Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke.

BACKGROUND: Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS: In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS: A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS: Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).

REEP1 mutations in SPG31: frequency, mutational spectrum, and potential association with mitochondrial morpho-functional dysfunction.

Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative disorders characterized at least by slowly progressive spasticity of the lower limbs. Mutations in REEP1 were recently associated with a pure dominant HSP, SPG31. We sequenced all exons of REEP1 and searched for rearrangements by multiplex ligation-dependent probe amplification (MLPA) in a large panel of 175 unrelated HSP index patients from kindreds with dominant inheritance (AD-HSP), with either pure (n = 102) or complicated (n = 73) forms of the disease, after exclusion of other known HSP genes. We identified 12 different heterozygous mutations, including two exon deletions, associated with either a pure or a complex phenotype. The overall mutation rate in our clinically heterogeneous sample was 4.5% in French families with AD-HSP. The phenotype was restricted to pyramidal signs in the lower limbs in most patients but nine had a complex phenotype associating axonal peripheral neuropathy (= 5/11 patients) including a Silver-like syndrome in one patient, and less frequently cerebellar ataxia, tremor, dementia. Interestingly, we evidenced abnormal mitochondrial network organization in fibroblasts of one patient in addition to defective mitochondrial energy production in both fibroblasts and muscle, but whether these anomalies are directly or indirectly related to the mutations remains uncertain.

Epidemiology of atrial fibrillation in France: extrapolation of international epidemiological data to France and analysis of French hospitalization data.

The prevalence of atrial fibrillation is steadily increasing throughout the world because of ageing populations and better management of coronary heart disease. An international literature review was conducted to estimate the prevalence and incidence of atrial fibrillation in France. A review of the literature on comorbidities was also performed. Finally, French mortality and hospitalization data were analysed using the PMSI database. The prevalence of atrial fibrillation is estimated to be between 600,000 and 1 million people; of these, two-thirds are aged >75 years. The incidence is estimated at between 110,000 and 230,000 new cases per year. In 2008, 412,000 hospitalized patients had a diagnosis of atrial fibrillation; this figure increased by 26% in the 3-year period between 2005 and 2008. These findings highlight the importance of targeting therapy, of upstream therapy, and of therapy that provides clear clinical and economic advantages over the well-established reductions already achieved in atrial fibrillation morbidity, mortality and cost. In addition, new prevention strategies should be developed, particularly secondary prevention strategies in patients with cardiovascular diseases.

Mitoxantrone therapy for acute posterior multifocal placoid pigment epitheliopathy with cerebral vasculitis.

Purpose. To report favorable outcome of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with cerebral vasculitis after treatment with immunosuppressive therapy by mitoxantrone. Design. Single case report. Method. A 22-year-old man presented with acute isolated bilateral loss of vision revealing APMPPE. Corticosteroid therapy was initiated and visual acuity gradually improved. Seventeen days later, visual function deteriorated again, associated with flu-like syndrome and severe headaches. A relapse of APMPPE was diagnosed, complicated with lymphocytic meningitis and cerebral ischemia. Intravenous therapy with mitoxantrone was performed in combination with methylprednisolone. Results. Headaches disappeared in a few days whereas visual acuity gradually improved and stabilized at 20/40 in the right eye and 20/32 in the left eye. No adverse event was observed. Clinical improvement was confirmed by magnetic resonance imaging. Conclusion. Cerebral vasculitis is the most severe complication of the extraocular manifestations of APMPEE. This diagnosis should be evoked when severe headaches or behavior disorder are associated with APMPEE.

Screening of unrecognized peripheral arterial disease (PAD) using ankle-brachial index in high cardiovascular risk patients free from symptomatic PAD.

OBJECTIVE: To determine the utility of ankle-brachial index (ABI) in screening for unrecognized peripheral arterial disease (PAD). Although PAD is a consistent predictor of cardiovascular morbidity and mortality, it is often under-diagnosed and under-treated. METHODS: In this prospective, observational, real-life, epidemiologic study (ELLIPSE) the prevalence of PAD (ABI < 0.9) was calculated in 2146 asymptomatic patients > or =55 years of age who were at high cardiovascular risk and who were hospitalized in departments of cardiology, diabetology, geriatrics, internal medicine, or neurology in metropolitan France. Univariate and multivariate analyses were performed to identify PAD risk factors. The discriminatory power of the model was evaluated by calculating the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: The ABI was <0.9 in 41.1% of patients. In the multivariate analysis, absence of > or =1 pulse (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.81 to 2.63; P < .0001), arterial bruit (OR, 1.92; 95%CI, 1.34 to 2.75; P < .0004), previous non-Q-wave myocardial infarction (OR, 1.50; 95%CI, 1.08 to 2.08; P = .02), regular smoking (OR, 1.49; 95%CI, 1.22 to 1.80; P < .0001), age > or =81 years (OR, 1.45; 95%CI, 1.15 to 1.82; P = .001), creatinine clearance <60 mL/min (OR, 1.33; 95%CI, 1.08 to 1.63; P = .008), and treated hypertension (OR, 1.28; 95%CI, 1.03 to 1.59; P = .03) were significantly associated with PAD. Although risk increased with the number of variables, the model, based on clinical symptoms and on medical history parameters, was not discriminatory (AUC = 0.66). On average, physicians took 15 minutes to perform the ABI test. CONCLUSIONS: The high prevalence of asymptomatic PAD in this patient population suggests that ABI should systematically be performed in high-risk hospitalized patients to ensure that appropriate secondary prevention programs are initiated.

Drugs and vascular dementia.

Between 20 and 35% of all dementias are vascular in origin, their etiology is due to cerebrovascular disease and the risk factors are known (e.g. hypertension, diabetes, smoking, or hyperlipidemia). Primary and secondary preventions are the basis of therapeutics. Symptomatic treatment is emerging, notably in the field of cognitive disorders. In that respect, monoamine oxidase inhibitors, and more recently acetylcholinesterase inhibitors, are in the process of being recognized as first-line treatments of established vascular dementia.

Choreic syndrome due to Hashimoto's encephalopathy.

We report on the instructive case of an elderly woman who became encephalopathic and concurrently developed chorea. Thyroid antibody studies were abnormal. She responded extremely well to oral corticosteroids.

Prognostic factors in the recovery of the ability to walk after stroke.

We have studied the recovery of walking ability on being discharged from a department of physical medicine and rehabilitation in patients with hemiplegia after stroke, and the factors influencing this recovery. This prospective study was based on 93 patients. The patients, who were considered to be ambulatory, were able to move 10 metres on their own or with supervision when they were discharged. The potentially influential factors studied were: age, the aetiology and the side of hemiplegia, co-morbidity, the delay in starting rehabilitation, the neurological damage evaluated by the middle cerebral artery scale of Orgogozo, the initial functional damage evaluated by the functional score carried out within the scale of Functional Independence Measure (FIM), the existence of aphasia, of a depressive or hemineglect syndrome, presence of superficial or profound sensory disorders, incontinence at the start of rehabilitation and at one month after stroke, the existence of cognitive or psychiatric disorders. The non-parametric Mann-Whitney, the chi2, and the correlation test were used. The threshold of significance was .05. Based on 93 patients (47 women and 46 men, average age 64.8) 87.1% were walking at discharge, on average 3 months after stroke. The predictive factors or those linked to an absence of recovery were the presence of superficial sensory disorders, the initial neurological damage, the initial functional damage, the presence of a depressive syndrome, and urinary incontinence. We stress the significance of the sensorimotor and initial functional damage, and of incontinence in establishing a prognosis for recovery of walking ability, in order to decide the objectives and the rehabilitative treatment for each patient.