[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to analyze the long-term mortality, functional recovery and long-term complications of cerebral vein and dural sinus thrombosis (CVDST) admitted to Portuguese hospitals. A follow-up of symptomatic CVDST admitted to Portuguese hospitals since 1980 was performed. Fifty-one patients (retrospective cases) were re-evaluated during 1996; 91 consecutively admitted patients from 6/1995 to 6/1998 were followed up to 1999. In 1996, 4 (8%) of the retrospective cases had died (3 patients died in the acute phase), 4 (8%) could not be reached, 33 (64%) had recovered completely (Rankin 0 or 1) and 3 (6%) were dependent. The prospective cases had a mean follow-up of 1 year: 6 (7%) patients died in the acute phase, one (1%) died during follow-up, 75 (82%) recovered completely, and only 1 (1%) was dependent. For the prospective cases, worsening after admission (OR = 18.2; 95% CI = 2.9–112.4) and encephalopathy as the presenting syndrome (OR = 7.1; 95% CI = 1.2–40.9) predicted death or dependency, while absence of aphasia (OR 6.7, 95% CI = 1.6–33) and no worsening after admission (OR = 5.9; 95% CI = 1.6–20) predicted total recovery. During follow-up of the prospective cases, 4 (5%) patients had thrombotic events, 8 (10%) patients experienced seizures, 9 (11%) complained of severe headaches and 1 patient suffered severe visual loss. The long-term functional prognosis of patients with CVDST was fairly good with complete recovery in the majority of cases. However, these patients had a moderate risk of further thrombotic events and seizures.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND PURPOSE: Lumbar puncture (LP) may precipitate cerebral venous thrombosis (CVT), but it is unclear if LP is deleterious in patients with CVT. We aimed to assess the safety of LP in the International Study on Cerebral Veins and Dural Sinus Thrombosis prospective cohort. METHODS: In 624 patients with CVT, we compared the prognosis of patients submitted or not to LP. The primary outcome was 'death or dependency at 6 months', as evaluated by the modified Rankin Scale (mRS; mRS = 3-6, with adjustment for variables associated with poor prognosis); secondary outcomes were: 'worsening after admission'; 'acute death'; and 'complete recovery at 6 months' (mRS = 0-1). We analyzed the same outcomes in subgroups of patients with brain lesions on the admission computer tomography/magnetic resonance imaging. RESULTS: LP was performed in 224 patients (35.9%). There was no difference in frequency of 'death or dependency at 6 months' between patients with or without LP [13.4% vs. 14.4%; odds ratio (OR) = 0.9, 95% confidence interval (CI) 0.6-1.5; P = 0.739]. LP was not associated with 'worsening after hospitalization' [21.5% vs. 23.5%; OR = 0.9, 95% CI 0.6-1.3; P = 0.577], 'acute death' [3.6% vs. 3.3%; OR = 1.1, 95% CI 0.5-2.7; P = 0.844] or 'complete recovery' [79.9% vs. 76.6%; OR = 1.2, 95% CI 0.8-1.7; P = 0.484]. In the subgroups of patients with brain lesions, the prognoses were not different between patients submitted or not to LP. CONCLUSION: LP was not associated with the functional outcome of patients with CVT, suggesting that LP was not harmful in these patients. These results should not be generalized to patients with large brain lesions and risk of herniation where LP is contraindicated.
European Journal of Neurology 03/2013; · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Studies suggest that N-terminal-pro-brain natriuretic peptide (NT-proBNP) can be a biomarker of cardioembolic stroke. However, the best time to measure it after stroke is unknown. We studied the time course of NT-proBNP in patients with ischemic stroke. METHODS: Consecutive acute ischemic stroke patients were admitted over 10 months to a Stroke Unit. Stroke type was classified according to TOAST. Blood samples were drawn within 24, 48, and 72 hours after stroke. Friedman test was used to compare NT-proBNP values across the 3 times in all, cardioembolic and non-cardioembolic stroke patients. Post hoc analysis with Wilcoxon signed-rank tests was conducted with a Bonferroni correction. Mann-Whitney test was used to compare median values of NT-proBNP between cardioembolic and non-cardioembolic stroke patients. ROC curves were drawn to determine NT-proBNP accuracy to diagnose cardioembolic stroke at 24, 48, and 72 hours after stroke onset. RESULTS: One hundred and one patients were included (29 cardioembolic) with a mean age of 64.5±12.3 years. NT-proBNP values for cardioembolic stroke were significantly higher (P < 0.001) than for non-cardioembolic stroke in the 3 time points. NT-proBNP was highest in the first 24-48 h after ischemic stroke and decreased significantly 72 h after stroke onset. The area under the curve for the three time points was similar. CONCLUSION: NT-proBNP levels were highest in the first 2 days after ischemic stroke and declined significantly thereafter. However, the area under the curve for the three time points was similar. The first 72 hours after ischemic stroke have a similar diagnostic accuracy to diagnose cardioembolic stroke.
[Show abstract][Hide abstract] ABSTRACT: Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial.
We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890.
2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364). No significant differences were reported in the safety variables nor in the rate of adverse events.
Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke.
The Lancet 06/2012; 380(9839):349-57. · 39.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance.
A total of 477 subjects with age-related WML were evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders.
MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes.
Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive decline.
[Show abstract][Hide abstract] ABSTRACT: Quantitative measurement of circulating D-dimer, a product of fibrin degradation, has been shown to be a very useful diagnostic tool in the management of patients with suspected deep vein thrombosis and/or pulmonary embolism. Whether D-dimer can play a similar role in the diagnostic approach to patients with suspected cerebral vein thrombosis (CVT) remains controversial.
Studies evaluating the diagnostic accuracy of the D-dimer test in the diagnosis of CVT were systematically searched for in the MEDLINE and EMBASE databases (up to July 2011). Weighted mean sensitivity and specificity with 95% confidence intervals (CIs) were calculated with a bivariate random-effects regression approach.
Fourteen studies, for a total of 1134 patients, were included. D-dimer accuracy was good, with a resulting weighted mean sensitivity of 93.9% (95% CI 87.5-97.1) and weighted mean specificity of 89.7% (95% CI 86.5-92.2), calculated with a bivariate approach. Potential risk factors for false-negative D-dimer results included isolated headache, longer duration of symptoms, and limited sinus involvement. ConclusIONS: Our findings suggest that D-dimer may be a useful diagnostic tool in the management of patients with suspected CVT. Future prospective studies are warranted to confirm our preliminary findings.
Journal of Thrombosis and Haemostasis 01/2012; 10(4):582-9. · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Apathy is a frequent disturbance in stroke patients. The aim of this case-control study was to elucidate whether apathy: (i) was secondary to stroke or related to hospitalization, (ii) was related to thalamic and striatocapsular stroke lesions, (iii) was independent from cognitive impairment and depression in the acute phase of stroke, (iv) was associated with clinical and demographical variables and (v) was associated with a worse functional outcome at discharge.
We assessed a sample of 94 consecutive patients with an acute (≤4 days) stroke (22 intracerebral haemorrhages, 72 cerebral infarcts), and a control group of 50 patients with acute coronary syndrome, with the 10-item Apathy Evaluation Scale-Clinical. We related apathy with cognition (MMSE), depression (Montgomery Åsberg Depression Rating Scale) and with outcome (modified Rankin Scale).
Apathy was present in 36 (38.3%) acute stroke patients but was also frequent in patients with acute coronary syndrome (24%). Stroke patients were more inaccurate in understanding their problems than patients with acute coronary syndrome (P=0.005). Logistic regression identified cerebral haemorrhage (OR=3.5), low educational level (OR=4.7) and a trend of right hemispherical lesion (OR=3.0) as independent predictors for apathy (R(2)=32.3%). Cognitive impairment and depression were not associated to apathy. Apathy was associated with a worse outcome (P=0.03).
Apathy was frequent in acute stroke patients, and it was predicted by acute intracerebral haemorrhage and right hemispherical acute stroke lesion.
European Journal of Neurology 09/2011; 19(2):291-7. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML.
Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression.
After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions (p = 0.021) and speed and motor control (p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score (p = 0.016).
Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.
[Show abstract][Hide abstract] ABSTRACT: The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly.
Journal of the neurological sciences 05/2011; 307(1-2):100-5. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over the last 20 years, evidence about the clinical correlates of cerebral white matter changes (WMC; also called leukoaraiosis) has been accumulating. WMC are now listed among the neuroimaging expressions of cerebral small-vessel disease and are no longer considered an innocuous finding because they are associated, in cross-sectional surveys, with various disturbances and, in follow-up studies, with poor prognosis. The Leukoaraiosis And DISability (LADIS) study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration that was started in 2001 with the aim of assessing the independent role of WMC in predicting disability in subjects aged 65-84. The main results of the LADIS study have been released in 2009 with the demonstration that severe WMC more than double the risk of transition from an autonomous to a dependent status after 3 years of follow-up. The LADIS study has also contributed more focused substudies assessing the possible role of WMC in the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, urinary disturbances, and also the role of other brain lesions (lacunar infarcts, cerebral atrophy, and corpus callosum morphology). The LADIS study provides a good example of harmonization of instruments (MRI protocol, clinical, neuropsychological, and functional scales) within an international collaboration. Currently, the LADIS study is providing data about the natural history of WMC. In this paper, we review the background and the main results of the LADIS study. This review puts forward some considerations for future studies in the field.
[Show abstract][Hide abstract] ABSTRACT: Objectives. To test the relation between white matter lesions (WML) location and physical performance, in aged patients. Methods. SUBJECTS: 29 patients (17 males), aged >65 (mean age 72.6 ± 5.2), with leukoaraiosis. WML was quantified with a visual scale; Apparent Diffusion Coefficient (ADC) was measured bilaterally in frontal periventricular lesioned white matter and frontal and parieto-occipital normal appearing white matter (NAWM). Motor performance was studied using the Short Physical Performance Battery (SPPB), single leg stand time, finger tapping and grooved pegboard tests (GPT). Results. There were significant correlations between the frontal region visual scale scores and SPPB chair stands (r = -0.379; P = .039) and Grooved Pegboard (r = 0.393; P = .032); frontal NAWM ADC values and SPPB standing balance (r = -0.450; P = .014) and SPPB 4 meter walk (r = -0.379; P = .043). Conclusion. Frontal WML are negatively related to motor performance in patients with leukoaraiosis. DWI results suggest that this may be true even for NAWM.
[Show abstract][Hide abstract] ABSTRACT: Behçet's disease (BD) is a chronic inflammatory multisystem disorder which can involve the central nervous system (CNS). Cerebral venous thrombosis (CVT) is one of its major neurological manifestations. We aimed to review the epidemiologic and clinical features of CVT in patients with BD, as well as the available data on therapeutic interventions and prognosis. Systematic review of all observational studies of BD patients was done. Search strategy included electronic searches of MEDLINE (1966-August 2009). Occurrence of CVT in BD and Neuro-Behçet patients, occurrence of CVT as the inaugural manifestation of BD, clinical and neuro-imaging characteristics of CVT, prothrombotic evaluation, treatment options and prognosis were extracted. A meta-analysis of available results was performed when feasible. Twenty-three studies were included, with 290 cases of CVT in patients with BD. The incidence of CVT per 1,000 person-years was 3 (95% CI: 1-8), being higher in retrospective studies (3.2, 95% CI: 1-10) than in prospective studies (2.7, 95% CI: 1-13). Among patients with neurologic involvement, the incidence rate was 15.1/1,000 person-years. The onset was progressive in 77% of the patients. Intracranial hypertension syndrome was a frequent presentation of CVT in BD. The most frequent sites of occlusion were the superior sagittal and the transverse sinus. Most of the studies did not evaluate the prevalence of prothrombotic disorders. Treated CVT was associated with a good prognosis. CVT is a frequent neurological manifestation of BD. When treated, BD-associated CVT bears a good prognosis. There is insufficient information regarding the role of concomitant prothrombotic disorders and specific treatments.
Journal of Neurology 01/2011; 258(5):719-27. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute and unexpected neuropsychiatric disturbances can herald subarachnoid haemorrhage (SAH). We investigated the risk factors for neuropsychiatric disturbances in acute SAH and analysed the relation between neuropsychiatric disturbances and location and amount of haematic densities and hydrocephalus.
We assessed a sample of 108 consecutive patients with an acute (≤ 4 days) SAH (61 aneurysmal, 47 non-aneurysmal SAH), before aneurysmal treatment, using DSM-IV-TR criteria and the Montgomery Åsberg Depression Rating Scale and Mania Rating Scale, the Denial of Illness Scale, the Catastrophic Reaction Scale and the Apathy Evaluation Scale, excluding patients with severe consciousness or language disturbance. Performance on each scale was related to (i) the total amount of haematic densities in 10 basal cisterns/fissures and in the four ventricles, using the Hijdra et al. rating scale, (ii) the haematic densities in the prepontine cistern and the convexity of the brain and (iii) hydrocephalus.
Depression (45%), apathy (42%), denial (21%) and catastrophic reaction (17%) were frequent in acute SAH patients. Mania was present in two patients. Denial was associated with higher haematic densities in the left and right basal sylvian fissure and in the 4th ventricle (P < 0.01) and with hydrocephalus (P = 0.05). Catastrophic reaction and depression were associated with previous mood disorder (P < 0.007). Apathy was associated with blood in the left or right lateral ventricles (P < 0.03).
In the first 4 days of SAH, depression, apathy, catastrophic reaction and denial were rather frequent. SAH haematic densities were associated with denial and apathy, but not with depression, mania or catastrophic reaction.
European Journal of Neurology 12/2010; 18(6):857-64. · 4.16 Impact Factor