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.

Italian translation and cross-cultural validation of an assessment tool for participation in stroke survivors: the Frenchay Activities Index.

PURPOSE: Participation needs to be assessed objectively, to state accurate rehabilitation objectives. The Frenchay Activities Index (FAI) is a widely used tool to measure participation in stroke patients. To date, no cross-culturally validated Italian version of FAI is available. This study provides a translation and cross-cultural adaptation of FAI into Italian, assessing its validity and reliability in sub-acute stroke patients. METHODS: According to international guidelines, a multistep translation and cultural adaptation protocol of forward and backward translations was conducted by qualified linguists and independent native English translators and revised by a healthcare committee. Patients admitted to intensive inpatient rehabilitation after stroke were recruited. Structural validity, reliability (internal consistency, inter- and intra-rater reliability and measurement error), and construct validity were studied. RESULTS: One hundred and seventy-three patients were included in this study. No significant observations in terms of comprehensibility and conceptual equivalence of the FAI Italian version emerged. The exploratory factorial analysis revealed the presence of two subscales (i.e., domestic chores and work/leisure). The internal consistency resulted good for the first and second subscale (α = 0.821 and 0.716, respectively). Intra- and inter-reliability showed an ICC > 0.90 for both subscales. SEM = 5.75% and 2.33% and MDC = 15.85% and 6.48% were found for the first and second subscale, respectively. Construct validity of first subscale was satisfactory, as 100.0% a priori hypotheses were met, while for the second subscale it was moderate, as 66.6% a priori hypotheses were respected. CONCLUSION: FAI-I provides a tool for professionals to measure participation in Italian stroke patients in health and social care settings.

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.

Role of Biological Markers for Cerebral Bleeding Risk STRATification in Patients with Atrial Fibrillation on Oral Anticoagulants for Primary or Secondary Prevention of Ischemic Stroke (Strat-AF Study): Study Design and Methodology.

Background and Objectives: 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. Cerebral small vessel disease (SVD) represents the pathologic substrate for primary intracerebral hemorrhage and ischemic stroke. We hypothesize that biological markers-both circulating and imaging-based-and their possible interaction, might improve the prediction of bleeding risk in AF patients under treatment with any type of oral anticoagulant. Materials and Methods: The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with AF, aged 65 years or older, and with no contraindications to magnetic resonance imaging (MRI), referring to Center of Thrombosis outpatient clinic of our University Hospital for the management of oral anticoagulation therapy. Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral MRI, and circulating biomarkers assessment at baseline and after 18 months. The main outcome is SVD progression-particularly microbleeds-as a selective surrogate marker of hemorrhagic complication. Stroke occurrence (ischemic or hemorrhagic) and the progression of functional, cognitive, and motor status will be evaluated as secondary outcomes. Circulating biomarkers may further improve predictive potentials. Results: Starting from September 2017, 194 patients (mean age 78.1 ± 6.7, range 65-97; 61% males) were enrolled. The type of AF was paroxysmal in 93 patients (48%), and persistent or permanent in the remaining patients. Concerning the type of oral anticoagulant, 57 patients (29%) were on vitamin K antagonists, and 137 (71%) were on direct oral anticoagulants. Follow-up clinical evaluation and brain MRI are ongoing. Conclusions: The Strat-AF study may be an essential step towards the exploration of the role of a combined clinical biomarker or multiple biomarker models in predicting stroke risk in AF, and might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting stroke risk and improvement in clinical outcomes in a cost-effective fashion.

Systemic Sclerosis: Exploring the Potential Interplay Between Thyroid Disorders and Pregnancy Outcome in an Italian Cohort.

BACKGROUND: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. OBJECTIVES: To analyze the interplay between TD and PF in a cohort of SSc women. METHODS: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. RESULTS: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). CONCLUSIONS: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.

The effect of transcutaneous vagus nerve stimulation on cortical excitability.

There is great interest about the therapeutic potentialities of transcutaneous vagus nerve stimulation (tVNS) applied to neuropsychiatric disorders. However, the mechanisms of action of tVNS and its impact on cortical excitability are unclear. To this regard, transcranial magnetic stimulation (TMS) can be useful because it is able of evaluating non-invasively excitatory and inhibitory circuitry of the human cortex. Aim of the present study is to investigate the effects of tVNS on cerebral cortex excitability in healthy volunteers by means of TMS. Ten healthy subjects participated in this randomized placebo-controlled double-blind study. Real tVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe, both of them for 60 min. We evaluated motor thresholds, motor evoked potential amplitude, recruitment curves, and short-interval intracortical inhibition (SICI) in right and left motor cortex. Such parameters were evaluated before and 60 min after the exposure to tVNS, for both the real and the sham stimulation. Cardiovascular parameters were monitored during the stimulation. A generalized linear model for repeated measures was implemented to assess the effect of time and stimulation type on cardiovascular and neurophysiological variables. SICI, a double-pulse TMS paradigm informative of GABA-A activity, was significantly increased in right motor cortex after real tVNS. Other neurophysiological parameters, as well as cardiovascular variables, remained unchanged. Our findings confirm that tVNS is a safe and effective way to stimulate vagus nerve and provide innovative data about the possible mechanisms of action that supports the potential therapeutic application of this technique.

Use of anti-tumor necrosis factor alpha therapy in patients with concurrent rheumatoid arthritis and hepatitis B or hepatitis C: a retrospective analysis of 32 patients.

The safety of tumor necrosis factor-alpha (TNF-α) inhibitors in the setting of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is controversial. The use of anti-TNF-α in rheumatoid arthritis (RA) is associated with an increased risk of hepatitis re-activation. This paper reports experience of using etanercept and adalimumab in 32 patients with RA and previous HBV or HCV infection. No cases of HBV or HCV reactivation were seen. In just over a fifth of patients, increased transaminases levels were seen, which were associated with concomitant use of disease-modifying antirheumatic drugs, isoniazid prophylaxis, or alcohol abuse. In our experience, anti-TNF-α therapy appears to be safe in RA patients with previous HBV or HCV infection, but monitoring remains necessary in these patients.

The serum metabolomic profiles of atrial fibrillation patients treated with direct oral anticoagulants or vitamin K antagonists.

AIMS: Long-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). MATERIALS AND METHODS: Serum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution 1H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches. KEY FINDINGS: Our data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs âˆ¼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40-0.51) are characteristic of serum profile of patients on DOACs' therapy. SIGNIFICANCE: Our results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.

Italian translation and transcultural validation of an assessment tool for community ambulation in stroke survivors: the modified Functional Walking Categories (mFWC).

BACKGROUND: Community ambulation ability is one of the most important functional loss after stroke. The assessment of the level of community walking plays an important role in the multidimensional bio-psycho-social approach, to improve quality of life and social participation of stroke survivors. The modified Functional Walking Categories (mFWC) is a worldwide widely used tool to assess community ambulation in stroke survivors, but no Italian version is yet available. OBJECTIVE: To cross-culturally adapt the mFWC into Italian and to assess its validity and reliability. METHODS: According to the international guidelines, a multistep translation and cultural adaptation were conducted and revised by a committee of experts. Patients admitted to intensive inpatient rehabilitation with a sub-acute stroke were recruited. Inter- and intra-rater reliability and construct validity were studied. RESULTS: Sixty patients with sub-acute stroke were prospectively enrolled in this study. Findings showed almost perfect intra- and inter-rater reliability (k = 1.000 [95% CI 1.000-1.000] and k = 0.984 [95% CI 0.955-1.000], respectively). The construct validity of the scale was satisfactory, as 100.0% a-priori hypotheses were met. CONCLUSIONS: The Italian mFWC offers a valid tool for measuring community ambulation in stroke patients. Our work provides a validated and a cross-cultural adapted Italian version of the mFWC to accurately measure community ambulation both in clinical and research settings in Italy.

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.

The Impact of Cerebral Amyloid Angiopathy on Functional Outcome of Patients Affected by Spontaneous Intracerebral Hemorrhage Discharged from Intensive Inpatient Rehabilitation: A Cohort Study.

Background: Sporadic CAA is recognized as a major cause of sICH and sABI. Even if intensive rehabilitation is recommended to maximize functional recovery after sICH, no data are available on whether CAA may affect rehabilitation outcomes. In this observational prospective study, to explore the impact of CAA on rehabilitation results, functional outcomes after intensive rehabilitation have been compared between patients affected by sICH with and without a diagnosis of CAA. Methods: All adults affected by sABI due to sICH and admitted to the IRU of IRCCS-Don-Gnocchi-Foundation were consecutively enrolled for 12 months. Demographic and clinical data were recorded upon admission and discharge. Results: Among 102 sICH patients (age: 66 (IQR = 16), 53% female), 13% were diagnosed as probable/possible-CAA. TPO and functional assessment were comparable upon admission, but CAA patients were significantly older (p = 0.001). After a comparable LOS, CAA patients presented higher care burden (ERBI: p = 0.025), poorer functional recovery (FIM: p = 0.02) and lower levels of global independence (GOSE > 4: p = 0.03). In multivariate analysis, CAA was significantly correlated with a lower FIM (p = 0.019) and a lower likelihood of reaching GOS-E > 4, (p = 0.041) at discharge, independently from age. Conclusions: CAA seems to be independently associated with poorer rehabilitation outcomes, suggesting the importance of improving knowledge about CAA to better predict rehabilitation outcomes.

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.

The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid ß in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484).

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.

Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage.

OBJECTIVE: To investigate whether enlarged perivascular spaces (PVS) within the basal ganglia or deep cerebral white matter are risk factors for intracranial hemorrhage in patients taking oral anticoagulants (OACs), independent of established clinical and radiologic risk factors, we conducted a post hoc analysis of Clinical Relevance of Microbleeds in Stroke (CROMIS-2) (atrial fibrillation [AF]), a prospective inception cohort study. METHODS: Patients with atrial fibrillation and recent TIA or ischemic stroke underwent standardized MRI prior to starting OAC. We rated basal ganglia PVS (BGPVS) and centrum semiovale PVS (CSOPVS), cerebral microbleeds (CMBs), white matter hyperintensities, and lacunes. We dichotomized the PVS rating using a threshold of >10 PVS in the relevant region of either cerebral hemisphere. The primary outcome was symptomatic intracranial hemorrhage (sICH). We identified risk factors for sICH using Cox regression. RESULTS: A total of 1,386 participants with available clinical and imaging variables were followed up for a mean of 2.34 years; 14 sICH occurred (11 intracerebral). In univariable analysis, diabetes, CMB presence, lacune presence, and >10 BGPVS, but not CSOPVS, were associated with sICH. In a multivariable model incorporating all variables with significant associations in univariable analysis, >10 BGPVS (hazard ratio [HR] 8.96, 95% [CI] 2.41-33.4, p = 0.001) and diabetes (HR 3.91, 95% CI 1.34-11.4) remained significant risk factors for sICH. CONCLUSION: Enlarged BGPVS might be a novel risk factor for OAC-related ICH. The strength of this association and potential use in predicting ICH in clinical practice should be investigated in larger cohorts.

Association Between Motor and Cognitive Performances in Elderly With Atrial Fibrillation: Strat-AF Study.

Background/Objective: Growing evidence suggests a close relationship between motor and cognitive abilities, but possible common underlying mechanisms are not well-established. Atrial fibrillation (AF) is associated with reduced physical performance and increased risk of cognitive decline. The study aimed to assess in a cohort of elderly AF patients: (1) the association between motor and cognitive performances, and (2) the influence and potential mediating role of cerebral lesions burden. Design: Strat-AF is a prospective, observational study investigating biological markers for cerebral bleeding risk stratification in AF patients on oral anticoagulants. Baseline cross-sectional data are presented here. Setting: Thrombosis outpatient clinic (Careggi University Hospital). Participants: One-hundred and seventy patients (mean age 77.7 ± 6.8; females 35%). Measurements: Baseline protocol included: neuropsychological battery, motor assessment [Short Physical Performance Battery (SPPB), and walking speed], and brain magnetic resonance imaging (MRI) used for the visual assessment of white matter hyperintensities, lacunar and non-lacunar infarcts, cerebral microbleeds, and global cortical and medial temporal atrophies. Results: Mean Montreal Cognitive Assessment (MoCA) total score was 21.9 ± 3.9, SPPB total score 9.5 ± 2.2, and walking speed 0.9 ± 0.2. In univariate analyses, both SPPB and walking speed were significantly associated with MoCA (r = 0.359, r = 0.372, respectively), visual search (r = 0.361, r = 0.322), Stroop (r = -0.272, r = -0.263), short story (r = 0.263, r = 0.310), and semantic fluency (r = 0.311, r = 0.360). In multivariate models adjusted for demographics, heart failure, physical activity, and either stroke history (Model 1) or neuroimaging markers (Model 2), both SPPB and walking speed were confirmed significantly associated with MoCA (Model 1: ß = 0.256, ß = 0.236; Model 2: ß = 0.276, ß = 0.272, respectively), visual search (Model 1: ß = 0.350, ß = 0.313; Model 2: ß = 0.344, ß = 0.307), semantic fluency (Model 1: ß = 0.223, ß = 0.261), and short story (Model 2: ß = 0.245, ß = 0.273). Conclusions: In our cohort of elderly AF patients, a direct association between motor and cognitive functions consistently recurred using different evaluation of the performances, without an evident mediating role of cerebral lesions burden.

Take a look at the eyes in Systemic Lupus Erythematosus: A novel point of view.

Systemic Lupus Erythematosus (SLE) is a connective tissue disease that involves multiple organs. Ocular structures and visual pathways can be affected in SLE because of disease-related eye involvement or drug toxicity. All the part of the eye may be interested with an external, anterior involvement, responsible of the dry eye disease, or posterior (retina) and neuro-ophtalmic manifestations. Retinopathy in SLE is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival. The early diagnosis is thus the key to a better management and successful treatment. Antimalarial drugs are the cornerstone of SLE treatment and recently the American Academy of Ophthalmology updated the recommendations for hydroxychloroquine retinal toxicity screening which includes the standard automated visual fields and the spectral domain optical coherent tomography. More recently new imaging techniques have been investigated to assess retinal function and reveal subclinical eye involvement. In this review we focalize on the evidence of eye manifestations in SLE, the eye drug toxicity related to antimalarial agents and steroids, and the methods employed for the eye screening. Moreover, the future perspectives on new techniques, such as the optical coherence tomography angiography, are dissected giving new insights on evaluation of microvasculature of the retina and choroid in SLE.