Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy

AimsDiabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM).MethodsKtrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).ResultsIn all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs.ConclusionsThis study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

Associations Among Diffusion Tensor Image Along the Perivascular Space (DTI-ALPS), Enlarged Perivascular Space (ePVS), and Cognitive Functions in Asymptomatic Patients With Carotid Plaque

Background and Aim: Carotid atherosclerosis (CAS) is a common pathogenesis of cerebrovascular disease closely related to stroke and silent cerebrovascular disease (SCD), while the insufficient brain perfusion mechanism cannot quite explain the mechanism. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate the glymphatic system activity and correlated DTI-ALPS with enlarged perivascular spaces (ePVS), carotid intima-media thickening (CIMT), mini-mental state examination (MMSE), and serological indicator in individuals with carotid plaque.Methods: Routine MRI and diffusion tensor images scan of the brain, carotid ultrasound, and blood examination were conducted on 74 individuals (52 carotid plaque subjects, 22 non-carotid plaque subjects), whose demographic and clinical characteristics were also recorded. DTI-ALPS index between patients with carotid plaque and normal controls were acquired and the correlations with other variables were analyzed.Results: The values of ALPS-index in the carotid plaque group was significantly lower compared to normal controls (2.12 ± 0.39, 1.95 ± 0.28, respectively, p = 0.034). The ALPS-index was negatively correlated with the basal ganglia (BG)-ePVS score (r = −0.242, p = 0.038) while there was no significant difference in the centrum semiovale (CSO)-ePVS score. Further analysis showed that there are more high-grade ePVS in the BG compared to the carotid plaque group than in the non-carotid plaque group (84.6% vs. 40.9%, p = 0.001).Conclusions: ALPS-index reflects the glymphatic system of the brain, which is associated with early high-risk cerebrovascular diseases. There may be damage in the function of the glymphatic system which induces the expansion of the perivascular space (PVS) in the BG in individuals with carotid plaque.

Techniques for visualizing fibroblast-vessel interactions in the developing and adult CNS

Fibroblasts are found associated with blood vessels in various locations across the CNS: in the meninges, the choroid plexus, and in the parenchyma within perivascular spaces. CNS fibroblasts have been characterized using transcriptional profiling and a Col1a1-GFP mouse line used to identify CNS fibroblasts in vivo. However, current methods for visualizing CNS fibroblasts are lacking and, in particular, prevent adequate assessment of fibroblast-vessel interactions. Here, we describe methods for whole mount visualization of meningeal and choroid plexus fibroblasts, and optical tissue clearing methods for visualization of parenchymal vessel-associated fibroblasts. Importantly, these techniques can be combined with immunohistochemistry methods for labeling different cell types in the meninges and blood vasculature as well as EdU-based cell proliferation assays. These methods are ideal for visualization of vessel-fibroblast interactions in these CNS structures and provide significant improvement over traditional sectioning and staining methods. We expect these methods will advance studies of CNS fibroblast development and functions in homeostasis, injury, and disease.

Pathomorphological markers of blast-induced brain injury

Background. Recently, interest in blast-induced brain injuries has been increasing due to military events and the use of explosive devices in eastern Ukraine. Considering the diagnostic uncertainty regarding the specific signs of brain injury after the distant action of an blast shock wave, the danger of prognostic consequences, the increase of the cases of explosive injury number, we consider that selected for study topic is relevant. Objective. Purpose – determination of pathomorphological changes of the brain after the action of the blast wave. Methods. To solving this purpose, a retrospective analysis of 280 cases of fatal military blast injuries was conducted. We selected 6 cases for microscopic examination of the brain. For histological examination, samples were taken from different parts of the brain. Results. Analysis of 280 deaths due to explosive trauma showed that 58.9% of the dead (165) had a traumatic brain injury, and in 131 cases it was accompanied by fractures of the bones of the vault and the base of the skull. Isolated traumatic brain injury was detected in only 33 cases (11.8%). Age distribution analysis of the dead people showed that 67.5% of the dead were between the ages of 21 and 40. Histopathological analysis of brain samples from the dead allowed to identify the characteristic signs of blast-induced brain injury in the form of diffuse formation of perivascular microhemorrhages with partial or complete separation of the vascular wall from the neuropil. Conclusion. The complex of microscopic signs in the brain, namely, the separation of vascular wall from neuroglia with the formation of perivascular space, fragmentation of these vessels walls, erythrocytes hemolysis, hemorrhage in the newly formed perivascular spaces, are direct evidences of the blast wave action.

Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE–HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.

Clinical Reasoning: A 55-Year-Old Woman With Recurrent Episodes of Aphasia and Vision Changes

A 55-year-old woman presented with recurrent episodes of headache, vision changes and language disturbances. Brain MRI showed multifocal white matter lesions, microhemorrhages, and enlarged perivascular spaces. After an extensive and unrevealing workup, she underwent a biopsy of brain and meninges that revealed thick and hyalinized leptomeningeal and cortical vessel walls that were strongly positive for ß-amyloid by immunohistochemical staining, suggestive of cerebral amyloid angiopathy (CAA). CAA can present as a spectrum of inflammatory responses to the deposition of amyloid-ß in the vessel walls. Her clinical presentation, radiological and histopathological findings supported a diagnosis of probable CAA-related inflammation (CAA-ri). Although an uncommon entity, it is important to recognize it because most patients respond to immunosuppressive therapy.

Giant tumefactive perivascular spaces in a pediatric patient: A rare radiological entity

Background: Giant tumefactive perivascular spaces (TPVS) are radiological rarities and may mimic other neurological structural lesions. Fewer than 80 cases have been reported in the literature with even fewer in the pediatric population. Case Description: The authors present an image report showcasing a 3-year-old boy presenting with uncontrolled seizures despite multiple anti-epileptic medications. His magnetic resonance imaging showed multiple, non-contrast enhancing cyst clusters within the left parieto-occipital region that was hyperintense on T2-weighted imaging, and isointense to cerebrospinal fluid. Due to a characteristic absence of perilesional edema seen on fluid-attenuated inversion recovery imaging or diffusion restriction on diffusion-weighted imaging (DWI) sequences, this was diagnosed as a giant TPVS. Conclusion: Accurate diagnosis of these rare radiological entities is based on pathognomonic findings that can help prevent unnecessary surgery and guide management for patients, particularly in the pediatric population as seen in our case.

Association of total cerebral small vessel disease burden with the cavitation of recent small subcortical infarcts

Background Recent small subcortical infarcts (RSSIs) could evolve into cavitation (lacunes) or non-cavitation (white matter hyperintensities or disappearance) during the chronic period, but the factors involved remain unclear. Purpose To explore the association between total cerebral small vessel disease (CSVD) burden and lesion cavitation. Material and Methods We retrospectively selected 202 inpatients with an isolated RSSI who underwent baseline and follow-up magnetic resonance imaging (median interval = 16.6 months; interquartile range [IQR]=8.2–30.1). Inpatients were divided into cavitation and non-cavitation groups depending on whether a fluid-filled cavity formed. Data including demographic, clinical, and radiological features were collected and analyzed. To determine total CSVD burden, four imaging markers, including lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, were rated and summed as a final practical score between 0 and 4. Results Overall, 137 (67.8%) patients progressed to cavitation and 65 (32.2%) to non-cavitation. Binary multivariable regression analysis showed that the baseline total CSVD burden ( P = 0.005) and infarct diameter ( P = 0.002) were independent risk factors for cavitation. A severe total burden (scores of 3–4) at baseline was independently related to cavitation ( P = 0.001). Moreover, the total CSVD burden score varied from 2 (IQR=1–3) at baseline to 3 (IQR=2–4) at follow-up. The extent of the increase in total burden was correlated with cavitation ( r = 0.201; P = 0.004). Conclusion Total CSVD burden, both the baseline value and extent of increase, was positively associated with cavitation. RSSIs with severe total CSVD burden at baseline have a greater potential to become cavitated.

Total Cerebral Small Vessel Disease Burden on MRI Correlates With Cognitive Impairment in Outpatients With Amnestic Disorders

Objectives: The main markers of cerebral small vessel disease (cSVD) on MRI may be entered into a scoring system, with the total score representing the overall burden of cSVD. An association between total cSVD score and cognitive dysfunction has been reported in several cohorts. The present study aimed to investigate this association in outpatients with amnestic disorders.Materials and Methods: Outpatients with amnestic complaints in a memory clinic (n = 289) were recruited retrospectively. All the patients had undergone clinical and cognitive evaluation at first presentation. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scale. The total cSVD score was based on the following markers on MRI: lacune; white matter hyperintensities, microbleed, and enlarged perivascular spaces. The association between total cSVD score and MoCA score was tested via Spearman's analysis and a linear regression model.Results: Among the 289 patients, rates for 0–4 cSVD markers respectively ranged from 30.4 to 2.8%. A multiple linear regression model revealed an inverse correlation between the total cSVD score and MoCA score. The association remained significant after adjusting for gender, age, education, levels of medial temporal lobe atrophy, and classical vascular risk factors [β = −0.729, 95% CI (−1.244, −0.213); P = 0.006]. When individual markers were individually analyzed after adjusting for the same factors, only microbleed associated with MoCA score [β = −3.007, 95% CI (−4.533, −1.480), P < 0.001].Conclusions: A significant association was demonstrated between total cSVD score and cognitive performance in the outpatients with amnestic disorders.