clinic to identify progression to dementia. RESULTS: Of 107 participants with MCI aged 68.4 ± 7.7 years, 33 (30.8%) progressed to dementia over 2.6-years of follow-up. Compared to participants with NCI (n = 12), participants who remained with MCI (n = 74) or progressed to dementia had lower corneal nerve measures (p < 0.0001). Progressors had lower corneal nerve measures, hippocampal, and whole brain volume (all p < 0.0001). However, CCM had a higher prognostic accuracy (72%-75% vs 68%-69%) for identifying individuals who progressed to dementia compared to hippocampus and whole brain volume. The adjusted odds ratio for progression to dementia was 6.1 (95% CI: 1.6-23.8) and 4.1 (95% CI: 1.2-14.2) higher with abnormal CCM measures, but was not significant for abnormal brain volume. INTERPRETATION: Abnormal CCM measures have a higher prognostic accuracy than brain volumetry for predicting progression from MCI to dementia. Further work is required to validate the predictive ability of CCM compared to other established biomarkers of dementia.

Optic cupping secondary to periventricular leukomalacia: A potential mimic for normal pressure glaucoma.

We herein present a case of periventricular leukomalacia (PVL) with secondary optic pathway denervation atrophy, which was initially labeled as normal tension glaucoma. However, given the discordant clinical and ophthalmologic findings, brain magnetic resonance imaging was requested which proved PVL to be the underlying process to the patient's decreased visual acuity. In addition to presenting the ophthalmologic findings, we are emphasizing the pivotal role of neuroimaging in ruling out central causes of optic atrophy/hypoplasia and making this clinical distinction by demonstrating optic pathway atrophy associated with PVL.

Acute ischemic stroke and convexity subarachnoid hemorrhage in large vessel atherosclerotic stenosis: Case series and review of the literature.

Atraumatic convexity subarachnoid hemorrhage (cSAH) is a rare non-aneurysmal SAH, commonly due to ipsilateral internal carotid artery (ICA) stenosis. It is unusual for the cSAH to occur contralaterally to the infarct. We report two cases of acute ischemic stroke associated with contralateral and ipsilateral cSAH that had different presentations.