Atrial fibrillation is a major cause of stroke in apneic patients: a prospective study.

OBJECTIVES: Large prospective studies have established that sleep-disordered breathing (SDB) is associated with an increased incidence of cardiovascular and cerebrovascular diseases. Heterogeneous results have been published about SDB and ischaemic stroke mechanism. The aim of this study was to evaluate the relationship between poststroke apneic syndrome and stroke aetiologies according to the ASCO classification. METHODS: A total of 134 patients with acute ischaemic cerebrovascular events were prospectively included. Patients with severe or infratentorial infarctions were excluded. Stroke risk factors and clinical characteristics were recorded in all patients. An overnight polygraphy was recorded (Embletta PDS). Apneic patients were defined if the polygraphy reported an apnea-hypopnea index ≥15. A standardized diagnosis workup, including serum biological investigation, evaluation of extra and intracranial arteries and heart morphology and function, was performed. Stroke mechanism was defined using ASCO and TOAST classifications. RESULTS: A proportion of 42% (56 of 134) of the patients were diagnosed as having sleep apneas. Apneic patients were older (p < 0.001), had higher BMI (p = 0.02), and more were hypertensive (p < 0.001). Using ASCO classification, a major cardioembolic source of stroke, mainly atrial fibrillation, was more frequently observed in apneic patients (41.1% vs. 20.5%, p < 0.05), while no difference was observed when considering atherosclerosis or small-vessel disease mechanisms. Univariate analysis showed that cardioembolic stroke depends on sex, age, left atrial size and OSA; however, age remained the only significant factor in multivariate analysis. CONCLUSION: This study confirms the high prevalence of sleep apneas in stroke-affected patients and identifies atrial fibrillation as a major source of stroke in this population. The strong correlation between age and SDB seems to drive the increased frequency of stroke related to atrial fibrillation in this population.

Magnetisation transfer parameters and stroke outcome.

Our aim was to evaluate the association between magnetisation transfer imaging (MTI) parameters measured 30 to 45 days after a cerebrovascular insult and post-stroke functional outcome at the same time. MTI offers the opportunity to depict subtle microstructural changes in infarcted areas. The clinical significance of the heterogeneity of brain damage within ischaemic stroke lesions is unknown. We prospectively included 58 patients with acute middle cerebral artery stroke. Diffusion-weighted imaging was performed within 12 hours after onset and the final infarct was documented by MRI with fluid-attenuated inversion recovery (FLAIR) and MTI at 30 to 45 days follow-up. We evaluated the association between MTI histogram parameters and the clinical outcome assessed by dichotomised (threshold >2) modified rankin scale (mRS) using multivariable logistic regression models adjusted on baseline characteristics. In multivariable analyses, stroke outcome was mostly driven by initial National Institutes of Health Stroke Scale (odds ratio [OR]=1.23; 95% confidence interval [CI]=1.07-1.41; p<0.01) while after adjustment of initial stroke severity magnetisation transfer ratio peak position was the only MRI parameter associated with functional status at 30 to 45 days post-stroke (OR=0.86; 95% CI=0.75-0.98; p=0.02); lower peak position values associated with higher mRS. Conversely, stroke volume measured on FLAIR sequence was not associated with stroke prognosis (p=0.87). The intensity of microstructural changes within the infarct core measured at 30 to 45 days follow-up is independently associated with the functional status evaluated at the same time. MTI and related parameters could be used as surrogate markers of treatment response in stroke clinical trials.

Change in leisure and social activities and risk of dementia in elderly cohort.

OBJECTIVE: To investigate the association of the change in practice of leisure and social activities with dementia risk taking into account the evolution of cognitive performances. DESIGN, SETTING, AND PARTICIPANTS: From the PAQUID prospective cohort re-examined every 2 years until the 20-year follow-up since 1988, 1461 subjects were seen at 10th year of follow-up. Engagement in 10 leisure and social activities was collected at baseline and at the 10-year follow-up visit for 805 subjects. Four categories of change in activity engagement were considered: subjects who remained active; remained inactive; became inactive and became active. Adjustment on confounders (age, gender, educational level, diabetes, stroke and depression) and rate of evolution of cognitive performances was made with the multivariate Cox proportional hazards model. MAIN OUTCOME MEASURES: Time to incident cases of dementia occurring between the 10th and the 20th year of follow-up. RESULTS: A total of 258 incident dementia cases were documented. The risk of dementia was lower for subjects remaining or becoming active (cumulative risk of dementia: 30%) compared to those remaining or becoming inactive (52% and 42%, respectively) (p<0.0001). Multivariate adjustment including rate of cognitive decline during the first decade of FU did not change these relationships. CONCLUSION: This prospective cohort study suggests a significant association between change in leisure and social activities during old age and risk of dementia.

A simple score to predict survival with dementia in the general population.

BACKGROUND/AIMS: This study was designed to develop a practical risk score for predicting 5-year survival after the diagnosis of dementia. METHODS: Using the Paquid Study (prospective, population-based, long-term cohort study), we created a prognosis score with incident cases of dementia and validated it in another prospective, population-based, long-term cohort study, the Three City Study. - RESULTS: Among the 3,777 subjects enrolled in the Paquid Study, 454 incident cases of dementia were included in this study. After a 5-year follow-up period, 319 (70.3%) were deceased. The score was constructed from three independent prognostic variables (gender, age at diagnosis and number of ADL restricted). The discriminant ability of the score was good with a c index of 0.754. Sensitivity was 64.7% and specificity 76.3%. In the validation cohort, the discriminant ability of the prognostic score with c statistics was 0.700. Sensitivity was 26.3% and specificity 95.4%. CONCLUSIONS: The prognostic factors selected in the predictive model are easily assessable, so this simple score could provide helpful information for the management of dementia, particularly to identify patients with duration of the disease greater than 5 years.

Assessment of quality of life in stroke patients with hemiplegia.

UNLABELLED: Stroke is a major public health issue. Even though most hemiplegic stroke patients may obtain a good functional outcome, many remain dissatisfied with their lives. Indeed, quality of life and subjective well-being should be taken into account in any assessment of stroke survival. OBJECTIVE: To assess long-term quality of life in stroke patients (compared with healthy controls) and the corresponding determinants and predictive factors. METHOD: The patient population consisted of 80 of the 217 first-stroke survivors treated between January and June 2005 in the Clinical Neurosciences Department at Bordeaux University Hospital. After a mean follow-up period of 2 years, 24 patients were interviewed in their homes and data from the 56 others were obtained in a telephone interview. Demographic information, clinical status on admission and functional status (as assessed by Barthel Index) and depression (on the ADRS) at the time of the study visit were recorded. Quality of life was assessed by using the Sickness Impact Profile (SIP-65) and Bränholm and Fugl-Meyer's Satisfaction with Life Scale (LiSat 11). The patients' data were compared with those from 149 healthy controls. RESULTS: Life satisfaction and quality of life were significantly impaired in stroke patients, compared with controls. All life domains were impaired. The worst scores were observed for independence and health-related items in the LiSat 11 and the physical and communication items in the SIP-65. Quality of life was strongly correlated with functional independence, the persistence of hemiplegia and depressive mood, which is in agreement with literature findings. Neither gender nor the initial Rankin score had a significant impact on these parameters. DISCUSSION-CONCLUSION: Quality of life at 2 years is significantly impaired in stroke survivors and seems more difficult to predict than functional independence. However, in addition to these objective results, our interviews suggest that receiving adequate social support might be as important to patients as recovering independence.

Final cerebral infarct volume is predictable by MR imaging at 1 week.

BACKGROUND AND PURPOSE: Stroke volume, an increasingly used end point in phase II trials, is considered stationary at least 30 days after the ictus. We investigated whether information conveyed by MR imaging measurements of the "final" infarct volume could be assessed as early as the subacute stage (days 3-6), rather than waiting for the chronic stage (days 30-45). MATERIALS AND METHODS: Ninety-five patients with middle cerebral artery stroke prospectively included in a multicenter study underwent MR imaging during the first 12 hours (MR imaging-1), between days 3 and 6 (MR imaging-2), and between days 30 and 45 (MR imaging-3). We first investigated the relationship between subacute (FLAIR-2) and chronic volumes (FLAIR-3), by using a linear regression model. We then tested the relationship between FLAIR volumes (either FLAIR-2 or FLAIR-3) and functional disability, measured by the mRS at the time of MR imaging-3, by using logistic regression. The performances of the models were assessed by using the AUC in ROC. RESULTS: A linear association between log FLAIR-2 and log FLAIR-3 volumes was observed. The proportion of FLAIR-3 variation, explained by FLAIR-2, was high (R(2) = 81%), without a covariate that improved this percentage. Both FLAIR-2 and FLAIR-3 were independent predictors of mRS (OR, 0.79 and 0.73; 95% CI, 0.64-0.97 and 0.56-0.96; P = .026 and .023). The performances of the models for the association between either FLAIR volume and mRS did not differ (AUC = 0.897 for FLAIR-2 and 0.888 for FLAIR-3). CONCLUSIONS: Stroke damage may be assessed by a subacute volume because subacute volume predicts the "true" final volume and provides the same clinical prognosis.

Stroke in under-75-year-olds: expectations, concerns and needs.

UNLABELLED: Most studies of functional outcomes in hemiplegic stroke patients use standard disability rating scales (such as the Barthel Index). However, planning the allocation of assistance and resources requires additional information about these patients' expectations and needs. AIMS OF THE STUDY: To assess functional independence in daily living and house holding, changes in home settings, type of technical aid and human helps, and expectations in hemiplegic patients 1 to 2 years after the stroke. METHODS: Sixty-one out of 94 patients admitted to the neurovascular unit of French university hospital for a first-ever documented stroke were consecutively enrolled. The study was restricted to patients under 75, since patients over 75 do not follow the same care network. Patients were examined at their homes or interviewed by phone 17 months (on average) after the stroke. Standard functional assessment tools (such as the Barthel Index and the instrumental activities of daily living [IADL] score) were recorded, along with descriptions of home settings and instrumental and human help. Lastly, patients and caregivers were asked to state their expectations and needs. RESULTS: Although only one person was living in a nursing home after the stroke, 23 (34%) of the other interviewees had needed to make home adjustments or move home. Seven patients (11%) were dependent in terms of the activities of daily living (a Barthel Index below 60) and 11 (18%) had difficulty in maintaining domestic activities and community living (an IADL score over 10). Although the remaining patients had made a good functional recovery, 23 were using technical aids and 28 needed family or caregiver assistance, including 23 patients with full functional independence scores. Twenty-five patients (42%) were suffering from depression as defined by the diagnosis and statistical manual of mental disorders (4th edition, text revision, DSM IV-R). The patients' prime concerns were related to recovery of independence, leisure activities and financial resources. Family members' expectations related to the complexity of administrative matters, lack of information and the delay in service delivery. DISCUSSION AND CONCLUSION: In under-75 hemiplegic stroke patients, high scores on standard disability rating scales do not always mean that no help is required.

[Update on vascular dementias]. / Mise au point sur les démences vasculaires.

The concept of vascular dementia greatly evolved since Hachinski's description of multi-infarct dementia. Vascular dementias are reviewed with emphasis on current diagnostic criteria, elusive natural history, neuroradiological aspects, difficult epidemiological features and intriguing links with Alzheimer's disease. The recent proposed shift from vascular dementias to a broader definition of "vascular cognitive disorders", including non demented subjects with "vascular cognitive impairment", is described, followed by a brief review of current treatments.

Early prevention at public health issue.

Alzheimer's Disease and related disorders have recently become a priority in France and two consecutive governmental plans have been undertaken in 2001-2004 and 2004-2007. The number of prevalent cases was estimated to be 850,000 in France with an incidence of 220,000 cases. Only 50% of these cases were actually diagnosed and about 32% were treated by antidementia drugs. If the incidence and the duration of the disease do not change, the number of cases will increase to 1,200,000 in 2020 and 2,100,000 cases in 2040. In absence of curative treatment, the prevention way is necessary if one wishes to control this phenomena. The development of Memory Clinics and "Centres de Mémoires de Ressources et de Recherche" in all regions in France is one of the important measures to develop primary and secondary prevention in subjects with cognitive complaints or MCI. Several factors could be the basis of this prevention 1) Vascular risk factors (High Blood Pressure, Diabetes, Obesity, Hypercholesterolemiae, Tobacco consumption) ; 2) physical exercise ; 3) Stimulating cognitive activities ; 4) Nutrition ; 5) depressive disorders and loneliness.

Restriction in complex activities of daily living in MCI: impact on outcome.

OBJECTIVE: To describe the restriction in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess the impact of IADL restriction on the progression to dementia and on MCI reversibility. METHODS: The study sample included 1,517 participants of the PAQUID cohort, visited at 8- and 10-year follow-ups. Subjects classified as having MCI had no dementia but a cognitive deficit according to five neuropsychological tests. Four IADL (telephone, transports, medication, finances) were assessed and considered restricted if at least two of them were not performed at the highest level of performance. Cross-sectional and longitudinal analyses were conducted. RESULTS: A total of 285 subjects were classified as having MCI at baseline, and 15.2% developed dementia within 2 years. MCI subjects were more frequently IADL restricted (34.3%) than controls (5.4%) but less than those with dementia (91.1%). The IADL-restricted MCI subjects were more likely to develop dementia over 2 years (30.7%) than the nonrestricted ones (7.8%). In multivariate analyses, the odds ratio for dementia was 7.4 (CI: 3.3 to 16.5) in the IADL-restricted MCI and 2.8 (CI: 1.3 to 6.0) in the non-IADL-restricted MCI compared with the non-IADL-restricted controls. IADL restriction also lowered the chance of reversibility to normal, observed in 10.7% of the restricted MCI and 34.7% of the nonrestricted MCI. CONCLUSIONS: Inclusion of instrumental activities of daily living restriction in the criteria of mild cognitive impairment improves the prediction of dementia and the stability of this status over time. Conversely, its exclusion results in inappropriate selection of subjects with a low probability of short-term progression to dementia.

Marchiafava-Bignami disease: diffusion-weighted MRI in corpus callosum and cortical lesions.

The clinical diagnosis of Marchiafava-Bignami disease (MBD) can be difficult. Acute demyelination of the corpus callosum is characteristic of the disease. The authors report the use of MR diffusion-weighted imaging (DWI) in six cases of acute MBD. They show that apparent diffusion coefficient restriction of the corpus callosum and cortical lesions were associated with a higher mortality rate and more severe cognitive sequelae.

Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.

BACKGROUND: AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS: Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION: Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.

[Stroke-like presentation of cerebral lymphoma]. / Lymphome cérébral primitif à présentation pseudovasculaire.

INTRODUCTION: The clinical presentation of primary cerebral lymphoma can take on many forms. CASE REPORT: We report the case of a patient who experienced recurrent neurological events mimicking stroke with normal brain MRI. A late performed MRI showed a mesencephalic lesion. A biopsy was obtained and led to the diagnosis of primary B cell lymphoma. CONCLUSION: This observation illustrates the diagnostic challenge of this rare disorder with a poor prognosis.

Effects of galantamine in patients with mild Alzheimer's disease.

BACKGROUND: Galantamine is an acetylcholinesterase inhibitor that modulates nicotinic receptors. It is effective in mild to moderate Alzheimer's disease (AD) but no trial has focused exclusively on mild AD. We performed a post-hoc sub-set analysis using data from four randomised trials to explore the efficacy of galantamine versus placebo in mild AD. METHODS: Participants in all studies met NINCDS-ADRDA criteria for probable AD. We examined data from patients with baseline Mini Mental State Examination (MMSE) 21-24 who received galantamine 24 mg/day (GAL) or placebo (PLAC). Scores for the Alzheimer's Disease Assessment Scale-cognitive subset (ADAS-cog), Clinician's Interview-Based Impression of Change (CIBIC), Disability Assessment for Dementia (DAD), and ACDS-ADL scales were compared. RESULTS: Of the 694 patients (362 GAL, 332 PLAC, mean baseline MMSE 22.4 +/- 1.1, mean age 74 +/- 7.9 years), 65% completed 6 months treatment (223 GAL, 229 PLAC). Mean change in ADAS-cog at 6 months was -1.5 (95% confidence interval -2.2, -0.8, p < 0.001) for GAL and +0.2 (-0.6, 0.9, p = 0.72) for PLAC. This difference was statistically significant (p = 0.001). Significantly more patients receiving galantamine were classified as 'improved' using the CIBIC (26.9% GAL vs 14.3% PLAC, p < 0.001). Galantamine was generally well tolerated; most common adverse events were nausea, vomiting and diarrhoea. CONCLUSIONS: Pooled data from four randomised trials of patients with mild AD indicate that patients who received galantamine 24 mg/day for 6 months improved cognition more often than those who received placebo and that a higher proportion receiving galantamine were globally improved. This suggests that patients with mild AD benefit from galantamine treatment.

[Cerebral infraction by calcified embolism: a spontaneous complication of calcified aortic stenosis]. / Infarctus cérébral par embolie calcaire: complication spontanée révélatrice d'un rétrécissement aortique calcifié.

Calcified aortic stenosis (CAS) is an unusual cause of cerebral infarct. The presence of cerebral intra-vascular or intra-parenchymatous calcifications, symptomatic or not, is suggestive of the diagnosis of CAS. We report two patients who experienced stroke induced by spontaneous calcic emboli from a calcified aortic valve and underline the importance of brain CT scan.

[Pulmonary venous thrombosis and neoplasia related cerebrovascular ischaemic events]. / Accidents vasculaires cérébraux et néoplasie: évoquer la thrombose veineuse pulmonaire.

Stroke in patients with malignant tumor are associated with various aetiologies. We report a case of lung adnocarcinoma with pulmonary vein thrombosis appending into the left atrial revealed by multiple cerebral infarcts.