Outcomes of Acute Stroke Patients Requiring Mechanical Ventilation: Study Protocol for the SPICE Multicenter Prospective Observational Study.

BACKGROUND: Care pathways and long-term outcomes of acute stroke patients requiring mechanical ventilation have not been thoroughly studied. METHODS AND RESULTS: Stroke Prognosis in Intensive Care (SPICE) is a prospective multicenter cohort study which will be conducted in 34 intensive care units (ICUs) in the Paris, France area. Patients will be eligible if they meet all of the following inclusion criteria: (1) age of 18 years or older; (2) acute stroke (i.e., ischemic stroke, intracranial hemorrhage, or subarachnoid hemorrhage) diagnosed on neuroimaging; (3) ICU admission within 7 days before or after stroke onset; and (4) need for mechanical ventilation for a duration of at least 24 h. Patients will be excluded if they meet any of the following: (1) stroke of traumatic origin; (2) refusal to participate; and (3) privation of liberty by administrative or judicial decision. The primary endpoint is poor functional outcome at 1 year, defined by a score of 4 to 6 on the modified Rankin scale (mRS), indicating severe disability or death. Main secondary endpoints will include decisions to withhold or withdraw care, mRS scores at 3 and 6 months, and health-related quality of life at 1 year. CONCLUSIONS: The SPICE multicenter study will investigate 1-year outcomes, ethical issues, as well as care pathways of acute stroke patients requiring invasive ventilation in the ICU. Gathered data will delineate human resources and facilities needs for adequate management. The identification of prognostic factors at the acute phase will help to identify patients who may benefit from prolonged intensive care and rehabilitation. TRIAL REGISTRATION: NCT03335995.

The hidden face of Wilson's disease.

In brief, the classic form of Wilson's disease (WD) is an autosomal-recessive condition with hepatic, neurologic, psychiatric and systemic manifestations. However, the diagnosis should not be excluded because of a family history consistent with autosomal-dominant transmission. The latest next-generation sequencing (NGS) studies have demonstrated a gap between phenotype and genetic prevalences, and also suggest that WD may still be underdiagnosed. In a majority of WD patients, early recognition and appropriate treatment can result in resolution of symptoms and/or improved quality of life. Thus, finding WD in patients aged>40 years or with thrombocytopenia, hemolytic anemia, unexplained bone pain, amenorrhea, repeated spontaneous abortion or renal lithiasis is of major importance. These symptoms can all be found on their own or in association with mild-to-incapacitating neurological and/or neuropsychiatric manifestations. While brain lesions of the lenticular, midbrain and dentate nuclei are classic, white-matter changes and cortical lesions may also be observed: these are often asymmetrical with frontal lobe predilection and, when extensive, associated with a poor prognosis. These lesions are due mainly to copper deposition, but may also be related to focal accumulation of other metals, such as iron and manganese. A new biological marker called 'relative exchangeable copper' (REC) facilitates diagnosis and familial screening. Patient monitoring is important to ensure treatment adherence, efficacy and tolerability, and to detect rare complications such as copper deficiency induced by chronic copper chelation and hepatocarcinoma in patients with cirrhosis. Currently used treatments are copper chelators and zinc salts. Therapeutic perspectives are liver transplantation, new copper chelators as tetrathiomolybdate, hepatocyte/tissue transfer and gene therapy.

Regional disparities in acute and post-acute care of stroke patients in France, 2015.

OBJECTIVE: The aim of this study was to assess regional variations of the hospital management of stroke patients during acute and post-acute phases in France in 2015. MATERIAL AND METHODS: Hospitalized patients coded with stroke as their main diagnosis or, if hospitalized in several different wards, any main ward diagnosis were identified in the 2015 French national hospital discharge database for acute care. Rates of hospitalization in stroke units (SUs) were assessed at a national level and in all metropolitan and overseas regions. All stroke survivors discharged at the end of the acute phase were subsequently identified in the national database for post-acute rehabilitation hospitalization (PARH) within 3 months. RESULTS: In the acute phase, half the stroke patients hospitalized for intracerebral hemorrhage, cerebral infarction or unspecified stroke were admitted to SUs. However, there were variations across metropolitan regions (from 30% to 69%) and in overseas regions (from 1% to 59%); these rates correlated with regional ratios of SU beds/100,000 inhabitants. There were also regional differences in PARH rates-in hemiplegic stroke patients, 62% were admitted for PARH (range: 58% to 67%) in metropolitan regions and, overseas, from 8% to 67%-as well as geographical discrepancies in PARH rates to specialized rehabilitation units. Hospitalization rates of hemiplegic stroke patients in neurological rehabilitation centers were 30% for the whole country, but ranged from 23% to 36% in metropolitan regions and from 2% to 45% in overseas regions. CONCLUSION: This study focused on hospital-based management of stroke patients. In spite of the creation of new SUs over the past decade in France, there are persistent regional differences in the number of SU beds/100,000 inhabitants and, consequently, in the rate of stroke patients managed in SUs. However, rates continue to improve with the creation of new SUs and the expansion of existing ones. Regional variations were also noted for post-acute hospitalization rates and PARH beds/places.

[Compliance with treatment in Wilson's disease: On the interest of a multidisciplinary closer follow-up]. / L'observance dans la maladie de Wilson : intérêt d'un suivi rapproché au long cours.

BACKGROUND: Compliance with treatment is very important for patients who suffer from Wilson's disease, a rare genetic disorder. They can benefit a long-life and effective treatment. The purpose of our study is to identify the level of compliance in Wilson's disease patients and features associated with compliance as well. METHODS: This is a prospective study carried out in the National Reference Center for Wilson Disease (based in Paris and Lyon) over a 8 months period. Patients were evaluated on the first (M0) and last month (M8) with a questionnaire evaluating the number of missed treatment doses, a self-questionnaire collecting the reasons for non-compliance, and analogic scales analyzing the doctor-patient relationship and their behavior towards the treatment. The severity of depression symptoms was investigated by the Beck Depression Inventory (BDI). A detailed phone call interview was conducted by a psychologist every two months to evaluate their compliance and feeling. RESULTS: Thirty-nine patients were included. The mean age of patients was 34 years (±9.9). At M0, 84.6% had a poor compliance with treatment. They were diagnosed more recently (P=0.049) with a higher proportion involving neurological disorders (P=0.007). Age, the type of treatment and the quality of the doctor-patient relationship were not associated with the outcome; 38.5% suffered from depressive symptoms. At M8, 56.8% of patients were poor compliants and 21.6% presented depressive symptoms. CONCLUSION: Wilsons's disease patients have important problems with compliance, without necessary being depressed. A close follow-up may help them become compliant, particularly those with neurological symptoms.

[Ecchymosis as the presenting manifestation of Wilson disease: A case report]. / Ecchymoses diffuses révélant une maladie de Wilson : à propos d'un cas.

INTRODUCTION: The presence of a psychiatric disorder during the course of an organic disease is a common cause of delayed diagnosis. CASE REPORT: We report a 16-year-old girl who was admitted with thrombocytopenia and had a two-year history of neuropsychiatric disorder which was attributed to a difficult family situation. Neurological examination showed a frontal lobe disorder and extrapyramidal manifestations. The thrombocytopenia was attributed to liver cirrhosis. These neurological and hepatic injuries were consistent with a metabolic disease, most likely Wilson disease. This was supported by the presence of a corneal Kayser-Fleischer ring and a decreased ceruloplasmin concentration. An urgent liver transplantation was required due to worsening neurological symptoms. CONCLUSION: Wilson disease is a rare genetic disease caused by copper toxicity. It is characterized by combined hepatic and neurologic damage to varying degrees and can develop at any age. Urgent treatment is required, but the diagnosis may be delayed by prevailing psychiatric symptoms.

Exchangeable copper: a reflection of the neurological severity in Wilson's disease.

BACKGROUND AND PURPOSE: The severity of Wilson's disease (WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (CuEXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. METHODS: Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging (MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. CuEXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. RESULTS: Extra-hepatic patients had significantly higher CuEXC values than those with the hepatic form (P < 0.0001). The overall ability of CuEXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 µmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, CuEXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score (r = 0.45, P = 0.016), the Kayser-Fleischer ring score (r = 0.46, P = 0.014) and the brain MRI score (r = 0.38, P = 0.048), but it was not correlated with the hepatic score. CONCLUSIONS: Exchangeable copper determination is useful when diagnosing WD as a value >2.08 µmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes.

Care pathways and healthcare use of stroke survivors six months after admission to an acute-care hospital in France in 2012.

INTRODUCTION: Care pathways and healthcare management are not well described for patients hospitalized for stroke. METHODS: Among the 51 million beneficiaries of the French national health insurance general scheme (77% of the French population), patients hospitalized for a first stroke in 2012 and still alive six months after discharge were included using data from the national health insurance information system (Sniiram). Patient characteristics were described by discharge destination-home or rehabilitation center (for < 3 months)-and were followed during their first three months back home. RESULTS: A total of 61,055 patients had a first admission to a public or private hospital for stroke (mean age; 72 years, 52% female), 13% died during their stay and 37% were admitted to a stroke management unit. Overall, 40,981 patients were still alive at six months: 33% of them were admitted to a rehabilitation center (mean age: 73 years) and 54% were discharged directly to their home (mean age 67 years). For each group, 45 and 62% had been previously admitted to a stroke unit. Patients discharged to rehabilitation centers had more often comorbidities, 39% were highly physically dependent and 44% were managed in specialized neurology centers. For patients with a cerebral infarction who were directly discharged to their home 76% received at least one antihypertensive drug, 96% an antithrombotic drug and 76% a lipid-lowering drug during the following month. For those with a cerebral hemorrhage, these frequencies were respectively 46, 33 and 28%. For those admitted to a rehabilitation center, more than half had at least one visit with a physiotherapist or a nurse, 15% a speech therapist, 10% a neurologist or a cardiologist and 15% a psychiatrist during the following three months back home (average numbers of visits for those with at least one visit: 23 for physiotherapists and 100 for nurses). Patients who returned directly back home had fewer physiotherapist (30%) or nurse (47%) visits but more medical consultations. The 3-month re-hospitalization rate for patients who were discharged directly to their home was 23% for those who had been admitted to a stroke unit and 25% for the others. In rehabilitation centers, this rate was 10% for patients who stayed < 3 months. CONCLUSIONS: These results illustrate the value of administrative databases to study stroke management, care pathways and ambulatory care. These data should be used to improve care pathways, organization, discharge planning and treatments.

First hospitalization for transient ischemic attack in France: Characteristics, treatments and 3-year outcomes.

INTRODUCTION: Characteristics of patients hospitalized for transient ischemic attack (TIA) management before and during this hospitalization and follow-up are not well documented on very large populations. METHODS: Among the 51 million beneficiaries of the French national health insurance general scheme (77% of French population), those subjects hospitalized for a first TIA in 2010 were included using the national health insurance information system (SNIIRAM). The frequencies of comorbidities during the previous five years and drug treatments received during the previous year and the first month after discharge were estimated from the SNIIRAM and then compared to data derived from the permanent randomized sample of all health insurance beneficiaries based on standardized morbidity ratios (SMR). The three-year outcome and factors associated with at least one readmission for TIA or ischemic stroke during the three months following the first hospitalization were investigated. RESULTS: A total of 18,181 patients were included (mean age: 69 years, 55% of women). The crude incidence of hospitalized TIA was 0.36 per 1000. Before hospitalization, patients presented a significantly higher rate of carotid and cerebral atherosclerosis (2.4% SMR=1.4), atrial fibrillation (9.1%, SMR=1.3), ischemic heart disease (13.7%, SMR=1.3), valvular heart disease (9.7%, SMR=1.5), and treatment with platelet aggregation inhibitors (29%, SMR=1.4), antihypertensives (60%, SMR=1.2) and antidiabetics (16%, SMR=1.5). These SMR decreased with age. One month after discharge from hospital, 82% of patients still alive filled at least one prescription for antithrombotic therapy (platelet aggregation inhibitor: 74%, vitamin K antagonist: 12%), one class of antihypertensive in 57% of patients, an antiarrhythmic in 9% of patients, an antidiabetic treatment in 14% of patients and a lipid-lowering agent in 53%. During the month following discharge from hospital, 3.2% of patients were readmitted at least once for TIA, 1.9% were readmitted for ischemic stroke and 1.5% of patients died. These figures were 3.9%, 2.4% and 2.9% at three months, and 7.2%, 5% and 16.3% at three years, respectively. On multivariate analysis, factors associated with readmission for TIA or ischemic stroke were age ≥ 65 years and antidiabetic treatment before hospitalization. In contrast, male gender, admission to a stroke unit and length of stay were associated with a lower readmission rate. CONCLUSIONS: These results illustrate the value of administrative databases to study TIA. Hospitalizations for TIA were relatively frequent and the recurrence rate was similar to that reported in similar recent studies. Level of primary and secondary prevention must be improved.

Management and 2-year follow-up of children aged 29 days to 17 years hospitalized for a first stroke in France (2009-2010).

INTRODUCTION: Childhood stroke is a little-known disease in France. The objective of this study was to report the characteristics, management, treatment and outcome of stroke in terms of survival and 2-year recurrence rates. METHOD: The study population included children aged 29 days to 17 years, identified by their first hospitalization for stroke (excluding transient ischemic attack) in 2009 and 2010 and not hospitalized for stroke between 2005 and 2008. Data were derived from the système national d'information inter-régimes de l'assurance maladie (SNIIRAM) [national health insurance information system]. RESULTS: For the 428 children with stroke in 2009 and the 441 children with stroke in 2010, the mean annual hospitalization rate was 3/100,000 children, comprising 0.5/100,000 for cerebral infarction (CI) and 1.5/100,000 for intracerebral hemorrhage (ICH). The youngest children presented the highest ICH rate, while, to a lesser extent, adolescents presented a higher proportion of CI. A male predominance was observed for ICH. Comorbidities were relatively common among these children prior to hospitalization: 21% had already been granted an affection de longue durée (ALD) [chronic disease] status and 37% had been hospitalized at least once during the previous year. The mean length of the hospital stay was 7.2 days and the hospital mortality was 3.9% (3.4% for ICH, 3.2% for CI). The 1-year mortality rate was 5.7% and the 2-year mortality rate was 6.0% (6% for ICH and 5% for CI). The readmission rate for stroke was 13% during the 1st year and 2% during the 2nd year. At 1 year, 18% of children (26% for CI) had been admitted at least once to a rehabilitation unit. CONCLUSION: This is the first study to report the epidemiology of childhood stroke in France. The validity of this study is supported by the fact that it demonstrated homogeneous descriptive indicators to those obtained by means of various methodologies in other populations. The high mortality, recurrence, and disability rates observed during the year following the initial stroke encourage continuation of the ongoing process of standardizing the management of childhood stroke in France.

Bone status and fractures in 85 adults with Wilson's disease.

UNLABELLED: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures. INTRODUCTION: Wilson's disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients. METHODS: In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67%) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied. RESULTS: Mean LS and FN Z-score was normal (-0.37 ± 1.20 at LS and -0.06 ± 1.20 at FN). BMI <19 kg/m(2) and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51%) and VF in 7 (8%) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF. CONCLUSION: Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.

Severe stroke: which medicine for which results?

In face of any severe stroke, the questions for health professionals in charge of the patient are: will the handicap be acceptable for the patient? But can we predict an acceptable handicap for the patient? For his family? When we know that the cognitive disorders, consequences of severe stroke often modify, in a major way, the behaviour of these patients? Given these difficulties for estimate vital and functional prognosis and even more the quality of life of patients with severe stroke, collective reflexions between physicians and nurses are essential, reflexions taking into account preferences and values of patients. Use of resuscitation resources for severe stroke patients implies to offer them the best rehabilitation. So, questions about health pathways for severe stroke are essential: which structures for these patients, which technologies, which medical, medico-social and social supports, which human accompaniment the society can propose to the patients and to their family, so that they have an acceptable quality of life.

Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology.

This historical article describes the life and work of the British physician Samuel Alexander Kinnier Wilson (1878-1937), who was one of the world's greatest neurologists of the first half of the 20th century. Early in his career, Wilson spent one year in Paris in 1903 where he learned from Pierre-Marie at Bicêtre Hospital. He subsequently retained uninterrupted links with French neurology. He also visited in Leipzig the German anatomist Paul Flechsig. In 1904, Wilson returned to London, where he worked for the rest of his life at the National Hospital for the Paralysed and Epileptic (later the National Hospital for Nervous Diseases, and today the National Hospital for Neurology and Neurosurgery) in Queen Square, and also at Kings' College Hospital. He wrote on 'the old motor system and the new', on disorders of motility and muscle tone, on the epilepsies, on aphasia, apraxia, tics, and pathologic laughing and crying, and most importantly on Wilson's disease. The other objective of our paper is to commemorate the centenary of Wilson's most important work published in 1912 in Brain, and also in Revue Neurologique, on an illness newly recognized and characterized by him entitled "Progressive lenticular degeneration, a familial nervous disease associated with liver cirrhosis". He analyzed 12 clinical cases, four of whom he followed himself, but also four cases previously published by others and a further two that he considered in retrospect had the same disease as he was describing. The pathological profile combined necrotic damage in the lenticular nuclei of the brain and hepatic cirrhosis. This major original work is summarized and discussed in the present paper. Wilson not only delineated what was later called hepato-lenticular degeneration and Wilson's disease, but also introduced for the first time the terms extrapyramidal syndrome and extrapyramidal system, stressing the role of the basal ganglia in motility. The present historical work emphasizes the special contributions made by Wilson to the study of movement disorders, including akinesia and bradykinesia in Parkinson's disease, and their relation to basal ganglia pathology.

Wilson's disease, 100 years later .

Texts published, in 1912, 100 years ago, by Sir K. Wilson on his eponymous disease in Brain, The Lancet and La Revue Neurologique highlight the relevance of his descriptions in the light of the current knowledge. Wilson's invocation of an "unknown toxin" appears today as a prophetic intuition as the presence of excess copper in the liver was mentioned for the first time a year later whereas the role of copper in this disease was not described until 1929. Progress has been made to better understand the physiology of Wilson's disease (WD). The ATP7B gene implicated in WD is located on chromosome 13 and more than 500 mutations and 100 polymorphisms have been to date identified. The phenotypic expression is highly variable, even within a family. This can partly be explained by environmental factors as nutrition. Modulator genes are also involved in the phenotypic expression of the disease. Most of symptoms observed in WD have already been described in detail by Wilson in 1912, but subsequent progress was made over the following 100 years, helping the physician diagnose WD. Hepatic and neurological symptoms are the most frequent expressions of the disease. Other extrahepatic features include renal manifestations, osteoarticular disorders, myocardial abnormalities, endocrine disturbances, realizing a multisystemic disease. The diagnosis of the disease is based on a combination of clinical symptoms, biological, radiological and genetic data and new tools (Brain MRI, relative exchangeable copper…) allow reducing delay to diagnosis. Therapeutic findings have also changed the disease prognosis. Treatment is based on the use of copper chelators to promote copper excretion from the body (D-penicillamine and Triethylenetetramine) and zinc salts to reduce copper absorption. Tetratiomolybdate appears to be a promising treatment. While significant progress has been made during this century, many physiological aspects of this disease remain unknown and require further research to find answers in the next 100 years.

Cognitive profile in Wilson's disease: a case series of 31 patients.

BACKGROUND: Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients. METHODS: Patients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N(-)) (n=13), and WD patients with neurological signs (WD-N(+)) (n=18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities. RESULTS: Both groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N(+) group performed less well than the WD-N(-) group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control. CONCLUSIONS: Cognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease.

Cost of stroke in France.

BACKGROUND AND PURPOSE: A cost of illness study was undertaken on behalf of the French Ministry of Health to estimate the annual cost of stroke in France with the goal of better understanding the current economic burden so that improved strategies for care may be developed. METHODS: Using primary data from exhaustive national databases and both top-down and bottom-up approaches, the stroke-related costs for healthcare, nursing care and lost productivity were estimated. RESULTS: The total healthcare cost of stroke patients in France in 2007 was €5.3 billion, 92% of which was borne by statutory health insurance. The average cost of incident cases was €16 686 per patient in the first year, while the annual cost of prevalent cases was a little less than half that amount (€8099). Nursing care costs were estimated at €2.4 billion. Lost productivity reached €255.9 million and that income loss for stroke patients was partially compensated by €63.3 million in social benefit payments. CONCLUSIONS: With healthcare costs representing 3% of total health expenditure in France, stroke constitutes an ongoing burden for the health system and overall economy. Nursing care added nearly half again the amount spent on healthcare, while productivity losses were more limited because nearly 80% of acute incident strokes were in patients over age 65. The high cost of illness underscores the need for improved prevention and interventions to limit the disabling effects of stroke.

[Could speech rate of Wilson's disease dysarthric patient be improved in dual task condition?]. / Le débit de parole du patient wilsonien dysarthrique peut-il être amélioré en condition de double tâche?

INTRODUCTION: Dysarthria is one of the first sign of neurological Wilson's disease and is often characterized by a decreased speech rate. The aim of this study is to determine the abilities of Wilson's disease dysarthric patients to control their speech rate. We examined the impact of dual-tasking on the speech rate of patients as compared to healthy control speakers and in relation with their ability to accelerate speech rate when instructed to do so. METHODS: Twenty-six patients and twenty-six age- and sex-matched healthy controls repeated a sentence during 20 seconds at a comfortable speech rate used as reference. They were then asked to perform the same repetition task but in dual task conditions, in which sentence repetition was done while performing three types of executive grapho-motor tasks. Finally, the ability to control speech rate was tested by asking the speakers to perform the sentence repetition task alone but at a fast rate of speech. RESULTS: A significantly slower speech rate was observed for all patients as compared to controls. In the dual-task conditions, while the speech rate of healthy speakers accelerated significantly, two behaviors are found for the patients. Forty-two percent of the patients reproduced the control pattern with a significant increased in speech rate, while the other group significantly decreased their speech rate. Comparison of the ability of the two groups to intentionally modulate speech rate, when instructed to accelerate, shows that significantly better acceleration was achieved by speakers in the former group compared with the latter. CONCLUSIONS: This study supports the finding that patients with Wilson's disease exhibit an impaired speech rate and also impaired control of speech rate. Indirect assessment of speech rate modulation with the help of a dual-task paradigm has proven to be useful to distinguish patient behaviors. This paradigm could also be envisioned as a tool for rehabilitation.

[Have centers of rare neurological diseases modified practices and the care of Wilson's disease?]. / Les centres maladies rares en neurologie ont-ils changé les pratiques et la prise en charge de la maladie de Wilson?

Wilson's disease is a particularly rare disease. It is a multisystemic affection related to a genetic abnormality of copper metabolism. Drug treatment is particularly effective if administered at an early stage of the disease and continued throughout life. The French Wilson's disease center, certified for only the one disorder, is easily identifiable by everyone, professionals and patients, which has allowed a rapid increase in the number of patients followed by the center, and considerably reduced the delay between first symptoms and diagnosis. Of its numerous ongoing research projects, it is important to mention the development of a new diagnostic test that would allow the speedy introduction of treatment of both the symptomatic forms and presymptomatic familial forms. Collaborations among professionals permit multidisciplinary care and improve the follow-up of patients in terms of all their medical and social aspects. In addition, the organization of the French Wilson's disease network serves as an exemplar for the implementation of Wilson's disease networks in other European countries and the development of collaborations between Wilson's disease patients'associations across Europe. At present, the center is also working to improve the care of patients presenting with other inherited or acquired pathologies related to copper and other heavy metals.

[Characteristics and prevention among patients with stroke: a study of 36,844 patients hospitalized in France]. / Caractéristiques et traitements des assurés du régime général hospitalisés pour accident vasculaire cérébral au cours du premier semestre 2008.

INTRODUCTION: This study evaluates comorbidities, primary and secondary drug prevention and two years survival among patients hospitalized for stroke during the first half of 2008. METHODS: First hospitalization with stroke diagnosis was identified by using the national hospital discharge database and linked to the reimbursement database of the beneficiaries covered by the general health insurance scheme (74% of the 64 million population). A medication was considered to be used when there were more than two reimbursements over the 6 months following or preceding hospitalization. RESULTS: Among the 36,844 patients with stroke, 31.6% had a main diagnosis of transient ischemic attack (TIA), 53.6% a cerebral infarct (CI) and 14.8% a cerebral hemorrhage (CH). For the 8429 patients aged less than 60 years, high frequency of low-income and full health insurance coverage (11% of the covered population) was found for CI (17.6%) and CH (24.6%). Specific refund for invalidating stroke before hospitalization was found for 16% of patients with CI and 10.5% of those with CH. During the two previous years, around 7% of all patients were hospitalized for stroke, 30% for arterial hypertension, 13% for cardiac electric disorders, 10% for coronary disease and 12% for diabetes. Death rates one month after hospitalization were 11.3% for CI and 33.8% for CH, and two years after 22.5% for CI, 43% for CH and 7.7% for TIA. At least one antihypertensive drug treatment was found for 55.2% of patients with a TIA before hospitalization and 62.9% after and respectively 59.4% and 65.8% for CI and 51.1% and 57.7% for CH. Before hospitalization, beta-blocker was the most frequent antihypertensive class (21 to 25.6% according to stroke type). After hospitalization, frequency increased for angiotensin-converting enzyme inhibitors among CI patients (31% vs. 18.7%) and calcium-channel blockers among CH patients (27.1% vs. 13.7%). Antiplatelet drugs were used by 58% of the patients with CI after hospitalization (27.8% before). An anticoagulant drug was present for 74.8% of patients with CI, 69.5% for TIA and 19.2% for CH. Among patients with ischemic stroke, half of them had a lipid-lowering drug after hospitalization. A combination of antihypertensive, anticoagulant and lipid lowering drugs was found for 32.9% of patients with a TIA, 39.9% for CI and 7.6% for CH after hospitalization. CONCLUSION: These patients presented frequently a history of stroke and comorbidities and their level of secondary prevention must be improved.

[Stroke care in the ICU: general supportive treatment. Experts' recommendations]. / Prise en charge de l'AVC en réanimation: mesures thérapeutiques générales. Recommandations formalisées d'experts.

The French Society of Intensive Care (SRLF) requested medical experts to publish recommendations on the management of stroke in the ICU for adult and pediatric patients. The following article describes the underlying evidence used by the experts to elaborate recommendations for general supportive treatment. Such treatment is fundamental for victims of acute stroke to avoid neurological worsening. Oxygen delivery in a normoxic patient is useless. However, if saturation is below 92 %, oxygen supplementation is needed. Hyper- and hypoglycemia worsen the neurological prognosis. As no glycemic target is known, administration of insulin is required for glucose levels higher that 10 mmol/l. Body temperature above 37.5° is associated with poorer outcome. In the acute phase of stroke, high blood pressure should not be lowered except in life-threatening situations, and if so the lowering should be done cautiously. The current consensus is to lower blood pressure if the systolic pressure is above 220 mmHg or if the diastolic pressure is above 120 mmHg for ischemic stroke. For hemorrhagic stroke and after thrombolysis, treatment is needed if systolic pressure rises above 180 mmHg and if diastolic pressure is above 105 mmHg. Small doses of heparin decrease the risk of deep venous thrombosis and pulmonary embolism without increasing cerebral bleeding. There is no consensus on the treatment of epileptic crises after stroke and no dedicated treatment. Further studies are needed to define adequate blood pressure and glycemic target values in order to limit secondary worsening after an acute stroke as well as the appropriate modalities for the treatment of epilepsy.