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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. [ABSTRACT FROM AUTHOR]

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) (r 2 –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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: This study assessed the association of cerebral ischemia with neurodegeneration in mild cognitive impairment (MCI) and dementia. Methods: Subjects with MCI, dementia and controls underwent assessment of cognitive function, severity of brain ischemia, MRI brain volumetry and corneal confocal microscopy. Results: Of 63 subjects with MCI (n = 44) and dementia (n = 19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both subcortical and cortical ischemia. Brain volume and corneal nerve measures were comparable between subjects with subcortical ischemia and no ischemia. However, subjects with subcortical and cortical ischemia had a lower hippocampal volume (P < 0.01), corneal nerve fiber length (P < 0.05) and larger ventricular volume (P < 0.05) compared to those with subcortical ischemia and lower corneal nerve fiber density (P < 0.05) compared to those without ischemia. Discussion: Cerebral ischemia was associated with cognitive impairment, brain atrophy and corneal nerve loss in MCI and dementia. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the reliability of high‐resolution CT scans (HRCT scans) in the diagnosis of tympanosclerosis and to determine its benefit to predict the post‐surgical hearing outcome based on comparing radiological and surgical findings. Methods: A retrospective study at a tertiary institute included 940 ears that underwent tyampanoplasty for chronic suppurative otitis media (CSOM) between January 2013 and March 2017. Preoperative temporal bone HRCT scans were analyzed to check for the prediction of tympanosclerosis and ossicular fixation. Intraoperatively, ossicular chain integrity was checked. Preoperative and postoperative audiometric evaluations using air‐bone gap (ABG) were compared. A postoperative pure‐tone ABG of 20 dB or less was considered as a successful hearing result. Results are compared with historical control groups, the study has been reviewed and approved by the IRB at the medical research center in Hamad Medical Corporation; however, it is a retrospective study so no informed consent was obtained from the patients. Results: The study included 940 ears that underwent tympanoplasties due to CSOM, where 238 out of 940 (25.3%) of ears showed tympanosclerosis during tympanoplasty, intraoperatively, tympanosclerosis was localized to the eardrum in 174 of the 238 involved ears (73.1%), A 64 out of 238 (26.9%) of the ears with tympanosclerosis showed ossicular fixation, divided as 45 ears with Incudo‐malleal fixation, 14 ears with stapes fixation, and 5 ears with triple ossicular fixation. HRCT scan of the temporal bone was suggestive of ossicular chain fixation in 79 cases distributed as 55 incudo‐malleal fixations, 19 stapes fixation, and 5 complete ossicular fixations, with a sensitivity of 96.8%, and specificity of 98%. The audiological results were analyzed, with a patient follow‐up after 6 months. Conclusions: Our study showed that CT scans when combined with the clinical findings can be an informative guide to otolaryngologists for preoperative evaluation and counseling of tympanosclerosis surgeries. [ABSTRACT FROM AUTHOR]

Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted structural neuroimaging marker of Alzheimer's disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic technique that detects neuronal loss in peripheral and central neurodegenerative disorders.Objective: To determine the diagnostic accuracy of CCM for mild cognitive impairment (MCI) and dementia compared to medial temporal lobe atrophy (MTA) rating on MRI.Methods: Subjects aged 60-85 with no cognitive impairment (NCI), MCI, and dementia based on the ICD-10 criteria were recruited. Subjects underwent cognitive screening, CCM, and MTA rating on MRI.Results: 182 subjects with NCI (n = 36), MCI (n = 80), and dementia (n = 66), including AD (n = 19, 28.8%), VaD (n = 13, 19.7%), and mixed AD (n = 34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 versus 17.2±6.5 and 15.8±7.4, p < 0.0001) in subjects with MCI and dementia compared to NCI. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL compared to MTA-right and MTA-left for MCI was 78% (67-90%), 82% (72-92%), 86% (77-95%) versus 53% (36-69%) and 40% (25-55%), respectively, and for dementia it was 85% (76-94%), 84% (75-93%), 85% (76-94%) versus 86% (76-96%) and 82% (72-92%), respectively.Conclusion: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration, was high and comparable with MTA rating for dementia but was superior to MTA rating for MCI. [ABSTRACT FROM AUTHOR]

Patient: Male, 25-year-old. Final Diagnosis: Spontaneous intracranial hypotension. Symptoms: Headache. Specialty: Anesthesiology • Medicine, General and Internal • Neurology • Radiology. Objective: Rare disease. Background: Spontaneous intracranial hypotension (SIH) is a rare cause of postural headache. In most patients, the site of cerebrospinal fluid (CSF) leak is at the cervical or thoracic spinal level. The imaging modalities to establish the diagnosis of SIH include computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, CT, and MRI myelography, and radionuclide cisternography. Treatment usually consists of conservative measures, but patients unresponsive to these treatments can be treated by epidural blood patch (EBP) administration at the site of CSF leak. Case Report: A 25-year-old-man presented with headache aggravated upon sitting or standing and relieved by lying supine or consuming coffee. There was no history of recent trauma, lumbar puncture, or spinal anesthesia. His neurological examination was unremarkable. MRI of his head and entire spine showed features of intracranial hypotension with no obvious CSF leak. He was treated conservatively but his symptoms persisted. CT spinal myelography showed significant leakage of contrast medium at the retrospinal region between C1 and C2 spinous processes. The patient underwent cervical EBP administration under fluoroscopic guidance. His symptoms resolved completely and he remains asymptomatic more than 6 months later. Conclusions: SIH is an important cause of postural headache. In patients with non-resolving symptoms, further investigations are warranted to identify potential CSF leak. Patients found to have a CSF leak at the level of the cervical spine can be safely and effectively treated by cervical EBP administration. [ABSTRACT FROM AUTHOR]

Objectives: Corneal confocal microscopy (CCM) is a noninvasive ophthalmic technique that identifies corneal nerve degeneration in a range of peripheral neuropathies and in patients with multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. We sought to determine whether there is any association of corneal nerve fiber measures with cognitive function and functional independence in patients with MCI and dementia. Methods: In this study, 76 nondiabetic participants with MCI (n = 30), dementia (n = 26), and healthy age‐matched controls (n = 20) underwent assessment of cognitive and physical function and CCM. Results: There was a progressive reduction in corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P < 0.0001) in patients with MCI and dementia compared to healthy controls. Adjusted for confounders, all three corneal nerve fiber measures were significantly associated with cognitive function (P < 0.05) and functional independence (P < 0.01) in MCI and dementia. The area under the ROC curve to distinguish MCI with CNFD, CNBD, and CNFL was 69.1%, 73.2%, and 73.0% and for dementia it was 84.8%, 84.2%, and 86.2%, respectively. Interpretation: CCM demonstrates corneal nerve fiber loss, which is associated with a decline in cognitive function and functional independence in patients with MCI and dementia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We are reporting the imaging findings of the rare entity of critical illness-associated cerebral microbleeds in a COVID-19-positive 66-year-old woman with hypoxic respiratory failure, who was eventually intubated and ventilated. Multiple scattered cerebral microhaemorrhages diffusely distributed in the juxtacortical white matter and internal capsule region, sparing the deep and periventricular white matter, basal ganglia, thalami and cortex were seen, which is a unique imaging finding in critically ill patients with respiratory failure and hypoxemia requiring mechanical ventilation. The mechanism underlying these microhaemorrhages relates to the endpoint of critical illness, rather than a specific underlying disease. [ABSTRACT FROM AUTHOR]

Abstract Immunocompromised status is associated with invasive fungal infections including mucormycosis. These infections are challenging to treat and associated with high overall mortality. Here we report a fatal case of invasive mucormycosis in a cirrhotic, diabetic patient. Despite the swift diagnosis and management; the fungal invasion of the right internal carotid artery lead to massive ischemic stroke. Timely diagnosis and management is crucial for management but it seems not always enough and new approaches for treatment must be sought. [ABSTRACT FROM AUTHOR]

Background: Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative diseases. Thin Corpus Callosum (TCC) associated HSP is a distinguished subgroup of complex forms. Purines and pyrimidine, the basic DNA and RNA components, are regulating the cell metabolism, having roles in signal transduction, energy preservation and cellular repair. Genetic defects in nucleotide metabolism related genes have been only recently implicated in brain and neurodegenerative diseases' pathogenesis. Case presentation: We present a consanguineous Qatari family with two brothers, 9 and 3 years, who displayed a characteristic phenotype of early onset and markedly-severe spasticity with tiptoe walking, delayed dysarthric speech, persistent truncal hypotonia, and multiple variable-sized areas of brownish skin discoloration appearing at different places on the body. A clinical diagnosis suggestive of complex hereditary spastic paraplegia (HSP) was set after the family had the second affected child. Whole genome sequencing identified a novel homozygous NT5C2 splice site mutation (NM_012229.4/NM_001134373.2: c.1159 + 1G > T) that recessively segregated in family members. Brain MRI revealed dysgenic and thin corpus callosum (TCC) with peri-trigonal white matter cystic changes in both affected boys, whereas a well-developed corpus callosum with normal white matter was shown in their apparently normal brother, who found to be a carrier for the mutant variant. This mutation led to skipping of exon 14 with removal of 58 amino acid residues at the C-terminal half. The aberrantly spliced NT5C2 showed substantial reduction in expression level in the in-vitro study, indicating marked instability of the mutant NT5C2 protein. Conclusion: The present report expands the phenotypic spectrum of SPG45 and confirms NT5C2-SPG45 as a member of the rare TCC SPG-subtypes. Homozygous alteration in NT5C2 seems essential to produce central white matter developmental defects. The study highlights the importance of cytosolic II 5'-nucleotidase (NT5C2) in maintaining the normal balance of purines' pool in the brain, which seems to play a pivotal role in the normal development of central white matter structures. [ABSTRACT FROM AUTHOR]

An outbreak of corona virus disease 2019 (COVID-19) began in China in December 2019, and rapidly spread to become a worldwide pandemic. Neurological complications encountered in hospitalized patients include acute arterial ischemic cerebrovascular stroke, cerebral venous thrombosis, critical illness-associated cerebral microbleeds, hypertensive hemorrhagic posterior reversible encephalopathy, meningoencephalitis/flare up of infections, flare up of multiple sclerosis, acute disseminated encephalomyelitis, cerebral hemodynamic/hypoxic changes such as watershed ischemic changes and hypoxic ischemic encephalopathy, and spine manifestations of Guillain Barre syndrome and viral myelitis. The purpose of our study is to illustrate the different neuroimaging features in critically ill hospitalized COVID-19 positive patients in the State of Qatar. [ABSTRACT FROM AUTHOR]

The author names “Dr. Pablo Garcia Bermejo” and “Dr. Muhammad Faisal Wadiwala” needed to be added as the 6th and 7th authors, respectively. The authors regret this error. [ABSTRACT FROM AUTHOR]