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BACKGROUND AND PURPOSE—: Cortical microinfarcts and secondary cortical degeneration have been demonstrated in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a severe monogenic cerebral small vessel disease. The aim of this study was to determine whether focal macroscopic cortical lesions can be detected using a specific in vivo magnetic resonance imaging approach. METHODS—: Three-dimensional T1 magnetic resonance imaging scans were obtained in 28 nondemented nondisabled CADASIL patients and 29 age- and sex-matched controls. The cortical mantle of patients and controls were extracted using Brainvisa by an experienced user and then evaluated during a dedicated reading session by a second reader after removing the white matter to stay blind to the clinical status. Thereafter, confirmed focal macroscopic cortical lesions were characterized using all available imaging data, including 7-T magnetic resonance imaging in some patients. RESULTS—: Three focal macroscopic cortical lesions were confirmed in 3 of 28 patients (11%) but none in controls. All lesions were observed in the close vicinity of severe signal changes in the underlying white matter. CONCLUSIONS—: Focal macroscopic cortical lesions can be detected using specific magnetic resonance imaging approaches in CADASIL patients long before the end stage of the disorder. The underlying mechanisms and precise clinical consequences of these cortical changes still need to be determined. © 2017 American Heart Association, Inc.


Ducros A.,Lariboisiere Hospital
The Lancet Neurology | Year: 2012

Recurrent thunderclap headaches, seizures, strokes, and non-aneurysmal subarachnoid haemorrhage can all reveal reversible cerebral vasoconstriction syndrome. This increasingly recognised syndrome is characterised by severe headaches, with or without other symptoms, and segmental constriction of cerebral arteries that resolves within 3 months. Reversible cerebral vasoconstriction syndrome is supposedly due to a transient disturbance in the control of cerebrovascular tone. More than half the cases occur post partum or after exposure to adrenergic or serotonergic drugs. Manifestations have a uniphasic course, and vary from pure cephalalgic forms to rare catastrophic forms associated with several haemorrhagic and ischaemic strokes, brain oedema, and death. Diagnosis can be hampered by the dynamic nature of clinicoradiological features. Stroke can occur a few days after initial normal imaging, and cerebral vasoconstriction is at a maximum on angiograms 2-3 weeks after clinical onset. The calcium channel blocker nimodipine seems to reduce thunderclap headaches within 48 h of administration, but has no proven effect on haemorrhagic and ischaemic complications. © 2012 Elsevier Ltd.


Mourad J.-J.,Avicenne Hospital | Levy B.I.,Lariboisiere Hospital
Current Hypertension Reports | Year: 2011

Antiangiogenic therapy has emerged as an important concept in the treatment of solidtumors. Vascular endothelial growth factor (VEGF) represents an important therapeutic ta get, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. Arterial hypertension has been commonly reported in all clinical trials testing inhibitors of angiogenesis(especially inhibitors of VEGF/VEGFR-2 signalling), with incidence ranging from 11% to 43% in all studies. The mechanism of elevated blood pressure in patients treated with antiangiogenic agents is not fully understood, but it is probably multifactorial, involving endothelial dysfunction and capillary rarefaction. Recently, several studies have suggested that early blood pressure rise was associated with better antitumoral efficacy and improved prognosis, making this commonly observed effect a prom sing marker of efficacy. © Springer Science+Business Media, LLC 2011.


Leroux E.,Lariboisiere Hospital | Valade D.,Lariboisiere Hospital | Taifas I.,Lariboisiere Hospital | Vicaut E.,Fernand Widal Hospital | And 3 more authors.
The Lancet Neurology | Year: 2011

Background: Suboccipital steroid injections can be used for preventive treatment of cluster headache but few data are available for the efficacy of this approach in clinical trials. We aimed to assess efficacy and safety of repeated suboccipital injections with cortivazol compared with placebo as add-on therapy in patients having frequent daily attacks. Methods: In our randomised, double-blind, placebo-controlled trial at the Emergency Headache Centre in Paris, France, we enrolled adults aged 18-65 years with more than two cluster headache attacks per day. We randomly allocated patients to receive three suboccipital injections (48-72 h apart) of cortivazol 3·75 mg or placebo, as add-on treatment to oral verapamil in patients with episodic cluster headache and as add-on prophylaxis for those with chronic cluster headache, on the basis of a computer-generated list (blocks of four for each stratum). Injections were done by physicians who were aware of treatment allocation, but patients and the evaluating physician were masked to allocation. The primary outcome was reduction of the number of daily attacks to a mean of two or fewer in the 72 h period 2-4 days after the third injection. We assessed all patients who received at least one dose of study drug in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00804895. Findings: Between November, 2008, and July, 2009, we randomly allocated 43 patients (15 with chronic and 28 with episodic cluster headache) to receive cortivazol or placebo. 20 of 21 patients who received cortivazol had a mean of two or fewer daily attacks after injections compared with 12 of 22 controls (odds ratio 14·5, 95% CI 1·8-116·9; p=0·012). Patients who received cortivazol also had fewer attacks (mean 10·6, 95% CI 1·4-19·9) in the first 15 days of study than did controls (30·3, 21·4-39·3; mean difference 19·7, 6·8-32·6; p=0·004). We noted no serious adverse events, and 32 (74%) of 43 patients had other adverse events (18 of 21 patients who received cortivazol and 14 of 22 controls; p=0·162); the most common adverse events were injection-site neck pain and non-cluster headache. Interpretation: Suboccipital cortivazol injections can relieve cluster headaches rapidly in patients having frequent daily attacks, irrespective of type (chronic or episodic). Safety and tolerability need to be confirmed in larger studies. Funding: None. © 2011 Elsevier Ltd.


Valade D.,Lariboisiere Hospital
Revue Neurologique | Year: 2013

The second edition of the International Classification of Headache Disorders revised in 2006 (ICHD-2R) gives a definition which requires 15 or more headache days per month over the past 3 months with at least eight headache days per month that meet criteria for migraine without aura or that responds to migraine specific treatment. Approximately 2% of the global population suffers of chronic migraine (CM). Frequency of headache and degree of disability distinguish CM from episodic migraine (EM). There is a high frequency of medication overuse. The treatment depends on evaluation with education, lifestyle modifications, and trigger management, behavioral and pharmacologic therapies. © 2013 Elsevier Masson SAS.


Delpech Y.,Lariboisiere Hospital | Barranger E.,Lariboisiere Hospital
Current Opinion in Oncology | Year: 2010

Purpose of review: Hysterectomy with bilateral salpingo-oophorectomy is the standard surgery for endometrial cancer. However, the indication and extent of surgical lymph node staging continues to be controversial if the carcinoma is confined to the uterus, even in the eyes of the experts. The survival benefit of this invasive staging technique has not been clearly demonstrated in this setting. Recent findings: We have focused our review on lymph node disease in patients with early endometrial cancer. We report on the important issues surrounding lymphadenectomy in endometrial cancer and the results of a recent large randomized trial that do not indicate a benefit of surgical staging. Other issues, including complications and the benefits of combining laparoscopy with lymphadenectomy, will also be discussed. Summary: Pelvic and para-aortic lymphadenectomies are not appropriate for low-risk patients with endometrioid uterine cancer. The risk-benefit balance for these patients seems rather in favor of not performing surgical staging. On the contrary, high-risk patients would seem to benefit from complete pelvic and para-aortic lymph node staging with adjuvant treatments tailored to the results of lymphadenectomy. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Debette S.,Lariboisiere Hospital | Debette S.,University of Paris Pantheon Sorbonne | Debette S.,Boston University
Current Opinion in Neurology | Year: 2014

PURPOSE OF REVIEW: Cervical artery dissection (CeAD) is a major cause of ischemic stroke in young and middle-aged adults, although relatively uncommon in the community. Recent large collaborative projects have provided new insights into mechanisms and risk factors of CeAD. RECENT FINDINGS: Pathologic changes observed at the media-adventitia border in temporal arteries of CeAD patients suggest a predisposing arterial wall weakness. In large multicenter series of CeAD patients, compared to age-matched healthy controls and patients with an ischemic stroke of another cause, hypertension and migraine, especially without aura, were confirmed as risk factors for CeAD, in addition to cervical trauma and recent infection. Hypercholesterolemia and being overweight were shown to be inversely associated with CeAD. Differences in risk factor profile and structural features between carotid and vertebral dissection suggest that their pathophysiology may partly differ. An association of CeAD with fibromuscular dysplasia and reversible cerebral vasoconstriction syndrome was described. Genetic risk factors of CeAD are still poorly understood. SUMMARY: Large cohorts of CeAD patients have refined our understanding of the pathophysiology and risk factors of CeAD, but the molecular mechanisms are still poorly understood. Ongoing high-throughput genetic projects will hopefully provide novel insight into the biological substrate of CeAD. © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins.


Panis Y.,Beaujon Hospital | Maggiori L.,Beaujon Hospital | Caranhac G.,Hox.Com Society | Bretagnol F.,Beaujon Hospital | Vicaut E.,Lariboisiere Hospital
Annals of Surgery | Year: 2011

OBJECTIVES: This study aimed to identify risk factors of postoperative 30-day mortality (POM) after colorectal cancer resection. SUMMARY: Meta-analyses have failed to demonstrate any significant benefit of laparoscopy in terms of postoperative mortality. This could be explained by the lack of a large sample size. METHODS: All patients who underwent colorectal resection for cancer between 2006 and 2008 in France were included. Data were extracted from the French National Health Service Database. A multivariate analysis evaluating risk factors for POM was performed including the following factors: age, gender, tumor location, associated comorbidities, emergency surgery, synchronous liver metastasis, malnutrition, and surgical approach. RESULTS: During the 3-year period, a total of 84,524 colorectal resections for colorectal cancer were performed: 22,359 through laparoscopy (26%) and 62,165 through laparotomy (74%). From 2006 to 2008, laparoscopic approach rate increased from 23% to 29% (P < 0.001). POM was 5.0%: 2% after laparoscopy and 6% after laparotomy (P < 0.001). In multivariate analysis, 7 independent factors were significantly associated with a higher POM: age 70 years or more [P < 0.001, odds ratio (OR): 3.28; (3.00-3.59)], respiratory comorbidity [P < 0.001, OR: 3.16; (2.91-3.37)], vascular comorbidity [P < 0.001, OR: 2.66; (2.48-2.85)], neurologic comorbidity [P < 0.001, OR: 1.78; (1.51-2.09)], emergency surgery [P < 0.001, OR: 2.68; (2.48-2.90)], synchronous liver metastasis [P < 0.001, OR: 2.63; (2.41-2.86)], and preoperative malnutrition [OR: 1.33; (1.19-1.50)]. Laparoscopic surgery [P < 0.001, OR: 0.59; (0.54-0.65)] was independently associated with a significant decreased POM. CONCLUSIONS: This all-inclusive national study showed that POM after colorectal cancer surgery is significantly reduced in case of age less than 70 years, elective surgery, and absence of synchronous liver metastasis, malnutrition, respiratory, neurologic, or vascular comorbidity. Furthermore, it is suggested that a laparoscopic surgery is independently associated with a decreased POM. This result, observed at a national level, must be considered when choosing the best surgical approach for colorectal cancer treatment. Copyright © 2011 by Lippincott Williams &Wilkins.


Vahedi K.,Lariboisiere Hospital | Alamowitch S.,Tenon Hospital | Alamowitch S.,University Pierre and Marie Curie
Current Opinion in Neurology | Year: 2011

Purpose of review: This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. COL4A1 encodes type IV collagen α1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. Recent findings: The human phenotypes are extremely variable between patients and between families, with disease onset as early as in the fetal period. COL4A1 mutations are responsible for a wide range of abnormalities affecting mainly the brain and the retinal vasculature, the anterior and posterior ocular structures and the renal glomerules. In the brain, intracerebral hemorrhage is the most frequent phenotype. It affects mainly young adults, children and more typically neonates. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. Summary: COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Bardin T.,Lariboisiere Hospital | Richette P.,Lariboisiere Hospital
Current Opinion in Rheumatology | Year: 2014

PURPOSE OF THE REVIEW: To define gout conditions and hyperuricemia. RECENT FINDINGS: Gout is defined as an arthritic condition resulting from the deposition of monosodium urate (MSU) crystals in and/or around joints, following long-standing hyperuricemia. Several recent ultrasound studies disclosed MSU deposits in a large proportion of asymptomatic hyperuricemic patients. A gout condition defined by asymptomatic MSU deposits can therefore be individualized. Such asymptomatic deposits appear to precede the occurrence of flares, which seem to be triggered by mobilization of preformed crystals. Hyperuricemia appears to be the main, if not the only, risk factor for gout. Recent studies also support the view that hyperuricemia is an independent risk factor for renal and cardiovascular diseases. The level at which uricemia becomes abnormal is still disputed. This lack of consensus precludes comparison of studies using different definitions and impairs the understanding of gout by doctors and patients. We propose to define hyperuricemia as greater than 6 mg/dl, as the life-long risk of gout seems to start at this level. This definition is identical to the minimum uricemia target of urate-lowering drugs (ULDs). SUMMARY: Asymptomatic MSU crystals deposits can now be identified and precede the onset of gout flares. Defining hyperuricemia as greater than 6 mg/dl would have the advantage to give the same value for normal and ULD-targeted uricemia, which would facilitate patients' adherence to this target. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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