Publications by authors named "Matthias Lamy"

8 Publications

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Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic.

Brain 2021 Jul 16. Epub 2021 Jul 16.

AP-HP, Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis, France.

Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known cerebral small vessel disease genes, including HTRA1, in 3,853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. An analysis of HTRA1 messenger RNA was performed in several stop codon carrier patients. Clinical and neuroimaging features were characterized in all probands. Twenty unrelated patients carrying a heterozygous HTRA1 variant leading to a premature stop codon were identified. A highly significant difference was observed when comparing our patient cohort with control databases (gnomAD v3.1.1 (p = 3.12 x 10-17, OR = 21.9), TOPMed freeze 5 (p = 7.6 x 10-18, OR = 27.1) and 1000 Genomes (p = 1.5 x 10-5). Messenger RNA analysis performed in eight patients showed a degradation of the mutated allele strongly suggesting a haploinsufficiency. Clinical and neuroimaging features are similar to those previously reported in heterozygous missense mutation carriers, except for penetrance, which seems lower. Altogether, our findings strongly suggest that heterozygous HTRA1 stop codons are pathogenic through a haploinsufficiency mechanism. Future work will help to estimate their penetrance, an important information for genetic counseling.
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http://dx.doi.org/10.1093/brain/awab271DOI Listing
July 2021

Predictors of Early Stroke or Death in Patients Undergoing Transcatheter Aortic Valve Implantation.

J Stroke Cerebrovasc Dis 2021 Aug 12;30(8):105912. Epub 2021 Jun 12.

Department of Neurology, CHU La Milétrie, Poitiers, France and University of Poitiers, France.

Background/objective: While postoperative stroke is a known complication of Transcatheter Aortic Valve Implantation (TAVI), predictors of early stroke occurrence have not been specifically reviewed. The objective of this study was to estimate the predictors and incidence of stroke during the first 30 days post-TAVI.

Methods: A cohort of 506 consecutive patients having undergone TAVI between January 2017 and June 2019 was extracted from a prospective database. Preoperative, intraoperative and postoperative characteristics were analyzed by univariate analysis followed by logistic regression to find predictors of the occurrence of stroke or death within the first 30 days after the procedure.

Results: Incidence of stroke within 30 days post-TAVI was 4.9%, [CI 95% 3.3-7.2], i.e., 25 strokes. Four out of the 25 patients (16%) with a stroke died within 30 days post-TAVI. After logistic regression analysis, the predictors of early stroke related to TAVI were: CHA2Ds2VASc score ≥ 5 (odds ratio [OR] 2.62; 95% CI: 1.06-6.49; p = .037), supra-aortic access vs. femoral access (OR: 9.00, 95%CI: 2.95-27.44; p = .001) and introduction post-TAVI of a single vs. two or three antithrombotic agents (OR: 5.13; CI 95%: 1.99 to 13.19; p = .001). Over the 30-day period, bleeding occurred in 28 patients (5.5%), in 25 of whom, it was associated with femoral or iliac artery access injury. Anti-thrombotic regimen was not associated with bleeding; two patients out of 48 (4.1%) bled with a single anti-thrombotic regimen vs. 26 patients out of 458 (5.6%) with a dual or triple anti-thrombotic regimen (p = 0.94). The overall 30-day mortality rate was 3.9%, [95% CI 2.5-6.0]. Patients with a single post-TAVI antithrombotic agent (OR: 44.07 [CI 95% 13.45-144.39]; p < .0001) and patients with previous coronary artery bypass surgery or coronary artery stenting (OR: 6.16, [CI 95% 1.99-21.29]; p = .002) were at significantly higher risk of death within the 30-day period.

Conclusion: In this large-scale single-center retrospective study, a single post-TAVI antithrombotic regimen independently predicted occurrence of early stroke or death. Dual or triple antithrombotic regimen was not associated with a higher risk of bleeding and should be considered as an option in patients undergoing TAVI.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105912DOI Listing
August 2021

Should We Screen for Janus Kinase 2 V617F Mutation in Cerebral Venous Thrombosis?

Cerebrovasc Dis 2017 14;44(3-4):97-104. Epub 2017 Jun 14.

Department of Neurology, S. Giovanni Calibita-Fatebenefratelli Hospital, Rome, Italy.

Background: The presence of Janus Kinase 2 (JAK2) V617F mutation represents a major diagnostic criterion for detecting myeloproliferative neoplasms (MPN) and even in the absence of overt MPN, JAK2 V617F mutation is associated with splanchnic vein thrombosis. However, the actual prevalence and diagnostic value of the JAK2 V617F mutation in patients with cerebral venous thrombosis (CVT) are not known. The aims of this study were to assess the prevalence of JAK2 V617F mutation in a large group of consecutive CVT patients, to detect clinical, biological, and radiological features associated with the mutation, and to determine the long-term venous thrombosis recurrence rate in CVT patients with JAK2 mutation but without overt MPN in order to recommend the best preventive treatment.

Methods: This was a prospective study conducted on consecutive patients with a first-ever radiologically confirmed CVT. JAK2 V617F mutation analysis was assessed in all the study subjects. JAK2 V617F-positive patients were followed up to detect new venous thrombotic events.

Results: Of the 125 included subjects, 7 were found to have JAK2 V617F mutation (5.6%; 95% CI 2.3-11.2). Older age (p = 0.039) and higher platelet count (p = 0.004) were independently associated with JAK2 V617F positivity in patients without overt MPN. During a mean follow-up period of 59 (SD 46) months, 2 JAK2 V617F-positive patients presented with 4 new venous thromboembolic events.

Conclusions: Screening for the JAK2 V617F mutation in CVT patients seems to be useful even in the absence of overt MPN and/or in the presence of other risk factors for CVT because of its relatively high prevalence and the risk of thrombosis recurrence.
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http://dx.doi.org/10.1159/000471891DOI Listing
June 2018

Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

Int J Stroke 2017 10 9;12(7):720-723. Epub 2017 Jan 9.

1 Department of Neurology, CHU de Nantes - Laënnec Nantes, France.

Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.
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http://dx.doi.org/10.1177/1747493016687578DOI Listing
October 2017

Venous Thrombotic Recurrence After Cerebral Venous Thrombosis: A Long-Term Follow-Up Study.

Stroke 2017 Feb 15;48(2):321-326. Epub 2016 Dec 15.

From the Department of Neurology, Poitiers University Hospital and University of Poitiers, France (P.P., P.A., J.C., M.L., A.B., P.C., J.-P.N.); Department of Neurology, S. Giovanni Calibita-Fatebenefratelli Hospital, Rome, Italy (P.P.); and Clinical Investigation Center INSERM CIC-P 802, Poitiers University Hospital, France (P.I.).

Background And Purpose: After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence.

Methods: Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation.

Results: One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1-247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with recurrence.

Conclusions: In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.
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http://dx.doi.org/10.1161/STROKEAHA.116.015294DOI Listing
February 2017

Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome after bilateral carotid paraganglioma resection: A case report.

Cephalalgia 2017 Jan 11;37(1):89-93. Epub 2016 Jul 11.

1 Department of Neurology, CHU Poitiers, University of Poitiers, 2 rue de la Milétrie, 86021 Poitiers, France.

Background Paraganglioma is a rare neuroendocrine tumour arising anywhere along the paravertebral sympathetic and parasympathetic chains. In the neck, paraganglioma may affect the carotid body (carotid body tumour). Case report We describe a 43-year-old woman who presented with a reversible vasoconstriction syndrome associated with a posterior reversible encephalopathy syndrome following a surgery for a left carotid paraganglioma (with a past medical history of surgery for a right carotid paraganglioma a few months before). Conclusion A consequence of a baroreflex modification is discussed in order to explain the rare occurrence of such symptoms.
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http://dx.doi.org/10.1177/0333102416629235DOI Listing
January 2017

Anti-NMDA Receptor Encephalitis During Pregnancy: A Case Report.

Medicine (Baltimore) 2015 Jul;94(26):e1034

From the Department of Neurology, CHU Poitiers, Poitiers (SM, JCP, AI, ML, JPN); Department of Neurology, Hôpital d'Angoulême, Angoulême France (CP); and Department of Gynecology, CHU Poitiers, Poitiers, France (FP).

Anti-N-methyl-D-aspartate receptor (anti-MMDAR) encephalitis is an immune-mediated encephalitis mainly affecting young women.We describe the case of a 21-year-old woman who developed a classical form of anti-NMDAR encephalitis during the 10th week of gestation. The patient had been treated with methylpredinsolone and intravenous immunoglobulins. Birth history of the child was normal, with normal APGAR score. The clinical symptoms of the patient have improved after a few months.This rare occurrence during pregnancy (only 9 other cases described) presents an opportunity to highlight the importance of making the earliest possible diagnosis of this treatable and potentially reversible encephalitis, and to educate gynecologists, psychiatrists, anesthetists, and neurologists on this potential cause of psychiatric and neurological manifestations during pregnancy.
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http://dx.doi.org/10.1097/MD.0000000000001034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504573PMC
July 2015

Paroxysmal sneezing at the onset of syncopes and transient ischemic attack revealing a papillary cardiac fibroelastoma.

Case Rep Neurol Med 2014 17;2014:734849. Epub 2014 Jun 17.

Department of Neurology, University of Poitiers, CHU Poitiers, 2 Rue de la Milétrie, 86021 Poitiers Cedex 05, France.

Sneezing can at times be associated with neurological disorders. The "sneeze center" is localized in the lateral medulla. We report the case of a 50-year-old man who presented three episodes of sneezing, two of them followed by an episode of transient gait instability and dizziness and the third one followed by an episode of transient left hemiparesis due to fibroelastoma of the aortic cardiac valve. To the best of our knowledge, this is the first description of a transient ischemic attack due to cardiac papillary fibroelastoma and revealed by violent episodes of sneezing.
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http://dx.doi.org/10.1155/2014/734849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086253PMC
July 2014
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