Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment.

Determinants of post-stroke cognitive impairment: analysis from VISTA.

BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs commonly and is linked with development of dementia. We investigated the relationship between demographic, clinical and stroke symptoms at stroke onset and the presence of PSCI at 1 and 3 years after stroke. METHODS: We accessed anonymized data from the Virtual International Stroke Trial Archive (VISTA), including demographic and clinical variables. Post-stroke cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤26. We assessed univariate relationships between baseline stroke symptoms and PSCI at 1 and 3 years following stroke, retaining the significant and relevant clinical factors as covariates in a final adjusted logistic regression model. RESULTS: We analysed data on 5435 patients with recent (median 33 days) stroke or transient ischaemic attack (TIA). Mean (±SD) age was 62.6 (±12.6) years; 3476 (65%) patients were male. Follow-up data were available for 2270 and 1294 patients at 1 and 3 years, respectively. At 1 year, 781 (34%) patients had MMSE≤26; at 3 years, 391 (30%) had MMSE≤26. After adjusting for age, stroke severity, hypertension, diabetes and type of qualifying event, initial stroke impairment (leg paralysis) was associated with increased rate of PSCI at 1 year (OR=1.62; 95% CI=1.20-2.20) and at 3 years (OR=1.95; 95% CI=1.23-3.09). Associations were consistent on subgroup analysis restricted to ischaemic stroke and transient ischaemic attack (N=4992). CONCLUSIONS: Besides well-known determinants of PSCI such as age, stroke severity and the presence of vascular risk factors, also leg paralysis is associated with subsequent of PSCI up to 3 years after stroke.

Small vessel disease and clinical outcomes after IV rt-PA treatment.

INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age±SD=68.7±15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.

Pregnancy in CADASIL.

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease caused by NOTCH3 gene mutations. CADASIL women are frequently considered at high risk of systemic vascular events during pregnancy and often prescribed with antithrombotic drugs. This decision is not evidence-based considering the lack of data about pregnancy outcome in CADASIL. We describe our experience on pregnancy in CADASIL patients. MATERIALS AND METHODS: We reviewed records of 50 CADASIL females followed in our center, and we collected prospective information in six patients for a total of 93 pregnancies. RESULTS: No woman had the disease onset or suffered from cerebral vascular ischemic events during pregnancy. Sixteen miscarriages (17.2%) were recorded. There were 72 vaginal births, and five cesarean sections. Considering the six patients followed prospectively (for a total of eight pregnancies), data on fetal growth and newborns weight were in line with those from the general population. Considering gestational complications, we recorded mild proteinuria without hypertension in one patient and hyperinsulinemia and pre-eclampsia in another affected by a known nephropathy. Antithrombotic drugs were used in three patients, in one for an unrelated coexisting prothrombotic condition. CONCLUSIONS: CADASIL does not seem to be associated with an unfavorable outcome of pregnancy either for women and fetuses. Patients and treating physicians should be reassured that pregnancy can be safely initiated in CADASIL, as there is no evidence to support a specific preventive antithrombotic treatment during pregnancy in CADASIL. Larger studies are needed to definitively confirm these conclusions.

Previous infection and the risk of ischaemic stroke in Italy: the IN2 study.

BACKGROUND AND PURPOSE: There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population. METHODS: This was a prospective case-control study involving 11 Italian stroke units. Controls were age- and sex-matched with cases, represented by patients admitted to hospital for acute ischaemic stroke. For each participant classical vascular risk factors and previous inflammatory and infectious events up to 1 month before were registered. Blood samples were collected to analyse inflammatory markers and titres of antibodies against C. pneumoniae. RESULTS: A total of 1002 participants were included (mean age 69 years) with 749 ischaemic stroke patients. Infections occurred within 1 month previously in 12% of the entire sample with a higher prevalence in the case group (14.4% vs. 3.9%). At multivariate analysis of the seropositivity of IgA antibodies against C. pneumoniae increased the risk of stroke significantly (relative risk 2.121; 95% confidence interval 1.255-3.584) and an early previous infection (up to 7 days before the event) contributed to a rise in probability of acute cerebral ischaemia (relative risk 3.692; 95% confidence interval 1.134-6.875). CONCLUSIONS: Early previous infections and persistent chronic infection of C. pneumoniae could contribute to increase the risk of ischaemic stroke significantly, in the elderly especially.

Is type 2 diabetes related to leukoaraiosis? an updated review.

A significantly increased interest has been dedicated to the study of the effects of diabetes mellitus (DM) on the brain. DM is associated with an increased risk of stroke and cognitive decline. In patients with DM, neuroimaging discloses with high-frequency structural changes, such as cerebral atrophy, infarcts and white matter lesions, also called leukoaraiosis (LA), an expression of small vessel disease. A previous review showed a relation between DM and both cerebral atrophy and lacunar infarcts, while the question about the relation between DM and LA remained unanswered. In this review, we provide an update on data on this last association. In the reviewed studies, we examined the presence of DM, other disease characteristics, such as duration and complications, and laboratory markers of the disease such as blood glycated hemoglobin (HbA1c), insulin resistance, insulin concentrations and their association with LA. About 40% of the reviewed studies reported a statistically significant association between DM and LA. Long-standing DM and a poor glycemic control were associated with severe LA. Studies using innovative MRI techniques, such as diffusion tensor imaging (DTI), reported a significant association between microstructural white matter alterations and DM. This review highlights more firmly than previously reported the existence of a relation between DM and both presence and severity of LA. These results are possibly due to more sensitive and advanced imaging techniques recently used to study the extent of LA. However, because of the heterogeneous methodology used in the reviewed studies, a definitive conclusion cannot be drawn.

Predictors of progression in patients presenting with minor subcortical stroke.

OBJECTIVES: Early neurological worsening is common in minor subcortical strokes (SS) and may lead to a poor outcome. We aimed to describe clinical and imaging features associated with progression. MATERIAL AND METHODS: Consecutive patients with SS were divided into progressive and non-progressive. Progression was defined as an increase of NIHSS motor score ≥ 1 point within 72 h from onset. Vascular risk factors and imaging features (vascular territory, size and number of slices in which the lesion was visible, the presence of leukoaraiosis) were compared in the two groups. We investigated potential independent determinants of progression using stepwise logistic regression. RESULTS: Thirty of 94 patients (31.9%) underwent progression. The distribution of vascular risk factors did not differ significantly between the two groups. Increasing number of risk factors was associated with a higher risk of progression (OR 2.2; 95% CI 1.1-4.5). Patients who progressed were more likely to have a lesion ≥ 15 mm in diameter (P = 0.004) or a lesion visible ≥ 3 slices (P = 0.007). After logistic regression stepwise adjustment for all the considered potential determinants, diameter ≥ 15 mm and severe leukoaraiosis proved to be independently associated with neurological worsening (OR = 6.3, 95% CI 2.0-19.6 and OR = 5.9, 95% CI 1.3-25.7, respectively). CONCLUSION: In a series of consecutive SS, early neurological worsening was associated with a high vascular risk profile, a larger infarct size and the presence of severe leukoaraiosis. Based on the knowledge that extensive microvascular changes are a feature of severe leukoaraiosis, we hypothesize that stroke progression could be promoted through an impaired compensatory flow in the penumbral area.

Clinical, familial, and neuroimaging features of CADASIL-like patients.

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3-negative patients with a phenotype closely resembling that of CADASIL. MATERIALS AND METHODS: We performed NOTCH3 analysis (exons 2-23) in 117 probands because of a clinician's suspicion of CADASIL. The CADASIL scale, a recently developed tool that allows to better select patients for NOTCH3 analysis, was retrospectively applied to NOTCH3-negative patients; the patient subgroup that scored higher than the screening cutoff for CADASIL was defined as CADASIL-like. RESULTS: Thirty-four CADASIL-like patients (mean age at onset 57.8 years [52.1-63.4], 50% males) were identified. Compared with 25 patients with CADASIL for clinical, familial, and neuroimaging features, only the following variables were significantly (α level <0.05) different in frequency between patients with CADASIL and CADASIL-like patients: a positive family history for stroke at age ≤ 60 years, more frequent in patients with CADASIL, and hypertension, more frequent in CADASIL-like patients. CONCLUSIONS: Our experience highlights the growing number of patients presenting with a high suspicion of a cerebral small vessel disease with an autosomal dominant pattern of inheritance and a phenotype closely similar to that of CADASIL but without NOTCH3 mutations. This group remains to be characterized from the genetic point of view. The role of other genes or NOTCH3 alterations on exons other than 2-23 or introns has to be further assessed.

Mild cognitive impairment etiologic subtyping using pragmatic and conventional criteria: preliminary experience in the Florence VAS-COG clinic.

BACKGROUND: Mild cognitive impairment (MCI) is an abnormal condition defined by the presence of cognitive decline not severe enough to fit dementia criteria. According to Winblad et al.'s criteria, the clinical distinction of MCI subtypes (amnestic/non-amnestic, single/multiple domain) is based on the cognitive profiling (conventional diagnosis) and infers possible different MCI etiologies. MCI prodromic of vascular dementia (Vasc-MCI) is thought to be characterized by a multiple domain profile. In our outpatient clinic (the "Florence VAS-COG clinic"), the diagnosis of MCI and of its different subtypes (vascular, degenerative, mixed) is based on a comprehensive evaluation of clinical and neuroimaging features (pragmatic diagnosis). AIMS: To compare the pragmatic and conventional diagnoses in terms of etiologic subtyping of MCI. METHODS: We retrospectively assessed the agreement between the two diagnoses in 30 MCI patients. Agreement was considered present when degenerative MCI was of the amnestic type (single or multiple domain) and Vasc-MCI was of the multiple domain type (amnestic or non-amnestic MCI). RESULTS: In 15/30 (50 %) patients, the diagnoses were in disagreement: 5/9 (56 %) patients diagnosed with a degenerative MCI type presented a non-amnestic cognitive profile (4 single domain and 1 multiple domain); 10/21 (48 %) Vasc-MCI were classified as non-amnestic single domain. CONCLUSIONS: The application of MCI etiologic subtyping using pragmatic or conventional diagnoses leads to different results. In our setting, not all the Vasc-MCI patients have a multiple domain profile. Our preliminary study suggests that the cognitive profile of Vasc-MCI is more heterogeneous than previously suggested.

Stroke units in Italy: engaging the public in optimizing existing resources.

BACKGROUND AND PURPOSE: The lack of a wide implementation of stroke units (SU)s in Italy appears to accompany the underuse of the operating units. Community awareness of acute stroke care options may affect stroke resource use. Our aim was to determine the level of knowledge about SUs and tissue-plasminogen activator (t-PA) treatment amongst Italian adults and investigate its relationship to local stroke services implementation. METHODS: A nation-based telephone survey was carried out in a sample of 1000 residents aged >18 years in May-June 2010. The questionnaire included close-ended questions regarding knowledge of SUs and t-PA treatment. Number and location of both SUs and t-PA treatments were provided by a concurrent national hospital-based survey. The prevalence and distribution of acute stroke care awareness in the community was examined and multivariate analyses were generated. RESULTS: Amongst the 1000 participants (474 men, mean age 48.8 ± 17.2), only 26.2% reported knowing about the availability of t-PA treatment and only 15% were aware of the existence of SUs. Awareness of both SUs and t-PA was significantly associated only with education. These associations remained significant in the multivariate analyses. The degree of stroke services implementation (in terms of SUs/inhabitant rates and number of t-PA treatments) was not associated with SU and t-PA awareness. CONCLUSIONS: This is the first European study that explored public knowledge about t-PA treatment and SUs. Italian adults proved insufficiently educated about SUs and t-PA; there is no higher awareness in areas with a greater supply of stroke services. This might partially explain the underuse of Italian SUs.

Effectiveness of public stroke educational interventions: a review.

BACKGROUND AND PURPOSE: Recognizing stroke symptoms and acting quickly can reduce death and disability, but public awareness of stroke risk factors, symptoms and what to do about them is still limited. Stroke educational campaigns are used worldwide but there are few published evaluations of such campaigns. METHODS: The literature from 1999 to 2012 on the effectiveness of stroke educational campaigns was reviewed and summarized with narrative synthesis. Web-based campaigns were also described. Three databases and one search engine were explored with two keywords (stroke campaign and stroke promotion). The reference lists of all included articles were also examined. RESULTS: Twenty-two intervention studies and five web-based campaigns were included in the review. Most interventions proved partially effective, in terms of gender preference (women) or type of information retained or media preferred. Only one intervention proved ineffective. Mass media campaigns can be effective but require sustained funding, and their ability to target high-risk subgroups, whether aging, linguistic or socioeconomic, is unclear. Three community-based participatory stroke promotion interventions proved partially effective, but the small sample sizes might have underpowered the results. Web-based campaigns are efficient in reaching a large number of people but tend to attract a selected and self-selected population. CONCLUSIONS: Stroke educational campaigns have the potential to improve knowledge and awareness and change the behavior of a large number of people. Health promoters and investigators must adopt flexibility and participatory mentality to develop cost-effective interventions. Both community-based campaigns and E-tools should be integrated within a comprehensive multifaceted stroke promotion strategy to expand their reach.

Influence of vascular risk factors and neuropsychological profile on functional performances in CADASIL: results from the MIcrovascular LEukoencephalopathy Study (MILES).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. METHODS: In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). RESULTS: We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥ 2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (ß = -0.418, P < 0.003) in CADASIL patients and the executive function index (ß = -0.321, P = 0.028) in ARL. CONCLUSIONS: This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.

Pseudobulbar paralysis in the Renaissance: Cosimo I de' Medici case.

Cosimo I de' Medici (1519-1574) was the first Grand Duke of Tuscany. He was one of the most important members of the Medici family. He was an excellent conqueror and a good politician. Moreover, he was able to attract and encourage artists, scientists and architects to promote Florence as the cultural capital of the Italian Renaissance. Historical chronicles report that he suffered from a stroke when he was 49 years old. Together with the acute manifestation of stroke, he displayed peculiar symptoms. He had gait disturbances and sphincter dysfunctions. His language became poor and hard to understand. His mood was very fluctuating and in the last years of his life he was a short-tempered man. In addition, he had a characteristic symptom, so-called pathological laughing and crying. The course of his disease was slow and stuttering. Taken together, these data seem to be one of the first reports of pseudobulbar paralysis. The disease of Cosimo I was probably due to a chronic cerebral vasculopathy, known as small vessels disease. We discuss this hypothesis regarding an ancient clinical case, with the support of current studies.

Updating on Italian stroke units: the "CCM study".

The stroke units (SUs) have been demonstrated to be efficient and cost effective for acute stroke care. Nevertheless, the level of stroke unit implementation in Italy does not correspond to expectations yet. This study is a survey, which aims at assessing the current status of in-hospital stroke care in the Italian regions and at updating SUs. The survey was conducted by means of a semi-structured questionnaire, based on 18 stroke care "quality indicators", submitted to all the Italian centres that had taken part in the SITS-MOST study, and to other centres advised by the coordinator of SITS studies and by regional opinion leaders of stroke. SUs were defined as acute wards, with stroke-dedicated beds and dedicated teams that had been formally authorised to administer rt-PA. A statistical analysis was performed by a descriptive statistics and logistic regression model. The study was carried out from November 2009 to September 2010. A total of 168 forms were sent out and 153 replies received. Seven centres, which had not performed any thrombolytic treatment, and 16 which did not fulfil the criteria for the definition of SU were excluded from the study. Most of the centres reported more than 100 stroke patient admissions per year, i.e., 122 (84%) from 100 to 500, 18 (12%) more than 500. The 19% of the centres admitted more than 30% of patients within 3 h from the symptom onset and only 30% admitted more than 30% of patients within 4.5 h. The mean number of thrombolyses performed in the last 6 months was 10 for centres with a doctor on duty 24 h a day, 6 for those that have a doctor on duty from 8 a.m. to 8 p.m. and a doctor on call for night, and 5 for centres with a doctor on call 24 h a day. The territorial distribution of the SUs is remarkably heterogeneous: 87 SUs (67%) are located in the North of Italy, 28 (22%) in the central part of Italy and only 15 (11%) in the South. The last few years have witnessed a rise in both the diffusion of SUs and access to thrombolytic therapy in Italy. Despite this, there are a few large areas, mostly in the south, where the requirements of healthcare legislation are not met, and access to a dedicated SU and thrombolytic treatment is still limited and poor.

The spatial distribution of age-related white matter changes as a function of vascular risk factors--results from the LADIS study.

White matter hyperintensities (WMH) are a frequent finding on brain MRI of elderly subjects, and have been associated with various risk factors, as well as with development of cognitive and functional impairment. While an overall association between WMH load and risk factors is well described, possible spatially restricted vulnerability remains to be established. The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74 ± 5 years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension. Different distribution patterns were found for men and women. Further, increased probability was found in association with self-reported alcohol and tobacco consumption, as well as in those with a history of migraine. It is concluded that the location of WMH is dependent on the risk factors involved pointing towards a regionally different pathogenesis and/or vulnerability of the white matter.

Stroke unit care in clinical practice: an observational study in the Florence center of the European Registers of Stroke (EROS) Project.

BACKGROUND: Randomized trials and meta-analyses indicate positive effects of stroke unit (SU) care on survival and dependency of patients with stroke. However, data on the advantages of SU in 'real-world' settings are limited. We prospectively assessed, in a large University Hospital, the effect of SU versus other conventional wards (OCW) care on all-cause mortality, death or dependency, death or institutionalization. METHODS: In a prospective observational study in the European Registers of Stroke Project, patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, 3-month and 1-year survival, and functional outcome. RESULTS: Overall, 355 patients (54.1% men, mean age 73.4 ± 14.5 years) were registered, 140 (39.4%) admitted to the SU, and 215 (60.6%) to OCW. OCW patients were older, whilst SU patients had more severe strokes according to NIHSS (P for trend = 0.025). SU patients were significantly more often treated by specialists in stroke medicine, stroke nurses, physiotherapists and speech therapists (all P < 0.001), psychologists (P = 0.025), dietitians (P < 0.001), and social workers (P = 0.003). MRI, carotid, and transcranial Doppler were significantly more often performed in SU patients (all P < 0.001). Intravenous fluids (P = 0.003) and intravenous anticoagulation (P < 0.001) were more often prescribed in SU. Controlling for case-mix, SU significantly reduced 1-year mortality (P = 0.020), death or dependency at 3 months (P = 0.006) and 1 year (P = 0.043), and death or institutionalization at 3 months (P = 0.001) and 1 year (P = 0.009). CONCLUSIONS: We confirmed the benefits of SU care in a clinical setting. Further analyses should define the contribution of individual components of care to stroke outcome.

Urgent carotid endarterectomy in patients with recent/crescendo transient ischaemic attacks or acute stroke.

OBJECTIVES: Objective of this study was to review the results of urgent carotid endarterectomy (CEA) performed in patients with recent (< 24 h) or crescendo (at least 2 episodes in 24 h) transient ischaemic attack (TIA) or with acute stroke in a single centre experience. MATERIALS AND METHODS: From January 2000 to December 2008, 75 patients underwent urgent CEA for severe internal carotid artery stenosis and recent/crescendo TIA (51 patients, TIA group) or acute stroke (24 patients, stroke group). In patients with acute stroke the intervention was proposed on the basis of clinical and instrumental features (patient conscious, patency of middle cerebral artery, no lesions or limited brain infarction at CT scan) according to neurologists' suggestion. Data from all the interventions were prospectively collected in a dedicated database, which included main pre-, intra- and postoperative parameters. Independent neurological assessment with National Institute of Health Stroke Scale (NIHSS) score calculation was performed before the operation and within the 30th postoperative day. Early (< 30 days) results were evaluated in terms of mortality, modifications in NIHSS values and stroke and death rates. The surveillance program consisted of clinical and ultrasonographic examinations at 1, 6 and 12 months and yearly thereafter. Follow-up results (survival, occurrence of ipsilateral stroke in TIA group, recurrence of stroke in stroke group) were analysed by Kaplan-Meier curves. RESULTS: Among patients presenting with TIA, 28 had crescendo TIAs and 23 had a recent TIA; In stroke group, two patients had a stroke in evolution, eight patients had a recent major non-disabling stroke and 14 patients had a recent minor stroke. Preoperative mean value of NIHSS score in stroke group was 4.7 (SD 3.2). There were 2 perioperative (< 30 days) deaths, both in stroke group, in one case due to acute respiratory failure and to fatal stroke in the other one (preoperative NIHSS value 9, postoperative 17), with a cumulative 30-day mortality rate of 2.7%, significantly higher in stroke group (8.3%) than in TIA group (no death, p = 0.03). No postoperative cerebral haemorrhage occurred. In TIA group one postoperative major stroke occurred, with a 30-day stroke and death rate of 1.9%. In surviving patients of stroke group NIHSS value improved in 13 cases, with a mean improvement of 2 points (SD 0.9); in 8 cases the value remained unchanged, while in the remaining case it increased from 2 to 4. Mean postoperative NIHSS score in stroke group was 3.9 (SD 3.7), significantly reduced in comparison with preoperative value (p < 0.001). Mean duration of follow-up was 34 months (SD 28.1). No ipsilateral stroke in patients of TIA group occurred; in stroke group a recurrent fatal stroke at 1 postoperative month was recorded. Estimated 48-month stroke-free survival rate TIA group was 95% and 79% in stroke group (p = 0.02). CONCLUSIONS: Urgent CEA in patients with recent/crescendo TIA provided in our experience excellent results, with low rates of perioperative and late stroke. In selected patients with acute stroke early surgery seems to provide acceptable results.

Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview.

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy characterized by migraine, cerebrovascular events, and cognitive impairment. Although recognized as a cardinal feature of the disease, psychiatric disturbances have rarely been the object of focused studies. We performed a structured evaluation of mood disorders in CADASIL. MATERIALS AND METHODS: Twenty-three patients with CADASIL (five men and 18 women) were assessed by psychiatrists using the Structured Clinical Interview for the DSM-IV, clinician version. For the quantitative assessment of current mood disorder symptoms, the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Scale (YMRS) were used. RESULTS: A lifetime depressive episode was recorded in 17/23 (73.9%) patients with CADASIL. Six (26.1%) patients with CADASIL reported a current depressive episode. A diagnosis of manic lifetime episode was made in 6 (26.1%) patients with CADASIL. The HRSD mean score in patients with current depression was 9.1 ± SD 8.1. The YMRS mean score was 14.2 ± SD 4.1 for manic CADASIL. CONCLUSION: This study confirms that mood disorders are frequent in CADASIL. The use of a structured psychiatric interview outlines a frequency of depression higher than that previously reported but also reveals a considerable frequency of bipolar disorders. If confirmed in larger series, these data suggest that a greater attention should be paid to the psychiatric aspects in CADASIL.

Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study.

BACKGROUND: Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults. METHOD: In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors. RESULTS: Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08). CONCLUSIONS: Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.