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.

Cohen syndrome and early-onset epileptic encephalopathy in male triplets: two disease-causing mutations in VPS13B and NAPB.

Cohen syndrome (CS) is a rare multisystem autosomal recessive disorder associated with mutations in VPS13B (vacuolar protein sorting homolog 13B). The NAPB-related neurodevelopmental disorder is characterized mainly by early-onset epileptic encephalopathy (EOEE) and is associated with mutations in NAPB that encodes for SNAP-beta (soluble NSF attachment protein beta). Here we describe male triplets, clinically presenting with the phenotype of subtle but distinctive facial features, intellectual disability, increased body weight, neonatal EOEE, and prominently variable abnormal behaviors of autism and sexual arousal. The EEG showed multifocal epilepsy, while the brain MRI showed no abnormalities. Diagnostic exome sequencing (ES), the applied next-generation sequencing approach, revealed the interesting finding of two novel homozygous variants in two genes: VPS13B missense variant (c.8516G > A) and NAPB splice-site loss (c.354 + 2 T > G). Sanger sequencing verified the segregation of the two recessive gene variants with the phenotype in family members. The prediction algorithms support the pathogenicity of these variants. Homozygosity mapping of ES data of this consanguineous family revealed multiple chromosomal regions of homozygosity stretches with the residing of VPS13B (chr8: 100830758G > A) and NAPB (Chr20: 23,375,774 A > C) variants within the largest homozygous blocks further supporting the disease-genes causal role. Interestingly, the functions of the two proteins; VPS13B, a transmembrane protein involved in intracellular protein transport, and SNAP-beta involved in neurotransmitters release at the neuronal synaptic complexes, have been associated with Golgi-mediated vesicular trafficking. Our ES findings provide new insights into the pathologic mechanism underlying the expansion of the neurodevelopmental spectrum in CS and further highlight the importance of Golgi and Golgi-membrane-related proteins in the development of neurodevelopmental syndromes associated with early-onset non-channelopathy epilepsy. To our knowledge, this is the first report documenting multifocal EOEE in CS patients with the association of a pathogenic NAPB variant.

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.

NT5C2 novel splicing variant expands the phenotypic spectrum of Spastic Paraplegia (SPG45): case report of a new member of thin corpus callosum SPG-Subgroup.

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.

Predictors of In-Hospital Mortality after Decompressive Hemicraniectomy for Malignant Ischemic Stroke.

OBJECTIVE: The purpose of this retrospective multicenter, pooled-data analysis was to determine the factors associated with in-hospital mortality in decompressive hemicraniectomy (DHC) for malignant middle cerebral artery (MMCA) stroke. PATIENTS AND METHODS: The authors reviewed pooled DHC database from 3 countries for patients with MMCA with hospital mortality in spite of DHC to identify factors that predicted in-hospital mortality after DHC. The identified factors were applied to the group of patients who were selected for DHC but either refused surgery and died or stabilized and did not undergo DHC. FINDINGS: There were 137 patients who underwent DHC. Multiple logistic regression analysis showed middle cerebral artery (MCA) with additional infarcts (odds ratio [OR], 7.9: 95% confidence interval [CI], 2.4-26; P = .001), preoperative midline shift of septum pellucidum of 1 cm or more (OR, 3.83: 95% CI, 1.13-12.96; P = .031), and patients who remained unconscious on day 7 postoperatively (8.82: 95% CI; OR, 1.08-71.9; P = .042) were significant independent predictors for in-hospital mortality. The identified factors were applied to the group of MMCA patients not operated (n = 19 refused, n = 47 stabilized) single (P < .001), and two predictive factors (P < .001) were significantly more common in patients who died. Whereas two predicative factors were identified in only 9%-18.2% of survivors, the presence of all three predictive factors was seen only in patients who expired (P < .001). The Hosmer-Lemeshow goodness-of-fit statistics (chi-square = 4.65; P value = .589) indicate that the model adequately describes the data. CONCLUSION: Direct physical factors, such as MCA with additional territory infarct, extent of midline shift, and postoperative consciousness level, bore a significant relationship to in-hospital mortality in MMCA patients undergoing DHC.

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.

Imaging features of fulminant cerebral malaria: A case report.

Cerebral malaria is associated with high mortality and morbidity in patients infected with Plasmodium Falciparum. The mechanisms of cerebral malaria include sequestration of parasitized red blood cells in brain capillaries, production of cytokines, immune cell/platelet accumulation, and release of microparticles, resulting in disruption of the blood-brain barrier, which caused brain injuries. The severity of this reflects on neurological findings ranging from simple delirium to profound coma. We herein present unique magnetic resonance imaging findings of a case of fulminant cerebral malaria as computed tomography studies usually underestimate the extent of cerebral involvement in malaria.

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 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.

Abnormal corneal nerve morphology and brain volume in patients with schizophrenia.

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.

Loss of corneal nerves and brain volume in mild cognitive impairment and dementia.

Introduction: This study compared the capability of corneal confocal microscopy (CCM) with magnetic resonance imaging (MRI) brain volumetry for the diagnosis of mild cognitive impairment (MCI) and dementia. Methods: In this cross-sectional study, participants with no cognitive impairment (NCI), MCI, and dementia underwent assessment of Montreal Cognitive Assessment (MoCA), MRI brain volumetry, and CCM. Results: Two hundred eight participants with NCI (n = 42), MCI (n = 98), and dementia (n = 68) of comparable age and gender were studied. For MCI, the area under the curve (AUC) of CCM (76% to 81%), was higher than brain volumetry (52% to 70%). For dementia, the AUC of CCM (77% to 85%), was comparable to brain volumetry (69% to 93%). Corneal nerve fiber density, length, branch density, whole brain, hippocampus, cortical gray matter, thalamus, amygdala, and ventricle volumes were associated with cognitive impairment after adjustment for confounders (All P's < .01). Discussion: The diagnostic capability of CCM compared to brain volumetry is higher for identifying MCI and comparable for dementia, and abnormalities in both modalities are associated with cognitive impairment.

Reliability of high-resolution CT scan in diagnosis of ossicular tympanosclerosis.

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.

Spectrum of neuroimaging findings in COVID-19.

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.

Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia.

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.

Acute Flaccid Myelitis in COVID-19.

Spinal cord imaging findings in COVID-19 are evolving with the increasing frequency of neurological symptoms among COVID-19 patients. Several mechanisms are postulated to be the cause of central nervous system affection including direct virus neuroinvasive potential, post infectious secondary immunogenic hyperreaction, hypercoagulability, sepsis and possible vasculitis as well as systemic and metabolic complications associated with critical illness. Only a few case reports of spinal cord imaging findings are described in COVID-19, which include transverse myelitis, acute disseminated encephalomyelitis and post-infectious Guillain Barre' syndrome. We are describing a case of myelitis which, to the best of our knowledge, is the first reported case of myelitis in COVID-19.

Critical illness-associated cerebral microbleeds in COVID-19.

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.

A Rare Case of Choroid Plexus Papilloma of the Third Ventricle in an Adult.

Colloid cysts are the commonest masses of the third ventricle. Third ventricle neoplasms are uncommon. They include tumors arising from the choroid plexus (papillomas, carcinomas), tumors arising from other than the choroid plexus (ependymomas, meningiomas), metastases, and lymphoma. Choroid plexus tumors usually occur in the lateral ventricle in children and fourth ventricle in adults, and often present with hydrocephalus. We herein describe the extremely rare occurrence of third ventricle choroid plexus papilloma in a 35-year-old man who presented to the emergency department with a long history of intermittent headaches, occasionally associated with photophobia. CT and MR imaging revealed a lobulated ovoid lesion in the third ventricle with minimal extension into the right lateral ventricle through the foramen of Monro, causing mild ventricular dilatation. Surgical resection was performed and histopathology revealed choroid plexus papilloma.

Spontaneous Intracranial Hypotension and Its Management with a Cervical Epidural Blood Patch: A Case Report.

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.

Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia.

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.

Functional magnetic resonance imaging of head and neck cancer: Performance and potential.

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.