Publications by authors named "Renaud Du Pasquier"

118 Publications

Recurrence of disease activity after fingolimod discontinuation in older patients previously stable on treatment.

Mult Scler Relat Disord 2021 Mar 21;51:102918. Epub 2021 Mar 21.

Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland. Electronic address:

Background: Discontinuing fingolimod (FTY) in older patients is a growing concern with little evidence supporting the decision to pursue treatment and reasonable doubt for disease reactivation after withdrawal.

Objective: To estimate the incidence of recurrence of disease activity (RDA) and rebound after FTY withdrawal in patients older than 50 years.

Methods: Retrospective analysis of all MS patients in our clinic who discontinued FTY after at least 6 months of treatment, according to disease activity on FTY and age at discontinuation. RDA was defined as the occurrence of either clinical and/or MRI activity in the 6 months after FTY withdrawal and rebound when the levels of disease activity surpassed pretreatment activity.

Results: From the 128 patients who discontinued FTY since 2011, up to 35.2% of patients experienced evidence of disease activity and 12.5% had a rebound. The incidence of both RDA and rebound was not different among individuals who had persistent disease activity on FTY to those who stopped FTY for other reasons than inefficacy (RDA: 25.5% vs 20.5%, p = 0.353 rebound: 14.5% vs 11%, p = 0.596). Negative predictive factors for RDA were younger age at disease onset (p = 0.036), highly active disease at baseline (p = 0.003) and previous treatment with NTZ (p = 0.013). Older age at FTY discontinuation did not reduce the risk of RDA in patients previously stable on treatment (OR 0.972, 95% CI 0.871-1.085, p = 0.613), although the incidence of RDA/rebound was half less in the older patients (36.5% in the <50 vs 19% in the ≥50 year-old, p = 0.174) and none of the patients over 60 experienced RDA.

Conclusion: Although there is a tendency for a lower risk of disease reactivation in the older patients, the incidence of RDA, and even rebound, is not negligible between the age of 50 and 60 years, even in patients with previously stable MS on FTY.
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http://dx.doi.org/10.1016/j.msard.2021.102918DOI Listing
March 2021

Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.

PLoS One 2021 2;16(3):e0246579. Epub 2021 Mar 2.

Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland.

Background: Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.

Results: Most participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function.

Conclusions: In this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924787PMC
March 2021

The association between depressive symptoms and neurocognitive impairment in people with well-treated HIV in Switzerland.

Int J STD AIDS 2021 Feb 25:956462420987434. Epub 2021 Feb 25.

Infectious Diseases Service, 30635Lausanne University Hospital, Lausanne, Switzerland.

Background: Depression may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Attributing NCI to depression rather than to HIV is complicated as depression may be both a causal factor and an effect of NCI. This study aimed to determine the association between depressive symptoms and NCI among PWH with well-controlled infection.

Methods: The Neurocognitive Assessment in the Metabolic and Ageing Cohort study is an ongoing, prospective, longitudinal study of PWH aged ≥45 years old nested within the Swiss HIV Cohort Study. Neurocognitive Assessment in the Metabolic and Ageing Cohort study participants underwent neurocognitive assessment and grading of depressive symptoms using the Centre for Epidemiological Studies Depression Scale. Neurocognitive impairment categories were defined using Frascati criteria. Participants with NCI related to neurological or psychiatric confounders other than depression were excluded. The cross-sectional association between the Centre for Epidemiological Studies Depression score and neurocognitive impairment was examined taking Centre for Epidemiological Studies Depression score as a continuous variable and then as a binary variable using two score thresholds, 16 and 27.

Results: Excluding 79 participants with confounding factors, 902 participants were studied: 81% were men; 96% had plasma viral loads <50 copies/ml; 35% had neurocognitive impairment; 28% had Centre for Epidemiological Studies Depression scores ≥16. Higher Centre for Epidemiological Studies Depression scores were associated with female sex ( = 0.0003), non-Caucasian origin ( = 0.011) and current/past intravenous drug use ( = 0.002). Whilst neurocognitive impairment was associated with higher Centre for Epidemiological Studies Depression scores, the Centre for Epidemiological Studies Depression score was a poor predictor of having neurocognitive impairment (area under the ROC curve 0.604). Applying a Centre for Epidemiological Studies Depression score threshold of 16 predicted the presence of neurocognitive impairment with a sensitivity of 38.3% (specificity 77.2%), increasing the threshold to 27 lowered sensitivity to 15.4% (specificity 93.6%).

Conclusion: In this large cohort of PWH in Switzerland, we did not observe a Centre for Epidemiological Studies Depression score threshold that was sensitive in predicting neurocognitive impairment. As neurocognitive impairment was however associated with higher Centre for Epidemiological Studies Depression scores, the data support the screening for and treatment of depression among PWH diagnosed with neurocognitive impairment.
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http://dx.doi.org/10.1177/0956462420987434DOI Listing
February 2021

[Recent Advances in Neurology].

Rev Med Suisse 2021 Jan;17(723):196-200

Service de neurologie, Département des neurosciences cliniques, CHUV, 1011 Lausanne.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease.
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January 2021

Pattern of cognitive deficits in severe COVID-19.

J Neurol Neurosurg Psychiatry 2021 05 20;92(5):567-568. Epub 2020 Nov 20.

Service of Neuropsychology and Neurorehabilitation, CHUV, Lausanne, Switzerland.

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http://dx.doi.org/10.1136/jnnp-2020-325173DOI Listing
May 2021

Advancing human induced pluripotent stem cell-derived blood-brain barrier models for studying immune cell interactions.

FASEB J 2020 12 30;34(12):16693-16715. Epub 2020 Oct 30.

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier (BBB) models established to date lack expression of key adhesion molecules involved in immune cell migration across the BBB in vivo. Here, we introduce the extended endothelial cell culture method (EECM), which differentiates hiPSC-derived endothelial progenitor cells to brain microvascular endothelial cell (BMEC)-like cells with good barrier properties and mature tight junctions. Importantly, EECM-BMEC-like cells exhibited constitutive cell surface expression of ICAM-1, ICAM-2, and E-selectin. Pro-inflammatory cytokine stimulation increased the cell surface expression of ICAM-1 and induced cell surface expression of P-selectin and VCAM-1. Co-culture of EECM-BMEC-like cells with hiPSC-derived smooth muscle-like cells or their conditioned medium further increased the induction of VCAM-1. Functional expression of endothelial ICAM-1 and VCAM-1 was confirmed by T-cell interaction with EECM-BMEC-like cells. Taken together, we introduce the first hiPSC-derived BBB model that displays an adhesion molecule phenotype that is suitable for the study of immune cell interactions.
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http://dx.doi.org/10.1096/fj.202001507RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686106PMC
December 2020

Vaccine-associated measles in a patient treated with natalizumab: a case report.

BMC Infect Dis 2020 Oct 14;20(1):753. Epub 2020 Oct 14.

Tropical, travel and vaccination clinic, Unisanté, Center for primary care and public health, Bugnon 44, 1011, Lausanne, Switzerland.

Background: Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment.

Case Presentation: A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient's symptoms resolved without any sequelae.

Conclusion: In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.
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http://dx.doi.org/10.1186/s12879-020-05475-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556935PMC
October 2020

Meningeal Relapse of Nodular Lymphocyte Predominant Hodgkin Lymphoma Transformed to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Case Report.

Front Oncol 2020 14;10:1745. Epub 2020 Sep 14.

Department of Laboratory Medicine and Pathology, Institute of Pathology, CHUV University Hospital and University of Lausanne, Lausanne, Switzerland.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis.
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http://dx.doi.org/10.3389/fonc.2020.01745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521157PMC
September 2020

Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes.

Front Neurol 2020 4;11:973. Epub 2020 Sep 4.

Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Basel University Hospital, University of Basel, Basel, Switzerland.

Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points. At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr- <0.017/Corr- < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr- < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility ( < 0.01), (ii) verbal memory ( < 0.01); (iii) verbal fluency ( < 0.05); and (iv) hand-motor function ( < 0.05). : Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances.
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http://dx.doi.org/10.3389/fneur.2020.00973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498574PMC
September 2020

RimNet: A deep 3D multimodal MRI architecture for paramagnetic rim lesion assessment in multiple sclerosis.

Neuroimage Clin 2020 4;28:102412. Epub 2020 Sep 4.

Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne, Switzerland; Medical Image Analysis Laboratory (MIAL), Center for Biomedical Imaging (CIBM), University of Lausanne, Switzerland; Department of Radiology, Lausanne University Hospital and University of Lausanne, Switzerland. Electronic address:

Objectives: In multiple sclerosis (MS), the presence of a paramagnetic rim at the edge of non-gadolinium-enhancing lesions indicates perilesional chronic inflammation. Patients featuring a higher paramagnetic rim lesion burden tend to have more aggressive disease. The objective of this study was to develop and evaluate a convolutional neural network (CNN) architecture (RimNet) for automated detection of paramagnetic rim lesions in MS employing multiple magnetic resonance (MR) imaging contrasts.

Materials And Methods: Imaging data were acquired at 3 Tesla on three different scanners from two different centers, totaling 124 MS patients, and studied retrospectively. Paramagnetic rim lesion detection was independently assessed by two expert raters on T2*-phase images, yielding 462 rim-positive (rim+) and 4857 rim-negative (rim-) lesions. RimNet was designed using 3D patches centered on candidate lesions in 3D-EPI phase and 3D FLAIR as input to two network branches. The interconnection of branches at both the first network blocks and the last fully connected layers favors the extraction of low and high-level multimodal features, respectively. RimNet's performance was quantitatively evaluated against experts' evaluation from both lesion-wise and patient-wise perspectives. For the latter, patients were categorized based on a clinically relevant threshold of 4 rim+ lesions per patient. The individual prediction capabilities of the images were also explored and compared (DeLong test) by testing a CNN trained with one image as input (unimodal).

Results: The unimodal exploration showed the superior performance of 3D-EPI phase and 3D-EPI magnitude images in the rim+/- classification task (AUC = 0.913 and 0.901), compared to the 3D FLAIR (AUC = 0.855, Ps < 0.0001). The proposed multimodal RimNet prototype clearly outperformed the best unimodal approach (AUC = 0.943, P < 0.0001). The sensitivity and specificity achieved by RimNet (70.6% and 94.9%, respectively) are comparable to those of experts at the lesion level. In the patient-wise analysis, RimNet performed with an accuracy of 89.5% and a Dice coefficient (or F1 score) of 83.5%.

Conclusions: The proposed prototype showed promising performance, supporting the usage of RimNet for speeding up and standardizing the paramagnetic rim lesions analysis in MS.
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http://dx.doi.org/10.1016/j.nicl.2020.102412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509077PMC
September 2020

Paramagnetic Rim Lesions are Specific to Multiple Sclerosis: An International Multicenter 3T MRI Study.

Ann Neurol 2020 11 9;88(5):1034-1042. Epub 2020 Sep 9.

Department of Neurology, Johns Hopkins University, Baltimore, MD.

In multiple sclerosis (MS), a subset of chronic active white matter lesions are identifiable on magnetic resonance imaging by their paramagnetic rims, and increasing evidence supports their association with severity of clinical disease. We studied their potential role in differential diagnosis, screening an international multicenter clinical research-based sample of 438 individuals affected by different neurological conditions (MS, other inflammatory, infectious, and non-inflammatory conditions). Paramagnetic rim lesions, rare in other neurological conditions (52% of MS vs 7% of non-MS cases), yielded high specificity (93%) in differentiating MS from non-MS. Future prospective multicenter studies should validate their role as a diagnostic biomarker. ANN NEUROL 2020;88:1034-1042.
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http://dx.doi.org/10.1002/ana.25877DOI Listing
November 2020

Clinical Reasoning: A 69-year-old man with rare complex visual symptoms.

Neurology 2020 08 30;95(7):316-320. Epub 2020 Jul 30.

From the Department of Clinical Neurosciences, Neurology Service, Lausanne University Hospital and University of Lausanne, Switzerland.

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http://dx.doi.org/10.1212/WNL.0000000000010218DOI Listing
August 2020

Vaccination in B-cell-depleted patients with multiple sclerosis.

Neurology 2020 10 29;95(14):613-614. Epub 2020 Jul 29.

From the Department of Neurology (J.K.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Department of Clinical Neurosciences (R.D.P.), Service of Neurology, Lausanne University Hospital and University of Lausanne, Switzerland; Department of Neurology (B.H.), School of Medicine, Technical University of Munich; and Munich Cluster for Systems Neurology (B.H.), Munich, Germany.

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http://dx.doi.org/10.1212/WNL.0000000000010378DOI Listing
October 2020

Progressive multifocal leukoencephalopathy responsive to withdrawal of imatinib in a patient with FIP1L1-PDGFRA positive myeloid neoplasm.

Leuk Lymphoma 2020 09 4;61(9):2226-2229. Epub 2020 May 4.

Department of Clinical Neurosciences, Service of Neurology, Neuroimmunology Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

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http://dx.doi.org/10.1080/10428194.2020.1759052DOI Listing
September 2020

CVSnet: A machine learning approach for automated central vein sign assessment in multiple sclerosis.

NMR Biomed 2020 05 3;33(5):e4283. Epub 2020 Mar 3.

Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland.

The central vein sign (CVS) is an efficient imaging biomarker for multiple sclerosis (MS) diagnosis, but its application in clinical routine is limited by inter-rater variability and the expenditure of time associated with manual assessment. We describe a deep learning-based prototype for automated assessment of the CVS in white matter MS lesions using data from three different imaging centers. We retrospectively analyzed data from 3 T magnetic resonance images acquired on four scanners from two different vendors, including adults with MS (n = 42), MS mimics (n = 33, encompassing 12 distinct neurological diseases mimicking MS) and uncertain diagnosis (n = 5). Brain white matter lesions were manually segmented on FLAIR* images. Perivenular assessment was performed according to consensus guidelines and used as ground truth, yielding 539 CVS-positive (CVS ) and 448 CVS-negative (CVS ) lesions. A 3D convolutional neural network ("CVSnet") was designed and trained on 47 datasets, keeping 33 for testing. FLAIR* lesion patches of CVS /CVS lesions were used for training and validation (n = 375/298) and for testing (n = 164/150). Performance was evaluated lesion-wise and subject-wise and compared with a state-of-the-art vesselness filtering approach through McNemar's test. The proposed CVSnet approached human performance, with lesion-wise median balanced accuracy of 81%, and subject-wise balanced accuracy of 89% on the validation set, and 91% on the test set. The process of CVS assessment, in previously manually segmented lesions, was ~ 600-fold faster using the proposed CVSnet compared with human visual assessment (test set: 4 seconds vs. 40 minutes). On the validation and test sets, the lesion-wise performance outperformed the vesselness filter method (P < 0.001). The proposed deep learning prototype shows promising performance in differentiating MS from its mimics. Our approach was evaluated using data from different hospitals, enabling larger multicenter trials to evaluate the benefit of introducing the CVS marker into MS diagnostic criteria.
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http://dx.doi.org/10.1002/nbm.4283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754184PMC
May 2020

[Neurology 2019].

Rev Med Suisse 2020 Jan;16(676-7):68-71

Département des neurosciences cliniques, CHUV et Université de Lausanne, 1011 Lausanne.

New studies confirm the possibility of late thrombolysis. Meta-analyses have confirmed that CGRP inhibitors are efficacious for migraines. Cladribine is a new oral treatment for relapsing-remitting multiple sclerosis. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a new clinical entity accounting for cognitive decline in old patients. The timing of levodopa introduction has no effect on the long-term course of idiopathic Parkinson's disease. Hypophosphatemia helps distinguish between seizures and syncopes in the emergency department. A second course of intravenous immunoglobulins provides no benefit for severe Guillain Barre syndrome. Outdoor therapy improves clinical scales in patients with disorder of consciousness. Ultrasound guided lumbar puncture improves the yield of the procedure.
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January 2020

Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis.

Can J Neurol Sci 2020 03;47(2):189-196

Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Objective: In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.

Methods: Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.

Results: Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.

Conclusion: In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.
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http://dx.doi.org/10.1017/cjn.2019.329DOI Listing
March 2020

Pembrolizumab as a treatment for PML? Waiting for Godot.

Neurol Neuroimmunol Neuroinflamm 2019 11 9;6(6):e629. Epub 2019 Oct 9.

From the Division of Neurology, Department of Clinical Neurosciences, University Hospital of Lausanne, University of Lausanne, Switzerland.

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http://dx.doi.org/10.1212/NXI.0000000000000629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807654PMC
November 2019

The "central vein sign" in patients with diagnostic "red flags" for multiple sclerosis: A prospective multicenter 3T study.

Mult Scler 2020 04 19;26(4):421-432. Epub 2019 Sep 19.

Department of Neurology, Center of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland.

Background: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective.

Objectives: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases.

Methods: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory "red flags" (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed.

Results: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%;  < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value.

Conclusion: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features.
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http://dx.doi.org/10.1177/1352458519876031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080603PMC
April 2020

Self-reported Neurocognitive Impairment in People Living With Human Immunodeficiency Virus (HIV): Characterizing Clusters of Patients With Similar Changes in Self-reported Neurocognitive Impairment, 2013-2017, in the Swiss HIV Cohort Study.

Clin Infect Dis 2020 Jul;71(3):637-644

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Background: Self-reported neurocognitive impairment (SRNI) in people living with human immunodeficiency virus type 1 (HIV-1) infection is frequent. We use longitudinal information on SRNI in the Swiss HIV Cohort Study (SHCS) to identify and characterize groups of patients with persisting SRNI over time.

Methods: We included all SHCS patients who were assessed for SRNI during at least 5 visits spanning at least 2.5 years in 2013-2017. We first compared patients with SRNI to those without SRNI over the whole study period. Second, we used a hierarchical cluster algorithm to identify groups of patients with similar changes of SRNI over time. In both analyses, we studied clinical and demographic factors potentially influencing SRNI.

Results: In total, 79 683 questionnaires of 11 029 patients contained information about SRNI, and 8545 of 11 029 (77.5%) patients had longitudinal information. The overall percentage of patients with SRNI decreased from 19.6% in 2013 to 10.7% in 2017. Compared to patients in the cluster with low-level SRNI over time, patients in the cluster with high-level persisting SRNI more often had a prior opportunistic infection of the central nervous system (CNS) (odds ratio [OR], 3.7; P < .001), imperfect adherence to antiretroviral therapy (ART) (OR, 2.8; P < .001), and depression (OR, 1.9; P < .001).

Conclusions: Although overall SRNI is decreasing in the SHCS, there is a group of patients with persisting SRNI over time. Past opportunistic infections of the CNS, imperfect adherence to ART, and depression were associated most with persisting SRNI. Patients with these characteristics should be preferentially tested for neurocognitive impairment.Although overall self-reported neurocognitive impairment (SRNI) is decreasing in the Swiss HIV Cohort Study, there is a group of patients with persisting SRNI over time, characterized by more past opportunistic infections of the central nervous system, imperfect adherence to antiretroviral therapy, and depression.
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http://dx.doi.org/10.1093/cid/ciz868DOI Listing
July 2020

Cross-Sectional and Cumulative Longitudinal Central Nervous System Penetration Effectiveness Scores Are Not Associated With Neurocognitive Impairment in a Well Treated Aging Human Immunodeficiency Virus-Positive Population in Switzerland.

Open Forum Infect Dis 2019 Jul 8;6(7):ofz277. Epub 2019 Jul 8.

Infectious Diseases Service, Lausanne University Hospital, Switzerland.

Background: Neurocognitive impairment (NCI) in people with human immunodeficiency virus (PWH) remains a concern despite potent antiretroviral therapy (ART). Higher central nervous system (CNS) penetration effectiveness (CPE) scores have been associated with better CNS human immunodeficiency virus (HIV) replication control, but the association between CPE and NCI remains controversial.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a subgroup of the Swiss HIV Cohort Study (SHCS) that invited patients aged ≥45 years enrolled in the SHCS and followed-up at NAMACO-affiliated centers in Switzerland to participate between May 2013 and November 2016. In total, 981 patients were enrolled, all of whom underwent standardized neurocognitive assessment. Neurocognitive impairment, if present, was characterized using Frascati criteria. The CPE scores of NAMACO study participants with undetectable plasma HIV-ribonucleic acid at enrollment (909 patients) were analyzed. Cross-sectional CPE scores (at neurocognitive assessment) were examined as potential predictors of NCI in multivariate logistic regression models. The analysis was then repeated taking CPE as a cumulative score (summarizing CPE scores from ART initiation to the time of neurocognitive assessment).

Results: Most patients were male (80%) and Caucasian (92%). Neurocognitive impairment was present in 40%: 27% with HIV-associated NCI (mostly asymptomatic neurocognitive impairment), and 13% with NCI related to other factors. None of the CPE scores, neither cross-sectional nor cumulative, was statistically significantly associated with NCI.

Conclusions: In this large cohort of aviremic PWH, we observed no association between NCI, whether HIV-associated or related to other factors, and CPE score, whether cross-sectional or cumulative.
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http://dx.doi.org/10.1093/ofid/ofz277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612860PMC
July 2019

Motor behavior unmasks residual cognition in disorders of consciousness.

Ann Neurol 2019 03 10;85(3):443-447. Epub 2019 Feb 10.

Department of Clinical Neurosciences, University Hospital CHUV, Lausanne, Switzerland.

Disorders of consciousness (DOC) are a common consequence of severe brain injuries, and clinical evaluation is critical to provide a correct diagnosis and prognosis. The revised Motor Behavior Tool (MBT-r) is a clinical complementary tool aiming to identify subtle motor behaviors that might reflect residual cognition in DOC. In this prospective study including 30 DOC patients in the early stage after brain injury, we show that the revised MBT-r has an excellent inter-rater agreement and has the ability to identify a subgroup of patients, underestimated by the Coma Recovery Scale-Revised, showing residual cognition and a subsequent recovery of consciousness. ANN NEUROL 2019;85:443-447.
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http://dx.doi.org/10.1002/ana.25417DOI Listing
March 2019

[Neurology].

Rev Med Suisse 2019 Jan;15(N° 632-633):74-77

Service de neurologie, Département des neurosciences cliniques, CHUV, 1011 Lausanne.

Thrombolysis and late thrombectomy can be performed in case of compatible radiological imaging. Anti-CGRP monoclonal antibodies seem more effective for the treatment of migraine. Siponimod can reduce significantly disability progression in secondarily progressive MS. Brand-to-generic levetiracetam switching does not cause recrudescence of epileptic seizures. A new definition of Alzheimer's disease using biomarkers of cerebrospinal fluid (CSF) and imaging provides a better understanding of the underlying mechanisms. The use of levodopa-carbidopa intestinal gel and a subcutaneous apomorphine infusion allow a reduction of motor fluctuations in Parkinson's disease. Eculizumab appears as an alternative treatment in severe forms of myasthenia gravis.
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January 2019

Natalizumab may control immune checkpoint inhibitor-induced limbic encephalitis.

Neurol Neuroimmunol Neuroinflamm 2018 Mar 11;5(2):e439. Epub 2018 Jan 11.

Department of Clinical Neurosciences (A.F.H., V.G., A.K., R.D.P.), Department of Oncology (A.F.H., R.d.M.), and Department of Radiology (P.H.), CHUV University Hospital & University of Lausanne, Switzerland.

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http://dx.doi.org/10.1212/NXI.0000000000000439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225924PMC
March 2018

Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines.

Stem Cell Reports 2018 11 25;11(5):1199-1210. Epub 2018 Oct 25.

Laboratory of Neuroimmunology, Neuroscience Research Centre, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland; Service of Neurology, Department of Clinical Neurosciences, CHUV, CHUV BH-10/131, 46, rue du Bugnon, Lausanne 1011, Switzerland. Electronic address:

Recent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we develop a serum-free protocol to differentiate human induced pluripotent stem cells (hiPSCs) into astrocytes. Gene expression and functional assays show that our protocol consistently yields a highly enriched population of resting mature astrocytes across the 13 hiPSC lines differentiated. Using this model, we first highlight the importance of serum-free media for astrocyte culture to generate resting astrocytes. Second, we assess the astrocytic response to IL-1β, TNF-α, and IL-6, all cytokines important in neuroinflammation, such as multiple sclerosis. Our study reveals very specific profiles of reactive astrocytes depending on the triggering stimulus. This model provides ideal conditions for in-depth and unbiased characterization of astrocyte reactivity in neuroinflammatory conditions.
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http://dx.doi.org/10.1016/j.stemcr.2018.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234919PMC
November 2018

Effect of national HIV testing recommendations and local interventions on HIV testing practices in a Swiss university hospital: a retrospective analysis between 2012 and 2015.

BMJ Open 2018 10 3;8(10):e021203. Epub 2018 Oct 3.

Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland.

Objectives: Despite HIV testing recommendations published by the Federal Office of Public Health (FOPH) since 2007, many individuals living with HIV are diagnosed late in Switzerland. The aim of this study is to examine the effect of the 2013 FOPH HIV testing recommendations on HIV testing rates.

Setting: Ten clinical services at Lausanne University Hospital, Lausanne, Switzerland.

Participants: Patients attending between 1 January 2012 and 31 December 2015.

Design: Retrospective analysis using two existing hospital databases. HIV testing rates calculated as the percentage of tests performed (from the Immunology Service database) per number of patients seen (from the central hospital database).

Primary And Secondary Outcome Measures: The primary outcome was testing rate change following the 2013 FOPH testing recommendations, comparing testing rates 2 years before and 2 years after their publication. Secondary outcomes were demographic factors of patients tested or not tested for HIV.

Results: 147 884 patients were seen during the study period of whom 9653 (6.5%) were tested for HIV, with 34 new HIV diagnoses. Mean testing rate increased from 5.6% to 7.8% after the recommendations (p=0.001). Testing rate increases were most marked in services involved in clinical trials on HIV testing, whose staff had attended training seminars on testing indications and practice. Testing rates were lower among older (aged >50 years), female and Swiss patients compared with younger, male and non-Swiss patients, both globally (p=0.001) and in specific clinical services.

Conclusions: This simple two-database tool demonstrates clinical services in which HIV testing practice can be optimised. Improved testing rates in services involved in clinical trials on testing suggest that local engagement complements the effect of national recommendations. While, overall, HIV testing rates increased significantly over time, testing rates were lower among patients with similar demographic profiles to individuals diagnosed late in Switzerland.
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http://dx.doi.org/10.1136/bmjopen-2017-021203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194398PMC
October 2018

Late Lyme neuroborreliosis with chronic encephalomyelitis.

Neurology 2018 09;91(13):627-628

From the Service of Neurology, Department of Clinical Neuroscience (I.B., R.D.P.), Department of Diagnostic and Interventional Radiology (V.D.), and Institute of Microbiology (P.M.), Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Switzerland.

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http://dx.doi.org/10.1212/WNL.0000000000006252DOI Listing
September 2018

Mouvements anormaux.

Rev Med Suisse 2018 Apr;14(604):867-868

Chef de service, Service de neurologie, HUG, Genève.

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April 2018

Efficacy of Natalizumab in Intermediate Uveitis Related to Multiple Sclerosis: A Case Report.

Klin Monbl Augenheilkd 2018 04 16;235(4):476-477. Epub 2018 Feb 16.

Department of Ophthalmology, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.

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http://dx.doi.org/10.1055/s-0043-124756DOI Listing
April 2018