Publications by authors named "Christian Denier"

57 Publications

Epidemiology, Clinical Features, and Outcome in a Cohort of Adolescents With Cerebral Venous Thrombosis.

Neurology 2021 Sep 20. Epub 2021 Sep 20.

Stroke Units and Departments of Neurology of: hôpital Bicêtre, Le Kremlin Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris Saclay University, France

Objective: We aimed to analyze the epidemiological, clinical, and paraclinical features of adolescents with cerebral venous thrombosis (CVT) and its therapeutic management and outcome.

Methods: This multicenter retrospective cohort included patients aged 10-18 years hospitalized for a first episode of CVT in two French regions between 1999 and 2019. The number of cases was compared to the number recorded by the French health insurance system. The Lariboisière hospital's CVT registry allowed comparisons with adults.

Results: 102 patients were included (52·9% female;median age 15·1 years). Estimated incidence was 0·37-0·38/100,000 adolescents/year. 45·5% of patients presented with focal deficits or seizures or in a coma. Male patients were younger than female patients (14·2 vs 15·6 years;p<0·01) and more often admitted to intensive care (52·1% vs 24·1%;p=0·0035). The lateral sinus was the most common CVT location (72·3%), and 29·4% of adolescents had associated venous infarction and/or hematoma. Most patients (94·1%) received anticoagulation. Treatment also included an endovascular procedure (2·9%), decompressive craniectomy (4·9%), and CSF shunt (6·9%). The most frequently identified CVT-associated condition was local infection in male (18·6%) and systemic disease in female patients (14·8%;p<0·001). The proportion of CVTs in adolescents without an identified associated condition or risk factor was low (1·9% vs 11·4% in adults;p<0·002). Adverse outcome at 1 year was more frequent than in adults (33·3% vs 11·8%;p=0·0001).

Interpretation: CVT in adolescents is rare and complex, with specific epidemiology, including differences in clinical presentation and associated conditions between sexes, and more severe outcomes than in adults. Careful specialized management and follow-up are therefore recommended.
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http://dx.doi.org/10.1212/WNL.0000000000012828DOI Listing
September 2021

Impact of Prior Antiplatelet Therapy on Outcomes After Endovascular Therapy for Acute Stroke: Endovascular Treatment in Ischemic Stroke Registry Results.

Stroke 2021 Sep 20:STROKEAHA121034670. Epub 2021 Sep 20.

Department of Neuroradiolology, CHU Strasbourg, France. (R.P.).

Background And Purpose: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset.

Methods: We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT-) treated by endovascular therapy, with and without intravenous thrombolysis. Multilevel mixed-effects logistic models including center as random effect were used to compare angiographic (rates of reperfusion at the end of procedure, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to APT subgroups. Comparisons were adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, intravenous thrombolysis, and time from onset to puncture), as well as for meaningful baseline between-group differences.

Results: A total of 2939 patients were analyzed, of whom 877 (29.8%) were on prior APT. Patients with prior APT were older, had more frequent vascular risk factors, cardioembolic stroke mechanism, and prestroke disability. Rates of complete reperfusion (37.9% in the APT- group versus 42.7 % in the APT+ group; aOR, 1.09 [95% CI, 0.88-1.34]; =0.41) and periprocedural complication (16.9% versus 13.3%; aOR, 0.90 [95% CI, 0.7-1.2]; =0.66) did not differ between the two groups. Symptomatic intracerebral hemorrhage (aOR, 0.93 [95% CI, 0.63-1.37]; =0.73), 3 months favorable clinical outcome (modified Rankin Scale score of 0-2; aOR, 0.98 [95% CI, 0.77-1.25]; =0.89), and mortality (aOR, 0.95 [95% CI, 0.72-1.26]; =0.76) at 90 days did not differ between the groups.

Conclusions: Prior APT does not influence angiographic and functional outcomes following endovascular therapy and should not be taken into account for acute revascularization strategies.
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http://dx.doi.org/10.1161/STROKEAHA.121.034670DOI Listing
September 2021

Reperfusion therapy for acute ischemic stroke in older people: An observational real-life study.

J Am Geriatr Soc 2021 Aug 10. Epub 2021 Aug 10.

Department of Neurology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, Paris Saclay University, Le Kremlin Bicêtre, France.

Background: While randomized clinical trials have shown the benefit of thrombolysis and endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), we aimed to describe in a real-life study the differences between older (>80 years old) and younger patients treated for AIS.

Methods: Thousand patients treated with thrombolysis and/or EVT were consecutively included in a prospective monocentric database (admitted from December 2015 to May 2019 in our comprehensive stroke center). Demographic data with detailed history, baseline physical examinations and treatments, laboratory and imaging data, prestroke functional status, and outcome 3 months after stroke were analyzed.

Results: Older patients (n = 357) had more baseline comorbidities and lower levels of prestroke independence (modified Rankin scale ≤2; 67.2% vs. 96.1%) and more severe strokes (median National Institute of Health Stroke Score [NIHSS] 15 vs. 12; p < 0.001) than younger patients (n = 643). There was no difference in the reperfusion treatments used or treatment timelines. In older patients, good functional status at 3 months was less common (29.7% vs. 61.3%) and mortality was higher (37.1% vs. 11.4%) than in younger patients. Younger age was independently associated with better prognosis (odds ratio [OR] 0.37, 95% confidence interval [CI]: 0.20-0.67; p = 0.001) and lower mortality (OR 4.38, 95% CI: 2.11-9.09; p < 0.001). Among older adults, features associated with good outcome at 3 months were age (OR 0.89, 95% CI: 0.81-0.97; p = 0.01), initial NIHSS (OR 0.89, 95% CI: 0.83-0.94; p < 0.0001), and absence of severe leukoaraiosis, anticoagulant treatment, and symptomatic intracerebral hemorrhage following reperfusion therapy (respectively, OR 0.42, 95% CI: 0.19-0.93; p = 0.03; OR = 0.07, 95% CI: 0.01-0.70; p = 0.02; and OR = 0.07, 95% CI: 0.01-0.61; p = 0.02).

Conclusion: Although reperfusion therapy was less successful in older patients, these patients may benefit from acute recanalization despite their age. With an increasing older adult population, high-quality prospective studies are still required to better predict functional outcome and clarify the criteria that would allow better selection of appropriate treatment.
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http://dx.doi.org/10.1111/jgs.17394DOI Listing
August 2021

FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction.

Stroke 2021 Jul 26:STROKEAHA121034191. Epub 2021 Jul 26.

National Reference Center for Hypereosinophilic syndromes (CEREO), France (J.T., M.G., M. Hamidou, G.L., J.-E.K., J.R.).

Background And Purpose: Ischemic stroke has been reported in various conditions associated with eosinophilia. fusion ([Fip1-like 1-platelet-derived growth factor receptor alpha]; ) leads to the proliferation of the eosinophilic lineage and thus to a clonal hypereosinophilic syndrome that is highly responsive to imatinib.

Methods: We previously reported on a nationwide retrospective study of 151 patients with -associated clonal hypereosinophilic syndrome. Patients from this cohort with a clinical history of ischemic stroke (as well as 2 additional cases) were further analyzed to better define their clinical picture and outcomes.

Results: Sixteen male patients (median age, 51 [43-59] years) with low-to-intermediate cardiovascular risk were included. Median National Institutes of Health Stroke Scale was 4 (range, 1-6). Most cerebral imaging disclosed multiple bilateral infarctions of watershed distribution (69%). Despite frequent cardiac involvement (50%), cardiac thrombus was evidenced in a single patient and, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment), 62.5% of strokes were presumably of undetermined etiology. Among the 15 patients treated with imatinib, and after a median follow-up of 4.5 years, stroke recurred in only 3 patients (consisting of either cardio embolic or hemorrhagic events, unrelated to the first episode).

Conclusions: + clonal hypereosinophilic syndrome is a diagnosis to consider in patients with unexplained ischemic stroke and hypereosinophilia (especially in the setting of multiple cortical borderzone distribution) and warrants prompt initiation of imatinib.
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http://dx.doi.org/10.1161/STROKEAHA.121.034191DOI Listing
July 2021

Discovery of Anti-SS-A Antibodies during Stroke Investigations in Young Adults: What Impact?

J Stroke Cerebrovasc Dis 2021 Aug 15;30(8):105896. Epub 2021 Jun 15.

Université Paris-Saclay, APHP, Service de Médecine Interne et Immunologie Clinique, CHU Bicêtre, 78 Rue du Général Leclerc, Le Kremlin Bicêtre 94270, France; Faculté de Médecine Paris Saclay, Le Kremlin Bicêtre, France; UMR CEA/INSERM U1184/Université Paris-Saclay, Centre de recherche des maladies virales, autoimmunes, hématologiques et bactériennes (IMVA-HB), Le Kremlin Bicêtre, France. Electronic address:

Objectives: French national guidelines recommend searching for anti-SS-A antibodies during the second-line assessment of stroke in adults < 55 years of age in the absence of an identified etiology. We aimed to assess the impact of finding anti-SS-A antibodies during the etiological investigations of stroke in young adults.

Methods: Medical files from all patients ≤ 55 years of age admitted to a single stroke unit during a five-year period and for whom anti-SS-A antibodies were positive were retrospectively analyzed.

Results: Twelve patients were included (9 women; median age 48.5 years), with a rate of anti-SS-A antibody positivity of 1.6% (95% confidence interval [0.71-2.55] %; 12/735 admissions). The etiologies of the 12 ischemic events based on the TOAST classification were large-artery atherosclerosis (n = 1), cardioembolism (n = 1), small-vessel disease (n = 1), other determined etiology (n = 3), multiple etiology (n = 1), and no determined etiology (n = 5). A connective tissue disease (CTD) was discovered in 8/12 patients (1 primary Sjögren's Syndrome, 1 mixed CTD, 1 systemic sclerosis, 2 antiphospholipid syndromes, 1 undetermined CTD, 2 lupus). Anti-SSA antibodies were not directly responsible for the stroke in any of the 12 cases. A link between the autoimmune disease and the neurological vascular episode could be hypothesized for four patients, but it never influenced the therapeutic decision.

Conclusions: Finding anti-SS-A antibodies during the etiological assessment of a stroke of young adults is rare. However, it may be worthwhile to refer the patient to a rheumatologist/an internist because CTD may be discovered and may require specific follow-up.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105896DOI Listing
August 2021

Collateral status reperfusion and outcomes after endovascular therapy: insight from the Endovascular Treatment in Ischemic Stroke (ETIS) Registry.

J Neurointerv Surg 2021 Jun 17. Epub 2021 Jun 17.

Department of Radiology, CH Bretagne Atlantique, Vannes, France.

Background: Studies have suggested that collateral status modifies the effect of successful reperfusion on functional outcome after endovascular therapy (EVT). We aimed to assess the association between collateral status and EVT outcomes and to investigate whether collateral status modified the effect of successful reperfusion on EVT outcomes.

Methods: We used data from the ongoing, prospective, multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry. Collaterals were graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) guidelines. Patients were divided into two groups based on angiographic collateral status: poor (grade 0-2) versus good (grade 3-4) collaterals.

Results: Among 2020 patients included in the study, 959 (47%) had good collaterals. Good collaterals were associated with favorable outcome (90-day modified Rankin Scale (mRS) 0-2) (OR 1.5, 95% CI 1.19 to 1.88). Probability of good outcome decreased with increased time from onset to reperfusion in both good and poor collateral groups. Successful reperfusion was associated with higher odds of favorable outcome in good collaterals (OR 6.01, 95% CI 3.27 to 11.04) and poor collaterals (OR 5.65, 95% CI 3.32 to 9.63) with no significant interaction. Similarly, successful reperfusion was associated with higher odds of excellent outcome (90-day mRS 0-1) and lower odds of mortality in both groups with no significant interaction. The benefit of successful reperfusion decreased with time from onset in both groups, but the curve was steeper in the poor collateral group.

Conclusions: Collateral status predicted functional outcome after EVT. However, collateral status on the pretreatment angiogram did not decrease the clinical benefit of successful reperfusion.
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http://dx.doi.org/10.1136/neurintsurg-2021-017553DOI Listing
June 2021

Endovascular reperfusion of M2 occlusions in acute ischemic stroke reduced disability and mortality: ETIS Registry results.

J Neurointerv Surg 2021 May 27. Epub 2021 May 27.

Neurology, Stroke Unit, CH Bretagne Atlantique, Vannes, France.

Background: The predictors of successful reperfusion and the effect of reperfusion after endovascular treatment (EVT) for M2 occlusions have not been well studied. We aimed to identify predictors of successful reperfusion and the effect of reperfusion on outcomes of EVT for M2 occlusions in current practice.

Methods: Patients with acute ischemic stroke due to isolated M2 occlusions who were enrolled in the prospective multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and March 2020 were included. The primary outcome was a favorable outcome, defined as modified Rankin Scale (mRS) score of 0-2 at 90 days. Successful reperfusion was defined as an improvement of ≥1 points in the modified Thrombolysis In Cerebral Infarction score between the first and the last intracranial angiogram.

Results: A total of 458 patients were included (median National Institutes of Health Stroke Scale (NIHSS) score 14; 61.4% received prior intravenous thrombolysis). Compared with the non-reperfused patients, reperfused patients had an increased rate of excellent outcome (OR 2.3, 95% CI 0.98 to 5.36; p=0.053), favorable outcome (OR 2.79, 95% CI 1.31 to 5.93; p=0.007), and reduced 90-day mortality (OR 0.39, 95% CI 0.19 to 0.79; p<0.01). Admission NIHSS score was the only predictor of successful reperfusion. First-line strategy was not a predictor of successful reperfusion or favorable outcome, but the use of a stent retriever, alone or with an aspiration catheter, was associated with higher rates of procedural complications and 90-day mortality.

Conclusions: Successful reperfusion of M2 occlusions reduced disability and mortality. However, safety is a concern, especially if the procedure failed.
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http://dx.doi.org/10.1136/neurintsurg-2021-017380DOI Listing
May 2021

Characteristics of arterial stroke in myeloproliferative neoplasms: A French monocentric study.

Am J Hematol 2021 07 22;96(7):E240-E243. Epub 2021 Apr 22.

Neurology Department, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Saclay, Hôpital Bicêtre, Le Kremlin Bicêtre, France.

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http://dx.doi.org/10.1002/ajh.26180DOI Listing
July 2021

Cocaine and Levamisole Cerebral Toxicity.

Ann Neurol 2021 06 12;89(6):1253-1254. Epub 2021 Feb 12.

Department of Neurology, University Hospital of Bicêtre, Le Kremlin-Bicêtre, France.

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http://dx.doi.org/10.1002/ana.26035DOI Listing
June 2021

Pre-procedural predictive factors of symptomatic intracranial hemorrhage after thrombectomy in stroke.

J Neurol 2021 May 3;268(5):1867-1875. Epub 2021 Jan 3.

Department of Neurology, Hôpital Bicêtre, Stroke Center, 78 rue du General Leclerc, 94270, Le Kremlin Bicêtre, France.

Objective: Symptomatic intracerebral hemorrhage (sICH) is a common complication of acute ischemic stroke (AIS) associated with limited treatments and poor outcomes. We aimed to identify predictive factors of sICH in patients with AIS following mechanical thrombectomy (MT) in a real-world setting.

Methods: Patients with large vessel occlusion of the anterior circulation treated with MT were consecutively included in a prospective monocentric cohort. Clinical, biological, and radiological parameters were collected to identify pre-procedural predictors for sICH.

Results: 637 patients were included in our study. Magnetic resonance imaging was performed on most patients (86.7%). sICH occurred in 55 patients (8.6%). 428 patients (67.2%) were treated with intravenous thrombolysis. After multivariate analysis, prior use of antiplatelet therapies (odd ratio (OR) 1.84, 95% confidence interval (CI) 1.01-3.32), high C-reactive protein (OR per standard deviation (SD) increase 1.28, 95% 1.01-1.63), elevated mean arterial blood pressure (OR per 10 mmHg increase 1.22, 95% CI 1.03-1.44), hyperglycemia (OR per one SD-log increase 1.38, 95% CI 1.02-1.87), and low ASPECTS (OR per 1-point decrease 1.42, 95% CI 1.12-1.80) were found to be independent predictive factors of sICH. The pre-procedural predictors did not change when the absence of successful recanalization was considered as a covariate. Patients with strokes of unknown onset time were not especially vulnerable for sICH.

Conclusion: sICH after MT was associated with several pre-procedural risk factors: prior use of antiplatelet therapies, high C-reactive protein and hyperglycemia at baseline, elevated mean arterial blood pressure, and low ASPECTS.
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http://dx.doi.org/10.1007/s00415-020-10364-xDOI Listing
May 2021

Susac syndrome following COVID-19 infection.

Acta Neurol Belg 2021 Jun 24;121(3):807-809. Epub 2020 Nov 24.

Department of Neurology, Centre Hospitalo-Universitaire de Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), 78 Rue du Général Leclerc, 94275, Le Kremlin-Bicêtre, France.

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http://dx.doi.org/10.1007/s13760-020-01554-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685681PMC
June 2021

Carotid webs management in symptomatic patients.

J Vasc Surg 2021 Apr 1;73(4):1290-1297. Epub 2020 Sep 1.

Vascular Center, Hôpital Marie Lannelongue, Groupe Hospitalier Paris Saint Joseph, Université Paris Saclay, Paris, France. Electronic address:

Background: Atypical fibromuscular dysplasia (AFMD), also known as carotid web, is a rare underdiagnosed shelf-like fibrous tissue arising from the posterior carotid artery bulb that is a cause of cryptogenic stroke of the anterior cerebral vascularization. Despite the recurrence and severity of strokes caused by embolization associated with AFMD, there are no recommendations on the best strategy to manage single and bilateral lesions, which have unsatisfactory outcomes when treated with medical treatment exclusively.

Methods: From January 2016 to April 2019, 365 patients were operated on for a carotid stenosis in our institution. This cohort included 11 patients (3%), with a median age of 41 years (range, 39-51 years), referred by a stroke unit, treated for a symptomatic (10 strokes and 1 recurrent transient ischemic attack) AFMD lesion. Preoperative workup revealed a contralateral similar lesion in 45% of patients (5/11), which all also underwent surgery during a subsequent hospitalization. The diagnosis was confirmed by histologic examination when open surgery was performed. The 30-day and 1-year outcomes were retrospectively reviewed.

Results: Of the 16 AFMD lesions operated, 13 were treated by open surgery (2 by classic endarterectomy and 11 by internal carotid resection-anastomosis) and 3 by carotid artery stenting, respectively, with a mean delay of 85.5 days and 20.5 days after the latest stroke. There was one complication after stenting (external iliac rupture) that was treated by a covered stent, and no perioperative complications after open surgery. The follow-ups at 30 days and 1 year were uneventful for all patients, without any deaths or stroke recurrences.

Conclusions: Symptomatic AFMD is a rare cause of cryptogenic stroke. Bilateral lesions are frequent. Early intervention is associated with favorable perioperative and 1-year outcomes. Open surgery is the first-line therapeutic option in this young patient population.
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http://dx.doi.org/10.1016/j.jvs.2020.08.035DOI Listing
April 2021

Validation of a new test for early assessment of unilateral neglect in acute stroke: The Rapid Unilateral Neglect Screening (RUNS) test.

Ann Phys Rehabil Med 2021 Jul 25;64(4):101399. Epub 2020 Jun 25.

Stroke Unit, Neurology Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Bicêtre Hôpitaux Universitaires Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

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http://dx.doi.org/10.1016/j.rehab.2020.05.006DOI Listing
July 2021

An Heidenhain variant of the Creutzfeldt-Jakob disease misdiagnosed as a DSM-5 conversion disorder: a case report.

CNS Spectr 2020 May 6:1-2. Epub 2020 May 6.

Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.

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http://dx.doi.org/10.1017/S1092852920001327DOI Listing
May 2020

Novel CCM2 missense variants abrogating the CCM1-CCM2 interaction cause cerebral cavernous malformations.

J Med Genet 2020 06 14;57(6):400-404. Epub 2020 Jan 14.

UMR-S1141, INSERM, Paris, Île-de-France, France

Background: Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Most deleterious variants are loss of function mutations in one of the three genes. These genes code for proteins that form a ternary cytosolic complex with CCM2 as a hub. Very few missense variants have been shown to be deleterious by modifying the ternary CCM complex stability.

Objectives: To investigate the causality of novel missense variants detected in patients with CCM.

Methods: The three CCM genes were screened in 984 patients referred for molecular screening. Interaction between CCM1 and CCM2 proteins was tested using co-immunoprecipitation experiments for the missense variants located in the phosphotyrosine binding (PTB) domain.

Results: 11 distinct rare missense variants were found. Six variants predicted to be damaging were located in the PTB domain, four of them were novel. When co-transfected with CCM1 in HEK293T cells, a loss of interaction between CCM1 and CCM2 was observed for all six variants.

Conclusion: We showed, using co-immunoprecipitation experiments, that CCM2 missense variants located in the PTB domain were actually damaging by preventing the normal interaction between CCM1 and CCM2. These data are important for diagnosis and genetic counselling, which are challenging in patients harbouring such variants.
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http://dx.doi.org/10.1136/jmedgenet-2019-106401DOI Listing
June 2020

Acute ischemic stroke in adolescents.

Neurology 2020 01 12;94(2):e158-e169. Epub 2019 Dec 12.

From the Stroke Units and Department of Neurology (T.R., N.L., C.D.), Hôpital Bicêtre, Le Kremlin Bicêtre, Assistance Publique-Hôpitaux de Paris, Paris Saclay University; Department of Neurology (Y.B.), University Région Bourgogne, Hôpital de Dijon; Pediatric Neurology Unit (C.B.), Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre; Stroke Units and Department of Neurology (B.L.), Hôpital Foch, Suresnes; Department of Neurology (E.J.), Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris; Department of Neurology (F.P.), Hôpital Andre Mignot, Versailles; Department of Neurology (D.S.), Hôpital Sud Francilien, Evry; Department of Neurology (M.Z.), Hôpital Saint Joseph, Paris; Department of Neurology (S.C.), Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris; Department of Neurology (C.L.), Hôpital Sainte Anne, Paris; Interventional Neuroradiology (L.S.), NEURI Centre, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre; French National Health Insurance (P.T.); and Pediatric Neurology Unit (M.K.), Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants malades, France.

Objective: Adolescence represents a transition period between childhood and adulthood, and only limited information exists about stroke characteristics in this population. Our aim was to describe the clinical and neuroradiologic features, etiologies, initial management, and outcome of ischemic stroke in adolescents.

Methods: This retrospective cohort study evaluated all consecutive patients 10 to 18 years with a first-ever ischemic stroke hospitalized between 2007 and 2017 in 10 French academic centers representing a population of ≈10 million. Extracted data from the national database served as validation.

Results: A total of 60 patients were included (53% male, median age 15.2 years). Diagnosis at first medical contact was misevaluated in 36%, more frequently in posterior than anterior circulation strokes (55% vs 20% respectively, odds ratio 4.8, 95% confidence interval 1.41-16.40, = 0.01). Recanalization treatment rate was high (n = 19, 32%): IV thrombolysis (17%), endovascular therapy (11.7%), or both IV and intra-arterial thrombolysis (3.3%); safety was good (only 1 asymptomatic hemorrhagic transformation). Despite thorough etiologic workup, 50% of strokes remained cryptogenic. The most common determined etiologies were cardioembolism (15%), vasculitis and autoimmune disorders (12%, occurring exclusively in female patients), and arterial dissections (10%, exclusively in male patients). Recurrent ischemic cerebrovascular events occurred in 12% (median follow-up 19 months). Recurrence rate was 50% in patients with identified vasculopathy but 0% after cryptogenic stroke. Functional outcome was favorable (Rankin Scale score 0-2 at day 90) in 80% of cases.

Conclusions: Ischemic strokes in adolescents harbor both pediatric and adult features, emphasizing the need for multidisciplinary collaboration in their management. Recanalization treatments appear feasible and safe.
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http://dx.doi.org/10.1212/WNL.0000000000008783DOI Listing
January 2020

Purple Urine after Catheterization.

N Engl J Med 2019 Oct;381(18):e33

Hôpital de Bicêtre, Le Kremlin Bicêtre, France

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http://dx.doi.org/10.1056/NEJMicm1905446DOI Listing
October 2019

KIF1C Variants Are Associated with Hypomyelination, Ataxia, Tremor, and Dystonia in Fraternal Twins.

Tremor Other Hyperkinet Mov (N Y) 2019 17;9. Epub 2019 Jul 17.

Department of Genetics, AP-HP, La Pitié-Salpêtrière University Hospital, Paris, FR.

Background: (Kinesin Family Member 1C) variants have been associated with hereditary spastic paraplegia and spastic ataxia.

Case Report: We report fraternal twins presenting with cerebellar ataxia and dystonic tremor. Their brain MRI showed a hypomyelinating leukoencephalopathy. Whole exome sequencing identified a homozygous variant in both patients.

Discussion: variants can manifest as a complex movement disorder with cerebellar ataxia and dystonic tremor. variants may also cause a hypomyelinating leukoencephalopathy.
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http://dx.doi.org/10.7916/tohm.v0.641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692767PMC
January 2020

Inherited Thrombotic Thrombocytopenic Purpura Revealed by Recurrent Strokes in a Male Adult: Case Report and Literature Review.

J Stroke Cerebrovasc Dis 2019 Jun 28;28(6):1537-1539. Epub 2019 Mar 28.

Department of Neurology, Bicêtre Hospital, AP-HP, University Paris Sud Saclay, Le Kremlin-Bicêtre, France.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). In this article, we describe the first case of a young male adult suffering from a hereditary TTP revealed by recurrent strokes, relapsing despite antiplatelet and anticoagulant therapy. Because of the persistent moderate thrombocytopenia, plasmatic ADAMTS13 activity was investigated and was found lower than 5% in the absence of anti-ADAMTS13 IgG. Direct sequencing of ADAMTS13 gene led to the diagnosis of Upschaw-Schulman syndrome (USS). Inherited TTP or USS is a rare autosomal recessive inherited disease leading to a severe deficiency of ADAMTS13 mostly beginning in childhood or in young female adult during pregnancy. Our patient was treated with fresh frozen plasma every 2 weeks. One year after diagnosis, he was free of neurological symptoms. Around 12 cases of inherited TTP diagnosed in adults (outside pregnancy) are described in literature. Only 4 of them exhibited a stroke. This case is the first late onset genetic TTP revealed by recurrent strokes, moderate thrombocytopenia without anemia.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.011DOI Listing
June 2019

Thrombectomy or intravenous thrombolysis in patients with NIHSS of 5 or less?

J Neuroradiol 2019 Jul 16;46(4):225-230. Epub 2019 Jan 16.

Interventional Neuroradiology NEURI Center, Hôpital Bicêtre, 78, rue du Général-Leclerc, 94270 Le Kremlin Bicêtre, France.

Background And Purpose: To compare outcomes of minor stroke patients with intracranial vessel occlusions (IVO) underwent mechanical thrombectomy (MT) versus those treated with intravenous thrombolysis alone (IVT).

Methods: We retrospectively reviewed two large prospective stroke databases from two European centers searching for patients admitted with minor stroke (i.e. NIHSS Score░≤░5), baseline mRS░=░0 and occlusion of the M1-M2 segment of the middle cerebral artery (MCA). Groups receiving (A) IVT alone and (B) MT+/-IVT were compared. Primary outcome measures were MT safety, successful recanalization rate (mTICI 2b-3) and NIHSS shift (discharge NIHSS minus admission NIHSS); secondary outcomes included discharge rates and excellent outcome (mRS 0-1) at 3 months. Univariate and multivariate analyses were performed.

Results: Thirty-two patients were enrolled in Group B (19░MT alone; 13 MT░+░IVT) and 24 in Group A. Successful recanalization (mTICI 2b-3) was obtained in 100% of cases in Group B vs 38% in Group A. Symptomatic hemorrhagic transformation rate did not differ between the two groups. Multivariate analysis reported MT as the only predictor of early (<░12░h) favorable NIHSS shift and lower NIHSS at discharge. Moreover, discharge at home and excellent outcome at 3-month follow-up were statistically associated with MT.

Conclusions: MT in patients with minor strokes and intracranial vessel occlusion (IVO) is safe and can determine a rapid improvement of NIHSS Score. MT seems also associated with a higher rate of patients discharged at home after hospitalization and better clinical outcome at 3-month follow-up. Larger randomized trials are warranted to confirm these results.
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http://dx.doi.org/10.1016/j.neurad.2019.01.089DOI Listing
July 2019

Acute-Onset Ataxia and Transient Cerebellar Diffusion Restriction Associated with a PRRT2 Mutation.

J Stroke Cerebrovasc Dis 2019 Feb 28;28(2):e3-e4. Epub 2018 Nov 28.

Neurology Department, Bicêtre Hospital, Assistance Publique des Hôpitaux de Paris, (AP-HP), Paris, France.

PRRT2 gene mutations cause paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions, hemiplegic migraine, and episodic ataxia. A 21-year-old woman reported an episode of dizziness and ataxic gait occurring after swimming. Brain MRI showed a hyperintense cerebellar lesion on diffusion-weighted imaging (DWI) with decreased apparent diffusion coefficient. The clinical course was favorable. Both clinical and MRI abnormalities regressed. Her brother had presented PKD since adulthood. A C.649dupC PRRT2 truncating mutation was identified in both patients. To our knowledge, this is the first case of an acute cerebellar ataxia associated with heterozygous PRRT2 mutation and transient cerebellar hyperintensity on DWI. Among the clinical and genetic heterogeneities of familial paroxysmal disorders, PRRT2 mutation may be considered in patients with episodic cerebellar ataxia and diffusion restriction on neuroimaging.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.021DOI Listing
February 2019

Ischemic strokes

Rev Prat 2017 Dec;67(10):e489-e490

Service de neurologie, hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France.

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December 2017

Motor and/or sensory deficit of the limbs

Rev Prat 2017 Dec;67(10):e479-e488

Service de neurologie, hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France.

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December 2017

Intranasal administration of progesterone: A potential efficient route of delivery for cerebroprotection after acute brain injuries.

Neuropharmacology 2019 02 6;145(Pt B):283-291. Epub 2018 Jun 6.

M et P Pharma AG, Schynweg 7, P.O. Box 138, 6376, Emmetten, Switzerland; Nova Southeastern University, Fort Lauderdale, FL, 33314, USA.

Progesterone has been shown to be cerebroprotective in different experimental models of brain injuries and neurodegenerative diseases. The preclinical data provided great hope for its use in humans. The failure of Phase 3 clinical trials to demonstrate the cerebroprotective efficiency of progesterone in traumatic brain injury (TBI) patients emphasizes that different aspects of the design of both experimental and clinical studies should be reviewed and refined. One important aspect to consider is to test different routes of delivery of therapeutic agents. Several studies have shown that the intranasal delivery of drugs could be used in different experimental models of central nervous system diseases. In this review, we will summarize the pharmacokinetic characteristics and practical advantages of intranasal delivery of progesterone. A special emphasis will be placed on describing and discussing our recent findings showing that intranasal delivery of progesterone after transient focal cerebral ischemia: 1) improved motor functions; 2) reduced infarct volume, neuronal loss, blood brain barrier disruption; and 3) reduced brain mitochondrial dysfunctions. Our data suggest that intranasal delivery of progesterone is a potential efficient, safe and non-stressful mode of administration that warrants evaluation for cerebroprotection in patients with brain injuries. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".
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http://dx.doi.org/10.1016/j.neuropharm.2018.06.006DOI Listing
February 2019

A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.

J Neurosci 2017 11 6;37(45):10998-11020. Epub 2017 Oct 6.

U1195 Inserm and University Paris-Sud and University Paris-Saclay, 94276 Kremlin-Bicêtre, France,

Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes. The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the female brain. An important role of endogenous progesterone in cerebroprotection was demonstrated by the conditional inactivation of its receptor in neural cells. These results show the importance of endogenous progesterone, its metabolites, and neural progesterone receptors in acute cerebroprotection after stroke. This new concept could be exploited therapeutically by taking into account the progesterone status of patients and by supplementing and reinforcing endogenous progesterone signaling for attaining its full cerebroprotective potential.
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http://dx.doi.org/10.1523/JNEUROSCI.3874-16.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596486PMC
November 2017

Regional Pediatric Acute Stroke Protocol: Initial Experience During 3 Years and 13 Recanalization Treatments in Children.

Stroke 2017 08 25;48(8):2278-2281. Epub 2017 May 25.

From the Department of Pediatric Intensive Care Unit (L.T., F.L., I.D.), Department of Pediatric Radiology (D.G., O.N.), and French Center for Pediatric Stroke, Pediatric Neurology (M.K.), APHP-Necker-Enfants malades Hospital, Paris, France; Department of Pediatric Neurology (N.M., C.B.), Department of Pediatric Radiology (B.H.), Department of Interventional Radiology (A.O.), and Department of Neurology (C.D.), APHP-Bicêtre Hospital, Le Kremlin-Bicêtre, France; and Department of Neuroradiology (O.N) and Department of Neurology (C.L.), INSERM UMR-S894, Université Paris-Descartes, Sainte-Anne Hospital, France.

Background And Purpose: To evaluate hyperacute management of pediatric arterial ischemic stroke, setting up dedicated management pathways is the first recommended step to prove the feasibility and safety of such treatments. A regional pediatric stroke alert protocol including 2 centers in the Paris-Ile-de-France area, France, was established.

Methods: Consecutive pediatric patients (28 days-18 years) with confirmed arterial ischemic stroke who had acute recanalization treatment (intravenous r-tPA [recombinant tissue-type plasminogen activator], endovascular procedure, or both) according to the regional pediatric stroke alert were retrospectively reviewed during a 40-month period.

Results: Thirteen children, aged 3.7 to 16.6 years, had recanalization treatment. Median time from onset to magnetic resonance imaging was 165 minutes (150-300); 9 out of 13 had large-vessel occlusion. Intravenous r-tPA was used in 11 out of 13 patients, with median time from onset to treatment of 240 minutes (178-270). Endovascular procedure was performed in patients time-out for intravenous r-tPA (n=2) or after intravenous r-tPA inefficiency (n=2). No intracranial or peripheral bleeding was reported. One patient died of malignant stroke; outcome was favorable in 11 out of 12 survivors (modified Rankin Scale score 0-2).

Conclusions: Hyperacute recanalization treatment in pediatric stroke, relying on common protocols and adult/pediatric ward collaboration, is feasible. Larger systematic case collection is encouraged.
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http://dx.doi.org/10.1161/STROKEAHA.117.016591DOI Listing
August 2017

Can developmental venous anomalies cause seizures?

J Neurol 2017 Dec 17;264(12):2495-2505. Epub 2017 Mar 17.

Neurology Department, Hôpital Bicêtre, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, 78 Rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.

Developmental venous anomalies (DVAs) are congenital anatomical variants of normal venous drainage of normal brain. Although DVAs are often discovered on the occasion of a seizure, their involvement in epilepsy is poorly studied. Our objective was to determine whether DVA can cause seizures, in the cases where there is no associated lesion, including no cavernoma or dysplasia. Based on clinical history, cerebral MRI, EEG recording, and F-FDG PET, we report 4 patients with DVA revealed by seizures. The first patient had a convulsive seizure caused by a hemorrhagic infarction due to thrombosis of her DVA. The second patient had a left temporo-parietal DVA next to a nonspecific lesion, possibly a sequelae of a venous infarction. The last two patients disclosed an isolated and uncomplicated DVA with a concordant epileptic focus confirmed on ictal video EEG recording. We reviewed literature and identified 21 other published cases of seizures caused by complications of a DVA and 9 patients that may have a direct link between epilepsy and an isolated and uncomplicated DVA. Seizures are linked to a DVA in two main situations: presence of an associated epileptogenic lesion, such as cavernoma or dysplasia, and occurrence of a complication of the DVA. Before concluding that a seizure is caused by a DVA, it is essential to perform full MRI protocols to search them. It remains rare and uncertain that isolated and uncomplicated DVA can cause seizures. In this last situation, physiopathological processes are probably different in each patient.
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http://dx.doi.org/10.1007/s00415-017-8456-5DOI Listing
December 2017

Cerebral infarction following subcutaneous immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy.

Muscle Nerve 2016 06 27;54(1):166-7. Epub 2016 May 27.

Department of Neurology and Stroke Center, Hôpital de Bicêtre, PARIS XI - Sud University, Le Kremlin Bicêtre, France.

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http://dx.doi.org/10.1002/mus.25076DOI Listing
June 2016

Contribution of plexus MRI in the diagnosis of atypical chronic inflammatory demyelinating polyneuropathies.

J Neurol Sci 2016 Jan 27;360:170-5. Epub 2015 Nov 27.

French National Reference Centre for Familial Amyloid Polyneuropathies and Other Rare Diseases, Bicêtre Hospital, APHP, Le Kremlin Bicêtre, France; Department of Neurology, Bicêtre Hospital, APHP, Le Kremlin Bicêtre, France; Univ Paris 11, INSERM U788, Bicêtre Hospital, APHP, Le Kremlin Bicêtre, France.

Nerve enlargement has early been recognized in CIDP and plexus MRI hypertrophy has been reported in typical CIDP cases. Our aim is to determine plexus MRI value in the diagnosis of CIDP with an initial atypical presentation, which, up to now, has not been demonstrated. Retrospective study of 33 consecutive patients suspected of CIDP. Plexus MRI was performed on the most affected territory (brachial or lumbar). Were assessed: plexus trophicity, T2-STIR signal intensity and gadolinium enhancement. Final CIDP diagnosis was made after comprehensive workup. A histo-radiological correlation was performed. Final CIDP diagnosis was made in 25 (76%) including 21 with initial atypical clinical presentation. Eleven CIDP patients (52%) with initial atypical clinical presentation had abnormal plexus MRI including 9 suggestive of CIDP (43%) and none of the patients with an alternative diagnosis. Hypertrophy of the proximal plexus and/or extraforaminal roots was found in 8 cases and Gadolinium enhancement in 2 cases. Abnormalities were more frequent on brachial (86%) than lumbosacral MRIs (29%) and asymmetrical (72%) and most often associated with histological signs of demyelination. The nerve biopsy was suggestive of CIDP in 9/13 patients with normal MRI. Plexus MRI seems useful in the diagnostic strategy of patients with suspicion of CIDP with atypical presentation. Nerve biopsy remains important when other investigations are inconclusive.
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http://dx.doi.org/10.1016/j.jns.2015.11.048DOI Listing
January 2016
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