Intra- and inter-rater consistency of dual assessment by radiologist and neurologist for evaluating DWI-ASPECTS in ischemic stroke.

OBJECTIVES: To estimate the intra -and inter-rater consistency of radiologist and neurologist working in pairs attributing DWI-ASPECTS (Diffusion Alberta Stroke Program Early CT Score) in patients with acute middle cerebral artery ischemic stroke referred for mechanical thrombectomy, intravenous thrombolysis or bridging therapy. METHODS: Five neurologists and 5 radiologists working in pairs and in hour period scored independently and in two reading sessions anonymized DWI-ASPECTS of 80 patients presenting with acute anterior ischaemic stroke in our center. We measured agreement between pairs using intraclass correlation coefficients (ICCs). A Fleiss kappa was used for dichotomized (0-6;7-10) and trichotomized (0-3;4-6;7-10) ASPECTS. The interrater distribution of the score in the trichotomized (0-3;4-6;7-10) ASPECTS was calculated. We determined the interrater (Cohen kappa) and intrarater (Fleiss kappa) agreement on the ASPECTS regions. RESULTS: The average DWI-ASPECTS was 6.35 (SD±2.44) for the first reading, and 6.47 (SD±2.44) for the second one. The ICC was 0.853 (95%CI, 0.798-0.896) for the interrater, and 0.862 (95%CI, 0.834-0.885) for the intrarater evaluation. Kappa coefficients were high for dichotomized (k=0.75) and trichotomized (k=0.64) ASPECTS. Evaluators agreement on the ASPECTS category (0-3), (4-6) and (7-10) was 88, 76 and 93% respectively. The anatomic region infarcted was well identified (k=0.70-0.77), except for the internal capsula (k=0.57). Interrater agreement was fair for M5 (k=0.37), moderate for internal capsula (0.52) and substantial for the other regions (0.60-0.79). CONCLUSIONS: Reliability of DWI-ASPECTS is good when determined by radiologist and neurologist working in pairs, which corresponds to our current clinical practice. However, discrepancies are possible for cut-off determination, which may impact the indication of thrombectomy, and for the determination of the exact infarcted region. Agreement to propose category (4-6) is lower than for (0-3) and (8-10) ASPECTS categories.

[TIMMA: Ultrasonographic scale of carotid atherosclerosis by vascular neurologists]. / TIMMA : échelle échographique de la surcharge athéromateuse en carotide pratiquée par des neurologues vasculaires.

BACKGROUND: Carotid atherosclerosis is a powerful predictive factor of vascular risk at the individual patient level. Ultrasonography is a reference technique for the evaluation of this condition. However, its use in common practice remains difficult due to a lack of standardization and inter-operator variability. We present a new and simple technique for the assessment of carotid atherosclerosis; and evaluate the ability of vascular neurologists to obtain results consistent with those of an expert in vascular ultrasound. MATERIAL AND METHODS: The TIMMA scale is an acronym for the five classes of carotid atherosclerosis in French, VIMMA in English: very important, important, moderate, minimal and absent. Combined, the first two classes make up the group "significant atheroma" and the last three classes make up the group "no significant atheroma". This scale was evaluated in 38 patients (76 carotid arteries) suffering from ischemic stroke or transient ischemic attack by five operators who are competent in carotid echocardiography: one TIMMA-trained (40 hours of training) vascular neurologist physician (VNP), three VNPs informed on the measurement method (1 hour of information) and one specialized vascular physician (SVP) who was considered to be the reference examiner. We evaluated the concordance between the VNPs and the SVP in classifying patients, firstly into the significant or not atheroma group and, secondly, into the five TIMMA classes. RESULTS: The evaluation of the two-group clustering scale found a concordance between the informed VNPs and the SVP on 76 carotid arteries of 86% (kappa=0.7) and between the trained VNP and the SVP on 58 carotid arteries of 90% (kappa=0.8). The positive and negative predictive values for significant atheroma diagnosis were 100% and 81%, respectively, for the informed VNPs, and 100% and 80% for the trained VNP. The evaluation of the Five-Class Scale showed a concordance between the informed VNPs and the SVP of 46% (kappa=0.3), and between the trained VNP and the SVP of 74% (kappa=0.7). CONCLUSION: TIMMA allows VNPs who are competent in carotid ultrasonography to reproducibly identify subjects with significant carotid atheroma. The contribution of this scale to the determination of cardiovascular risk should be evaluated.

Patient eligibility for thrombectomy after acute stroke: Northern French Alps database analysis.

BACKGROUND: Since 2015, the emergence of mechanical thrombectomy as standard care in acute stroke has involved organizational changes not only for stroke centers, but also for entire emergency regional networks. The aim of our study was to assess the proportion of ischemic stroke patients, admitted to stroke units in the Northern French Alps within the first 6h of onset, eligible for thrombectomy. METHODS: This study retrospectively analyzed the clinical and radiological data of all acute stroke patients hospitalized at three stroke units of the Northern French Alps Emergency Network (RENAU) in 2014. Eligible patients had proximal arterial occlusions of the anterior and posterior cerebral circulation, as confirmed by brain imaging, which could be treated by thrombectomy within 6h of symptom onset. RESULTS: Of the 435 cases of acute ischemic stroke, 152 patients were treated by intravenous thrombolysis (IV rtPA). Of these patients, 83 (55%) had intracranial occlusions and were eligible for combined thrombectomy. Of the 283 patients not treatable by IV rtPA, 32 patients (11%) were eligible for primary thrombectomy. CONCLUSION: Thrombectomy could be performed in 26% of our acute ischemic stroke patients (n=115/435), and a large increase in endovascular procedures is expected over the next few years that will require close collaboration among all partners in the emergency networks. Using our RENAU stroke database, it will be possible to compare various factors contributing to effective activity.

Strengthening good governance: exploiting synergies between the Performance of Veterinary Services Pathway and the International Health Regulations (2005).

The ability to minimise the harmful impact of biological threats relies on our capacity to rapidly detect unusual events, including the accidental or deliberate release of pathogenic or toxic agents, and immediately implement control measures. The development of this capacity for each country is the aim of the International Health Regulations (IHR) (2005), a legally binding document adopted by 196 States Parties, including all Member States of the World Health Organization (WHO). Each country's animal health sector contributes to the implementation of the IHR through surveillance, disease reporting and its response to zoonotic diseases, foodborne diseases and other events that emerge at the interface between human and animal health. The World Organisation for Animal Health (OIE) Performance of Veterinary Services (PVS) Pathway allows countries to undertake a comprehensive evaluation of their Veterinary Services and identify areas that need improvement. The OIE and WHO have conducted an in-depth analysis of the differences and synergies between the tools used by WHO to monitor the implementation of the IHR and the OIE PVS Pathway, revealing a wide range of similarities, complementarities and synergies. Taking advantage of the outcomes and outputs from the assessment and gap analysis tools used in the IHR Monitoring Framework and the OIE PVS Pathway, and exploiting the strength of these institutional frameworks, WHO and the OIE have jointly developed methods to facilitate communication between the animal health and human health sectors. This enhanced dialogue improves operational coordination and more efficiently informs policy-makers on strategic investments to strengthen their preparedness for controlling the spread of zoonotic diseases.

La faculté de minimiser l'impact néfaste des menaces biologiques dépend de la capacité des pays à détecter rapidement tout événement inhabituel, en particulier la dissémination accidentelle ou délibérée d'agents pathogènes ou toxiques, et à mettre en œuvre des mesures immédiates pour maîtriser ces événements. Le Règlement sanitaire international (RSI) (2005), un document juridiquement contraignant adopté par les 196 États parties, dont les États membres de l'Organisation mondiale de la santé (OMS) a précisément pour objectif de développer cette capacité dans chaque pays. Le secteur de la santé animale d'un pays participe à la mise en œuvre du RSI à travers une surveillance appropriée, la notification des maladies et l'adoption de mesures en cas de zoonoses, de maladies d'origine alimentaire et de tout autre événement émergeant à l'interface entre la santé humaine et la santé animale. Le Processus relatif aux performances des Services vétérinaires (Processus PVS) de l'Organisation mondiale de la santé animale (OIE) fournit aux pays la possibilité d'entreprendre une évaluation complète de leurs Services vétérinaires et d'identifier les domaines susceptibles d'être améliorés. L'OIE et l'OMS ont analysé de manière approfondie les différences et les synergies entre les outils utilisés par l'OMS pour vérifier la mise en œuvre du RSI, d'une part, et le Processus PVS de l'OIE, d'autre part, ce qui a mis en lumière de nombreuses similitudes, complémentarités et synergies. Sur la base des résultats et des données produites par les outils d'évaluation et d'analyse des écarts du Cadre de suivi du RSI et du Processus PVS de l'OIE, l'OMS et l'OIE ont exploité la puissance de ces cadres institutionnels pour mettre au point conjointement des méthodes visant à améliorer la communication entre les secteurs de la santé animale et de la santé humaine. Ce dialogue renforcé a pour effets d'améliorer la coordination opérationnelle et d'informer plus efficacement les décideurs politiques sur les investissements stratégiques permettant de mettre en place les conditions de préparation nécessaires pour lutter contre la propagation des zoonoses.

La aptitud de reducir al mínimo los efectos perjudiciales de las amenazas biológicas depende de nuestra capacidad para detectar con rapidez episodios inusuales, como la liberación accidental o deliberada de agentes patógenos o tóxicos, e instituir de inmediato medidas de control. El Reglamento Sanitario Internacional (RSI) (2005) es un documento jurídicamente vinculante aprobado por 196 Estados Partes, entre ellos todos los Estados Miembros de la Organización Mundial de la Salud (OMS), que precisamente tiene por objetivo dotar de esta capacidad a todos y cada uno de los países. El sector zoosanitario de cada país contribuye a la aplicación del RSI con actividades de vigilancia, notificación de enfermedades y respuesta ante enfermedades zoonóticas, enfermedades de transmisión alimentaria u otros episodios que puedan darse en la interfaz de la salud humana con la sanidad animal. El proceso de evaluación de las prestaciones de los Servicios Veterinarios (Proceso PVS) de la Organización Mundial de la Salud (OIE) sirve a los países para llevar a cabo una evaluación completa de sus Servicios Veterinarios y determinar aquellos ámbitos en que se requieran mejoras. La OIE y la OMS han analizado a fondo las diferencias y sinergias existentes entre las herramientas que utiliza la OMS para seguir de cerca la aplicación del RSI y el Proceso PVS de la OIE, labor que ha puesto de relieve un buen número de semejanzas, sinergias y aspectos complementarios de diversa índole. Partiendo de los resultados y productos que deparan las herramientas de evaluación y análisis de carencias utilizadas en el Marco de seguimiento del RSI y el Proceso PVS de la OIE, y aprovechando la solidez de estos marcos institucionales, la OMS y la OIE han definido conjuntamente métodos para facilitar la comunicación entre los sectores de la salud humana y la sanidad animal. La existencia de un diálogo más fluido se traduce en una mejor coordinación operativa y permite informar con más eficacia a los planificadores de las inversiones estratégicas necesarias para reforzar las medidas de preparación destinadas a controlar la propagación de enfermedades zoonóticas.

Network visualization for outbreak response: Mapping the Ebola Virus Disease (EVD) chains of transmission in N'Zérékoré, Guinea.

BACKGROUND: During the 2014-2015 Ebola Virus Disease (EVD) outbreak in N'Zérékoré, Forested Guinea, modes of transmission remained unexamined for a number of new cases. We used network visualization to investigate EVD transmission chains (TC) in seven sub-prefectures of N'Zérékoré in order to adapt outbreak response. METHODS: Between August 2014 and February 2015, the EVD outbreak response team including the World Health Organization (WHO) and local health authorities routinely collected information among new cases regarding hospital visits, cases within a household, participation in burials, as well as dates of symptom onset, serial intervals (SI) and exposure to EVD. SI's were defined as the interval between symptom onset in an index case and symptom onset in a secondary case infected by that index case. Cases who reported hospital visits, contact with a case in the household or participating in burials were attributed to these exposures. RESULTS: We identified seven TC (two urban and five rural) gathering characteristics of 109 probable/confirmed cases. Overall, 61% (66 cases, SI range: 7-20 days) were household related, 32% (35 cases, SI range 8-30 days) were household or burial related and 7% (8 cases, SI range: 4-20 days) were hospital-related. In the urban chains (18 cases, SI range: 7-20 days), 12 cases were household related and 6 cases were hospital related, none where household or burial related. In the rural chains (84 cases, SI range: 7-30 days), 60% (50 cases) were household related, 1% (1 case) was hospital related and 39% (34 cases) were household or burial related. No cases reported multiple exposures. CONCLUSIONS: Network visualization during field response is crucial in enhancing local control strategies, refining outbreak response and aiding rapid response teams in insuring psychosocial and socio-economic recovery. Urban settings need to focus on reducing hospital EVD transmission whereas rural settings should focus on raising awareness of transmission within a household and safeguarding EVD burials.

[Epidemiological aspects of Ebola virus disease in Guinea (december 2013-april 2016)]. / Aspects épidémiologiques de la maladie à virus Ebola en Guinée (décembre 2013­avril 2016).

Ebola Zaire species variant Makona between its emergence in December 2013 and April 2016, resulted in an epidemic of Guinea importance and unprecedented gravity with 3814 reported cases of which 3358 were confirmed (88.0%) and 2544 were died (66.7%). The epidemic has evolved in phases: a silent phase without identification of all fatal cases until February 2014; a first outbreak from March 2014, when the alarm is raised and the virus detected, which lasted until July 2014; a second increase, which was the most intense, from August 2014 to January 2015 focused primarily on the forest Guinea; and a final increase from February 2015 centered on lower Guinea and the capital Conakry. Adapting strategies in 2015 (initiative "Zero Ebola in 60 days" active case search and suspicious deaths and awareness of active prefectures, microbanding the last affected communities and raking around these localities) and ring vaccination of contacts around confirmed cases has allowed to gradually control the main outbreak in October 2015. But a survivor was originally resurgence in forest areas between March and April 2016 with 10 cases including 8 deaths. The epidemic has particularly affected the forest Guinea region (44% and 48% of Guinean cases and deaths), elderly women (≥ 50 years), and health professionals (211 cases including 115 deaths); however, almost one-third of the patients (32.6%) was not provided supportive care in the Ebola centers. The epidemic is currently marked by the resurgence of small foci, from excreting subjects cured of the virus who have been controlled so far successfully. The survivors are the subject of special attention. It is necessary to learn lessons from the response to better prepare for the future, to improve knowledge about the natural history of the Ebola virus disease, and to rethink communication in this regard with the public and its leaders.

Social and cultural factors behind community resistance during an Ebola outbreak in a village of the Guinean Forest region, February 2015: a field experience.

BACKGROUND: During the Ebola outbreak in Guinea, community resistance obstructed case investigation and response. We investigated a cluster of Ebola cases that were hiding in the forest, refusing external help, to identify sociocultural determinants related to community resistance. METHODS: Participant observation, interviews and focus group discussions were carried out. RESULTS: Most villagers feared the Ebola treatment centre (ETC) as there was the belief that people were killed in ETCs for organ trade. Four survivors accompanied back to the village from the ETC shared their experiences and reassured their neighbours. Subsequently, community compliance with contact tracing improved, leading to the timely detection of cases. CONCLUSIONS: Engaging Ebola virus disease survivors improved community compliance. Understanding the sociocultural context and community perceptions may improve community engagement and prevent Ebola virus transmission.

Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management.

While Friedreich's ataxia (FRDA) and ataxia telangiectasia (AT) are known to be the two most frequent forms of autosomal recessive cerebellar ataxia (ARCA), knowledge on the other forms of ARCA has been obtained only recently, and they appear to be rarer. Little is known about the epidemiological features and the relative frequency of the ARCAs and only few data are available about the comparative features of ARCAs. We prospectively studied 102 suspected ARCA cases from Eastern France (including 95 from the Alsace region) between 2002 and 2008. The diagnostic procedure was based on a sequential strategic scheme. We examined the clinical, paraclinical and molecular features of the large cohort of patients and compared features and epidemiology according to molecular diagnosis. A molecular diagnosis could be established for 57 patients; 36 were affected with FRDA, seven with ataxia plus oculomotor apraxia type 2 (AOA2), four with AT, three with ataxia plus oculomotor apraxia type 1 (AOA1), three with Marinesco-Sjögren syndrome, two with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), one with ataxia with vitamin E deficiency (AVED) and one with autosomal recessive cerebellar ataxia type 2 (ARCA2). The group of patients with no identified mutation had a significantly lower spinocerebellar degeneration functional score corrected for disease duration (SDFS/DD ratio; p = 0.002) and comprised a significantly higher proportion of cases with onset after 20 years (p < 0.01). Extensor plantar reflexes were rarer and cerebellar atrophy was more frequent in the group of patients with a known non-Friedreich ARCA compared to all other patients (p < 0.0001 and p = 0.0003, respectively). Lower limb areflexia and electroneuromyographic evidences of peripheral neuropathy were more frequent in the Friedreich ataxia group than in the group with a known non-Friedreich ataxia and were more frequent in the later group than in the group with no identified mutation (p = 0.0001 and p = 0.01, respectively). The overall prevalence of ARCA in Alsace is 1/19,000. We can infer the prevalence of FRDA in Alsace to be 1/50,000 and infer that AT is approximately eight times less frequent than FRDA. MSS, AOA2 and ARSACS appear only slightly less frequent than AT. Despite the broad variability of severity, Friedreich ataxia patients are clinically distinct from the other forms of ARCA. Patients with no identified mutation have more often a pure cerebellar degenerative disease or a spastic ataxia phenotype. It appears that ARCA cases can be divided into two major groups of different prognosis, an early-onset group with a highly probable genetic cause and an adult-onset group with better prognosis for which a genetic cause is more difficult to prove but not excluded. ARCAs are rare, early-disabling and genetically heterogeneous diseases dominated by FRDA. Several of the recently identified ARCAs, such as AVED, ARSACS, AOA1, AOA2 and MSS, have a prevalence close to AT and should be searched for extensively irrespective of ethnic origins. The strategic scheme is a useful tool for the diagnosis of ARCAs in clinical practice.

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

[Emergent pathogens, international surveillance and international health regulations (2005)]. / Les pathogènes émergents, la veille internationale et le Règlement sanitaire international (2005).

In order to address the vitality of the microbial world, to detect emerging infectious diseases, to determine their potential threat to public health, and to establish effective interventions, the World Health Organization (WHO) has developed and coordinates the Global Outbreak Alert and Response Network (GOARN) which connects several surveillance networks. Some of these networks are specific to epidemic-prone diseases, such as influenza, dengue, yellow fever or meningitis. Others were especially designed to track unusual events--such as the emergence of SARS--that are naturally-occurring, accidental, or deliberately created (biological weapons, bio-terrorism). Lastly, a special effort is being made at the international level to modernize the International Health Regulations, now obsolete, and to support all the countries in the reinforcement of their outbreak alert and response capacity.

Implementing the International Health Regulations (2005) in Europe.

The adoption of the International Health Regulations (2005) (also referred to as IHR(2005) or the revised Regulations) provides a remarkable new legal tool for the protection of international public health. Upon entry into force on 15 June 2007, Article 2 ('Purpose and scope') provides that the overall focus of the efforts of States Parties (and World Health Organization's efforts under the revised Regulations will be to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with the public health risks and which avoid unnecessary interference with international traffic. Health measures under the revised Regulations will be implemented with respect for travellers' human rights, with several specific new requirements in this area. To comply with the IHR(2005), States Parties (WHO member states that will be bound by the IHR(2005)) will have to have core public health capacities in disease surveillance and response, as well as additional capacities at designated international ports, airports and land crossings. This unique collective commitment will require close collaboration between WHO and the States Parties, but also intersectoral collaboration within the States themselves, including collaboration among different administrative or governmental levels, a particular issue for federal states, and horizontally across ministries and disciplines. Collaboration among States Parties is a key aspect of the revised Regulations, whether among neighbours, or with trading partners, members of regional economic integration organisations or other regional groups, or simply members of the international community. This collaboration is particularly relevant for the Member States of the European Union.

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

[Progression of cerebral venous thromboses. A retrospective study]. / Evolution des thromboses veineuses cérébrales. Une étude rétrospective.

OBJECTIVES: The management of patients with presumed cerebral venous thrombosis has been recently modified by magnetic resonance imaging and evidence that the early use of heparin decreases mortality and morbidity. Long term outcome of patients with cerebral venous thrombosis (CVT) has rarely been described. We present the results of a follow-up study. METHODS: Twenty patients admitted between 1987 and 1999 for CVT were retrospectively studied. Outcome and follow-up were obtained from direct observation or telephone interviews. RESULTS: There were 16 women and 4 men aged a mean of 39 years (range: 19 to 72). The population was followed-up for a mean of 34 months (range: 12-96). All the patients were initially treated with full-dose heparin. Thirteen of the 20 patients (65%) exhibited no after effects. Seven patients (35%) remained neurologically impaired. The outcome of clinical forms with intracranial hypertension appeared better, but the existence of an initial neurological deficit is of poor prognosis. The small cohort in our series did not permit us to identify other poor prognostic factors. One patient (5%) exhibited subsequent epilepsy. Only one patient (5%) suffered for a second CVT. One patient died from an ovarian neoplasm. No systemic venous thromboembolic relapse was reported. Three patients had non complicated pregnancies. CONCLUSION: Recurrent CVT and systemic venous thrombo-embolic episodes are rare although heparin treatment was suspended early in more than half of the patients. This would question the indication of long-term antivitamin K, which is clearly indicated in auto-immune diseases but is debatable in cases of thrombophilia.

[Thrombophilias associated with cerebral venous thrombosis]. / Thrombophilies et thromboses veineuses cérébrales.

Many coagulation disorders have been associated with cerebral venous thrombosis. These disorders may be primary like protein C and S deficiency, antithrombine III deficiency and activated protein C resistance. Antiphospholipid antibodies represent an acquired disorders of coagulation. A prothrombotic state induced by more common factor including oral contraceptive, pregnancy and puerperium increases the venous thrombosis risk.

p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis.

The activity of the cyclin-dependent kinase inhibitor p27 is controlled by its concentration and subcellular localization. However, the mechanisms that regulate its intracellular transport are poorly understood. Here we show that p27 is phosphorylated on Ser10 in vivo and that mutation of Ser10 to Ala inhibits p27 cytoplasmic relocalization in response to mitogenic stimulation. In contrast, a fraction of wild-type p27 and a p27(S10D)-phospho-mimetic mutant translocates to the cytoplasm in the presence of mitogens. G1 nuclear export of p27 and its Ser10 phosphorylation precede cyclin-dependent kinase 2 (Cdk2) activation and degradation of the bulk of p27. Interestingly, leptomycin B-mediated nuclear accumulation accelerates the turnover of endogenous p27; the p27(S10A) mutant, which is trapped in the nucleus, has a shorter half-life than wild-type p27 and the p27(S10D) mutant. In summary, p27 is efficiently degraded in the nucleus and phosphorylation of Ser10 is necessary for the nuclear to cytoplasmic redistribution of a fraction of p27 in response to mitogenic stimulation. This cytoplasmic localization may serve to decrease the abundance of p27 in the nucleus below a certain threshold required for activation of cyclin-Cdk2 complexes.