The Venular Side of Cerebral Amyloid Angiopathy: Proof of Concept of a Neglected Issue.

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

Decreased CSF Levels of beta-Amyloid in Patients With Cortical Superficial Siderosis

Background: Cortical superficial siderosis (cSS) represents a key neuroimaging marker of cerebral amyloid angiopathy (CAA) that is associated with intracranial hemorrhages and cognitive impairment. Nevertheless, the association between cSS and core cerebrospinal fluid (CSF) biomarkers for dementia remain unclear. Methods: One hundred and one patients with probable (79%, 80/101) or possible (21%, 21/101) CAA according to the modified Boston criteria and mild cognitive impairment according to Petersen criteria were prospectively included between 2011 and 2016. CSF analyses of ß-amyloid 42, ß-amyloid 40, total tau and phosphorylated tau were performed using sandwich-type enzyme-linked immunosorbent-assay. All patients received MRI and Mini-Mental-State Examination (MMSE). Logistic regression analysis was used to adjust for possible confounders. Results: cSS was present in 61% (62/101). Of those, 53% (33/62) had disseminated cSS and 47% (29/62) focal cSS. ß-amyloid 42 was lower in patients with cSS than in patients without cSS (OR 0.2; 95% CI 0.08–0.6; p = 0.0052) and lower in patients with disseminated cSS than in those with focal cSS (OR 0.02; 95% CI 0.003–0.2; p = 0.00057). Presence of cSS had no association with regard to ß-amyloid 40, total tau and phosphorylated tau. Conclusions: Our results demonstrate that the presence and extent of cSS are associated with reduced CSF ß-amyloid 42 levels. Further studies are needed to investigate the underlying mechanisms of this association

Quantitative dopamine transporter imaging assessment in Parkinson’s disease (PD) patients carrying GBA gene mutations compared with Idiopathic PD patients: A case-control study

Background: Genetic risk factors impact around 15% of Parkinson’s disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative-based data, various studies have been published on GBA-PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei. Methods: This retrospective study included two consecutive homogenous cohorts of GBA-PD and idiopathic (I-PD) patients. Each consecutive GBA-PD patient has been matched with a 1:1 pairing method with a consecutive I-PD subject according to age, age at disease onset, sex, Hoehn & Yahr (H&Y) staging scale and comorbidity level (CCI). Semiquantitative volumetric data by the DaTQUANTTM software integrated in the DaTSCAN exam performed at time of the diagnosis (SPECT imaging performed according to current guidelines of I-123 FPCIT SPECT imaging) were extrapolated. Bilateral specific binding ratios (SBR) at putamen and caudate levels were calculated, using the occipital lobes uptake. The Mann–Whitney test was performed to compare the two cohorts while the Spearman’s test was used to find correlations between motor and volumetric data in each group. Bonferroni correction was used to account for multiple comparisons. Results: Two cohorts of 25 patients each (GBA-PD and I-PD), were included. By comparing GBA-PD and I-PD patients, lower SBR values were found in the most affected anterior putamen and left caudate of the GBA-PD cohort. Furthermore, in the GBA-PD cohort the SBR of the most affected posterior putamen negatively correlated with the H&Y scale. However, none of these differences or correlations remained significant after Bonferroni correction for multiple comparisons. Conclusions: We observed differences in SBR values in GBA-PD patients compared with I-PD. However, these differences were no longer significant after Bonferroni multiple comparisons correction highlighting the need for larger, longitudinal studies

An unexpected evolution of symptomatic mild middle cerebral artery (MCA) stenosis: asymptomatic occlusion

<p>Abstract</p> <p>Background</p> <p>The intracranial localization of large artery disease is recognized as the main cause of ischemic stroke in the world, considering all countries, although its global burden is widely underestimated. Indeed it has been reported more frequently in Asians and African-American people, but the finding of intracranial stenosis as a cause of ischemic stroke is relatively common also in Caucasians. The prognosis of patients with stroke due to intracranial steno-occlusion is strictly dependent on the time of recanalization. Moreover, the course of the vessel involvement is highly dynamic in both directions, improvement or worsening, although several data are derived from the atherosclerotic subtype, compared to other causes.</p> <p>Case description</p> <p>We report the clinical, neurosonological and neuroradiological findings of a young woman, who came to our Stroke Unit because of the abrupt onset of aphasia during her work. An urgent neurosonological examination showed a left M1 MCA stenosis, congruent with the presenting symptoms; magnetic resonance imaging confirmed this finding and identified an acute ischemic lesion on the left MCA territory. The past history of the patient was significant only for a hyperinsulinemic condition, treated with metformine, and a mild overweight. At this time a selective cerebral angiography was not performed because of the patient refusal and she was discharged on antiplatelet and lipid-lowering therapy, having failed to identify autoimmune or inflammatory diseases. Within 1 month, she went back to our attention because of the recurrence of aphasia, lasting about ten minutes. Neuroimaging findings were unchanged, but the patient accepted to undergo a selective cerebral angiography, which showed a mild left distal M1 MCA stenosis.</p> <p>During the follow-up the patient did not experienced any recurrence, but a routine neurosonological examination found an unexpected evolution of the known MCA stenosis, i.e. left M1 MCA occlusion. Neuroradiological imaging did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the left M1 MCA occlusion.</p> <p>Conclusions</p> <p>Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at our knowledge.</p

Prior Stroke in PFO Patients Is Associated With Both PFO-Related and -Unrelated Factors.

Background and Purpose: To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO). Methods: We studied cross-sectional data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design. Results: We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke. Conclusion: In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors

The COVID-19 pandemic and neurology: A survey on previous and continued restrictions for clinical practice, curricular training, and health economics

Background and Purpose The COVID-19 pandemic has significantly impacted health systems worldwide. Here, we assessed the pandemic's impact on clinical service, curricular training, and financial burden from a neurological viewpoint during the enforced lockdown periods and the assumed recovery by 2023. Methods An online 18-item survey was conducted by the European Academy of Neurology (EAN) NeuroCOVID-19 Task Force among the EAN community. The survey was online between February and March 2023. Questions related to general, demographic, clinical, work, education, and economic aspects. Results We collected 430 responses from 79 countries. Most health care professionals were aged 35–44 years, with >15 years of work experience. The key findings of their observations were as follows. (i) Clinical services were cut back in all neurological subspecialties during the most restrictive COVID-19 lockdown period. The most affected neurological subspecialties were services for patients with dementia, and neuromuscular and movement disorders. The levels of reduction and the pace of recovery were distinct for acute emergencies and in- and outpatient care. Recovery was slow for sleep medicine, autonomic nervous system disorders, neurorehabilitation, and dementia care. (ii) Student and residency rotations and grand rounds were reorganized, and congresses were converted into a virtual format. Conferences are partly maintained in a hybrid format. (iii) Affordability of neurological care and medication shortage are emerging issues. Conclusions Recovery of neurological services up to spring 2023 has been incomplete following substantial disruption of neurological care, medical education, and health economics in the wake of the COVID-19 pandemic. The continued limitations for the delivery of neurological care threaten brain health and call for action on a global scale

Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a study protocol.

INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated. METHODS AND ANALYSIS: To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case-control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease. ETHICS AND DISSEMINATION: BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders