Lesion Load Research Articles

Microstructural alterations measured by diffusion tensor imaging following transcatheter aortic valve replacement and their association with cerebral ischemic injury and cognitive function — a prospective study

PurposeWe assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR).MethodsTAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student’s t-test (p < 0.0071) and ANOVA covarying for sex, ILL (p < 0.05) with post hoc analysis of ILL groups (p < 0.0167). Repeated-measures linear mixed-effect model (p < 0.05) was performed to investigate the effect of time and ILL on cognition.ResultsAt 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p ≤ 0.0046); MD (body, both cingulate gyri: p ≤ 0.0050); RD (left cingulate gyrus: p = 0.0021); FA (splenium: p < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) (p ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p ≤ 0.0050; MD-left cingulate gyrus: p = 0.0087).Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores (p ≤ 0.0483).ConclusionSignificant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition.Trial registration number.NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

Validation of a Denoising Method Using Deep Learning-Based Reconstruction to Quantify Multiple Sclerosis Lesion Load on Fast FLAIR Imaging.

Accurate quantification of WM lesion load is essential for the care of patients with multiple sclerosis. We tested whether the combination of accelerated 3D-FLAIR and denoising using deep learning-based reconstruction could provide a relevant strategy while shortening the imaging examination. Twenty-eight patients with multiple sclerosis were prospectively examined using 4 implementations of 3D-FLAIR with decreasing scan times (4 minutes 54 seconds, 2 minutes 35 seconds, 1 minute 40 seconds, and 1 minute 15 seconds). Each FLAIR sequence was reconstructed without and with denoising using deep learning-based reconstruction, resulting in 8 FLAIR sequences per patient. Image quality was assessed with the Likert scale, apparent SNR, and contrast-to-noise ratio. Manual and automatic lesion segmentations, performed randomly and blindly, were quantitatively evaluated against ground truth using the absolute volume difference, true-positive rate, positive predictive value, Dice similarity coefficient, Hausdorff distance, and F1 score based on the lesion count. The Wilcoxon signed-rank test and 2-way ANOVA were performed. Both image-quality evaluation and the various metrics showed deterioration when the FLAIR scan time was accelerated. However, denoising using deep learning-based reconstruction significantly improved subjective image quality and quantitative performance metrics, particularly for manual segmentation. Overall, denoising using deep learning-based reconstruction helped to recover contours closer to those from the criterion standard and to capture individual lesions otherwise overlooked. The Dice similarity coefficient was equivalent between the 2-minutes-35-seconds-long FLAIR with denoising using deep learning-based reconstruction and the 4-minutes-54-seconds-long reference FLAIR sequence. Denoising using deep learning-based reconstruction helps to recognize multiple sclerosis lesions buried in the noise of accelerated FLAIR acquisitions, a possibly useful strategy to efficiently shorten the scan time in clinical practice.

Minocycline treatment in clinically isolated syndrome and serum NfL, GFAP, and metalloproteinase levels

Background: In the trial of Minocycline in Clinically Isolated Syndrome (MinoCIS), minocycline significantly reduced the risk of conversion to clinically definite multiple sclerosis (CDMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in MS, and minocycline modulates matrix metalloproteinases (MMPs). Objective: To assess the value of blood NfL and GFAP as a biomarker of baseline and future disease activity and its utility to monitor treatment response in minocycline-treated patients with clinically isolated syndrome (CIS). Methods: We measured NfL, GFAP, and MMPs in blood samples from 96 patients with CIS from the MinoCIS study and compared biomarkers with clinical and radiologic characteristics and outcome. Results: At baseline, NfL levels correlated with T2 lesion load and number of gadolinium-enhancing lesions. Baseline NfL levels predicted conversion into CDMS at month 6. GFAP levels at baseline were correlated with T2 lesion volume. Minocycline treatment significantly increased NfL levels at 3 months but not at 6 months, and decreased GFAP levels at month 6. Minocycline decreased MMP-7 concentrations at month 1. Discussion: Blood NfL levels are associated with measures of disease activity in CIS and have prognostic value. Minocycline increased NfL levels at month 3, but reduced GFAP and MMP-7 levels.

Integrity of the Left Arcuate Fasciculus Segments Significantly Affects Language Performance in Individuals with Acute/Subacute Post-Stroke Aphasia: A Cross-Sectional Diffusion Tensor Imaging Study.

Objective: To investigate the correlation between the left arcuate fasciculus (AF) segments and acute/subacute post-stroke aphasia (PSA). Methods: Twenty-six patients underwent language assessment and MRI scanning. The integrity of the AF based on a three-segment model was evaluated using diffusion tensor imaging. All patients were classified into three groups according to the reconstruction of the left AF: completely reconstructed (group A, 8 cases), non-reconstructed (group B, 6 cases), and partially reconstructed (group C, 12 cases). The correlations and intergroup differences in language performance and diffusion indices were comprehensively estimated. Results: A correlation analyses showed that the lesion load of the language areas and diffusion indices on the left AF posterior and long segments was significantly related to some language subsets, respectively. When controlled lesion load was variable, significant correlations between diffusion indices on the posterior and long segments and comprehension, repetition, naming, and aphasia quotient were retained. Multiple comparison tests revealed intergroup differences in diffusion indices on the left AF posterior and long segments, as well as these language subsets. No significant correlation was found between the anterior segment and language performance. Conclusions: The integrity of the left AF segments, particularly the posterior segment, is crucial for the residual comprehension and repetition abilities in individuals with acute/subacute PSA, and lesion load in cortical language areas is an important factor that should be taken into account when illustrating the contributions of damage to special fiber tracts to language impairments.

Newer disease modifying treatments in pediatric onset multiple sclerosis: Experience from a single center.

Disease modifying treatments (DMTs) for multiple sclerosis include injectable drugs (iDMTs) like interferons (IFNs) or glatiramer acetate (GA), and newer agents (nDMTs) in oral and intravenous forms. nDMTs are usually applied in escalation and less frequently as initial treatment in pediatric-onset (POMS). We intended to evaluate the effect of nDMTs in comparison with iDMTs by retrospective examination of our patients with POMS. Clinical records of POMS cases who received nDMTs either as escalation or initial treatment and who had at least 12 months' follow-up in our clinic were examined in two groups: patients who were started on iDMTs and later switched to nDMTs (Group A), and those who received nDMTs from the beginning (Group B). Presenting symptoms, annualized relapsing rate (ARR), recent Expanded Disability Status Scale (EDSS), lesion load and presence of contrast enhancing (CE) lesions on magnetic resonance imaging (MRI) were compared. Total 43 patients were included: 33 in Group A and 10 in Group B. Age at onset, female/male ratio, duration since disease onset and duration under nDMT were similar in both groups. Initial involvement was predominantly brainstem and cerebellar in Group A and sensorial, brainstem/cerebellar, and optic nerve in Group B. The most frequently used nDMT was fingolimod in Group A (n=17, 51.5%) and teriflunomide (n=6, 60%) in Group B. Median ARR before any treatment was 2 in Group A and 1.5 in Group B (p>0.05); it decreased to median 1 under iDMTs in Group A and to 0 under nDMTs. Mean follow-up was 6.7±5 years (1-19, median 6 years) in Group A and 3.9±3.7 years (range 1-12, median 2 years) in Group B. At the latest follow-up median EDSS scores were 1 in Group A and 0 in Group B. ARR had increased and lesion load on MRI went up progressively in both groups during follow-up. However, the rate of patients with CE lesions diminished in Group B. This single-center study of POMS shows the ARR decreases under any treatment, more markedly under nDMTs, and nDMTs reduce the rate of patients with CE lesions on MRI without a clear effect on lesion load. The ARR tends to increase after the first 2 years of both iDMT and nDMT, suggesting a re-evaluation at that time. The ARR decreases shorty after treatment is changed from an iDMT to a nDMT.

Association of Lesion Location and Fatigue Symptoms After Ischemic Stroke: A VLSM Study.

Background:Poststroke fatigue (PSF) is a common symptom in stroke survivors, yet its anatomical mechanism is unclear. Our study was aimed to identify which brain lesions are related to the PSF in patients with acute stroke.MethodPatients with first-ever acute ischemic stroke consecutively admitted from the first affiliated hospital of the University of Science and Technology of China (USTC) between January 2017 and June 2020. Fatigue was scored using the Fatigue Severity Scale. All the participants were assessed by 3.0 T brain MRI including diffusion-weighted imaging. The infarct lesions were delineated manually and transformed into a standard template. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and the occurrence and severity of fatigue. The same analyses were carried out by flipping the left-sided lesions. Multivariate logistic regressions were applied to verify the associations.ResultsOf the 361 patients with acute stroke, 142 (39.3%) patients were diagnosed with fatigue in the acute phase and 116 (35.8%) at 6 months after the index stroke. VLSM analysis indicated clusters in the right thalamus which was significantly associated with the occurrence and severity of PSF at 6-month follow-up. In contrast, no significant cluster was found in the acute phase of stroke. The flipped analysis did not alter the results. Multivariate logistic regression verified that lesion load in the right thalamus (OR 2.67, 95% CI 1.46–4.88) was an independent predictor of 6-month PSF.ConclusionOur findings indicated that lesions in the right thalamus increased the risk of fatigue symptoms 6 months poststroke.

Grey matter atrophy in patients with benign multiple sclerosis.

BackgroundBrain atrophy appears during the progression of multiple sclerosis (MS) and is associated with the disability caused by the disease.MethodsWe investigated global and regional grey matter (GM) and white matter (WM) volumes, WM lesion load, and corpus callosum index (CCI), in benign relapsing‐remitting MS (BRRMS, n = 35) with and without any treatment and compared those to aggressive relapsing‐remitting MS (ARRMS, n = 46). Structures were analyzed by using an automated MRI quantification tool (cNeuro®).ResultsThe total brain and cerebral WM volumes were larger in BRRMS than in ARRMS (p = .014, p = .017 respectively). In BRRMS, total brain volumes, regional GM volumes, and CCI were found similar whether or not disease‐modifying treatment (DMT) was used. The total (p = .033), as well as subcortical (p = .046) and deep WM (p = .041) lesion load volumes were larger in BRRMS patients without DMT. Cortical GM volumes did not differ between BRRMS and ARRMS, but the volumes of total brain tissue (p = .014) and thalami (p = .003) were larger in patients with BRRMS compared to ARRMS. A positive correlation was found between CCI and whole‐brain volume in both BRRMS (r = .73, p < .001) and ARRMS (r = .80, p < .01).ConclusionsThalamic volume is the most prominent measure to differentiate BRRMS and ARRMS. Validation of automated quantification of CCI provides an additional applicable MRI biomarker to detect brain atrophy in MS.

Comparative real-time PCR quantification of cytomegalovirus in severe early childhood caries and caries-free children

The present study was undertaken to evaluate cytomegalovirus (CMV) load in carious lesions in children with severe early childhood caries (S-ECC) and compare it with caries-free (CF), healthy children, by quantitative real-time polymerase chain reaction (PCR). Dental plaque samples were collected from 57 subjects including S-ECC (n = 33) and CF (n = 24) patients. The two groups were matched in terms of age, gender, and socioeconomic status. After deoxyribonucleic acid (DNA) extraction, SYBR Green real-time PCR was used to quantify CMV DNA. The CMV DNA was detected in seven patients in theS-ECC group. The mean of decayed, missing, and filled tooth surfaces (dmfs) was 11.90 ± 5.95 in the S-ECC group. There was no significant difference in gender between the two groups. There was a significant relationship between CMV positivity in children and theS-ECC group (p = 0.043). Results of this study suggest a relationship between the presence of CMV in the oral cavity and S-ECC. We can design clinical trials to confirm these results and improve children's dental care.

MOG encephalomyelitis after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2): case report and comprehensive review of the literature

BackgroundIn around 20% of cases, myelin oligodendrocyte glycoprotein (MOG) immunoglobulin (IgG)-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) first occurs in a postinfectious or postvaccinal setting.ObjectiveTo report a case of MOG-EM with onset after vaccination with the Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 (Comirnaty®) and to provide a comprehensive review of the epidemiological, clinical, radiological, electrophysiological and laboratory features as well as treatment outcomes of all published patients with SARS-CoV-2 vaccination-associated new-onset MOG-EM.MethodsCase report and review of the literature.ResultsIn our patient, MOG-IgG-positive (serum 1:1000, mainly IgG1 and IgG2; CSF 1:2; MOG-specific antibody index < 4) unilateral optic neuritis (ON) occurred 10 days after booster vaccination with BNT162b2, which had been preceded by two immunizations with the vector-based Oxford AstraZeneca vaccine ChAdOx1-S/ChAdOx1-nCoV-19 (AZD1222). High-dose steroid treatment with oral tapering resulted in complete recovery. Overall, 20 cases of SARS-CoV2 vaccination-associated MOG-EM were analysed (median age at onset 43.5 years, range 28–68; female to male ratio = 1:1.2). All cases occurred in adults and almost all after immunization with ChAdOx1-S/ChAdOx1 nCoV-19 (median interval 13 days, range 7–32), mostly after the first dose. In 70% of patients, more than one CNS region (spinal cord, brainstem, supratentorial brain, optic nerve) was affected at onset, in contrast to a much lower rate in conventional MOG-EM in adults, in which isolated ON is predominant at onset and ADEM-like phenotypes are rare. The cerebrospinal fluid white cell count (WCC) exceeded 100 cells/μl in 5/14 (36%) patients with available data (median peak WCC 58 cells/μl in those with pleocytosis; range 6–720). Severe disease with tetraparesis, paraplegia, functional blindness, brainstem involvement and/or bladder/bowel dysfunction and a high lesion load was common, and treatment escalation with plasma exchange (N = 9) and/or prolonged IVMP therapy was required in 50% of cases. Complete or partial recovery was achieved in the majority of patients, but residual symptoms were significant in some. MOG-IgG remained detectable in 7/7 cases after 3 or 6 months.ConclusionsMOG-EM with postvaccinal onset was mostly observed after vaccination with ChAdOx1-S/ChAdOx1 nCoV-19. Attack severity was often high at onset. Escalation of immunotherapy was frequently required. MOG-IgG persisted in the long term.

Grey-matter sodium concentration as an individual marker of multiple sclerosis severity

Objective: Quantification of brain injury in patients with variable disability despite similar disease duration may be relevant to identify the mechanisms underlying disability in multiple sclerosis (MS). We aimed to compare grey-matter sodium abnormalities (GMSAs), a parameter reflecting neuronal and astrocyte dysfunction, in MS patients with benign multiple sclerosis (BMS) and non-benign multiple sclerosis (NBMS). Methods: We identified never-treated BMS patients in our local MS database of 1352 patients. A group with NBMS was identified with same disease duration. All participants underwent 23Na magnetic resonance imaging (MRI). The existence of GMSA was detected by statistical analysis. Results: In total, 102 individuals were included (21 BMS, 25 NBMS and 56 controls). GMSA was detected in 10 BMS and 19 NBMS (11/16 relapsing-remitting multiple sclerosis (RRMS) and 8/9 secondary progressive multiple sclerosis (SPMS) patients) (p = 0.05). On logistic regression including the presence or absence of GMSA, thalamic volume, cortical grey-matter volume and T2-weighted lesion load, thalamic volume was independently associated with BMS status (odds ratio (OR) = 0.64 for each unit). Nonetheless, the absence of GMSA was independently associated when excluding patients with significant cognitive alteration (n = 7) from the BMS group (OR = 4.6). Conclusion: Detection of GMSA in individuals and thalamic volume are promising to differentiate BMS from NBMS as compared with cortical or whole grey-matter atrophy and T2-weighted lesions.

Automated multimodal segmentation of acute ischemic stroke lesions on clinical MR images

Magnetic resonance (MR) imaging (MRI) is commonly used to diagnose, assess and monitor stroke. Accurate and timely segmentation of stroke lesions provides the anatomico-structural information that can aid physicians in predicting prognosis, as well as in decision making and triaging for various rehabilitation strategies. To segment stroke lesions, MR protocols, including diffusion-weighted imaging (DWI) and T2-weighted fluid attenuated inversion recovery (FLAIR) are often utilized. These imaging sequences are usually acquired with different spatial resolutions due to time constraints. Within the same image, voxels may be anisotropic, with reduced resolution along slice direction for diffusion scans in particular. In this study, we evaluate the ability of 2D and 3D U-Net Convolutional Neural Network (CNN) architectures to segment ischemic stroke lesions using single contrast (DWI) and dual contrast images (T2w FLAIR and DWI). The predicted segmentations correlate with post-stroke motor outcome measured by the National Institutes of Health Stroke Scale (NIHSS) and Fugl-Meyer Upper Extremity (FM-UE) index based on the lesion loads overlapping the corticospinal tracts (CST), which is a neural substrate for motor movement and function. Although the four methods performed similarly, the 2D multimodal U-Net achieved the best results with a mean Dice of 0.737 (95% CI: 0.705, 0.769) and a relatively high correlation between the weighted lesion load and the NIHSS scores (both at baseline and at 90 days). A monotonically constrained quintic polynomial regression yielded R2 = 0.784 and 0.875 for weighted lesion load versus baseline and 90-Days NIHSS respectively, and better corrected Akaike information criterion (AICc) scores than those of the linear regression. In addition, using the quintic polynomial regression model to regress the weighted lesion load to the 90-Days FM-UE score results in an R2 of 0.570 with a better AICc score than that of the linear regression. Our results suggest that the multi-contrast information enhanced the accuracy of the segmentation and the prediction accuracy for upper extremity motor outcomes. Expanding the training dataset to include different types of stroke lesions and more data points will help add a temporal longitudinal aspect and increase the accuracy. Furthermore, adding patient-specific data may improve the inference about the relationship between imaging metrics and functional outcomes.

Performance Comparison of Different Neuroimaging Methods for Predicting Upper Limb Motor Outcomes in Patients after Stroke.

Several neuroimaging methods have been proposed to assess the integrity of the corticospinal tract (CST) for predicting recovery of motor function after stroke, including conventional structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI). In this study, we aimed to compare the predicative performance of these methods using different neuroimaging modalities and optimize the prediction protocol for upper limb motor function after stroke in a clinical environment. We assessed 28 first-ever stroke patients with upper limb motor impairment. We used the upper extremity module of the Fugl-Meyer assessment (UE-FM) within 1 month of onset (baseline) and again 3 months poststroke. sMRI (T1- and T2-based) was used to measure CST-weighted lesion load (CST-wLL), and DTI was used to measure the fractional anisotropy asymmetry index (FAAI) and the ratio of fractional anisotropy (rFA). The CST-wLL within 1 month poststroke was closely correlated with upper limb motor outcomes and recovery potential. CST‐wLL ≥ 2.068 cc indicated serious CST damage and a poor outcome (100%). CST‐wLL < 1.799 cc was correlated with a considerable rate (>70%) of upper limb motor function recovery. CST-wLL showed a comparable area under the curve (AUC) to that of the CST-FAAI (p = 0.71). Inclusion of extra-CST-FAAI did not significantly increase the AUC (p = 0.58). Our findings suggest that sMRI-derived CST-wLL is a precise predictor of upper limb motor outcomes 3 months poststroke. We recommend this parameter as a predictive imaging biomarker for classifying patients' recovery prognosis in clinical practice. Conversely, including DTI appeared to induce no significant benefits.

Altered grey matter integrity and network vulnerability relate to epilepsy occurrence in patients with multiple sclerosis.

The aim of this study was to investigate the relevance of compartmentalized grey matter (GM) pathology and network reorganization in multiple sclerosis (MS) patients with concomitant epilepsy. From 3-T magnetic resonance imaging scans of 30 MS patients with epilepsy (MSE group; age 41 ± 15 years, 21 females, disease duration 8 ± 6 years, median Expanded Disability Status Scale [EDSS] score 3), 60 MS patients without epilepsy (MS group; age 41 ± 12 years, 35 females, disease duration 6 ± 4 years, EDSS score 2), and 60 healthy subjects (HS group; age 40 ± 13 years, 27 females) the regional volumes of GM lesions and of cortical, subcortical and hippocampal structures were quantified. Network topology and vulnerability were modelled within the graph theoretical framework. Receiver-operating characteristic (ROC) curve analysis was applied to assess the accuracy of GM pathology measures to discriminate between MSE and MS patients. Higher lesion volumes within the hippocampus, mesiotemporal cortex and amygdala were detected in the MSE compared to the MS group (all p &lt; 0.05). The MSE group had lower cortical volumes mainly in temporal and parietal areas compared to the MS and HS groups (all p &lt; 0.05). Lower hippocampal tail and presubiculum volumes were identified in both the MSE and MS groups compared to the HS group (all p &lt; 0.05). Network topology in the MSE group was characterized by higher transitivity and assortativity, and higher vulnerability compared to the MS and HS groups (all p &lt; 0.05). Hippocampal lesion volume yielded the highest accuracy (area under the ROC curve 0.80 [0.67-0.91]) in discriminating between MSE and MS patients. High lesion load, altered integrity of mesiotemporal GM structures, and network reorganization are associated with a greater propensity for epilepsy occurrence in people with MS.

Cerebral Microbleeds and Structural White Matter Integrity in Patients With Traumatic Brain Injury-A Diffusion Tensor Imaging Study.

Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI.

CSF tap test in idiopathic normal pressure hydrocephalus: still a necessary prognostic test?

ObjectiveTo assess whether gait, neuropsychological, and multimodal MRI parameters predict short-term symptom reversal after cerebrospinal fluid (CSF) tap test in idiopathic normal pressure hydrocephalus (iNPH).MethodsThirty patients (79.3 ± 5.9 years, 12 women) with a diagnosis of probable iNPH and 46 healthy controls (74.7 ± 5.4 years, 35 women) underwent comprehensive neuropsychological, quantitative gait, and multimodal MRI assessments of brain morphology, periventricular white-matter microstructure, cortical and subcortical blood perfusion, default mode network function, and white-matter lesion load. Responders were defined as an improvement of at least 10% in walking speed or timed up and go test 24 h after tap test. Univariate and multivariable tap test outcome prediction models were evaluated with logistic regression and linear support vector machine classification.ResultsSixteen patients (53%) respondedpositively to tap test. None of the gait, neuropsychological, or neuroimaging parameters considered separately predicted outcome. A multivariable classifier achieved modest out-of-sample outcome prediction accuracy of 70% (p = .028); gait parameters, white-matter lesion load and periventricular microstructure were the main contributors.ConclusionsOur negative findings show that short-term symptom reversal after tap test cannot be predicted from single gait, neuropsychological, or MRI parameters, thus supporting the use of tap test as prognostic procedure. However, multivariable approaches integrating non-invasive multimodal data are informative of outcome and may be included in patient-screening procedures. Their value in predicting shunting outcome should be further explored, particularly in relation to gait and white-matter parameters.

P375 RECURRENT CEREBRAL ISCHEMIC ATTACKS IN PATIENT ON DIRECT ACTING ORAL ANTICOAGULANTS FOR ATRIAL FIBRILLATION

Abstract We present the case of an 81 year old man suffering from hypertensive heart disease with dilated evolution, dyslipidemia and previous TIAs; on one occasion documentation of cardioembolic origin of the event: AF paroxysm. CHA2DS2–VASc Score = 6. In therapy with DOAC: Dabigatran 110 mg x 2. Placed in therapy with Mysoline for inconstant tremors of the limbs and doubt of absences. Three days after the start of this therapy, the patient was hospitalized for dysarthria (2 h); NIHSS: 0 and ABCD2 score: 4; Brain CT: not acute lesions; centralization to Hub stroke not indicated and DOAC dosage not performed in the PS; at the verification of the DOAC concentration at the peak, during the infra–hospital intake, values of 123 ng / ml; no changes in blood pressure at onset, unchanged CHA2DS2 Vasc Score and HAS–BLED, unchanged blood tests, verified correct intake (CP count), kept the original packaging of the drug, there were no changes in body weight and there was no associated GE pathology; however, primidone was found to be a drug able to decreasing the plasma levels of Dabigatran as an inducer of P–gp glycoprotein. Tp confirmed with Dabigatran and Mysoline replaced with Clonazepam. Subsequent new hospitalization for dysarthria (2 h); centralized in Hub stroke; NIHSS: 1 (slight deviation of the buccal rim–outcome); pressure rise upon access to the PS; peak DOAC concentration 53 ng / ml; CT angiography of the neck and intracranial vessels with evidence of significant underlying vascular lesion load already in itself a contraindication to reperfusion tp which has been excluded; no brain CT lesions; hypothesized in the acute phase switch to another DOAC that has been performed; switch to Apixaban 5 mg 1 tablet x 2 and potentiation of antihypertensive treatment. NMR program of brain in sedation for claustrophobia. Subsequent new hospitalization for septic state and profound drowsiness; severe alteration of blood tests; subacute ischemic hypodensity in the peripheral territory of the left posterior brain; exitus of the patient. Many patients with AF remain at high residual risk of stroke despite an apparent appropriate dosage of oral anticoagulant drugs. However, a multidisciplinary and integrated investigation strategy of all known risk factors does not always give an effective answer, as in the case presented, and there is a lack of information in the literature regarding management options in such circumstances.

Eugenol derivatives with 1,2,3-triazole moieties: Oral treatment of cutaneous leishmaniasis and a quantitative structure-activity relationship model for their leishmanicidal activity

Leishmaniasis is a group of neglected vector-borne tropical diseases caused by protozoan parasites of the genus Leishmania that multiply within phagocytic cells and have a wide range of clinical manifestations. Cutaneous leishmaniasis (CL) is a serious public health that affects more than 98 countries, putting 350 million people at risk. There are no vaccines that have been proven to prevent CL, and the treatment relies on drugs that often have severe side effects, justifying the search for new antileishmanial treatments. In the present investigation, it is demonstrated that 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) presents significant antileishmanial activity (IC50 of 7.4 μmol L−1 and 1.6 μmol L−1 for promastigote and amastigote forms, respectively), low cytotoxicity against macrophage cells (IC50 of 211.9 μmol L−1), and a selective index of 132.5. Under similar conditions, compound 7k outperformed glucantime and pentamidine, two commonly used drugs in clinics. In vivo assays on CL-infected female BALB/c mice demonstrated that compound 7k had activity similar to intralesional glucantime when administered orally, with decreased lesion and parasitic load, and a low systemic toxic effect. Given the importance of understanding the relationship between compound structure and biological activity in the research and development of new drugs, the development of a quantitative structure-activity relationship (QSAR) model for the leishmanicidal activity presented by the eugenol derivatives with 1,2,3-triazole functionalities is also described herein. This study demonstrates the therapeutic potential of orally active eugenol derivatives against CL and provides useful insights into the relationship between the chemical structures of triazolic eugenol derivatives and their biological profile.

Prefrontal-amygdala emotion regulation and depression in multiple sclerosis.

Depression is among the most common comorbidities in multiple sclerosis and has severe psychosocial consequences. Alterations in neural emotion regulation in amygdala and prefrontal cortex have been recognized as key mechanism of depression but never been investigated in multiple sclerosis depression. In this cross-sectional observational study, we employed a functional MRI task investigating neural emotion regulation by contrasting regulated versus unregulated negative stimulus perception in 16 persons with multiple sclerosis and depression (47.9 ± 11.8 years; 14 female) and 26 persons with multiple sclerosis but without depression (47.3 ± 11.7 years; 14 female). We tested the impact of depression and its interaction with lesions in amygdala-prefrontal fibre tracts on brain activity reflecting emotion regulation. A potential impact of sex, age, information processing speed, disease duration, overall lesion load, grey matter fraction, and treatment was taken into account in these analyses. Patients with depression were less able (i) to downregulate negative emotions than those without (t = −2.25, P = 0.012, β = −0.33) on a behavioural level according to self-report data and (ii) to downregulate activity in a left amygdala coordinate (t = 3.03, PFamily-wise error [FWE]-corrected = 0.017, β = 0.39). Moreover, (iii) an interdependent effect of depression and lesions in amygdala-prefrontal tracts on activity was found in two left amygdala coordinates (t = 3.53, pFWE = 0.007, β = 0.48; t = 3.21, pFWE = 0.0158, β = 0.49) and one right amygdala coordinate (t = 3.41, pFWE = 0.009, β = 0.51). Compatible with key elements of the cognitive depression theory formulated for idiopathic depression, our study demonstrates that depression in multiple sclerosis is characterized by impaired neurobehavioural emotion regulation. Complementing these findings, it shows that the relation between neural emotion regulation and depression is affected by lesion load, a key pathological feature of multiple sclerosis, located in amygdala-prefrontal tracts.

Disseminated Cysticercosis in Indian Scenario - Experience from a Teaching University Hospital.

Neurocysticercosis (NCC) due to Taenia Solium is a major public health problem. Our objective was to study patients with disseminated cysticercosis (DCC) who had NCC in the brain along with an additional site in the body and assess their clinical, radiological profile, and response to therapy. A chart review of DCC with a high lesion load of NCC ≥20 (DNCC) in the brain was performed. Sixteen (M:F = 13:3) patients were diagnosed with DNCC with a mean age of presentation of 35.1 ± 14.2 years. Headache was the predominant symptom, followed by seizures (93.75%), vomiting (43.75%), behavioral disturbances (31.25%), fever (12.5%), encephalopathy (12.5%), visual disturbances (6.25%), and muscle pain and limb weakness (6.25%). CT brain showed multiple active parenchymal cysts in all, and calcifications in 68.75%. MRI brain revealed involvement of cortex and subcortical structures in all, followed by cerebellum (81.25%) and brainstem (75%). Intramedullary spinal lesion was observed in 12.5% cases. Albendazole with steroids was used in 15 patients. In 93.3% patients, there was complete improvement in seizures; 12.5% subjects had persistent memory and behavioral abnormalities. One subject required decompressive craniectomy; mortality was observed in two subjects. We hereby report one of the largest case series on disseminated cysticercosis with a high lesion load of NCC in the brain. A comprehensive clinical, imaging, therapeutic response with repeat imaging and long-term follow-up has given us a better understanding of this difficult-to-treat neurological disorder. We suggest cautious use of anti-parasitic therapy under the cover of corticosteroids to prevent irreversible neurological sequelae.

Inhibition of Galectin-3 Impairs Antifungal Immune Response in Fungal Keratitis.

Galectin-3 is one of the galectin family members which are master regulators of immune homeostasis, especially in infectious diseases. However, its mechanism of immune regulation in fungal keratitis has not been thoroughly studied. Our study is aimed at clarifying the role of galectin-3 in the fungal keratitis mouse model in vivo, thereby providing a new biomarker of antifungal therapy. In our study, aspergillus, the most common pathogenic fungi of fungal keratitis, was identified and isolated by corneal tissue fungus culture. Then, the RNA expression levels of galectin family members in corneas of the mouse model with aspergillus fumigatus keratitis were screened by transcriptome sequencing (RNA-seq). The expression of the galectin-3 was detected by quantitative real-time Polymerase Chain Reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence in the corneal tissue of the fungal keratitis mouse model. Recruitment of neutrophils and the co-immunofluorescence of galectin-3 and related markers in corneal tissue were determined by flow cytometry analysis and immunofluorescence staining. The regulatory role of galectin-3 for proinflammatory cytokines and neutrophils was validated by the knockout mouse model. Galectin-3 knockout deteriorated the condition for the inhibition of galectin-3 was benefecial for fungi to survive and thrive in corneal lesions. These results demonstrated that in the ocular fungal infection, galectin-3 is capable of regulating the pathogenesis of fungal keratitis by modulating neutrophil recruitment. The deterioration of fungal keratitis and increased fungal load in corneal lesions of galectin-3 knockout mice proved the regulatory role of galectin-3 in fungal keratitis. In conclusion, galectin-3 is going to be an essential target to modulate neutrophil recruitment and its related antifungal immune response in fungal keratitis.