Long-Term Treatment with the Calcitonin Gene-Related Peptide Receptor Antagonist Erenumab in CADASIL: Two Case Reports.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of cerebral small vessel disease, caused by a mutation in the NOTCH3 gene on chromosome 19. The main clinical features include migraine (often with aura), early onset, recurrent subcortical ischemic strokes, mood disturbances, and cognitive impairment, frequently leading to dementia and disability with a reduction in life expectancy. Cerebral chronic global hypoperfusion, due to impaired cerebrovascular reactivity, seems to play a primary role in CADASIL. Migraine is the most common early feature of the disease, and to date, there are no consensus guidelines for treatment. Given the vasomodulatory influence of many antimigraine drugs, there is concern about their use in this disease. In particular, the calcitonin gene-related peptide (CGRP) system serves as a vasodilatory protective mechanism during cerebral and cardiac ischemia. Blocking this system could exacerbate ischemic events. Herein, we describe two CADASIL patients who were treated with the calcitonin gene-related peptide (CGRP) receptor antagonist erenumab for chronic migraine, reporting a significant reduction in the frequency of attacks and intensity of pain, and an improvement in quality of life without adverse effects.

Cognitive profile in cerebral small vessel disease: comparison between cerebral amyloid angiopathy and hypertension-related microangiopathy.

Cerebral amyloid angiopathy (CAA) is recognized as a cause of cognitive impairment, but its cognitive profile needs to be characterized, also respect to hypertension-related microangiopathy (HA). We aimed at comparing difference or similarity of CAA and HA patients' cognitive profiles, and their associated factors. Participants underwent an extensive clinical, neuropsychological, and neuroimaging protocol. HA patients (n = 39) were more frequently males, with history of vascular risk factors than CAA (n = 32). Compared to HA, CAA patients presented worse performance at MoCA (p = 0.001) and semantic fluency (p = 0.043), and a higher prevalence of amnestic MCI (46% vs. 68%). In univariate analyses, multi-domain MCI was associated with worse performance at MoCA, Rey Auditory Verbal Learning Test (RAVLT), and semantic fluency in CAA patients, and with worse performance at Symbol Digit Modalities Test (SDMT) and phonemic fluency in HA ones. In multivariate models, multi-domain deficit remained as the only factor associated with RAVLT (ß = - 0.574) in CAA, while with SDMT (ß = - 0.364) and phonemic fluency (ß = - 0.351) in HA. Our results highlight different patterns of cognitive deficits in CAA or HA patients. While HA patients' cognitive profile was confirmed as mainly attentional/executive, a complex cognitive profile, characterized also by deficit in semantic memory, seems the hallmark of CAA patients.

Trunk Control Test as a Main Predictor of the Modified Barthel Index Score at Discharge From Intensive Post-acute Stroke Rehabilitation: Results From a Multicenter Italian Study.

OBJECTIVES: To verify whether trunk control test (TCT) upon admission to intensive inpatient post-stroke rehabilitation, combined with other confounding variables, is independently associated with discharge mBI. DESIGN: Multicentric retrospective observational cohort study. SETTING: Two Italian inpatient rehabilitation units. PARTICIPANTS: A total of 220 post-stroke adult patients, within 30 days from the acute event, were consecutively enrolled. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The outcome measure considered was the modified Barthel Index (mBI), one of the most widely recommended tools for assessing stroke rehabilitation functional outcomes. RESULTS: All variables collected at admission and significantly associated with mBI at discharge in the univariate analysis (TCT, mBI at admission, pre-stroke modified Rankin Scale [mRS], sex, age, communication ability, time from the event, Cumulative Illness Rating Scale, bladder catheter, and pressure ulcers) entered the multivariate analysis. TCT, mBI at admission, premorbid disability (mRS), communication ability and pressure ulcers (P<.001) independently predicted discharge mBI (adjusted R2=68.5%). Concerning the role of TCT, the model with all covariates and without TCT presented an R2 of 65.1%. On the other side, the model with the TCT only presented an R2 of 53.1%. Finally, with the inclusion of both TCT and all covariates, the model showed an R2 increase up to 68.5%. CONCLUSIONS: TCT, with other features suggesting functional/clinical complexity, collected upon admission to post-acute intensive inpatient stroke rehabilitation, independently predicted discharge mBI.

The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study.

In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.

Fractal dimension of the cortical gray matter outweighs other brain MRI features as a predictor of transition to dementia in patients with mild cognitive impairment and leukoaraiosis.

Background: The relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T2 hyperintensities in the cerebral WM, also known as leukoaraiosis. Methods: Sixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria. We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T2 hyperintensities, and diffusion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T1 weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model. Results: After 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia. Discussion: Our findings confirm the complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features.

Cognitive phenotypes and factors associated with cognitive decline in a cohort of older patients with atrial fibrillation: The Strat-AF study.

BACKGROUND AND PURPOSE: The multifactorial relationship between atrial fibrillation (AF) and cognitive impairment needs to be elucidated. The aim of this study was to assess, in AF patients on oral anticoagulants (OACs), the prevalence of cognitive impairment, defined according to clinical criteria or data-driven phenotypes, the prevalence of cognitive worsening, and factors associated with cognitive outcomes. METHODS: The observational prospective Strat-AF study enrolled AF patients aged ≥ 65 years who were receiving OACs. The baseline and 18-month protocol included clinical, functional, and cognitive assessment, and brain magnetic resonance imaging. Cognitive outcomes were: empirically derived cognitive phenotypes; clinical diagnosis of cognitive impairment; and longitudinal cognitive worsening. RESULTS: Out of 182 patients (mean age 77.7 ± 6.7 years, 63% males), 82 (45%) received a cognitive impairment diagnosis, which was associated with lower education level and functional status, and higher level of atrophy. Cluster analysis identified three cognitive profiles: dysexecutive (17%); amnestic (25%); and normal (58%). Compared to the normal group, the dysexecutive group was older, and had higher CHA2 DS2 -VASc scores, while the amnestic group had worse cognitive and functional abilities, and medial temporal lobe atrophy (MTA). Out of 128 followed-up patients, 35 (27%) had cognitive worsening that was associated with lower education level, worse cognitive efficiency, CHA2 DS2 -VASc score, timing of OAC intake, history of stroke, diabetes, non-lacunar infarcts, white matter hyperintensities and MTA. In multivariate models, belonging to the dysexecutive or amnestic group was a main predictor of cognitive worsening. CONCLUSIONS: In our cohort of older AF patients, CHA2 DS2 -VASc score, timing of OAC intake, and history of stroke influenced presence, type and progression of cognitive impairment. Empirically derived cognitive classification identified three groups with different clinical profiles and better predictive ability for cognitive worsening compared to conventional clinical diagnosis.

Intravenous thrombolysis in CADASIL: report of two cases and a systematic review.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease responsible for recurrent ischemic strokes, often with a progressive course leading to dementia and disability. On MRI, lacunes, microbleeds, and severe white matter alterations are typical features of the disease. In case of acute stroke, because of the bleeding risk associated with the disease and the doubtful efficacy of fibrinolytic treatment in a disease with poor evidence of thrombosis, the efficacy of intravenous thrombolysis remains unproven. Nevertheless, stroke is a frequent occurrence in CADASIL patients, and clinicians not unlikely may face in the emergency room the situation of a CADASIL patient with an acute stroke within the time window for thrombolysis. OBJECTIVE: We report on two CADASIL patients treated with intravenous alteplase for acute ischemic stroke, and we present a review of literature aimed to report epidemiological data, efficacy and safety of intravenous thrombolysis in CADASIL patients. METHODS: We performed a systematic review of medical literature published until August 2, 2022. Case reports and series in English language reporting on CADASIL patients and acute stroke were included. RESULTS: Both patients were treated with intravenous thrombolysis without complications and had a good clinical outcome. The systematic review identified three case reports of CADASIL patients who were treated with intravenous alteplase for acute ischemic stroke; no bleedings complications were described. CONCLUSIONS: Available data on intravenous thrombolysis in CADASIL patients are scarce but suggest that this treatment can be taken into consideration for these patients.

Can CHA2DS2-VASc and HAS-BLED Foresee the Presence of Cerebral Microbleeds, Lacunar and Non-Lacunar Infarcts in Elderly Patients With Atrial Fibrillation? Data From Strat-AF Study.

Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic risk. In this context, validity of congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke, vascular disease, age 65-74 years and sex category (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS-BLED) scales, used to respectively evaluate thrombotic and hemorrhagic risks, is incomplete. In patients with AF, brain MRI has led to the increased detection of "asymptomatic" brain changes, particularly those related to small vessel disease, which also represent the pathologic substrate of intracranial hemorrhage, and silent brain infarcts, which are considered risk factors for ischemic stroke. Routine brain MRI in asymptomatic patients with AF is not yet recommended. Our aim was to test predictive ability of risk stratification scales on the presence of cerebral microbleeds, lacunar, and non-lacunar infarcts in 170 elderly patients with AF on oral anticoagulants. Ad hoc developed R algorithms were used to evaluate CHA2DS2-VASc and HAS-BLED sensitivity and specificity on the prediction of cerebrovascular lesions: (1) Maintaining original items' weights; (2) augmenting weights' range; (3) adding cognitive, motor, and depressive scores. Accuracy was poor for each outcome considering both scales either in phase 1 or phase 2. Accuracy was never improved by the addition of cognitive scores. The addition of motor and depressive scores to CHA2DS2-VASc improved accuracy for non-lacunar infarcts (sensitivity = 0.70, specificity = 0.85), and sensitivity for lacunar-infarcts (sensitivity = 0.74, specificity = 0.61). Our results are a very first step toward the attempt to identify those elderly patients with AF who would benefit most from brain MRI in risk stratification.

Critical issue on the extinction and inattention subtest of NIHSS scale: an analysis on post-acute stroke patients attending inpatient rehabilitation.

OBJECTIVES: This study aims to evaluate the diagnostic performance of NIHSS extinction and inattention item, compared to the results of the Oxford Cognitive Screen (OCS) heart subtest. Additionally, the possible role of the NIHSS visual field subtest on the NIHSS extinction and inattention subtest performance is explored and discussed. METHODS: We analysed scores on NIHSS extinction and inattention subtest, NIHSS visual field subtest, and OCS heart subtest on a sample of 118 post-stroke patients. RESULTS: Compared to OCS heart subtest, the results on NIHSS extinction and inattention subtest showed an accuracy of 72.9% and a moderate agreement level (Cohen's kappa = 0.404). Furthermore, a decrease in NIHSS accuracy detecting neglect (61.1%) was observed in patients with pathological scores in NIHSS visual field item. CONCLUSIONS: Extreme caution is recommended for the diagnostic performance of extinction and inattention item of NIHSS. Signs of neglect may not be detected by NIHSS, and may be confused with visual field impairment. TRIAL REGISTRATION: This study refers to an observational study protocol submitted to ClinicalTrials.gov with identifier: NCT03968627 . The name of the registry is "Development of a National Protocol for Stroke Rehabilitation in a Multicenter Italian Institution" and the date of the registration is the 30th May 2019.

Detection of subclinical atrial fibrillation after cryptogenic stroke using implantable cardiac monitors.

BACKGROUND: Implantable cardiac monitor (ICM) revealed subclinical atrial fibrillation (SCAF) in up to 30% of cryptogenic stroke (CS) patients in randomized trials. However, real world data are limited. OBJECTIVES: We investigated SCAF occurrence, treatments, clinical outcomes and predictors of SCAF in a multicenter real-world population subjected to ICM after CS. METHODS: From September 2016 to November 2019, 20 Italian centers collected data of consecutive patients receiving ICM after CS and followed with remote and outpatient follow-up according to clinical practice. All device-detected AF events were confirmed by the cardiologist to diagnose SCAF. RESULTS: ICM was implanted in 334 CS patients (mean age±SD 67.4±11.5 years, 129 (38.6%) females, 242 (76.1%) with CHA2DS2-VASC score≥4). During a follow-up of 23.6 (IQR 14.6-31.5) months, SCAF was diagnosed in 92 (27.5%) patients. First episode was asymptomatic in 81 (88.1%). SCAF daily burden ≥5 minutes was 22.0%, 24.1% and 31.5% at 6, 12, and 24 months after ICM implantation. Median time to first day with AF was 60 (IQR 18-140) days. Female gender, age>69 years, PR interval>160 ms and cortical-subcortical infarct type at enrolment were independently associated with an increased risk of SCAF. CONCLUSIONS: In a real-world population, ICM detected SCAF in more than a quarter of CS patients. This experience confirms the relevance of implanting CS patients, for maximizing the possibilities to detect AF, following failure of Holter monitoring, according to guidelines. However, there is need to demonstrate that shift to oral anticoagulation following SCAF detection is associated with reduced risk of recurrent stroke.

Blood-brain barrier leakage and hemorrhagic transformation: The Reperfusion Injury in Ischemic StroKe (RISK) study.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT). METHODS: We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (Ktrans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time. RESULTS: We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (Ktrans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per Ktrans point increase; OR 2.34; 95% CI 1.06-5.17 for Ktrans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per Ktrans point increase). CONCLUSION: Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

Predictors of Function, Activity, and Participation of Stroke Patients Undergoing Intensive Rehabilitation: A Multicenter Prospective Observational Study Protocol.

Background: The complex nature of stroke sequelae, the heterogeneity in rehabilitation pathways, and the lack of validated prediction models of rehabilitation outcomes challenge stroke rehabilitation quality assessment and clinical research. An integrated care pathway (ICP), defining a reproducible rehabilitation assessment and process, may provide a structured frame within investigated outcomes and individual predictors of response to treatment, including neurophysiological and neurogenetic biomarkers. Predictors may differ for different interventions, suggesting clues to personalize and optimize rehabilitation. To date, a large representative Italian cohort study focusing on individual variability of response to an evidence-based ICP is lacking, and predictors of individual response to rehabilitation are largely unexplored. This paper describes a multicenter study protocol to prospectively investigate outcomes and predictors of response to an evidence-based ICP in a large Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation. Methods: All patients with diagnosis of ischemic or hemorrhagic stroke confirmed both by clinical and brain imaging evaluation, admitted to four intensive rehabilitation units (adopting the same stroke rehabilitation ICP) within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled (expected sample: 270 patients). Measures will be taken at admission (T0), at discharge (T1), and at follow-up 6 months after a stroke (T2), including clinical data, nutritional, functional, neurological, and neuropsychological measures, electroencephalography and motor evoked potentials, and analysis of neurogenetic biomarkers. Statistics: In addition to classical multivariate logistic regression analysis, advanced machine learning algorithms will be cross-validated to achieve data-driven prognosis prediction models. Discussion: By identifying data-driven prognosis prediction models in stroke rehabilitation, this study might contribute to the development of patient-oriented therapy and to optimize rehabilitation outcomes. Clinical Trial Registration: ClinicalTrials.gov, NCT03968627. https://www.clinicaltrials.gov/ct2/show/NCT03968627?term=Cecchi&cond=Stroke&draw=2&rank=2.

Efficacy and Safety of the Association of Nimodipine and Choline Alphoscerate in the Treatment of Cognitive Impairment in Patients with Cerebral Small Vessel Disease. The CONIVaD Trial.

BACKGROUND: No approved treatment is available for patients with vascular cognitive impairment (VCI) due to cerebral small vessel disease (SVD). OBJECTIVE: The CONIVaD (Choline Alphoscerate and Nimodipine in Vascular Dementia) study aimed to investigate the feasibility, efficacy, and safety of a combined treatment with choline alphoscerate and nimodipine in patients with SVD and mild-to-moderate cognitive impairment. METHODS: Within this pilot, single-center (university hospital), double-blinded, randomized clinical trial, patients were randomized to two arms: 1-year treatment with nimodipine 30 mg three times a day (TID) plus choline alphoscerate 600 mg twice a day (BID) (arm 1) or nimodipine 30 mg TID plus placebo BID (arm 2). Patients underwent an evaluation at baseline and after 12 months. Cognitive decline, defined as a ≥ 2-point loss on the Montreal Cognitive Assessment, was the primary endpoint. Functional, quality of life, other cognitive measures, and safety were secondary endpoints. Treatment adherence was measured by the count of medicine bottles returned by patients. RESULTS: Sixty-two patients were randomized (31 each arm). Fourteen patients (22%) dropped out for reasons including consent withdrawal (n = 9), adverse reactions (n = 4), and stroke (n = 1). Forty-eight patients (mean ± SD age 75.1 ± 6.8 years), well balanced between arms, completed the study. Regarding adherence, of the prescribed total drug dose, > 75% was taken by 96% of patients for choline alphoscerate, 87.5% for placebo, and 15% for nimodipine. No statistically significant differences were found between the treatment groups for the primary cognitive outcome, nor for the secondary outcomes. Eight patients had non-serious adverse reactions; five presented adverse events. CONCLUSION: Patients' adherence to treatment was low. With this limitation, the combined choline alphoscerate-nimodipine treatment showed no significant effect in our cohort of VCI patients with SVD. The safety profile was good overall. TRIAL REGISTRATION: Clinical Trial NCT03228498. Registered 25 July 2017.

Gender differences in post-stroke functional outcome at discharge from an intensive rehabilitation hospital.

BACKGROUND: Gender differences in stroke functional recovery after rehabilitation are poorly investigated. Our aim was to compare functional outcomes at discharge from an intensive rehabilitation hospital after stroke in men and women, and to analyze their prognostic factors. METHODS: Retrospective observational study of consecutive stroke patients discharged from an intensive neurological rehabilitation hospital, from January 2018 to June 2019. Modified Rankin Scale (mRS) at discharge was the main outcome measure. RESULTS: Among the 208 included patients (mean age 73.4 ± 13.6 years), 105 (50.5%) were women. Women were significantly older (75.3 ± 13.8 vs. 71.4 ± 13.2 years, respectively, p = 0.041), and less often had a history of smoking habit (27% vs. 50%, p < 0.001). No gender differences emerged for vascular risk factors and comorbidities, pre-stroke functional status, length of hospital stay, stroke type, and number of clinical deficits. At admission to the rehabilitation hospital, mRS score distributions were not different (p = 0.795). At discharge, mRS score distributions and destinations did not differ between men and women (p = 0.391, p = 0.785, respectively). A significant interaction between gender and the change in mRS score from admission to discharge was found (F = 6.6, p = 0.011) taking into account age, stroke type, and number of initial clinical deficits. Dividing the cohort according to age, elderly women showed a better functional recovery compared to men. CONCLUSIONS: At admission to an intensive rehabilitation hospital, men and women presented a similar functional and clinical status and a substantial overlap of functional recovery after stroke. At higher ages, the potential for recovery appeared better in women compared to men.

Longitudinal changes in MoCA performances in patients with mild cognitive impairment and small vessel disease. Results from the VMCI-Tuscany Study.

Objectives: The Montreal Cognitive Assessment (MoCA) is a cognitive screening test largely employed in vascular cognitive impairment, but there are no data about MoCA longitudinal changes in patients with cerebral small vessel disease (SVD). We aimed to describe changes in MoCA performance in patients with mild cognitive impairment (MCI) and SVD during a 2-year follow-up, and to evaluate their association with transition to major neurocognitive disorder (NCD). Materials and Methods: Within the prospective observational VMCI-Tuscany Study, patients with MCI and SVD underwent a comprehensive clinical, neuropsychological, and functional evaluation at baseline, and after 1 and 2 years. Results: Among the 138 patients (mean age 74.4 ± 6.9 years; males: 57%) who completed the study follow-up, 44 (32%) received a major NCD diagnosis. Baseline MoCA scores (mean±SD) were lower in major NCD patients (20.5 ± 5) than in reverter/stable MCI (22.2 ± 4.3), and the difference approached the statistical threshold of significance (p=.051). The total cohort presented a decrease in MoCA score (mean±SD) of -1.3 ± 4.2 points (-2.6 ± 4.7 in major NCD patients, -0.7 ± 3.9 in reverter/stable MCI). A multivariate logistic model on the predictors of transition from MCI to major NCD, showed MoCA approaching the statistical significance (OR=1.09, 95% CI=1.00-1.19, p=.049). Discussion: In our sample of MCI patients with SVD, longitudinal changes in MoCA performances were consistent with an expected more pronounced deterioration in patients who received a diagnosis of major NCD. MoCA sensitivity to change and predictive utility need to be further explored in VCI studies based on larger samples and longer follow-up periods.

Assessment of cerebrovascular disease with computed tomography in COVID-19 patients: correlation of a novel specific visual score with increased mortality risk.

PURPOSE: Cerebrovascular disease (CVD) is considered a major risk factor for fatal outcome in COVID-19. We aimed to evaluate the possible association between computed tomography (CT) signs of chronic CVD and mortality in infected patients. MATERIALS AND METHODS: We performed a double-blind retrospective evaluation of the cerebral CT scans of 83 COVID-19 patients looking for CT signs of chronic CVD. We developed a rapid visual score, named CVD-CT, which summarized the possible presence of parietal calcifications and dolichosis, with or without ectasia, of intracranial arteries, areas of chronic infarction and leukoaraiosis. Statistical analysis was carried out with weighted Cohen's K test for inter-reader agreement and logistic regression to evaluate the association of in-hospital mortality with CVD-CT, chest X-ray (CXR) severity score (Radiographic Assessment of Lung Edema-RALE) for radiological assessment of pulmonary disease, sex and age. RESULTS: CVD-CT (odds ratio 1.6, 95% C.I. 1.2-2.1, p = 0.001) was associated with increased risk of mortality. RALE showed an almost significant association (odds ratio 1.05, 95% C.I. 1-1.1, p 0.06), whereas age and sex did not. CONCLUSION: CVD-CT is associated with risk of mortality in COVID-19 patients. The presence of CT signs of chronic CVD may be correlated to a condition of fragility of the circulatory system, which constitutes a key risk factor for death in infected patients.

Coronary microvascular function is impaired in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients. METHODS: Seventeen patients with genetically confirmed CADASIL, aged <60 years (mean age 40 ± 9 years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12-lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) by 13 NH3 positron emission tomography (PET). Coronary flow reserve (CFR) was defined as Reg-MBF/resting MBF. PET results were compared to those of 15 healthy controls who were age and sex matched. RESULTS: Twelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46 ± 0.54 vs. 3.09 ± 0.44 ml/g/min, respectively; p < 0.01; CFR 2.74 ± 0.36 vs. 3.28 ± 0.66, respectively, p < 0.01). No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden on MRI. CONCLUSIONS: CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients.

Comparison between Ischemic and Hemorrhagic Strokes in Functional Outcome at Discharge from an Intensive Rehabilitation Hospital.

Comparison studies on recovery outcomes in ischemic (IS) and hemorrhagic strokes (HS) have yielded mixed results. In this retrospective observational study of consecutive IS and HS patients, we aimed at evaluating functional outcomes at discharge from an intensive rehabilitation hospital, comparing IS vs. HS, analyzing possible predictors. Modified Rankin Scale (mRS) at discharge was the main outcome. Out of the 229 patients included (mean age 72.9 ± 13.9 years, 48% males), 81 had HS (35%). Compared with IS (n = 148), HS patients were significantly younger (75 ± 12.5 vs. 68.8 ± 15.4 years, p = 0.002), required longer hospitalizations both in acute (23.9 ± 36.7 vs. 35.2 ± 29.9 days, p = 0.019) and rehabilitation hospitals (41.5 ± 31.8 vs. 77.2 ± 51.6 days, p = 0.001), and had more severe initial clinical deficit (mean number of neurological impairments: 2.0 ± 1.1 vs. 2.6 ± 1.4, p = 0.001) and mRS scores at admission (p = 0.046). At discharge, functional status change, expressed as mRS, was not significantly different between IS and HS (F = 0.01, p = 0.902), nor was the discharge destination (p = 0.428). Age and clinical severity were predictors of functional outcome in both stroke types. On admission in an intensive rehabilitation hospital, HS patients presented a worse functional and clinical status compared to IS. Despite this initial gap, the two stroke types showed an overlapped trajectory of functional recovery, with age and initial stroke severity as the main prognostic factors.