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1.  Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study 
PLoS ONE  2015;10(7):e0132033.
Recent studies in multiple sclerosis (MS) showed longer survival times from clinical onset than older hospital-based series. However estimated median time ranges widely, from 24 to 45 years, which makes huge difference for patients as this neurological disease mainly starts around age 20 to 40. Precise and up-to-date reference data about mortality in MS are crucial for patients and neurologists, but unavailable yet in France.
Estimate survival in MS patients and compare mortality with that of the French general population.
We conducted a multicenter observational study involving clinical longitudinal data from 30,413 eligible patients, linked to the national deaths register. Inclusion criteria were definite MS diagnosis and clinical onset prior to January, 1st 2009 in order to get a minimum of 1-year disease duration.
After removing between-center duplicates and applying inclusion criteria, the final population comprised 27,603 MS patients (F/M sex ratio 2.5, mean age at onset 33.0 years, 85.5% relapsing onset). During the follow-up period (mean 15.2 +/- 10.3 years), 1569 deaths (5.7%) were identified; half related to MS. Death rates were significantly higher in men, patients with later clinical onset, and in progressive MS. Overall excess mortality compared with the general population was moderate (Standardized Mortality Ratio 1.48, 95% confidence interval [1.41-1.55]), but increased considerably after 20 years of disease (2.20 [2.10-2.31]).
This study revealed a moderate decrease in life expectancy in MS patients, and showed that the risk of dying is strongly correlated to disease duration and disability, highlighting the need for early actions that can slow disability progression.
PMCID: PMC4492994  PMID: 26148099
2.  Accuracy and cutoff values of delayed heart to mediastinum ratio with 123I-metaiodobenzylguanidine cardiac scintigraphy for Lewy body disease diagnoses 
BMC Neurology  2015;15:83.
Different studies have found diminished cardiac metaiodobenzylguanidine (MIBG) uptake in Lewy body (LB) related conditions (Parkinson’s disease (PD) and Lewy body dementia (LBD)). However, delayed heart/mediastinum (d-H/M) ratio diagnostic cutoff points are debated in parkinsonian syndromes.
We performed a monocentric retrospective analysis on 62 consecutive parkinsonian patients who underwent an 123I-MIBG scintigraphy, brain imaging and dopaminergic imaging using 123I-Ioflupane single photon emission computed tomography (SPECT) from 2009 to 2013. The optimal d-H/M ratio was determined from a Receiver Operating Characteristic (ROC) curve and the sensitivity (Se), specificity (Sp) and likelihood ratios (LR) were calculated. 42 patients were diagnosed with LB diseases (20 PD, 22 LBD) and 20 patients with other diseases.
123I-MIBG scintigraphy helped to distinguish PD (p < 0.001) and LBD (p = 0.03) from other diseases. The optimal d-H/M ratio was 1.48 (0.85 area under the ROC curve). Se and Sp were 83.3 %, and 85 % respectively with positive and negative LR of 5.5 and 0.2 respectively. Patients with LBD had a lower d-H/M ratio than patients with PD (result not statistically significant) and a cutoff point at 1.2 could help to differentiate the two diseases. We did not find any correlation between the d-H/M ratio and clinical or 123I-Ioflupane SPECT data.
According to our population, the d-H/M ratio at 1.48 led to the best performance diagnosis with good Se, Sp and accuracy. In addition, a d-H/M ratio cutoff at 1.2 could help to differentiate PD from LBD.
PMCID: PMC4448316  PMID: 25971430
Sympathetic innervation; Parkinson's disease; parkinsonism; MIBG; Myocardium; Lewy body dementia; Diagnosis
3.  Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis 
Beecham, Ashley H | Patsopoulos, Nikolaos A | Xifara, Dionysia K | Davis, Mary F | Kemppinen, Anu | Cotsapas, Chris | Shahi, Tejas S | Spencer, Chris | Booth, David | Goris, An | Oturai, Annette | Saarela, Janna | Fontaine, Bertrand | Hemmer, Bernhard | Martin, Claes | Zipp, Frauke | D’alfonso, Sandra | Martinelli-Boneschi, Filippo | Taylor, Bruce | Harbo, Hanne F | Kockum, Ingrid | Hillert, Jan | Olsson, Tomas | Ban, Maria | Oksenberg, Jorge R | Hintzen, Rogier | Barcellos, Lisa F | Agliardi, Cristina | Alfredsson, Lars | Alizadeh, Mehdi | Anderson, Carl | Andrews, Robert | Søndergaard, Helle Bach | Baker, Amie | Band, Gavin | Baranzini, Sergio E | Barizzone, Nadia | Barrett, Jeffrey | Bellenguez, Céline | Bergamaschi, Laura | Bernardinelli, Luisa | Berthele, Achim | Biberacher, Viola | Binder, Thomas M C | Blackburn, Hannah | Bomfim, Izaura L | Brambilla, Paola | Broadley, Simon | Brochet, Bruno | Brundin, Lou | Buck, Dorothea | Butzkueven, Helmut | Caillier, Stacy J | Camu, William | Carpentier, Wassila | Cavalla, Paola | Celius, Elisabeth G | Coman, Irène | Comi, Giancarlo | Corrado, Lucia | Cosemans, Leentje | Cournu-Rebeix, Isabelle | Cree, Bruce A C | Cusi, Daniele | Damotte, Vincent | Defer, Gilles | Delgado, Silvia R | Deloukas, Panos | di Sapio, Alessia | Dilthey, Alexander T | Donnelly, Peter | Dubois, Bénédicte | Duddy, Martin | Edkins, Sarah | Elovaara, Irina | Esposito, Federica | Evangelou, Nikos | Fiddes, Barnaby | Field, Judith | Franke, Andre | Freeman, Colin | Frohlich, Irene Y | Galimberti, Daniela | Gieger, Christian | Gourraud, Pierre-Antoine | Graetz, Christiane | Graham, Andrew | Grummel, Verena | Guaschino, Clara | Hadjixenofontos, Athena | Hakonarson, Hakon | Halfpenny, Christopher | Hall, Gillian | Hall, Per | Hamsten, Anders | Harley, James | Harrower, Timothy | Hawkins, Clive | Hellenthal, Garrett | Hillier, Charles | Hobart, Jeremy | Hoshi, Muni | Hunt, Sarah E | Jagodic, Maja | Jelčić, Ilijas | Jochim, Angela | Kendall, Brian | Kermode, Allan | Kilpatrick, Trevor | Koivisto, Keijo | Konidari, Ioanna | Korn, Thomas | Kronsbein, Helena | Langford, Cordelia | Larsson, Malin | Lathrop, Mark | Lebrun-Frenay, Christine | Lechner-Scott, Jeannette | Lee, Michelle H | Leone, Maurizio A | Leppä, Virpi | Liberatore, Giuseppe | Lie, Benedicte A | Lill, Christina M | Lindén, Magdalena | Link, Jenny | Luessi, Felix | Lycke, Jan | Macciardi, Fabio | Männistö, Satu | Manrique, Clara P | Martin, Roland | Martinelli, Vittorio | Mason, Deborah | Mazibrada, Gordon | McCabe, Cristin | Mero, Inger-Lise | Mescheriakova, Julia | Moutsianas, Loukas | Myhr, Kjell-Morten | Nagels, Guy | Nicholas, Richard | Nilsson, Petra | Piehl, Fredrik | Pirinen, Matti | Price, Siân E | Quach, Hong | Reunanen, Mauri | Robberecht, Wim | Robertson, Neil P | Rodegher, Mariaemma | Rog, David | Salvetti, Marco | Schnetz-Boutaud, Nathalie C | Sellebjerg, Finn | Selter, Rebecca C | Schaefer, Catherine | Shaunak, Sandip | Shen, Ling | Shields, Simon | Siffrin, Volker | Slee, Mark | Sorensen, Per Soelberg | Sorosina, Melissa | Sospedra, Mireia | Spurkland, Anne | Strange, Amy | Sundqvist, Emilie | Thijs, Vincent | Thorpe, John | Ticca, Anna | Tienari, Pentti | van Duijn, Cornelia | Visser, Elizabeth M | Vucic, Steve | Westerlind, Helga | Wiley, James S | Wilkins, Alastair | Wilson, James F | Winkelmann, Juliane | Zajicek, John | Zindler, Eva | Haines, Jonathan L | Pericak-Vance, Margaret A | Ivinson, Adrian J | Stewart, Graeme | Hafler, David | Hauser, Stephen L | Compston, Alastair | McVean, Gil | De Jager, Philip | Sawcer, Stephen | McCauley, Jacob L
Nature genetics  2013;45(11):10.1038/ng.2770.
Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value < 1.0 × 10-4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value < 5.0 × 10-8); three found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals.
PMCID: PMC3832895  PMID: 24076602
4.  Impact of tissue plasminogen activator on the neurovascular unit: from clinical data to experimental evidence 
About 15 million strokes occur each year worldwide. As the number one cause of morbidity and acquired disability, stroke is a major drain on public health-care funding, due to long hospital stays followed by ongoing support in the community or nursing-home care. Although during the last 10 years we have witnessed a remarkable progress in the understanding of the pathophysiology of ischemic stroke, reperfusion induced by recombinant tissue-type plasminogen activator (tPA—Actilyse) remains the only approved acute treatment by the health authorities. The objective of the present review is to provide an overview of our present knowledge about the impact of tPA on the neurovascular unit during acute ischemic stroke.
PMCID: PMC3210341  PMID: 21878948
acute stroke; clinical trials; excitotoxicity; interventional neuroradiology; neurovascular unit; thrombolysis
5.  Inflammatory-like presentation of CADASIL: a diagnostic challenge 
BMC Neurology  2012;12:78.
CADASIL is an autosomal dominant genetic leukoencephalopathy linked to mutations in the Notch3 gene. In rare cases, widespread brain lesions on T2 MRI mimicking multiple sclerosis are observed. From a national registry of 268 patients with adult-onset leukodystrophy, we identified two patients with an atypical presentation of CADASIL without co-occurrence of another systemic disease.
Case presentations
Patient 1 experienced progressive gait disability and patient 2 relapsing optic neuritis and sensory-motor deficit in the leg. Both patients responded to corticotherapy and patient 2 was also responsive to glatiramer acetate. No oligoclonal bands were found in the CSF, and MRI showed myelitis and lesions with gadolinium enhancement in brain (patient 1) or incomplete CADASIL phenotype (patient 2).
In rare cases, an inflammatory-like process can occur in CADASIL. In these patients, immunomodulatory treatments, including corticosteroids, could be effective.
PMCID: PMC3488471  PMID: 22905984
CADASIL; Multiple sclerosis; Leukoencephalopathy; Notch3; Cerebral vasculitis
6.  Stroke in hereditary hemorrhagic telangiectasia patients. New evidence for repeated screening and early treatment of pulmonary vascular malformations: two case reports 
BMC Neurology  2011;11:84.
Paradoxical embolism due to pulmonary arteriovenous malformations is the main mechanism of brain infarction in patients with hereditary hemorrhagic telangiectasia. International Guidelines have recently been published to clarify the performance of screening tests and the effectiveness of treatment for pulmonary arteriovenous malformations.
Case Presentation
We present two cases of hereditary hemorrhagic telangiectasia patients of our hospital who experienced an acute stroke secondary to paradoxical embolism.
These two cases show that the guidelines must be followed to prevent the occurrence of ischemic stroke in patients with hereditary hemorrhagic telangiectasia, and that although they may be adequate in most cases, there are some patients who need a more personalized approach.
PMCID: PMC3148967  PMID: 21740592

Results 1-6 (6)