Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain ...volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35-0.86 and P = 0.50) or cognitive function (P = 0.35-0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61-0.64) or diabetes (P = 0.057-0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia.
BACKGROUNDStroke 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.METHODSThe 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.RESULTSOf 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.CONCLUSIONThis 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.
Functional magnetic resonance imaging (MRI) of tumors of the head and neck usually encompasses diffusion-weighted imaging (DWI) and intravenous (IV) contrast T1 dynamic perfusion imaging (DCE-MRI or ...PWI). Both techniques can characterize different tissues by probing into their microstructure, providing a novel approach in oncological imaging. In this pictorial review, we will cover the important technical aspects of DWI and PWI, the pathophysiological background and the current applications and potential of these functional MRI techniques in the imaging of head and neck cancer.
Axonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in ...different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) (clinically isolated syndrome (n = 9); relapsing-remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21) underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm
, 95% CI - 18.24 to - 11.59, P < .0001), CNFL for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm
, 95% CI - 8.94 to - 5.77, P < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm
, 95% CI - 9.55 to - 5.6, P < .0001 and CNFrD for ACCMetrics: 1.52 ± 0.02 vs. 1.45 ± 0.04, 95% CI - 0.09 to - 0.05, P < .0001; for deepNerve: 1.29 ± 0.03 vs. 1.19 ± 0.07, 95% - 0.13 to - 0.07, P < .0001. Corneal nerve parameters were comparably reduced in different courses of MS. There was excellent reproducibility between the algorithms. Significant corneal axonal loss is detected in different courses of MS including patients with clinically isolated syndrome.
Aneurysmal subarachnoid hemorrhage has a high mortality with significant impact on quality of life despite effective management strategies including endovascular treatment and/or microsurgical ...clipping. Although the modalities have undergone clinical comparison, they have not been evaluated on patient-reported outcomes (PROs). This study compared endovascular versus microsurgical treatment using a PRO measure.
We conducted a cross-sectional telephonic survey of adult patients conducted at Hamad General Hospital, Doha, Qatar between 2017 and 2019. Candidate study participants were identified from procedure logs and hospital electronic health records for endovascular treatment (N = 32) versus microsurgical clipping (N = 32) of cerebral aneurysm. The primary outcome measure was the short version of the Stroke-Specific Quality of Life (SS-QoL) measure. The secondary outcome measure was the screened clinician-reported modified Rankin Scale (mRS) for all screened patients (n = 137). Mean scores were compared for the 2 treatment groups.
The SS-QoL mean score was 4.23 (standard deviation ± 0.77) in endovascular treatment and 4.19 ± 0.19 in surgical clipping (P = 0.90). In exploratory analysis, mean physical domain score was 3.17 ± 0.60 versus 2.98 ± 0.66 in endovascular treatment and surgical clipping groups, respectively. Mean psychosocial domain scores were 4.43 ± 0.85 versus 4.18 ± 0.0.92, respectively. In multivariable analysis, none of the clinical variables were significantly related to SS-QoL except vasospasm irrespective of intervention received. In secondary outcome analysis, modified Rankin Scale score was higher for endovascular treatment (P = 0.04).
Published evidence has supported clinical benefits of endovascular treatment for cerebral aneurysm treatment, but this study did not find any difference in PROs. Future studies of treatments should include PRO to identify potential differences from the patient's perspective.
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.
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.
Etiology of a large vessel occlusion is relevant in the management of acute ischemic stroke patients and often difficult to determine in the acute phase.
We aim to investigate whether the ...angiographic appearance of the occlusion is related to its etiology and outcome.
Patients without cervical carotid occlusions who underwent mechanical thrombectomy in our center from April 2015 to September 2018 were studied. Demographics, clinical and radiological variables and outcome measures, including etiological classification of stroke, were collected. Underlying intracranial atherosclerosis was estimated according to the presence of stenosis after recanalization. Patients were assigned to groups based on the appearance of the occlusion observed in the first angiogram as "tapered" or "non-tapered." Differences were searched amongst them.
131 patients met inclusion criteria. 31 (23.6%) were "tapered" and 100 (76.3%) non-tapered. Tapered presented lower mean baseline NIHSS (10.3 ± 6.2 vs. 16.1 ± 7.2;
< 0.001), smaller acute infarct cores as CTP CBV ASPECTS (8.6 ± 1.6 vs. 7.2 ± 2.4;
= 0.003), higher proportion of instant re-occlusions (26.7 vs. 8.2%;
= 0.025), fewer complete recanalization (45.2 vs. 71.0%;
= 0.028), and more persistent occlusions (37.5 vs. 10.6%;
= 0.011) on follow up MRA. There were no differences in reperfusion rates (83.9 vs. 84.0%;
= 0.986) nor in good long term functional outcome (50.0 vs. 51.1%;
= 0.921). Intracranial atherosclerosis etiology was more common in tapered than in non-tapered occlusions (54.8 vs. 18.0%;
< 0.001).
The angiographic appearance of an occlusion in mechanical thrombectomy patients may determine its etiology, predict likelihood of successful recanalization, and risk of reocclusion.
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 (r
) ≤ -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.
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.
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