Lesion Load Research Articles

Unveiling of the antileishmanial activities of Linalool loaded zinc oxide nanocomposite through its potent antioxidant and immunomodulatory effects

This study aimed to produce linalool loaded zinc oxide nanocomposite (LZNPs) and assess its in vitro and in vivo antileishmanial effects against Leishmania major. LZNPs was produced through the synthesis of an ethanolic solution containing polyvinyl alcohol. The average size of LZNPs was determined to be 105 nm. The findings indicated that LZNPs displayed significant (p < 0.01) antileishmanial effects on promastigotes and amastigotes. Following exposure of promastigotes to LZNPs, there was a notable rise in the percentage of early and late apoptotic cells from 9.0 to 57.2 %. The gene expression levels of iNOS, IFN-γ, and TNF-α in macrophages were upregulated in a dose-dependent approach following exposure to LZNPs. LZNPs alone and in conjunction with glucantime (Glu) resulted in a reduction in the diameter and parasite load of CL lesions in infected mice. Treatment of the CL-infected mice with LZNPs at 25 and 50 mg/kg mainly in combination with Glu-reduced the tissue level of malondialdehyde (MDA), increased both gene and protein expression of the antioxidant enzymes as well as raised the expression level of IFN-γ and IL-12 cytokines, whereas caused a significant reduction in the expression level of IL-4. The present study shows that LZNPs has potent antileishmanial effects and controls CL in a mice model through its antioxidant and immunomodulatory properties. Further investigation, especially in clinical trials, could explore the potential use of this nanocomposite in managing and treating CL.

Characteristics, Prevalence, and Clinical Relevance of Juxtacortical Paramagnetic Rims in Patients With Multiple Sclerosis.

A subgroup of patients with multiple sclerosis (MS) presents focal paramagnetic rims at the border between cortex and white matter (juxtacortical paramagnetic rims [JPRs]). We investigated the presence of this finding in our in vivo MS cohort and explored its potential clinical relevance. Moreover, we exploited postmortem MRI of fixed whole MS brains to (1) detect those rims and (2) investigate their histologic correlation. Quantitative susceptibility mapping (QSM) and magnetization-prepared 2 rapid acquisition gradient-echo (MP2RAGE) images at 3T-MRI of 165 patients with MS from the in vivo cohort were screened for JPRs and the presence of cortical lesions. Five postmortem brains from patients with MS were imaged with 3T-MRI to obtain QSM and MP2RAGE sequences. Tissue blocks containing JPRs were excised and paraffin-embedded slices stained by immunohistochemistry for myelin basic protein (for myelin) and anti-CR3/43 (for major histocompatibility complex II-positive microglia/macrophages). DAB-Turnbull stain was performed to detect iron. JPRs are present in approximately 10% of in vivo patients and are associated with increased cortical lesion load. One of the 5 postmortem brains showed JPRs. Histologically, JPRs correspond to an accumulation of activated iron-laden phagocytes and are associated with demyelination of the whole overlying cortical ribbon. JPRs are a novel potential MRI biomarker of focal cortical demyelination, which seems related to global cortical pathology and might be useful for diagnostic and stratification purposes in a clinical setting.

Integration of network pharmacology with experimental validation to reveal the mechanism of action of Longdan Xiegan Decoction against HSV2 infection and determine its effective components

Ethnopharmacological relevanceTraditional Chinese Medicine (TCM) has made enormous strides recently in the discovery of anti-herpes simplex virus (HSV) drugs under the guidance of TCM theory. Longdan Xiegan Decoction (LXD), a formulation recorded in the Pharmacopoeia of the People's Republic of China, has proved to be effective against HSV infection. However, its effective components and action mechanism remain unclear. Aim of the studyTo investigate the effective components and mechanisms of LXD in treating HSV infection based on network pharmacology and experimental validation. Materials and methodsThe anti-HSV activities of key compounds predicted by network analysis were detected by antiviral tests. High-performance liquid chromatography (HPLC) was applied to identify the main components of the LXD aqueous extract. Time-of-addition assay and infectivity inhibition reversibility assay were conducted to identify the potential antiviral mechanisms of licochalcone B (LCB). Additionally, we assessed the antiviral effect of LCB in vivo by use of body weight, viral load, histological analysis, and scoring of genital lesions in an HSV2-infected mouse model. ResultsOur data demonstrated that some components exhibited significant anti-HSV1/2 activity in vitro, including quercetin, kaempferol, wogonin, formononetin, naringenin, baicalein, isorhamnetin, glabridin, licochalcone A, echinatin, oroxylin A, isoliquiritigenin, pinocembrin, LCB and acacetin. HPLC analysis showed that LCB was the main component of LXD aqueous extract. In vitro experiments revealed that LCB not only inactivated HSV2 particles, but also inhibited HSV2 multiplication through the inhibition of the phosphorylation of Akt and its downstream targets. In vivo experiments confirmed that LCB could significantly reduce viral titer, delay weight loss, and alleviate pathological changes in vaginal tissue in vaginal infection mouse models. ConclusionLCB acted as the main component of LXD, with significant anti-HSV2 infection effects both in vivo and in vitro. This study provides additional evidence of the healing efficacy of LXD against HSV infection and presents an efficient analytical method for further investigation of the mechanisms of TCM in prevention and treatment of various diseases.

Analysis of the prevalence of anticoagulant therapy in patients with cognitive disorders and cerebral amyloid angiopathy (CAA)

To investigate the prevalence of coincident anticoagulation in patients with cognitive disorders and possible or probable cerebral amyloid angiopathy (CAA) as well as the relationship between the presence of oral anticoagulation and CAA-specific lesion load. Patients with subjective cognitive decline (SCD), amnestic and non-amnestic mild cognitive impairment (aMCI/naMCI), Alzheimer's disease (AD), mixed dementia (MD) and vascular dementia (VD) who presented to our outpatient dementia clinic between February 2016 and October 2020 were included in this retrospective analysis. Patients underwent cranial magnetic resonance imaging (MRI). MRI data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. Presence of anticoagulant therapy was determined by chart review. Within the study period, 458 patients (209 male, 249 female, mean age 73.2 ± 9.9years) with SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) and VD (n = 4) were analyzed. Atotal of 109 patients (23.8%) were diagnosed with possible or probable CAA. CAA prevalence was highest in aMCI (39.4%) and MD (28.4%). Of patients with possible or probable CAA, 30.3% were under platelet aggregation inhibition, 12.8% were treated with novel oral anticoagulants and 3.7% received phenprocoumon treatment. Regarding the whole study cohort, patients under oral anticoagulation showed more cerebral microbleeds (p = 0.047). There was no relationship between oral anticoagulation therapy and the frequency of cortical superficial siderosis (p = 0.634). CAA is afrequent phenomenon in older patients with cognitive disorders. Almost half of CAA patients receive anticoagulant therapy. Oral anticoagulation is associated with ahigher number of cortical and subcortical microbleeds.

Magnetic resonance neurography in spinal cord injury: Imaging findings and clinical significance.

It is unknown whether changes to the peripheral nervous system following spinal cord injury (SCI) are relevant for functional recovery or the development of neuropathic pain below the level of injury. Magnetic resonance neurography (MRN) at 3 T allows detection and localization of structural and functional nerve damage. This study aimed to combine MRN and clinical assessments in individuals with chronic SCI and nondisabled controls. Twenty participants with chronic SCI and 20 controls matched for gender, age, and body mass index underwent MRN of the L5 dorsal root ganglia (DRG) and the sciatic nerve. DRG volume, sciatic nerve mean cross-sectional area (CSA), fascicular lesion load, and fractional anisotropy (FA), a marker for functional nerve integrity, were calculated. Results were correlated with clinical assessments and nerve conduction studies. Sciatic nerve CSA and lesion load were higher (21.29 ± 5.82 mm2 vs. 14.08 ± 4.62 mm2 , p < 0.001; and 8.70 ± 7.47% vs. 3.60 ± 2.45%, p < 0.001) in individuals with SCI compared to controls, whereas FA was lower (0.55 ± 0.11 vs. 0.63 ± 0.08, p = 0.022). DRG volumes were larger in individuals with SCI who suffered from neuropathic pain compared to those without neuropathic pain (223.7 ± 53.08 mm3 vs. 159.7 ± 55.66 mm3 , p = 0.043). Sciatic MRN parameters correlated with electrophysiological results but did not correlate with the extent of myelopathy or clinical severity of SCI. Individuals with chronic SCI are subject to a decline of structural peripheral nerve integrity that may occur independently from the clinical severity of SCI. Larger volumes of DRG in SCI with neuropathic pain support existing evidence from animal studies on SCI-related neuropathic pain.

Personalized Use of Disease-Modifying Therapies in Multiple Sclerosis.

Multiple sclerosis is an important neurological disease affecting millions of young patients globally. It is encouraging that more than ten disease-modifying drugs became available for use in the past two decades. These disease-modifying therapies (DMTs) have different levels of efficacy, routes of administration, adverse effect profiles and concerns for pregnancy. Much knowledge and caution are needed for their appropriate use in MS patients who are heterogeneous in clinical features and severity, lesion load on magnetic resonance imaging and response to DMT. We aim for an updated review of the concept of personalization in the use of DMT for relapsing MS patients. Shared decision making with consideration for the preference and expectation of patients who understand the potential efficacy/benefits and risks of DMT is advocated.

Adaptation of the Concept of Brain Reserve for the Prediction of Stroke Outcome: Proxies, Neural Mechanisms, and Significance for Research.

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies-quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging.

Age-related decline in cerebral oxygen consumption in multiple sclerosis

Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (−15%, p = 0.002) and decreased significantly with age in patients relative to the controls (−1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

Stratified predictions of upper limb motor outcomes after stroke.

Longitudinal observations of upper limb motor recovery after stroke have suggested that certain subgroups may exhibit distinct recovery patterns. Here we sought to examine whether the predictive ability for post-stroke upper limb motor outcomes could be enhanced by applying conventional stratification strategies. For 60 individuals who suffered the first stroke, upper limb motor impairment was assessed with the upper extremity Fugl-Meyer assessment (UE-FMA) at 2 weeks as a baseline and then 3 months post-stroke. Brain structural damage at baseline was assessed by MRI data-derived markers ranging from traditional lesion size to the lesion load and to the disconnectome. Linear regression models for predicting upper limb motor outcomes (UE-FMA score at 3 months post-stroke) based on baseline upper limb motor impairment (UE-FMA score at 2 weeks post-stroke), brain structural damage, and their combinations were generated, and those with the best predictive performance were determined for individual subgroups stratified according to initial impairment (severe and non-severe), lesion location (cortical and non-cortical), and neurophysiological status (motor evoked potential-positive and motor evoked potential-negative). The best predictions were made by baseline upper limb motor impairment alone for subgroups with less functional impairment (non-severe) or less structural involvement (non-cortical), but by the combination of baseline upper limb motor impairment and brain structural damage for the other subgroups. The predictive models tailored for subgroups determined according to initial impairment and neurophysiological status yielded a smaller overall error than that for the whole group in upper limb motor outcome predictions. The predictive ability for upper limb motor outcomes could be enhanced beyond the one-size-fits-all model for all individuals with stroke by applying specific stratification strategies, with stratification according to initial impairment being the most promising. We expect that predictive models tailored for individual subgroups could lead closer to the personalized prognosis of upper limb motor outcomes after stroke.

Enlarged choroid plexus in multiple sclerosis is associated with increased lesion load and atrophy in white matter but not gray matter atrophy

BackgroundEnlargement of the choroid plexus (CP) is reported to associate with inflammatory activity and contribute to brain atrophy in patients with multiple sclerosis (pwMS). However, a recent study in healthy volunteers (HVTs) has suggested that CP enlargement can be attributed to ventriculomegaly. ObjectivesTo clarify the pathological significance of the enlargement of CP in multiple sclerosis (MS). MethodsA total of 102 pwMS (89 with relapsing-remitting MS and 13 with secondary progressive MS) and 41 HVTs were cross-sectionally evaluated using brain volumetry. The CP volume was compared between disease groups and investigated for the relationships with other brain regional volumes. ResultsCP volume was significantly larger in pwMS than in HVTs in the univariate analysis, but not in multivariable analysis. Meanwhile, the CP and lateral ventricle (LV) volumes were significantly correlated. CP enlargement was significantly associated with increased lesion load and cerebral white matter (WM) atrophy, even after adjusting for LV volume. In contrast, multivariable analyses revealed that LV enlargement, but not CP enlargement, was associated with total gray matter (GM) atrophy. ConclusionCP enlargement was closely associated with LV enlargement. After adjusting for LV volume, CP enlargement in pwMS was associated with increased lesion load and WM atrophy but not GM atrophy.

The volume and the distribution of premorbid white matter hyperintensities: Impact on post-stroke aphasia.

White matter hyperintensities (WMH) are a radiological manifestation of progressive white matter integrity loss. The total volume and distribution of WMH within the corpus callosum have been associated with pathological cognitive ageing processes but have not been considered in relation to post-stroke aphasia outcomes. We investigated the contribution of both the total volume of WMH, and the extent of WMH lesion load in the corpus callosum to the recovery of language after first-ever stroke. Behavioural and neuroimaging data from individuals (N = 37) with a left-hemisphere stroke were included at the early subacute stage of recovery. Spoken language comprehension and production abilities were assessed using word and sentence-level tasks. Neuroimaging data was used to derive stroke lesion variables (volume and lesion load to language critical regions) and WMH variables (WMH volume and lesion load to three callosal segments). WMH volume did not predict variance in language measures, when considered together with stroke lesion and demographic variables. However, WMH lesion load in the forceps minor segment of the corpus callosum explained variance in early subacute comprehension abilities (t = -2.59, p = .01) together with corrected stroke lesion volume and socio-demographic variables. Premorbid WMH lesions in the forceps minor were negatively associated with early subacute language comprehension after aphasic stroke. This negative impact of callosal WMH on language is consistent with converging evidence from pathological ageing suggesting that callosal WMH disrupt the neural networks supporting a range of cognitive functions.

Data-driven biomarkers better associate with stroke motor outcomes than theory-based biomarkers.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have associated motor outcomes with the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to model chronic motor outcomes after stroke and compares the accuracy of these associations to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients from the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Stroke Recovery Working Group. Using the explained variance metric to measure the strength of the association between chronic motor outcomes and imaging biomarkers, we compared theory-based biomarkers, like lesion load to known motor tracts, to three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had stronger associations with chronic motor outcomes accuracy than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R 2 = 0.210, P < 0.001), performing significantly better than the theory-based biomarkers of lesion load of the corticospinal tract (R 2 = 0.132, P < 0.001) and of multiple descending motor tracts (R 2 = 0.180, P < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R 2 = 0.200, P < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R 2 = 0.167, P < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved the strength of associations for theory-based and data-driven biomarkers. Combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R 2 = 0.241, P < 0.001. Overall, these results demonstrate that out-of-sample associations between chronic motor outcomes and data-driven imaging features, particularly when lesion data is represented in terms of structural disconnection, are stronger than associations between chronic motor outcomes and theory-based biomarkers. However, combining both theory-based and data-driven models provides the most robust associations.

White matter disconnection impacts proprioception post-stroke.

Proprioceptive impairments occur in approximately 50-64% of people following stroke. While much is known about the grey matter structures underlying proprioception, our understanding of the white matter correlates of proprioceptive impairments is less well developed. It is recognised that behavioural impairments post-stroke are often the result of disconnection between wide-scale brain networks, however the disconnectome associated with proprioception post-stroke is unknown. In the current study, white matter disconnection was assessed in relation to performance on a robotic arm position matching (APM) task. Neuroimaging and robotic assessments of proprioception were collected for 203 stroke survivors, approximately 2-weeks post-stroke. The robotic assessment was performed in a KINARM Exoskeleton robotic device and consisted of a nine-target APM task. First, the relationship between white matter tract lesion load and performance on the APM task was assessed. Next, differences in the disconnectome between participants with and without impairments on the APM task were examined. Greater lesion load to the superior longitudinal fasciculus (SLF II and III), arcuate fasciculus (all segments) and fronto-insular tracts were associated with worse APM task performance. In those with APM task impairments, there was, additionally, disconnection of the posterior corpus callosum, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus and optic radiations. This study highlights an important perisylvian white matter network supporting proprioceptive processing in the human brain. It also identifies white matter tracts, important for relaying proprioceptive information from parietal and frontal brain regions, that are not traditionally considered proprioceptive in nature.

Cerebrovascular lesion loads and accelerated brain aging: insights into the cognitive spectrum.

White matter hyperintensities (WMHs) and cerebral microbleeds are widespread among aging population and linked with cognitive deficits in mild cognitive impairment (MCI), vascular MCI (V-MCI), and Alzheimer's disease without (AD) or with a vascular component (V-AD). In this study, we aimed to investigate the association between brain age, which reflects global brain health, and cerebrovascular lesion load in the context of pathological aging in diverse forms of clinically-defined neurodegenerative conditions. We computed brain-predicted age difference (brain-PAD: predicted brain age minus chronological age) in the Comprehensive Assessment of Neurodegeneration and Dementia cohort of the Canadian Consortium on Neurodegeneration in Aging including 70 cognitively intact elderly (CIE), 173 MCI, 88 V-MCI, 50 AD, and 47 V-AD using T1-weighted magnetic resonance imaging (MRI) scans. We used a well-established automated methodology that leveraged fluid attenuated inversion recovery MRIs for precise quantification of WMH burden. Additionally, cerebral microbleeds were detected utilizing a validated segmentation tool based on the ResNet50 network, utilizing routine T1-weighted, T2-weighted, and T2* MRI scans. The mean brain-PAD in the CIE cohort was around zero, whereas the four categories showed a significantly higher mean brain-PAD compared to CIE, except MCI group. A notable association trend between brain-PAD and WMH loads was observed in aging and across the spectrum of cognitive impairment due to AD, but not between brain-PAD and microbleed loads. WMHs were associated with faster brain aging and should be considered as a risk factor which imperils brain health in aging and exacerbate brain abnormalities in the context of neurodegeneration of presumed AD origin. Our findings underscore the significance of novel research endeavors aimed at elucidating the etiology, prevention, and treatment of WMH in the area of brain aging.

Characterizing upper extremity fine motor function in the presence of white matter hyperintensities: A 7 T MRI cross-sectional study in older adults

BackgroundWhite matter hyperintensities (WMH) are a prevalent radiographic finding in the aging brain studies. Research on WMH association with motor impairment is mostly focused on the lower-extremity function and further investigation on the upper-extremity is needed. How different degrees of WMH burden impact the network of activation recruited during upper limb motor performance could provide further insight on the complex mechanisms of WMH pathophysiology and its interaction with aging and neurological disease processes. Methods40 healthy elderly subjects without a neurological/psychiatric diagnosis were included in the study (16F, mean age 69.3 years). All subjects underwent ultra-high field 7 T MRI including structural and finger tapping task-fMRI. First, we quantified the WMH lesion load and its spatial distribution. Secondly, we performed a data-driven stratification of the subjects according to their periventricular and deep WMH burdens. Thirdly, we investigated the distribution of neural recruitment and the corresponding activity assessed through BOLD signal changes among different brain regions for groups of subjects. We clustered the degree of WMH based on location, numbers, and volume into three categories; ranging from mild, moderate, and severe. Finally, we explored how the spatial distribution of WMH, and activity elicited during task-fMRI relate to motor function, measured with the 9-Hole Peg Test. ResultsWithin our population, we found three subgroups of subjects, partitioned according to their periventricular and deep WMH lesion load. We found decreased activity in several frontal and cingulate cortex areas in subjects with a severe WMH burden. No statistically significant associations were found when performing the brain-behavior statistical analysis for structural or functional data. ConclusionWMH burden has an effect on brain activity during fine motor control and the activity changes are associated with varying degrees of the total burden and distributions of WMH lesions. Collectively, our results shed new light on the potential impact of WMH on motor function in the context of aging and neurodegeneration.

Outcome Prediction by Combining Corticospinal Tract Lesion Load with Diffusion-tensor Fractional Anisotropy in Patients after Hemorrhagic Stroke.

The objective of this study was to evaluate the predictive precision of combining the corticospinal tract lesion load (CST-LL) with the diffusion-tensor fractional anisotropy of the corticospinal tract (CST-FA) in the lesioned hemispheres regarding motor outcomes. Patients with putaminal and/or thalamic hemorrhage who had undergone computed tomography (CT) soon after onset in our hospital were retrospectively enrolled. The CST-LL was calculated after registration of the CT images to a standard brain. Diffusion-tensor imaging was performed during the second week after onset. Standardized automated tractography was employed to calculate the CST-FA. Outcomes were assessed at discharge from our affiliated rehabilitation facility using total scores of the motor component of the Stroke Impairment Assessment Set (SIAS-motor total; null to full, 0 to 25). Multivariate regression analysis was performed with CST-LL and CST-FA as explanatory variables and SIAS-motor total as a target value. Twenty-five patients participated in this study. SIAS-motor total ranged from 0 to 25 (median, 17). CST-LL ranged from 0.298 to 7.595 (median, 2.522) mL, and the lesion-side CST-FA ranged from 0.211 to 0.530 (median, 0.409). Analysis revealed that both explanatory variables were detected as statistically significant contributory factors. The estimated t values indicated that the contributions of these two variables were almost equal. The obtained regression model accounted for 63.9% of the variability of the target value. Incorporation of the CST-LL with the lesion-side CST-FA enhances the precision of the stroke outcome prediction model.

Diffusion tensor imaging and voxel-based morphometry in differentiating multiple sclerosis and its mimics

BackgroundThe discrimination between multiple sclerosis (MS) and other white matter lesions in adults is still problematic as multiple diseases have similar clinical and radiological findings, especially at the disease onset. This case–control study aimed to evaluate the efficacy of diffusion tensor imaging (DTI) and brain morphometry in the differentiation between adult MS and its magnetic resonance imaging (MRI) mimics.MethodsFifty-eight patients (49 women and 9 men; mean age 35.74 ± 11.86 years, range 18–50 years) with clinically suspected MS and age- and sex-matched fifteen healthy subjects were included. All study subjects underwent MRI using 3D FLAIR, 3D T1 MPRAGE, axial T2WI fast spin echo, and DTI sequences. The included patients were classified into MS and mimics groups according to MC Donald’s criteria 2017. Image post-processing using the region of interest (ROI) analysis for DTI parameters and automated voxel brain morphometry and segmentation was done for all study groups. Statistical comparison between the two patient groups and between them and the control group was performed regarding DTI indices (fractional anisotropy [FA], mean diffusivity [MD], and relative anisotropy [RA]) and brain morphometry parameters (including white matter volume (WMV), grey matter volume (GMV), cerebrospinal fluid volume (CSFV), T2 lesion load and deep grey matter volume).ResultsA statistically significant difference was observed between the MD, FA, and RA values of the patients and control groups. The MD values were significantly higher in the MS than in its mimics with a cut-off value of > 1.058 × 10−3 mm2/s (p < 0.001). Compared to the mimics group, the MS patients showed significantly lower WMV (33.31 ± 4.40 versus 35.71 ± 4.58; p = 0.047) and higher CSFV (16.38 ± 5.93 versus 13.06 ± 3.09; p = 0.012) with no significant difference regarding the GMV.ConclusionsMD analysis of DTI, WMV, and CSFV are useful quantitative measurements in confirming the diagnosis of MS and differentiating it from its imaging mimics.

Preserved Corticospinal Tract Revealed by Acute Perfusion Imaging Relates to Better Outcome After Thrombectomy in Stroke.

The indication for mechanical thrombectomy (MT) in stroke patients with large vessel occlusion has been constantly expanded over the past years. Despite remarkable treatment effects at the group level in clinical trials, many patients remain severely disabled even after successful recanalization. A better understanding of this outcome variability will help to improve clinical decision-making on MT in the acute stage. Here, we test whether current outcome models can be refined by integrating information on the preservation of the corticospinal tract as a functionally crucial white matter tract derived from acute perfusion imaging. We retrospectively analyzed 162 patients with stroke and large vessel occlusion of the anterior circulation who were admitted to the University Medical Center Lübeck between 2014 and 2020 and underwent MT. The ischemic core was defined as fully automatized based on the acute computed tomography perfusion with cerebral blood volume data using outlier detection and clustering algorithms. Normative whole-brain structural connectivity data were used to infer whether the corticospinal tract was affected by the ischemic core or preserved. Ordinal logistic regression models were used to correlate this information with the modified Rankin Scale after 90 days. The preservation of the corticospinal tract was associated with a reduced risk of a worse functional outcome in large vessel occlusion-stroke patients undergoing MT, with an odds ratio of 0.28 (95% CI, 0.15-0.53). This association was still significant after adjusting for multiple confounding covariables, such as age, lesion load, initial symptom severity, sex, stroke side, and recanalization status. A preinterventional computed tomography perfusion-based surrogate of corticospinal tract preservation or disconnectivity is strongly associated with functional outcomes after MT. If validated in independent samples this concept could serve as a novel tool to improve current outcome models to better understand intersubject variability after MT in large vessel occlusion stroke.

Accelerated brain ageing in participants with higher cerebrovascular lesion load across aging, cognitive impairment, and mixed presentation

AbstractBackgroundWe aimed to investigate the association between cortical brain age and white matter hyperintensities (WMH) in diverse forms of clinically‐defined vascular conditions. Our hypothesis was that a higher WMH burden would be associated with higher cortical brain age in all clinical subtypes.MethodWe used standardized MRI data obtained from participants in the COMPASS‐ND cohort of the CCNA. We used a standard linear support vector regression algorithm to estimate brain age, matching chronological age to cortical anatomical measurements obtained with the FreeSurfer toolbox on T1‐weighted MRI, sex, and intracranial volume. We calculated brain‐PAD (i.e., predicted brain age minus real age) and applied bias adjustment to remove age‐dependency in the estimates. A validated automated technique utilizing T2‐weighted and fluid attenuated inversion recovery MRIs was used to compute WMH loads.ResultParticipants included 107 CIE, 240 mild cognitive impairment (MCI), 115 vascular‐MCI (V‐MCI), 81 probable Alzheimer’s disease (AD), and 50 V‐AD. There was a significant difference in brain‐PAD [ F (4,599) = 56, P &lt; 0.001, ANCOVA test] among groups, whilst adjusting for sex and chronological age. All four categories of patients exhibited a significantly higher mean brain‐PAD than CIE (P &lt; 0.001), with the AD cohort having the highest brain‐PAD. There was a significant difference in WMH loads [ F (4,586) = 48, P &lt; 0.001, ANCOVA test] between groups, whilst adjusting for sex and age. All cohorts showed a positive correlation between brain‐PAD and WMH, indicating accelerated ageing in people with higher WMHs. We observed moderate and significant correlations between brain‐PAD and WMH loads for V‐MCI (r = 0.34, P &lt; 0.001) and V‐AD (r = 0.36, P = 0.001) but weaker, while significant correlations in CIE (r = 0.20, P = 0.035) and AD cohorts (r = 0.24, P = 0.025).ConclusionWe observed a positive and significant link between brain‐PAD and WMH in all categories. This finding indicates on the importance of treatment and prevention strategies for vascular risk factors, which might be able to slow down the progression of cerebrovascular lesions and delay the effect on cortical thickness.

White Matter Correlates of Speech in Cerebrovascular Disease

AbstractBackgroundAnalyses of spoken discourse (speech beyond single words or sentences) can detect cognitive impairment in cerebrovascular disease (CVD) [Roberts, et al. (2021). Top Lang Disord 41(1):73‐98]. However, the neurological basis for altered spoken discourse in CVD is poorly defined. This study examined the association between spoken discourse and visible white matter damage detected using structural magnetic resonance imaging (MRI) and potential early‐stage damage in normal‐appearing white matter (NAWM) detected using diffusion tensor imaging (DTI) to better define the link between CVD‐related neurodegeneration and altered speech.MethodSpoken discourse and 3T MRI data were obtained from the CVD cohort of the Ontario Neurodegenerative Disease Research Initiative (n = 127). Spoken discourse analyses were completed previously [Roberts et al., 2021]. White matter hyperintensities (WMH) and the NAWM portions of the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus – parietal (SLFp) and temporal (SLFt) endings, and uncinate fasciculus (UNC) were segmented in each hemisphere (Figure 1). Mean values of fractional anisotropy (FA) and mean diffusivity (MD) within NAWM, and normalized WMH volume were calculated for each of the white matter tracts. Three canonical correlation analyses examined associations between 10 spoken discourse measures and the imaging metrics (WMH volume, FA, MD) in each tract.ResultCanonical correlations were significant for FA (rc = 0.51, p&lt;0.05) and MD (rc = 0.56, p&lt;0.05) but not WMH volume (rc = 0.42, p = 0.69). Among the white matter tracts, the strongest canonical loadings were seen for FA and MD in the left SLFp (FA: 0.80; MD: ‐0.61) and left SLFt (FA: 0.60; MD: ‐0.40) (Figure 2). Higher FA and lower MD in the left SLFp and left SLFt were associated with fluency, information content, and syntax performance.ConclusionSpoken discourse performance was associated with microstructural integrity of NAWM but not visible white matter damage. These results suggest that DTI metrics provide a more relevant assessment of white matter tract function in relation to speech than a volumetric measure of tract lesion load. Of the white matter tracts investigated in this study, spoken discourse performance in CVD was most strongly linked to white matter microstructure in the parietal and temporal endings of the left superior longitudinal fasciculus.