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Introduction: Cerebral amyloid angiopathy–related inflammation (CAA-ri) derives from inflammatory response to β-amyloid (Aβ) protein deposition within the cerebral blood vessel walls. We report a case that accentuates those clinical and imaging features that can contribute to raise suspicion for the condition and lead to early treatment initiation. Case presentation: A 72-year-old man was referred with one-month history of cognitive decline along with behavioral alterations. Brain MRI showed fluid attenuated inversion recovery (FLAIR) asymmetrical multifocal white matter hyperintensities (WMHs) along with multiple cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on T2*-weighted gradient-recalled echo (T2*-GRE) images. Metabolic, infectious, and neoplastic causes were excluded, and subsequently corticosteroids were administered to the patient resulting in clinical recovery. Imaging on follow-up disclosed remission of WMHs, while CMBs load increased significantly. Discussion: Clinical neurologists' acquaintance with the clinical and imaging features of CAA-ri allows prompt diagnosis and medication initiation, that is essential for a conceivably treatable condition. [ABSTRACT FROM AUTHOR]

Background and Purpose Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer’s disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH). Methods We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models. Results We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P

Background: Acute high-altitude illness (AHAI) refers to a series of syndromes including acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Among these, HACE is a severe and potentially life-threatening condition that can occur when individuals ascend to high altitudes. It is often characterized by ataxia, confusion, and altered mental status. Without appropriate treatment, HACE can rapidly progress to coma, but seizures are infrequent in occurrence. Case presentation: Here, we report a severe HACE patient with coma and status epilepticus. The patient is a 23-year-old male who was visiting Lhasa for the first time. He initially experienced headaches and dizziness on the first day, and then he was found in coma with limb convulsions on the next day. Immediate medical attention was sought, and brain CT and MRI scans showed reversible white matter lesions, especially in the corpus callosum and subcortical white matter. Although the lesions disappeared on T1 and T2 sequences, microbleeds were observed on the SWI sequence. After treatment with tracheal intubation, glucocorticoids and hyperbaric oxygen, the cerebral edema has resolved and the clinical symptoms improved, the patient has no seizures anymore. Conclusions: HACE typically follows AMS and poses a significant risk to life. Clinical manifestations mainly include ataxia, alterations of behavior, and impaired consciousness, with severe cases progressing to coma. Seizures, though rarely observed, may occur. Imaging shows reversible white matter lesions, with microbleeds being a significant and persistent imaging marker over time. Administration of glucocorticoids plays a crucial role in treatment. Despite experiencing seizures, this patient did not experienced any further episodes once his condition improved. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non‐hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non‐hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty‐eight percent of the sample had non‐hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01–1.07), female sex (OR = 1.68, 95% CI = 1.11–2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02–4.35). DISCUSSION: Two‐thirds of patients from a memory clinic cohort had non‐hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. Highlights: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non‐hemorrhagic markers.The prevalence of non‐hemorrhagic CAA markers in memory clinic patients is unknown.Two‐thirds of patients in our memory clinic presented non‐hemorrhagic CAA markers.The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers.The hemorrhagic risk of patients presenting these type of markers remains unclear. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid protein in the walls of cerebral blood vessels. This deposition of amyloid causes damage to the cerebral vasculature, resulting in blood‐brain barrier disruption, cerebral hemorrhage, cognitive decline, and dementia. The role of the immune system in CAA is complex and not fully understood. While the immune system has a clear role in the rare inflammatory variants of CAA (CAA related inflammation and Abeta related angiitis), the more common variants of CAA also have immune system involvement. In a protective role, immune cells may facilitate the clearance of beta‐amyloid from the cerebral vasculature. The immune system can also contribute to CAA pathology, promoting vascular injury, blood‐brain barrier breakdown, inflammation, and progression of CAA. In this review, we summarize the role of the immune system in CAA, including the potential of immune based treatment strategies to slow vascular disease in CAA and associated cognitive impairment, white matter disease progression, and reduce the risk of cerebral hemorrhage. Highlights: The immune system has a role in cerebral amyloid angiopathy (CAA) which is summarized in this review.There is an inflammatory response to beta‐amyloid that may contribute to brain injury and cognitive impairment.Immune cells may facilitate the clearance of beta‐amyloid from the cerebral vasculature.Improved understanding of the immune system in CAA may afford novel treatment to improve outcomes in patients with CAA. [ABSTRACT FROM AUTHOR]

BackgroundChronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.MethodsCKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and gut-derived uremic toxins on brain microvascular endothelial barrier.ResultsCKD was induced in aged C57BL/6J mice with significant increases in both serum creatinine and cystatin C levels (p

Objectives: Cerebral microbleeds (MBs) are recently described entity on magnetic resonance (MR) neuroimaging and are considered one of the markers of small vessel disease. We aimed to study the clinicoradiological features of cerebral MBs that were diagnosed in MR neuroimaging. Materials and Methods: We studied 109 South Indian patients, who presented to a tertiary care institution for MR neuroimaging with cerebral MBs as diagnosed on MR neuroimaging based on either the gradient T2* imaging or susceptibility-weighted imaging. The clinical details and coexisting MR features of infarcts, macrohemorrhages, lacunar infarcts, and white matter leukoaraiosis were evaluated and analyzed. Results: Of 109 patients, 79 were males and 30 were females. Associated clinical comorbidities noted include hypertension (62.39%), diabetes (23.85%), and alcoholism (31.19%) apart from the history of anti-platelet/anti-coagulant usage (15.5%), previous cardiac disease (12.84%), and previous stroke/transient ischemic attacks (9.17%). Other co-existing neuroimaging abnormalities noted include cortical infarcts (27.52%), old hemorrhages (29.36%), lacunar infarcts (56.88%), and white matter leukaraiosis (67.89%). Conclusion: The clinicoradiological features of cerebral MBs in South Indian patients are similar to other Asian and Western studies with significant coexistence of clinical comorbidities and imaging features of small vessel changes. Further studies with a larger sample are needed to correlate the grade of MBs to the individual risk of these clinicoradiological characteristics. [ABSTRACT FROM AUTHOR]

Objectives: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. Method: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. Results: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). Conclusion: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin‐1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre‐/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross‐sectionally evaluated regional Pittsburgh compound B‐positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging‐based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. Highlights: Mutation position influences Aβ burden, SVD, and dementia.PSEN1 pre‐200 group had stronger associations between Aβ burden and disease stage.PSEN1 post‐200 group had stronger associations between SVD markers and disease stage.PSEN1 post‐200 group had worse dementia score than pre‐200 in late disease stage.Diffusion tensor imaging‐based SVD markers mediated mutation position effects on dementia in the late stage. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β aggregation in the media and adventitia of the leptomeningeal and cortical blood vessels. CAA is one of the strongest vascular contributors to Alzheimer's disease (AD). It frequently co-occurs in AD patients, but the relationship between CAA and AD is incompletely understood. CAA may drive AD risk through damage to the neurovascular unit and accelerate parenchymal amyloid and tau deposition. Conversely, early AD may also drive CAA through cerebrovascular remodeling that impairs blood vessels from clearing amyloid-β. Sole reliance on autopsy examination to study CAA limits researchers' ability to investigate CAA's natural disease course and the effect of CAA on cognitive decline. Neuroimaging allows for in vivo assessment of brain function and structure and can be leveraged to investigate CAA staging and explore its associations with AD. In this review, we will discuss neuroimaging modalities that can be used to investigate markers associated with CAA that may impact AD vulnerability including hemorrhages and microbleeds, blood-brain barrier permeability disruption, reduced cerebral blood flow, amyloid and tau accumulation, white matter tract disruption, reduced cerebrovascular reactivity, and lowered brain glucose metabolism. We present possible areas for research inquiry to advance biomarker discovery and improve diagnostics. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of CMB in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), using meta-analytic methods. Sixty-five MRI studies were included after a systematic search on major electronic databases. We found that the prevalence of CMB was comparable across the three dementia subtypes (31–36%) and was highly influenced by the MRI techniques used. CMB in AD were associated with a history of hypertension and amyloid-β burden. In contrast, CMB in DLB, despite being predominantly lobar, were associated with hypertension, but not amyloid-β burden. These findings suggest that the underlying pathophysiology of CMB in DLB might differ from that of AD. There was substantially larger number of AD studies identified and more studies evaluating CMB in Lewy body dementias are warranted. • Microbleeds were present in approximately one-third of common dementia diagnoses. • The prevalence of microbleeds is highly influenced by MRI techniques. • The pathophysiology of microbleeds might differ between dementia subtypes. • More studies investigating microbleeds in Lewy body dementias are needed. [ABSTRACT FROM AUTHOR]

Introduction. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterised by bilateral calcification in the brain, especially in the basal ganglia, leading to neurological and neuropsychiatric manifestations. White matter hyperintensities (WMH) have been described in patients with PFBC and pathogenic variants in the gene for platelet-derived growth factor beta polypeptide (PDGFB), suggesting a manifest cerebrovascular process. We present below the cases of two PFBC families with PDGFB variants and stroke or transient ischaemic attack (TIA) episodes. We examine the possible correlation between PFBC and vascular events as stroke/TIA, and evaluate whether signs for vascular disease in this condition are systemic or limited to the cerebral vessels. Material and methods. Two Swedish families with novel truncating PDGFB variants, p.Gln140* and p.Arg191*, are described clinically and radiologically. Subcutaneous capillary vessels in affected and unaffected family members were examined by light and electron microscopy. Results. All mutation carriers showed WMH and bilateral brain calcifications. The clinical presentations differed, with movement disorder symptoms dominating in family A, and psychiatric symptoms in family B. However, affected members of both families had stroke, TIA, and/or asymptomatic intracerebral ischaemic lesions. Only one of the patients had classical vascular risk factors. Skin microvasculature was normal. Conclusions. Patients with these PDGFB variants develop microvascular changes in the brain, but not the skin. PDGFB-related small vessel disease can manifest radiologically as cerebral haemorrhage or ischaemia, and may explain TIA or stroke in patients without other vascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds (CMBs) influence long‐term prognoses of stroke patients. Streptococcus mutans expressing the collagen‐binding protein Cnm induces cerebrovascular inflammation, impairing blood brain barrier integrity and causing cerebral bleeding. Here, we examine the association of Cnm‐positive S. mutans with CMBs. Methods: Acute stroke patients were selected from a single‐center registry database. Oral carriage of Cnm‐positive or Cnm‐negative S. mutans was determined using polymerase chain reaction assays. The associations of Cnm‐positive S. mutans with CMB number and specifically the presence of >10 CMBs were examined using quasi‐Poisson and logistic regression models, respectively. Results: This study included 3154 stroke patients, of which 428 patients (median [interquartile range] age, 73.0 [63.0–81.0] years; 269 men [62.9%]) underwent oral bacterial examinations. In total, 326 patients harbored S. mutans. After excluding four patients without imaging data, we compared patients with Cnm‐positive (n = 72) and Cnm‐negative (n = 250) S. mutans. Harboring Cnm‐positive S. mutans was independently associated with the presence of >10 CMBs (adjusted odds ratio 2.20 [1.18–4.10]) and higher numbers of deep and lobar CMBs (adjusted risk ratio 1.61 [1.14–2.27] for deep; 5.14 [2.78–9.51] for lobar), but not infratentorial CMBs, after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy. Conclusions: Harboring Cnm‐positive S. mutans was independently associated with a higher number of CMBs in deep and lobar locations. Reducing Cnm‐positive S. mutans in the oral cavity may serve as a novel therapeutic approach for stroke. [ABSTRACT FROM AUTHOR]

Resumen: Introducción: La inflamación relacionada con la angiopatía amiloide es una entidad caracterizada por una respuesta inflamatoria alrededor de los depósitos de beta amiloide de la microcirculación cerebral. Métodos: Revisión retrospectiva de una serie de pacientes con inflamación relacionada con angiopatía amiloide, que cumplieran criterios clínico-radiológicos o con diagnóstico histopatológico confirmado. Resultados: Se incluyeron siete pacientes, cinco varones, con edad media de 79 años. El inicio fue agudo o subagudo en seis de los casos. La clínica más frecuente fue deterioro cognitivo (n = 6), alteraciones de conducta (n = 5), crisis epilépticas (n = 5), focalidad neurológica (n = 4) y cefalea (n = 2). El líquido cefalorraquídeo fue anormal en tres de cinco casos (pleocitosis linfocitaria e hiperproteinorraquia). Las imágenes de resonancia magnética cerebral más frecuentes consistieron en microhemorragias (n = 7), hiperintensidades subcorticales en secuencia T2-FLAIR (n = 7) y realce leptomeníngeo (n = 6). La afectación fue bilateral en tres de los casos, con predominio en regiones parieto-occipitales (n = 5). Se realizó una tomografía por emisión de positrones (PET) de amiloide en dos pacientes, resultando positiva en uno. Se obtuvo la confirmación histopatológica mediante una biopsia en dos de los casos. Todos los sujetos recibieron tratamiento inmunosupresor, objetivándose una respuesta clínica y radiológica inicial favorable, con recaída radiológica en dos de los casos tras la retirada del tratamiento, y mejorando tras la reinstauración. Conclusiones: El diagnóstico resulta imprescindible de cara a iniciar un tratamiento precoz, ya que ha demostrado mejorar el pronóstico y disminuir las recurrencias. Si bien el diagnóstico definitivo es histopatológico, los criterios clínico-radiológicos permiten el diagnóstico de esta entidad sin necesidad de biopsia. Abstract: Introduction: Cerebral amyloid angiopathy–related inflammation (CAA-ri) is an entity characterised by an inflammatory response to β-amyloid deposition in the walls of cerebral microvessels. Methods: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. Results: The study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (n = 6), behavioural alterations (n = 5), epileptic seizures (n = 5), focal neurological signs (n = 4), and headache (n = 2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (n = 7), subcortical white matter hyperintensities on T2-FLAIR sequences (n = 7), and leptomeningeal enhancement (n = 6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (n = 5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. Conclusions: Early diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.

Numerous studies report linkage between chronic kidney disease (CKD) and cerebrovascular disease. This association has been particularly strong for cerebral small vessel disease. Significant findings have emerged from studies ranging from case reports, small case series, and larger cohort investigations. The latter show a relationship between declining renal function, microvascular disease, and cognitive impairment. One troubling aspect has been the relative paucity of mechanistic investigations addressing the CKD-cerebrovascular disease linkage. Nevertheless, mechanistic observations have begun to emerge, showing cerebral microhemorrhage development in animal models of CKD independent of hypertension, an important co-morbidity in clinical studies. Initial cell culture studies show endothelial monolayer disruption by CKD serum, consistent with blood-brain barrier injury. It is noteworthy that CKD serum is known to contain multiple plausible mediators of microvascular injury. Further studies are on the horizon to address the critical question of potential linkage of renal dysfunction with vascular cognitive impairment.

The spatial distribution patterns of cerebral microbleeds are associated with different types of cerebral small vessel disease (CSVD). This study aims to examine the disparities in brain imaging markers of CSVD among patients diagnosed with possible amyloid and non-amyloid small vessel disease. The head MR scans including susceptibility-weighted imaging (SWI) sequences from 351 patients at our institute were collected for analysis. CSVD imaging markers were quantified or graded across various CSVD dimensions in the patient images. Patients were categorized into the cerebral amyloid angiopathy group (CAA), hypertensive arteriopathy group (HA), or mixed small vessel disease group (Mixed), based on the spatial distribution of microbleeds. White matter lesions (WML) were segmented using an artificial neural network and assessed via a voxel-wise approach. Significant differences were observed among the three groups in several indices: microbleed count, lacune count at the centrum semiovale and basal ganglia levels, grade of enlarged perivascular space (EPVS) at the basal ganglia, and white matter lesion volume. These indices were substantially higher in the Mixed group compared to the other groups. Additionally, the incidences of cerebral hemorrhages (χ2 = 7.659, P = 0.006) and recent small subcortical infarcts (χ2 = 4.660, P = 0.031) were significantly more frequent in the HA group than in the CAA group. These results indicate that mixed spatial distribution patterns of microbleeds demonstrated the highest burden of cerebral small vessel disease. Microbleeds located in the deep brain regions were associated with a higher incidence of recent small subcortical infarcts and cerebral hemorrhages compared to those in the cortical areas.

Background This study explored the risk factors, neuroimaging features, and prognostic implications of nonhypertensive white matter hyperintensity (WMH) in patients with acute ischemic stroke and transient ischemic attack. Methods and Results We included 2283 patients with hypertension and 1003 without from a pool of 10 602. Associations of moderate‐to‐severe WMH with known risk factors, functional outcome, and a composite of recurrent stroke, myocardial infarction, and all‐cause mortality were evaluated. A subset of 351 patients without hypertension and age‐ and sex‐matched pairs with hypertension and moderate‐to‐severe WMH was created for a detailed topographic examination of WMH, lacunes, and microbleeds. Approximately 35% of patients without hypertension and 65% of patients with hypertensive stroke exhibited moderate‐to‐severe WMH. WMH was associated with age, female sex, and previous stroke, irrespective of hypertension. In patients without hypertension, WMH was associated with initial systolic blood pressure and was more common in the anterior temporal region. In patients with hypertension, WMH was associated with small vessel occlusion as a stroke mechanism and was more frequent in the periventricular region near the posterior horn of the lateral ventricle. The higher prevalence of occipital microbleeds in patients without hypertension and deep subcortical lacunes in patients with hypertension were also observed. Associations of moderate‐to‐severe WMH with 3‐month functional outcome and 1‐year cumulative incidence of the composite outcome were significant (both P

Small vessel diseases (SVD) is an umbrella term including several entities affecting small arteries, arterioles, capillaries, and venules in the brain. One of the most relevant and prevalent SVDs is cerebral amyloid angiopathy (CAA), whose pathological hallmark is the deposition of amyloid fragments in the walls of small cortical and leptomeningeal vessels. CAA frequently coexists with Alzheimer's Disease (AD), and both are associated with cerebrovascular events, cognitive impairment, and dementia. CAA and AD share pathophysiological, histopathological and neuroimaging issues. The venular involvement in both diseases has been neglected, although both animal models and human histopathological studies found a deposition of amyloid beta in cortical venules. This review aimed to summarize the available information about venular involvement in CAA, starting from the biological level with the putative pathomechanisms of cerebral damage, passing through the definition of the peculiar angioarchitecture of the human cortex with the functional organization and consequences of cortical arteriolar and venular occlusion, and ending to the hypothesized links between cortical venular involvement and the main neuroimaging markers of the disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Sporadic cerebral amyloid angiopathy (CAA) is a small vessel disease, resulting from progressive amyloid-β deposition in the media/adventitia of cortical and leptomeningeal arterioles. We sought to assess the prevalence of baseline characteristics, clinical and radiological findings, as well as outcomes among patients with CAA, in the largest study to date conducted in Greece. Methods: Sixty-eight patients fulfilling the Boston Criteria v1.5 for probable/possible CAA were enrolled and followed for at least twelve months. Magnetic Resonance Imaging was used to assess specific neuroimaging markers. Data regarding cerebrospinal fluid biomarker profile and Apolipoprotein-E genotype were collected. Multiple logistic regression analyses were performed to identify predictors of clinical phenotypes. Cox-proportional hazard regression models were used to calculate associations with the risk of recurrent intracerebral hemorrhage (ICH). Results: Focal neurological deficits (75%), cognitive decline (57%), and transient focal neurological episodes (TFNEs; 21%) were the most common clinical manifestations. Hemorrhagic lesions, including lobar cerebral microbleeds (CMBs; 93%), cortical superficial siderosis (cSS; 48%), and lobar ICH (43%) were the most prevalent neuroimaging findings. cSS was independently associated with the likelihood of TFNEs at presentation (OR: 4.504, 95%CI:1.258–19.088), while multiple (>10) lobar CMBs were independently associated with cognitive decline at presentation (OR:5.418, 95%CI:1.316–28.497). cSS emerged as the only risk factor of recurrent ICH (HR:4.238, 95%CI:1.509–11.900) during a median follow-up of 20 months. Conclusions: cSS was independently associated with TFNEs at presentation and ICH recurrence at follow-up, while a higher burden of lobar CMBs with cognitive decline at baseline. These findings highlight the prognostic value of neuroimaging markers, which may influence clinical decision-making. [ABSTRACT FROM AUTHOR]

Small vessel disease (SVD) is a highly prevalent disorder of the brain's microvessels and a common cause of dementia as well as ischaemic and haemorrhagic strokes. Though much about the underlying pathophysiology of SVD remains poorly understood, a wealth of recently published evidence strongly suggests a key role of microvessel endothelial dysfunction and a compromised blood–brain barrier (BBB) in the development and progression of the disease. Understanding the causes and downstream consequences associated with endothelial dysfunction in this pathological context could aid in the development of effective diagnostic and prognostic tools and provide promising avenues for potential therapeutic interventions. In this scoping review, we aim to summarise the findings from clinical studies examining the role of the molecular mechanisms underlying endothelial dysfunction in SVD, focussing on biochemical markers of endothelial dysfunction detectable in biofluids, including cell adhesion molecules, BBB transporters, cytokines/chemokines, inflammatory markers, coagulation factors, growth factors, and markers involved in the nitric oxide cascade. [ABSTRACT FROM AUTHOR]

Acute hemorrhagic encephalomyelitis (AHEM) is the most severe form of acute disseminated encephalomyelitis (ADEM). Patients with AHEM usually have unfavorable outcomes with high mortality rate. We reported a middle-aged male, who was diagnosed with AHEM and died 35 days after admission even under intensive immune therapy. Clinical courses were recorded and serial MR images were demonstrated to illustrate the rapidly changes in brain parenchyma. By highlighting these aspects, we hope to provide valuable insights for future studies and potential advancements in the management of AHEM. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prospective studies on cerebral microbleeds (CMB) have departed from individuals who already have CMB at baseline. Therefore, main outcomes have usually been the composite of new lesions appearing on the follow-up among patients who already had CMB together with those who de novo developed CMB. Using the Atahualpa Project Cohort, we aimed to assess correlates of incident CMB in community-dwelling older adults free of CMB at baseline. Methods: Atahualpa residents aged ≥ 60 years received baseline clinical interviews and a brain MRI. Those who were free of CMB at baseline and received follow-up brain MRI at the end of the study were included. Multivariate logistic and Poisson regression models were fitted to assess the association and the incidence rate ratio (IRR) of incident CMB according to clinical and neuroimaging variables. Results: The mean age of 241 study participants was 65.6 ± 6.1 years (57% women). After 6.5 years of follow-up, 25 subjects (10.4%) developed incident CMB. A total of 37 CMB were noticed in these 25 patients. A parsimonious logistic regression model demonstrated an association between the Edmonton Frail Scale (EFS) and incident CMB (p =.043). Multivariate logistic regression models showed an association between WMH progression and incident CMB (p =.011). Using Poisson regression models, the IRR for WMH progression at follow-up was increased in subjects with incident CMB (p =.029). Conclusions: Study results show a significant relationship between the EFS, WMH progression, and incident CMB. This knowledge will allow the implementation of preventive policies to reduce incident CMB and its consequences. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) encompasses a broad clinical spectrum united by pathology of the small vessels of the brain. CSVD is commonly identified using brain magnetic resonance imaging with well characterized markers including covert infarcts, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. The pathophysiology of CSVD is complex involving genetic determinants, environmental factors, and their interactions. While the role of vascular risk factors in CSVD is well known and its management is pivotal in mitigating the clinical effects, recent research has identified novel genetic factors involved in CSVD. Delineating genetic determinants can promote the understanding of the disease and suggest effective treatments and preventive measures of CSVD at the individual level. Here we review CSVD focusing on recent advances in the genetics of CSVD. The knowledge gained has advanced understanding of the pathophysiology of CSVD, offered promising early results that may improve subtype identification of small vessel strokes, has led to additional identification of mendelian forms of small vessel strokes, and is getting closer to influencing clinical care through pharmacogenetic studies. [ABSTRACT FROM AUTHOR]

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies.

Abstract Background Cerebral small vessel disease (SVD) is associated with acute events such as lacunar and hemorrhagic strokes, or chronic events such as cognitive deficit in the form of subcortical dementia, mood deficit in the form of late onset depression, sphincteric affection, and gait apraxia. Under conditions of moderate blood flow deficit, the inability of sclerotic vessels to dilate due to impairment of the cerebral autoregulation, renders the periventricular white matter seriously ischemic. Therefore, it is important to detect the implications of cerebral large artery disease on the severity of SVD, and the ability of transcranial duplex (TCD) to evaluate it in people at risk. Methods Fifty lacunar stroke patients were recruited, and evaluated using MRI brain to assess SVD score, carotid duplex and TCD to assess extracranial and intracranial stenoses, respectively. Results Both intracranial and extracranial stenoses showed significant relation to the severity of cerebral SVD. Moreover, there were significant relation between intracranial stenosis and presence of lacuna and EPVS. Conclusion Cerebral large artery disease contributes to the pathogenesis and severity of cerebral SVD. Therefore, TCD may be a useful tool for the prediction of occurrence of cerebral SVD in high-risk individuals, especially hypertensives.

Abstract Introduction Cerebral microbleeds (CMBs) are more frequent in patients with Alzheimer’s disease (AD) than in the general population. However, their clinical significance remains poorly understood. We carried out a multimodal approach to evaluate the impact of CMBs at a clinical, neuropsychological, and survival level, as well as on core AD biomarkers in the cerebrospinal fluid (CSF) in AD patients. Methods We prospectively recruited 98 patients with mild-moderate AD. At baseline, they underwent brain MRI, and AD CSF biomarkers and APOE genotypes were analysed. An extensive neuropsychological battery was performed at baseline and after 1 year of follow-up. We analysed the stroke incidence and mortality with survival analyses. Results Forty-eight (48.5%) patients had at least one CMBs. Eight (8.2%) patients had strictly nonlobar CMBs, 39 (40.2%) had any lobar CMB locations. The incidence of stroke was higher in AD patients with lobar CMBs than in those without CMBs (p 0.05). At the cognitive level, CMBs patients deteriorated more rapidly at 12 months according to MMSE scores, with no differences observed at 24 months. We did not observe differences in the other tests, except for an increase in caregiver burden in the CMBs group. The presence of cerebral amyloidosis and APOE ε4 were associated with a greater presence of CMBs. Conclusion CMBs are associated with an increased risk of ischemic stroke in AD patients without differences in mortality. Patients with CMBs did not seem to have different consequences associated with cognitive decline except for an increase in caregiver overload.

Abstract Background Both cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are related to cognitive impairment and dementia. This study aimed to clarify CAA- and HA-related small vessel disease (SVD) imaging marker associations with cognitive dysfunction and Alzheimer disease (AD) subtypes. Methods A sample of 137 subjects with clinically diagnosed late-onset AD identified from the dementia registry of a single center from January 2017 to October 2021 were enrolled. Semi-quantitative imaging changes (visual rating scale grading) suggestive of SVD were analyzed singularly and compositely, and their correlations with cognitive domains and AD subtypes were examined. Results Patients with typical and limbic-predominant AD subtypes had worse cognitive performance and higher dementia severity than minimal-atrophy subtype patients. Deep white matter hyperintensity (WMH) presence correlated inversely with short-term memory (STM) performance. The three composite SVD scores correlated with different cognitive domains and had distinct associations with AD subtypes. After adjusting for relevant demographic factors, multivariate logistic regression (using minimal-atrophy subtype as the reference condition) revealed the following: associations of the typical subtype with periventricular WMH [odds ratio (OR) 2.62; 95% confidence interval (CI), 1.23–5.57, p = 0.012], global SVD score (OR 1.67; 95%CI, 1.11–2.52, p = 0.009), and HA-SVD score (OR 1.93; 95%CI, 1.10–3.52, p = 0.034); associations of limbic-predominant subtype with HA-SVD score (OR 2.57; 95%CI, 1.23–5.37, p = 0.012) and most global and domain-specific cognitive scores; and an association of hippocampal-sparing subtype with HA-SVD score (OR 3.30; 95%CI, 1.58–6.85, p = 0.001). Conclusion Composite SVD imaging markers reflect overall CAA and/or HA severity and may have differential associations with cognitive domains and AD subtypes. Our finding supports the possibility that the clinical AD subtypes may reflect differing burdens of underlying CAA and HA microangiopathologies.

Objectives: Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear. Methods: We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments. Results: The CDR was significantly higher in patients with BPS (p = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS (p = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS (p = 0.037). There was no significant difference in total SVD and CAA-SVD score (p = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS (p = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS (p = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity. Conclusion: Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds (MBs) are a hallmark of cerebral small vessel disease (CSVD) and can be found on T2*-weighted sequences on MRI. Quantitative susceptibility mapping (QSM) is a postprocessing method that also enables MBs identification and furthermore allows to differentiate them from calcifications. Aims: We explored the implications of using QSM at submillimeter resolution for MBs detection in CSVD. Methods: Both 3 and 7 Tesla (T) MRI were performed in elderly participants without MBs and patients with CSVD. MBs were quantified on T2*-weighted imaging and QSM. Differences in the number of MBs were assessed, and subjects were classified in CSVD subgroups or controls both on 3T T2*-weighted imaging and 7T QSM. Results: 48 participants [mean age (SD) 70.9 (8.8) years, 48% females] were included: 31 were healthy controls, 6 probable cerebral amyloid angiopathy (CAA), 9 mixed CSVD, and 2 were hypertensive arteriopathy [HA] patients. After accounting for the higher number of MBs detected at 7T QSM (Median = Mdn; Mdn7T-QSM = 2.5; Mdn3T-T2 = 0; z = 4.90; p < 0.001) and false positive MBs (6.1% calcifications), most healthy controls (80.6%) demonstrated at least one MB and more MBs were discovered in the CSVD group. Conclusions: Our observations suggest that QSM at submillimeter resolution improves the detection of MBs in the elderly human brain. A higher prevalence of MBs than so far known in healthy elderly was revealed. [ABSTRACT FROM AUTHOR]

Cerebral malaria is a commonly encountered complication associated with Plasmodium falciparum malaria. However, it is rare with Plasmodium vivax malaria. We report magnetic resonance imaging findings in two cases of P. vivax malaria.

Abstract Background Gait disturbances may appear prior to cognitive dysfunction in the early stage of silent cerebrovascular disease (SCD). Subtle changes in gait characteristics may provide an early warning of later cognitive decline. Our team has proposed a vision-based artificial intelligent gait analyzer for the rapid detection of spatiotemporal parameters and walking pattern based on videos of the Timed Up and Go (TUG) test. The primary objective of this study is to investigate the relationship between gait features assessed by our artificial intelligent gait analyzer and cognitive function changes in patients with SCD. Methods This will be a multicenter prospective cohort study involving a total of 14 hospitals from Shanghai and Guizhou. One thousand and six hundred patients with SCD aged 60–85 years will be consecutively recruited. Eligible patients will undergo the intelligent gait assessment and neuropsychological evaluation at baseline and at 1-year follow-up. The intelligent gait analyzer will divide participant into normal gait group and abnormal gait group according to their walking performance in the TUG videos at baseline. All participants will be naturally observed during 1-year follow-up period. Primary outcome are the changes in Mini-Mental State Examination (MMSE) score. Secondary outcomes include the changes in intelligent gait spatiotemporal parameters (step length, gait speed, step frequency, step width, standing up time, and turning back time), the changes in scores on other neuropsychological tests (Montreal Cognitive Assessment, the Stroop Color Word Test, and Digit Span Test), falls events, and cerebrovascular events. We hypothesize that both groups will show a decline in MMSE score, but the decrease of MMSE score in the abnormal gait group will be more significant. Conclusion This study will be the first to explore the relationship between gait features assessed by an artificial intelligent gait analyzer and cognitive decline in patients with SCD. It will demonstrate whether subtle gait abnormalities detected by the artificial intelligent gait analyzer can act as a cognitive-related marker for patients with SCD. Trial registration This trial was registered at ClinicalTrials.gov ( NCT04456348 ; 2 July 2020).

Cerebral small vessel disease (CSVD) encompasses a broad clinical spectrum united by pathology of the small vessels of the brain. CSVD is commonly identified using brain magnetic resonance imaging with well characterized markers including covert infarcts, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. The pathophysiology of CSVD is complex involving genetic determinants, environmental factors, and their interactions. While the role of vascular risk factors in CSVD is well known and its management is pivotal in mitigating the clinical effects, recent research has identified novel genetic factors involved in CSVD. Delineating genetic determinants can promote the understanding of the disease and suggest effective treatments and preventive measures of CSVD at the individual level. Here we review CSVD focusing on recent advances in the genetics of CSVD. The knowledge gained has advanced understanding of the pathophysiology of CSVD, offered promising early results that may improve subtype identification of small vessel strokes, has led to additional identification of mendelian forms of small vessel strokes, and is getting closer to influencing clinical care through pharmacogenetic studies.

BackgroundCerebral microbleeds (MBs) are a hallmark of cerebral small vessel disease (CSVD) and can be found on T2*-weighted sequences on MRI. Quantitative susceptibility mapping (QSM) is a postprocessing method that also enables MBs identification and furthermore allows to differentiate them from calcifications.AimsWe explored the implications of using QSM at submillimeter resolution for MBs detection in CSVD.MethodsBoth 3 and 7 Tesla (T) MRI were performed in elderly participants without MBs and patients with CSVD. MBs were quantified on T2*-weighted imaging and QSM. Differences in the number of MBs were assessed, and subjects were classified in CSVD subgroups or controls both on 3T T2*-weighted imaging and 7T QSM.Results48 participants [mean age (SD) 70.9 (8.8) years, 48% females] were included: 31 were healthy controls, 6 probable cerebral amyloid angiopathy (CAA), 9 mixed CSVD, and 2 were hypertensive arteriopathy [HA] patients. After accounting for the higher number of MBs detected at 7T QSM (Median = Mdn; Mdn7T−QSM = 2.5; Mdn3T−T2 = 0; z = 4.90; p < 0.001) and false positive MBs (6.1% calcifications), most healthy controls (80.6%) demonstrated at least one MB and more MBs were discovered in the CSVD group.ConclusionsOur observations suggest that QSM at submillimeter resolution improves the detection of MBs in the elderly human brain. A higher prevalence of MBs than so far known in healthy elderly was revealed.

MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episode) is one of the most common syndromic mitochondrial disorders (MID) and is due to the variant m.3243A>G in MT-TL1 in approximately 80% of cases. MELAS is a multisystem disorder with stroke-like episodes (SLEs) as a pathognomonic feature. The morphological correlate of SLEs in cerebral imaging are stroke-like lesions (SLLs). SLLs present on cerebral MRI with a T2, FLAIR, DWI, and PWI-hyperintense and OEF-hypointense lesion that is not confined to a vascular territory and extends to a nadir before disappearing or terminating as a structural lesion. Occasionally, these features are accompanied by microbleeds within the SLL, usually along the cortex. These microbleeds are thought to result from laminar cortical necrosis, and end-stage of a SLL or seizures, a common manifestation of SLEs. [ABSTRACT FROM AUTHOR]

Background and purpose: Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs. Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women. Results: A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0-7) vs. 2 (0-7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0-2) vs. 0 (0-1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs]. Conclusion: The progression of CMB over 2 years was significantly greater in women than in men. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (cSVD) is the leading cause of vascular cognitive impairments and dementia, cerebral hemorrhages and lacunar strokes, as well as the most common form of asymptomatic vascular brain lesion. Major forms of cSVD are age- and arterial hypertension (AH)-associated arteriolosclerosis and cerebral amyloid angiopathy. The etiologies and the underlying mechanisms of disease development and progression remain unclear for a substantial group of cSVD types. Significant difficulties in the study of this pathology are explained by technical limitations in assessing smallest vessels in vivo. A modified correlation between MRI equivalents and their morphological manifestations in cSVD to use them subsequently as a surrogate marker of lesions in small vessels has allowed clinicians to establish disease progression regularities and the association of the latter with clinical symptoms. This review presents the results of studies showing the clinical significance and role of the leading MRI features in the assessment of disease progression, including white matter hyperintensity (WMH, formerly known as leukoaraiosis), lacunes, enlarged perivascular spaces, and microbleeds. The recognition of MRI features as diagnostic criteria for cSVD was specified by international experts in the Standards for Reporting Vascular Changes on Neuroimaging (the STRIVE criteria). Despite the enormous importance of this standardization for the improvement of concepts about the significance of different factors in the development and understanding of heterogeneity of cSVD forms, this categorization cannot provide for the prediction of the disease course in a particular patient and assess the treatment efficacy in short- and medium-term prospects. One of the approaches to solution was based on the use of diffusion methodologies for assessing a microstructural lesion in the visually unaltered brain matter. The obtained consistent association of the expressiveness of microstructural alterations with clinical impairments substantiates the expediency of multimodal MRI studies aimed to evaluate the pathophysiological mechanisms of disease progression, beginning from the subclinical brain lesion stage. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (SVD) is associated with acute events such as lacunar and hemorrhagic strokes, or chronic events such as cognitive deficit in the form of subcortical dementia, mood deficit in the form of late onset depression, sphincteric affection, and gait apraxia. Under conditions of moderate blood flow deficit, the inability of sclerotic vessels to dilate due to impairment of the cerebral autoregulation, renders the periventricular white matter seriously ischemic. Therefore, it is important to detect the implications of cerebral large artery disease on the severity of SVD, and the ability of transcranial duplex (TCD) to evaluate it in people at risk. Methods: Fifty lacunar stroke patients were recruited, and evaluated using MRI brain to assess SVD score, carotid duplex and TCD to assess extracranial and intracranial stenoses, respectively. Results: Both intracranial and extracranial stenoses showed significant relation to the severity of cerebral SVD. Moreover, there were significant relation between intracranial stenosis and presence of lacuna and EPVS. Conclusion: Cerebral large artery disease contributes to the pathogenesis and severity of cerebral SVD. Therefore, TCD may be a useful tool for the prediction of occurrence of cerebral SVD in high-risk individuals, especially hypertensives. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. Methods: In a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3 days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored. Results: The incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p < 0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p < 0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR = 3.19, 95% CI 1.51–6.76, p = 0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR = 13.34, 95% CI 3.09–57.51, p = 0.001). Conclusions: A significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly. [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding the prevalence of clinical, neuroimaging, and genetic markers among patients diagnosed with Cerebral Amyloid Angiopathy–related inflammation (CAA-ri). We sought to determine these characteristics in patients diagnosed in our center and to summarize available literature published either as single-case reports or small case series (<5 patients). Methods: We reported our single-center experience of patients diagnosed with CAA-ri according to international criteria during a seven-year period (2015–2022), and we abstracted data from 90 previously published cases. Results: Seven patients (43% women, mean age 70 ± 13 years) were diagnosed with CAA-ri in our center. The most common symptom at presentation was focal neurological dysfunction (71%), and the most prevalent radiological finding was the presence of T2/FLAIR white matter hyperintensities (100%). All patients were treated with corticosteroids and had a favorable functional outcome. Among 90 previously published CAA-ri cases (51% women, mean age 70 ± 9 years), focal neurological dysfunction was the most common symptom (76%), followed by a cognitive decline (46%) and headache (34%). The most prevalent neuroimaging findings were cerebral microbleeds (85%), asymmetric T2/FLAIR white matter hyperintensities (81%), and gadolinium-enhancing T1-lesions (37%). Genetic testing for the Apolipoprotein-E gene was available in 27 cases; 59% carried the APOE ε4/ε4 genotype. The majority of the published CAA-ri cases (78%) received corticosteroid monotherapy, while 17 patients (19%) were treated with additional immunosuppressive treatment. Favorable functional outcome following treatment was documented in 70% of patients. Conclusion: Improving the vigilance of clinicians regarding the early recognition and accurate diagnosis of CAA-ri is crucial for swift therapy initiation, which may result in improved functional outcomes. [ABSTRACT FROM AUTHOR]

The complications of coronavirus disease 2019 (COVID-19), the clinical entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are not limited to the respiratory system. Leukoencephalopathy with microbleeds is increasingly seen in patients with COVID-19. New information is needed to delineate better the clinical implications of this infectious disease. A 46-year-old man with confirmed SARS-CoV-2 infection was admitted to the intensive care unit (ICU) with severe COVID-19. After transfer to the general wards, the patient was noted drowsy, disorientated, with slow thinking and speech. A brain MRI showed bilateral symmetrical hyperintense lesions in the deep and subcortical whiter matter, involving the splenium of the corpus callosum, as well as multiple microhemorrhages implicating the splenium and subcortical white matter. No contrast-enhanced lesions were observed in brain CT or MRI. CSF analysis showed no abnormalities, including a negative rtRT-PCR for SARS-CoV-2. An outpatient follow-up visit showed near-complete clinical recovery and resolution of the hyperintense lesions on MRI, without microbleeds change. We present the case of a survivor of severe COVID-19 who presented diffuse posthypoxic leukoencephalopathy, and microbleeds masquerading as acute necrotizing encephalopathy. We postulate that this kind of cerebral vasogenic edema with microbleeds could be the consequence of hypoxia, inflammation, the prothrombotic state and medical interventions such as mechanical ventilation and anticoagulation. [ABSTRACT FROM AUTHOR]

Objectives: Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA), white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative, artificial intelligence (AI)–based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls. Methods: A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate (BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores and imaging markers. Results: AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%. Conclusions: The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs. Key Points: • AD-RAI score at baseline was associated with Corsi score (visuospatial memory) decline. • BrainAGE score was associated with Trail Making B (executive functions) decrease. • AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs. [ABSTRACT FROM AUTHOR]

Abstract Background Extracorporeal circulation (ECC) is now being increasingly used in critical care settings. Epileptic seizures are a recognized but under reported complication in patients receiving this care. Acute symptomatic post-operative seizures have been described, as well as remote seizure, mostly in the form of convulsive seizures. Epilepsy has also been reported, although with lower frequency and mainly with convulsive seizures, while different seizure semiology is rarely described. Case presentation We report a case series of four patients developing epilepsy with homogeneous features following heart surgery with ECC. We present neurophysiological and neuroradiological data and we describe the peculiar characteristics of epilepsies in terms of seizure semiology, frequency, and drug response. The main features are: an insulo-temporal or parieto-occipital semiology, often multifocal and without loss of consciousness or motor manifestations, a high frequency of seizures but with low impact on daily life, and a good response to anti-epileptic therapy. Conclusions We hypothesize a pathogenetic mechanism and we discuss the clinical implications of identifying these forms of epilepsy which tend to be often under-recognized.

Disseminated microinfarctions are uncommonly encountered in clinical practice. Here we describe a patient with long-standing cerebral microbleeds who developed acute cognitive decline in the setting of acute hypotension. Magnetic resonance imaging showed acute disseminated microinfarctions, with no change in microbleeds. This case emphasizes the important relationship between ischemic and hemorrhagic microvascular disease of the brain, especially in the setting of acute blood pressure changes compounding preexisting microvascular injury.

Background and purposeSex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs.MethodsThe CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women.ResultsA total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0–7) vs. 2 (0–7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0–2) vs. 0 (0–1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs].ConclusionThe progression of CMB over 2 years was significantly greater in women than in men.