Publications by authors named "Stéphane Kremer"

89 Publications

A covariate-constraint method to map brain feature space into lower dimensional manifolds.

Netw Neurosci 2021 1;5(1):252-273. Epub 2021 Mar 1.

Université Grenoble Alpes, CNRS, Inria, Grenoble, France.

Human brain connectome studies aim to both explore healthy brains, and extract and analyze relevant features associated with pathologies of interest. Usually this consists of modeling the brain connectome as a graph and using graph metrics as features. A fine brain description requires graph metrics computation at the node level. Given the relatively reduced number of patients in standard cohorts, such data analysis problems fall in the high-dimension, low-sample-size framework. In this context, our goal is to provide a machine learning technique that exhibits flexibility, gives the investigator an understanding of the features and covariates, allows visualization and exploration, and yields insight into the data and the biological phenomena at stake. The retained approach is dimension reduction in a manifold learning methodology; the originality is that the investigator chooses one (or several) reduced variables. The proposed method is illustrated in two studies. The first one addresses comatose patients; the second one compares young and elderly populations. The method sheds light on the differences between brain connectivity graphs using graph metrics and potential clinical interpretations of these differences.
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http://dx.doi.org/10.1162/netn_a_00176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935034PMC
March 2021

Inferior Colliculus's Hypermetabolism: A New Finding on Brain FDG PET and Perfusion MRI in a Patient With COVID-19.

Clin Nucl Med 2021 May;46(5):413-414

From the Service de Radiologie, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg.

Abstract: We present the case of a 64-year-old man presenting an episode of confusion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection with a positive oropharyngeal swab polymerase chain reaction test. He was hospitalized for dyspnea related to pneumonia demonstrated on chest CT. FDG PET performed after the confusion phase, but still in the COVID-19 (coronavirus disease 2019)-positive phase, showed high glucose metabolism of the inferior colliculi. Morphological MRI was normal. The first-pass perfusion MRI shows hyperperfusion of the inferior colliculi, corresponding to FDG PET hypermetabolism.
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http://dx.doi.org/10.1097/RLU.0000000000003592DOI Listing
May 2021

Ocular MRI Findings in Patients with Severe COVID-19: A Retrospective Multicenter Observational Study.

Radiology 2021 Feb 16:204394. Epub 2021 Feb 16.

From the Department of Neuroradiology, Rothschild Foundation Hospital, Paris, France (A.L., F.H.); Department of Neuroradiology, CHU Lyon, Lyon, France (F.C.); Department of Neuroradiology, CHU Strasbourg, Strasbourg, France (F.L., S.K.).

COVID-19 may affect various organs. This paper reports 9 patients (1/9 [11%] woman and 8/9 [89%] men, mean age 56 ± 13 years) with globe MRI abnormalities obtained from a multicenter cohort of 129 patients presenting with severe COVID-19 from March 4th to May 1st, 2020. 9/129 (7%) patients had one or several FLAIR-WI hyperintense nodules of the posterior pole of the globe. All patients had nodules in the macular region, 8/9 (89%) had bilateral nodules, 2/9 (22%) had nodules outside the macular region. Screening of these patients might improve the management of potentially severe ophthalmological manifestations of the virus. See also the editorial by Kirsch.
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http://dx.doi.org/10.1148/radiol.2021204394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887777PMC
February 2021

Acute-onset delirium in intensive care COVID patients: association of imperfect brain repair with foodborne micro-pollutants.

Eur J Neurol 2021 Feb 14. Epub 2021 Feb 14.

Plant Imaging and Mass Spectrometry, Institut de biologie moléculaire des plantes, CNRS, Strasbourg, France.

Background And Purpose: COVID-19 affects the brain in various ways, amongst which delirium is worrying. An assessment was made of whether a specific, long-lasting, COVID-19-related brain injury develops in acute respiratory distress syndrome patients after life-saving re-oxygenation.

Methods: Ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury and seven controls with non-COVID encephalopathy were studied. The assessment took place when the intractable delirium started at weaning off ventilation support. Brain magnetic resonance imaging (MRI) was performed followed by standard cerebrospinal fluid (CSF) analyses and assessment of CSF erythropoietin concentrations (as a marker for the assessment of tissue repair), and of non-targeted CSF metabolomics using liquid chromatography high resolution mass spectrometry.

Results: Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] vs. 9 [4.5; 12.5] days, p = 0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p = 0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter haemorrhages only in COVID+. In the latter, CSF erythropoietin concentration was lower (1.73 [1.6; 2.06] vs. 3.04 [2.9; 3.91] mIU/ml, p = 0.01), and CSF metabolomics indicated (a) increased compounds such as foodborne molecules (sesquiterpenes), molecules from industrialized beverages and micro-pollutants (diethanolamine); and (b) decreased molecules such as incomplete breakdown products of protein catabolism and foodborne molecules (glabridin). At 3-month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+.

Conclusions: Some COVID+ are at risk of a specific delirium. Imperfect brain repair after re-oxygenation and lifestyle factors might influence long-lasting brain injuries in a context of foodborne micro-pollutants.
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http://dx.doi.org/10.1111/ene.14776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014494PMC
February 2021

Cerebral vasculitis of medium-sized vessels as a possible mechanism of brain damage in COVID-19 patients.

J Neuroradiol 2020 Dec 16. Epub 2020 Dec 16.

Hôpitaux Universitaires de Strasbourg, Service d'imagerie 2, Hôpital de Hautepierre, Strasbourg, France; Engineering science, computer science and imaging laboratory (ICube), Integrative Multimodal Imaging in Healthcare, UMR 7357, University of Strasbourg-CNRS, Strasbourg, France. Electronic address:

Background And Purpose: Cerebral complications related to COVID-19 were recently reported, and the underlying mechanisms of brain damage remain uncertain, probably multifactorial. Among various hypotheses suggested, a possible vasculitis was issued but never confirmed. Herein, we aimed to describe brain MRIs focused on the intracranial vessel wall in a population of COVID-19 patients with neurologic manifestations.

Materials And Methods: Between March 1 and May 31, 2020, 69 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI allowing the study of the intracranial vessel wall at Strasbourg University hospitals and were retrospectively included. During the same period, 25 consecutive patients, without suspicion of SARS-CoV-2 infection, underwent a brain MRI urgently, with the same imaging protocols. A vasculitis seemed likely when imaging demonstrated vessel wall thickening with homogeneous and concentric enhancement.

Results: Among the 69 COVID-19 patients included, 11 (16%) presented arterial vessel wall thickening with homogeneous and concentric enhancement, compatible with cerebral vasculitis. These neuroimaging findings were not found among the 25 patients without SARS-CoV-2 infection, and the difference was statistically significant (p = 0.03). Middle cerebral arteries, basilar artery, and posterior cerebral arteries were the most frequent vessels involved. For nine of them, imaging demonstrated ischemic or hemorrhagic complications.

Conclusion: Cerebral vasculitis of medium-sized vessels seems to be one of the mechanisms at the origin of brain damage related to COVID-19.
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http://dx.doi.org/10.1016/j.neurad.2020.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833894PMC
December 2020

Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors.

Viruses 2020 12 2;12(12). Epub 2020 Dec 2.

Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization "blind spot" was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients' humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.
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http://dx.doi.org/10.3390/v12121380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761562PMC
December 2020

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
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http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

A case of acute disseminate encephalomyelitis after SARS-CoV-2 related acute respiratory distress syndrome.

J Neuroradiol 2020 Nov 18. Epub 2020 Nov 18.

Division of Cardiovascular Medicine, University Hospital of Strasbourg, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.neurad.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673217PMC
November 2020

Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses.

J Neurol 2020 Nov 21. Epub 2020 Nov 21.

Hôpitaux Universitaires de Strasbourg, Service d'imagerie 2, Hôpital de Hautepierre, 1 avenue Molière, 67200, Strasbourg, France.

Background And Purpose: During the COVID-19 outbreak, the presence of extensive white matter microhemorrhages was detected by brain MRIs. The goal of this study was to investigate the origin of this atypical hemorrhagic complication.

Methods: Between March 17 and May 18, 2020, 80 patients with severe COVID-19 infections were admitted for acute respiratory distress syndrome to intensive care units at the University Hospitals of Strasbourg for whom a brain MRI for neurologic manifestations was performed. 19 patients (24%) with diffuse microhemorrhages were compared to 18 control patients with COVID-19 and normal brain MRI.

Results: The first hypothesis was hypoxemia. The latter seemed very likely since respiratory failure was longer and more pronounced in patients with microhemorrhages (prolonged endotracheal intubation (p = 0.0002), higher FiO (p = 0.03), increased use of extracorporeal membrane oxygenation (p = 0.04)). A relevant hypothesis, the role of microangiopathy, was also considered, since patients with microhemorrhages presented a higher increase of the D-Dimers (p = 0.01) and a tendency to more frequent thrombotic events (p = 0.12). Another hypothesis tested was the role of kidney failure, which was more severe in the group with diffuse microhemorrhages (higher creatinine level [median of 293 µmol/L versus 112 µmol/L, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04]).

Conclusions: Blood-brain barrier dysfunction secondary to hypoxemia and high concentration of uremic toxins seems to be the main mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients.
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http://dx.doi.org/10.1007/s00415-020-10313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679237PMC
November 2020

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML.

Eur Radiol 2021 May 6;31(5):2944-2955. Epub 2020 Nov 6.

Hôpitaux Universitaires de Strasbourg, Service d'imagerie 2, Hôpital de Hautepierre, Strasbourg, France.

Objectives: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection.

Materials And Methods: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement.

Results: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response.

Conclusion: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML.

Key Points: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution "the milky way," and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
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http://dx.doi.org/10.1007/s00330-020-07362-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644389PMC
May 2021

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients.

Crit Care 2020 08 8;24(1):491. Epub 2020 Aug 8.

Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, 1, place de l'Hôpital, F-67091, Strasbourg, Cedex, France.

Background: Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients.

Methods: We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms.

Results: The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2.

Conclusions And Relevance: Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources.

Trial Registration: NA.
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http://dx.doi.org/10.1186/s13054-020-03200-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414289PMC
August 2020

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

Neurology 2020 09 17;95(13):e1868-e1882. Epub 2020 Jul 17.

From the Hôpitaux Universitaires de Strasbourg (S.K., F.L., S.B., F.-D.A., T.W.), Service d'imagerie 2, Hôpital de Hautepierre; Engineering Science, Computer Science and Imaging Laboratory (S.K., N.M.), UMR 7357, University of Strasbourg-CNRS; Service de Neurologie (M. Anheim), Hôpitaux Universitaires de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (M. Anheim), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Fédération de Médecine Translationnelle de Strasbourg (M. Anheim), Université de Strasbourg; Hôpitaux universitaires de Strasbourg (H.M., F.M., J.H.), Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil; INSERM (French National Institute of Health and Medical Research) (H.M., F.M.), UMR 1260, Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg; Médecine Intensive-Réanimation (M.S., F.S.), Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg; Service de Neuroradiologie (H.O., F.B., J.M.), Hôpitaux Civils de Colmar; Service d'Imagerie (A. Khalil, A.G.), Unité de Neuroradiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard; Université Paris Diderot (A. Khalil), Paris; Service de Neurologie (S. Carré, C.L.), Centre Hospitalier de Haguenau; Service de Radiologie (M. Alleg), Centre Hospitalier de Haguenau; Service de Neuroradiologie, (E.S., R.A., F.Z.) Hôpital Central, CHU de Nancy; CHIC Unisanté (L.J., P.N., Y.T.M.), Hôpital Marie Madeleine, Forbach; Neuroimaging Department (G.H., J. Benzakoun, C.O., G. Boulouis, M.E.-G., B.K.), GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Université de Paris, INSERM U1266, F-75014; CHU Rennes (J.-C.F., B.C.-N.), Department of Neuroradiology; CHU Rennes (A.M.), Medical Intensive Care Unit; Department of Neuroradiology (P.-O.C., F.R., P.T.), University Hospital of Dijon, Hôpital François Mitterrand; Service de Radiologie (C.B.), CHU de Saint-Etienne; Service de Réanimation (X.F.), CH de Roanne; Service de Neuroradiologie (G.F., S.S.), CHU de Limoges; Radiology Department (I.d.B., G. Bornet), Hôpital Privé d'Antony; Department of Diagnostic and Interventional Neuroradiology (H.D.), University Hospital, Nantes; Neuroradiology Department (J. Berge), CHU de Bordeaux; Service de Neuroradiologie (A. Kazémi), CHU de Lille; Assistance Publique Hôpitaux de Paris (N.P.), Service de Neuroradiologie, Hôpital Pitié-Salpêtrière; Sorbonne Université (N.P.), Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013; Service de Neuroradiologie Diagnostique (A.L.), Foundation A. Rothschild Hospital, Paris; EA CHIMERE 7516 (J.-M.C.), Université de Picardie Jules Verne; Service de NeuroRadiologie, pôle Imagerie Médicale, Centre Hospitalo-Universitaire d'Amiens; Hôpitaux Universitaires de Strasbourg (P.-E.Z., M.M.), UCIEC, Pôle d'Imagerie, Strasbourg; Observatoire Français de la Sclérose en Plaques (J.-C.B.), Lyon; Nephrology and Transplantation Department (S. Caillard), Hôpitaux Universitaires de Strasbourg; Inserm UMR S1109 (S. Caillard), LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; Hôpitaux Universitaires de Strasbourg (O.C., P.M.M.), Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil; Hôpitaux Universitaires de Strasbourg (S.F.-K.), Laboratoire de Virologie Médicale; Radiology Department (M.O.), Nouvel Hôpital Civil, Strasbourg University Hospital; CHU de Strasbourg (N.M.), Service de Santé Publique, GMRC, F-67091 Strasbourg; Immuno-Rhumatologie Moléculaire (S.F.-K., J.H.), INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; MRI Center (F.C.), Centre Hospitalier Lyon Sud, Hospices Civils de Lyon; and Université Lyon 1 (F.C.), CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Objective: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.

Methods: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.

Results: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome ( = 0.006) and more frequently had corticospinal tract signs ( = 0.02). Patients with encephalitis were younger ( = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement ( = 0.009).

Conclusions: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.

Clinicaltrialsgov Identifier: NCT04368390.
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http://dx.doi.org/10.1212/WNL.0000000000010112DOI Listing
September 2020

Coronavirus Disease 2019: Associated Multiple Organ Damage.

Open Forum Infect Dis 2020 Jul 21;7(7):ofaa249. Epub 2020 Jun 21.

Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2.
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http://dx.doi.org/10.1093/ofid/ofaa249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336548PMC
July 2020

Signal changes in enhanced T1-weighted images related to gadolinium retention: A three-time-point imaging study.

J Neuroradiol 2021 Mar 30;48(2):82-87. Epub 2020 Jun 30.

Service de Radiologie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, 1 Avenue Molière, 67200 Strasbourg Cedex, France. Electronic address:

Background And Purpose: Concern has grown about the finding of gadolinium deposits in the brain after administering gadolinium-based contrast agents (GBCAs). The mechanism is unclear, and related questions remain unanswered, including the stability over time. Therefore, we conducted a three-time-point study to explore T1-weighted (W) signal changes in the dentate nucleus (DN) and globus pallidus (GP), after the first, fifth, and tenth injections of either a macrocyclic agent (gadoterate meglumine) or a linear agent (gadobenate dimeglumine).

Materials And Methods: For this retrospective, multicenter, longitudinal study, two groups of 18 (gadoterate meglumine) and 19 (gadobenate dimeglumine) patients were identified. The evolution of the signal over time was analyzed using DN/pons (DN/P) and GP/thalamus (GP/T) ratios.

Results: DN/P and GP/T ratios tended to increase after the fifth administration of gadobenate dimeglumine, following by a downward trend. A trend in a decrease in DN/P and GP/T ratios were found after the fifth and tenth administrations of gadoterate meglumine.

Conclusion: After exposure to gadobenate dimeglumine, the signal intensity (SI) tended to increase after the fifth injection owing to gadolinium accumulation, however, a SI increase was not found after the tenth administration supporting the hypothesis of a slow elimination of the previously retained gadolinium (wash-out effect) from the brain or of a change in form (by dechelation), causing the signal to fade. No increasing SI was found in the DN and GP after exclusive exposure to gadoterate meglumine, thus confirming its stability. We found, instead, a trend for a significative gadolinium elimination over time.
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http://dx.doi.org/10.1016/j.neurad.2020.06.002DOI Listing
March 2021

Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology.

J Neuroradiol 2020 Nov 18;47(6):441-449. Epub 2020 Jun 18.

MRI center, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France; Université Lyon 1, CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.
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http://dx.doi.org/10.1016/j.neurad.2020.05.008DOI Listing
November 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

More on Neurologic Features in Severe SARS-CoV-2 Infection. Reply.

N Engl J Med 2020 06 26;382(26):e110. Epub 2020 May 26.

University of Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1056/NEJMc2015132DOI Listing
June 2020

New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions.

J Neuroradiol 2020 Jun 31;47(4):250-258. Epub 2020 Jan 31.

MRI center, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France; Observatoire Français de la Sclérose en Plaques, Lyon, France; Université Lyon 1, CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Purpose: New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients' quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.

Methods: A consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up.

Recommendations: The French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re-baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences.
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http://dx.doi.org/10.1016/j.neurad.2020.01.083DOI Listing
June 2020

Tumefactive inflammatory leukoencephalopathy in cocaine users: Report of three cases.

Mult Scler Relat Disord 2020 Feb 4;38:101496. Epub 2019 Nov 4.

Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address:

Background: Cocaine is the most common illicit stimulant drug used in Europe, and it can potentially affect the central nervous system due to a direct effect, or by means of additive drugs. Levamisole has been increasingly used as an additive drug since it extends the stimulating effects of cocaine. This has led to an increase in the detection of levamisole adverse reactions, including levamisole-induced multifocal inflammatory leukoencephalopathy (MIL), a potentially lethal monophasic cerebral demyelinating disease.

Methods: We present three adult patients who developed a MIL with tumefactive demyelinating lesions, leading to encephalopathy and motor manifestations. All these patients had in common a history of chronic or acute use of cocaine. Imaging findings revealed a tumefactive MIL, following a Balo's Concentric Sclerosis (BCS) pattern in two cases.

Results: The pathophysiology of levamisole-induced MIL may depend on an immunological mechanism, producing multiple demyelinating lesions affecting the subcortical and periventricular white matter, basal ganglia and/or brainstem. Atypical demyelinating lesions are an unusual finding in levamisole-induced MIL. Specifically, the BCS pattern is a rare finding in these patients: to our knowledge, only two more cases mimicking BCS have been reported in the literature, which have also occurred in chronic cocaine users.

Conclusions: Based on the history and images of our patients and other two similar case reports, we suggest a probable pathophysiological relationship between levamisole-adulterated cocaine use and the occurrence of MIL with atypical demyelinating lesions, even when they present following a BCS imaging pattern.
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http://dx.doi.org/10.1016/j.msard.2019.101496DOI Listing
February 2020

Contrast-to-Dose Relationship of Gadopiclenol, an MRI Macrocyclic Gadolinium-based Contrast Agent, Compared with Gadoterate, Gadobenate, and Gadobutrol in a Rat Brain Tumor Model.

Radiology 2020 01 29;294(1):117-126. Epub 2019 Oct 29.

From the Department of Research and Innovation, Imaging and Biological Research Division, Guerbet Group, BP57400, 95943 Roissy CDG, France (P.R., V.V., A.L.G., G.L., S.B., C.C.); and Radiologie 2, CHU de Strasbourg, I-Cube, Université de Strasbourg, Strasbourg, France (S.K., G.B.).

Background Detection of cerebral lesions at MRI may benefit from a chemically stable and more sensitively detected gadolinium-based contrast agent (GBCA). Gadopiclenol, a macrocyclic GBCA with at least twofold higher relaxivity, is currently undergoing clinical trials in humans. Purpose To determine the relationship between MRI contrast enhancement and the injected dose of gadopiclenol in a glioma rat model compared with those of conventional GBCA at label dose. Materials and Methods Between April and July 2012, 32 rats implanted with C6 glioma received two intravenous injections at a 24-hour interval. The injections were randomly selected among five doses of gadopiclenol (0.025, 0.05, 0.075, 0.1, and 0.2 mmol/kg) and three reference GBCAs (gadoterate meglumine, gadobutrol, and gadobenate dimeglumine) at 0.1 mmol/kg. MRI tumor enhancement was assessed on T1-weighted images before and up to 30 minutes after injection. Two blinded radiologists visually and qualitatively scored contrast enhancement, border delineation, and visualization of tumor morphology. Quantitatively, variations in contrast-to-noise ratio (ΔCNR) between tumor and contralateral parenchyma were calculated at each time point and were compared for each treatment at 5 minutes by using a mixed model after normality test. Results A total of 24 rats underwent the complete protocol ( = 5-7 per group). A linear dose-dependent ΔCNR relationship was observed between 0.025 and 0.1 mmol/kg for gadopiclenol ( = 0.99). No difference in ΔCNR was observed between the three reference GBCAs ( ≥ .55). Gadopiclenol resulted in twofold higher ΔCNR at 0.1 mmol/kg ( < .001 vs gadobutrol and gadoterate, = .002 vs gadobenate) and similar ΔCNR at 0.05 mmol/kg ( = .56, > .99, and = .44 compared with gadobutrol, gadobenate, and gadoterate, respectively). For both readers, 0.05 mmol/kg of gadopiclenol improved contrast enhancement, border delineation, and visualization of tumor morphology (scores > 3 compared with scores between 2 and 3 for the marketed GBCA). Conclusion Gadopiclenol at 0.05 mmol/kg yielded comparable change in contrast-to-noise ratio and morphologic characterization of brain tumors compared with gadobenate, gadoterate, or gadobutrol at 0.1 mmol/kg. Published under a CC BY 4.0 license. See also the editorial by Tweedle in this issue.
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http://dx.doi.org/10.1148/radiol.2019182953DOI Listing
January 2020

Mutations in KARS cause a severe neurological and neurosensory disease with optic neuropathy.

Hum Mutat 2019 10 18;40(10):1826-1840. Epub 2019 Jun 18.

Laboratoire de Génétique Médicale, INSERM U1112, Institut de Génétique Médicale d'Alsace, Université de Strasbourg, Strasbourg, France.

Mutations in genes encoding aminoacyl-tRNA synthetases have been reported in several neurological disorders. KARS is a dual localized lysyl-tRNA synthetase and its cytosolic isoform belongs to the multiple aminoacyl-tRNA synthetase complex (MSC). Biallelic mutations in the KARS gene were described in a wide phenotypic spectrum ranging from nonsyndromic deafness to complex impairments. Here, we report on a patient with severe neurological and neurosensory disease investigated by whole-exome sequencing and found to carry biallelic mutations c.683C>T (p.Pro228Leu) and c.871T>G (p.Phe291Val), the second one being novel, in the KARS gene. The patient presented with an atypical clinical presentation with an optic neuropathy not previously reported. At the cellular level, we show that cytoplasmic KARS was expressed at a lower level in patient cells and displayed decreased interaction with MSC. In vitro, these two KARS variants have a decreased aminoacylation activity compared with wild-type KARS, the p.Pro228Leu being the most affected. Our data suggest that dysfunction of cytoplasmic KARS resulted in a decreased level of translation of the nuclear-encoded lysine-rich proteins belonging to the respiratory chain complex, thus impairing mitochondria functions.
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http://dx.doi.org/10.1002/humu.23799DOI Listing
October 2019

Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions.

J Neurol 2019 Jul 23;266(7):1743-1755. Epub 2019 Apr 23.

Department of Radiology, Strasbourg University Hospital, Strasbourg, France.

Background: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear.

Objectives: Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions.

Methods: We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed.

Results: Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1-12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD.

Discussion: Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
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http://dx.doi.org/10.1007/s00415-019-09328-7DOI Listing
July 2019

Diffusion tensor imaging reveals diffuse white matter injuries in locked-in syndrome patients.

PLoS One 2019 10;14(4):e0213528. Epub 2019 Apr 10.

Service d'imagerie 2, Hopitaux Universitaires de Strasbourg, Strabourg, France.

Locked-in syndrome (LIS) is a state of quadriplegia and anarthria with preserved consciousness, which is generally triggered by a disruption of specific white matter fiber tracts, following a lesion in the ventral part of the pons. However, the impact of focal lesions on the whole brain white matter microstructure and structural connectivity pathways remains unknown. We used diffusion tensor magnetic resonance imaging (DT-MRI) and tract-based statistics to characterise the whole white matter tracts in seven consecutive LIS patients, with ventral pontine injuries but no significant supratentorial lesions detected with morphological MRI. The imaging was performed in the acute phase of the disease (26 ± 13 days after the accident). DT-MRI-derived metrics were used to quantitatively assess global white matter alterations. All diffusion coefficient Z-scores were decreased for almost all fiber tracts in all LIS patients, with diffuse white matter alterations in both infratentorial and supratentorial areas. A mixture model of two multidimensional Gaussian distributions was fitted to cluster the white matter fiber tracts studied in two groups: the least (group 1) and most injured white matter fiber tracts (group 2). The greatest injuries were revealed along pathways crossing the lesion responsible for the LIS: left and right medial lemniscus (98.4% and 97.9% probability of belonging to group 2, respectively), left and right superior cerebellar peduncles (69.3% and 45.7% probability) and left and right corticospinal tract (20.6% and 46.5% probability). This approach demonstrated globally compromised white matter tracts in the acute phase of LIS, potentially underlying cognitive deficits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213528PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457498PMC
December 2019

Resting-state functional MRI demonstrates brain network reorganization in neuromyelitis optica spectrum disorder (NMOSD).

PLoS One 2019 29;14(1):e0211465. Epub 2019 Jan 29.

Department of radiology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: The relation between brain functional connectivity of patients with neuromyelitis optica spectrum disorder (NMOSD) and the degree of disability remains unclear.

Objective: Compare brain functional connectivity of patients with NMOSD to healthy subjects in resting-state functional MRI (rs-fMRI).

Methods: We compared the rs-fMRI connectivity in 12 NMOSD patients with 20 healthy subjects matched for age and sex. Graph theory analysis was used to quantify the role of each node using a set of metrics: degree, global efficiency, clustering and modularity. To summarize the abnormal connectivity profile of brain regions in patients compared to healthy subjects, we defined a hub disruption index κ.

Results: Concerning the global organization of networks in NMOSD, a small-world topology was preserved without significant modification concerning all average metrics. However, visual networks and the sensorimotor network showed decreased connectivity with high interindividual variability. The hub disruption index κ was correlated to the Expanded Disability Status Scale (EDSS).

Conclusion: These results demonstrate a correlation between disability according to the EDSS and neuronal reorganization using the rs-fMRI graph methodology. The conservation of a normal global topological structure despite local modifications in functional connectivity seems to show brain plasticity in response to the disability.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211465PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351056PMC
November 2019

Beam hardening artifacts of liquid embolic agents: comparison between Squid and Onyx.

J Neurointerv Surg 2019 Jul 19;11(7):706-709. Epub 2018 Dec 19.

Interventional Neuroradiology Department, Strasbourg University Hospitals, Strasbourg, France.

Background: Initial clinical experience with Squid shows subjectively reduced artifacts on post-embolization CT scans compared with Onyx. To further investigate these observations, we aimed to perform a comparison of artifacts between Squid and Onyx in a controlled in vitro model.

Materials And Methods: Onyx 18 and all four variants of Squid (Squid 18, Squid 18 low density (LD), Squid 12, Squid 12 LD) were each injected in dimethylsulfoxide (DMSO) compatible test tubes. The tubes containing precipitated embolic material were inserted in a CT phantom for conventional and flat panel CT acquisitions. Beam hardening artifacts were quantified using objective and subjective measurements.

Results: Objective evaluation of artifacts within regions of interest (ROIs) placed around the embolic material on CT and flat panel CT images demonstrated significantly lower noise and Hounsfield unit (HU) range values for all four Squid products compared with Onyx 18. On both CT and flat panel CT, LD variants of Squid 18 and Squid 12 had significantly lower noise and HU range values than their normal density counterparts on longitudinal ROIs. When using subjective measures for diagnostic value within ROIs placed around the embolic material on both CT and flat panel CT images, the number of non-diagnostic ROIs was significantly higher for Onyx 18 than for all four Squid variants.

Conclusion: All four variants of Squid induced fewer beam hardening artifacts than Onyx 18 on CT and flat panel CT acquisitions. LD variants of Squid induced fewer artifacts than their normal density counterparts.
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http://dx.doi.org/10.1136/neurintsurg-2018-014542DOI Listing
July 2019

Occult Cerebral Abscess Revealed by FDG PET/CT in a Case of Unresponsive Wakefulness Syndrome.

Clin Nucl Med 2019 Jan;44(1):57-58

Service de Réanimation Chirurgicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

A 51-year-old woman developed profound coma complicating subarachnoid hemorrhage after aneurysmal rupture. An external ventricular drain was inserted. FDG PET/CT was performed for prognostication purposes and showed global cortical hypometabolism. This was consistent with the clinical findings of an unresponsive wakefulness syndrome. During the follow-up, ventriculitis was diagnosed. Because of no clinical improvement under focused, high-dose antimicrobial treatment, a second FDG PET/CT was performed. It showed an improved diffuse cortical fixation and an intense intraventricular hyperfixation, suggestive of intraventricular abscess. A third functional imaging, performed to monitor treatment, showed progressive metabolic recovery with especially uptake in frontoparietal areas over time.
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http://dx.doi.org/10.1097/RLU.0000000000002335DOI Listing
January 2019

Imaging spectrum of Bing-Neel syndrome: how can a radiologist recognise this rare neurological complication of Waldenström's macroglobulinemia?

Eur Radiol 2019 Jan 19;29(1):102-114. Epub 2018 Jun 19.

From the 2nd Radiology Department, University Hospital of Strasbourg, Avenue Molière 1, 67098, Strasbourg, France.

Objectives: Bing-Neel syndrome (BNS) is a rare neurological complication of Waldenström's macroglobulinemia. The aim of this study is to describe the spectrum of radiological manifestations of this syndrome and their prevalence in order to facilitate its early diagnosis.

Methods: Twenty-four patients with BNS were diagnosed between 1994 and 2016 in eight centres in France. We retrospectively examined the medical records of these patients as well as the corresponding literature, focusing on imaging studies. Recorded data were statistically analysed and radiological findings described.

Results: The mean age of our patients was 62.4 years (35-80 years). The vast majority of patients were men, with a male to female ratio of 9:1. Findings included parenchymal or meningeal involvement or both. The most common finding was leptomeningeal infiltration, either intracranial or spinal, with a prevalence reaching 70.8%. Dural involvement was present in 37.5% of patients. In 41.7% (10/24) of patients, there was parenchymal involvement with a higher prevalence of brain comparing to medullar involvement (33.3% and 23.1% respectively). High T2 signal of the parenchyma was identified in 41.7% of patients and high signal in diffusion was evident in 25% of them. Intraorbital or periorbital involvement was also detected in four cases. A proposition regarding the appropriate imaging protocol completed our study.

Conclusion: BNS's diagnosis remains challenging. Central nervous system MRI findings in the setting of known or suspected Waldenström's macroglobulinemia appear to be highly suggestive of BNS and appropriate imaging protocols should be implemented for their depiction.

Key Points: • Diagnosis of Bing-Neel syndrome (BNS) remains challenging and recent expert recommendations include MRI in the diagnostic criteria for the syndrome. • The most common radiological manifestations of BNS are leptomeningeal/dural infiltration or parenchymal involvement of brain or spinal cord, but many atypical forms may exist with various presentations. • Appropriate imaging protocol for BNS should include enhanced MRI studies of both brain and spine.
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http://dx.doi.org/10.1007/s00330-018-5543-7DOI Listing
January 2019

Pre- and post-surgery MRSI predictive value in adult oligodendroglioma prognosis.

Magn Reson Imaging 2018 10 11;52:75-83. Epub 2018 Jun 11.

Service de Biophysique et Médecine Nucléaire, Hôpitaux Universitaires de Strasbourg, France; ICube, Université de Strasbourg/CNRS (UMR 7357), Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de Médecine, Strasbourg, France.

Purpose: The aim of this study was to study the relationship between MRSI, before and after surgery, and patient survival. The accuracy of pre-operative MRSI in differentiating low- from high-grade oligodendrogliomas (ODGs) was also studied.

Methods: Two hundred patients with ODG were retrospectively included in this study between 2000 and 2016. All patients underwent MRSI before any treatment or biopsy and/or after surgery for an intra-axial brain tumour. The R software was used for statistical data analysis. p < 0.05 was considered statistically significant. Kaplan-Meier curves were calculated for patients with low-grade ODG and high-grade ODG pre- and post-operatively, to study survival (overall survival, OS). The best threshold of each MRSI metabolite ratio was obtained using receiver operating characteristic curves (ROCs).

Results: One hundred patients underwent pre-operative MRSI and 170 post-operative MRSI. N-acetylaspartate (NAA), lactate (Lac), choline (Cho) and creatine (Cr) were measured. Kapan-Meier curves showed that survival was poorer for a nCho/Cr > 3.02 in the pre-operative and nCho/Cr > 2.04, Lac/Cr > 0.743 and nCho/NAA > 3.63 in the post-operative period. Post-operative MRSI predicts survival better than pre-operative MRSI. nCho/Cr and Lac/Cr distinguished low- from high-grade ODG with a good positive predictive value.

Conclusion: MRSI is associated with survival. It is a non-invasive tool which completes histopathology and can predict patients' prognosis, thus improving patient management.
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http://dx.doi.org/10.1016/j.mri.2018.06.007DOI Listing
October 2018

Case 254: Posttraumatic Migrating Fat Embolus Causing Fat Emboli Syndrome.

Radiology 2018 Jun;287(3):1073-1080

From the Department of Radiology, University Hospital of Strasbourg, 1 Avenue Molière, F-67098 Strasbourg, France (S.M., S.K., G.B.); and ICube Laboratory, University of Strasbourg, Strasbourg, France (S.K., G.B.).

History An otherwise healthy 18-year-old man was admitted to the emergency department with a closed displaced fracture of the left femoral shaft ( Fig 1 ) after a high-velocity motorbike accident. At admission, other physical examination findings were unremarkable. Initial unenhanced and contrast material-enhanced (120 mL of Iomeron 400; Bracco Imaging, Milan, Italy) computed tomography (CT) was performed in the arterial and venous phases from the head to the knees. No abnormalities were noted in the brain or chest at initial CT. [Figure: see text] Within a few hours, the patient developed sudden mental confusion and severe hypoxemia, with rapidly worsening tachypnea and perturbed arterial blood gas with low partial pressure of oxygen (61 mmHg [8.1 kPa]; normal range, 75-100 mmHg [10.0-13.3 kPa]) and low partial pressure of carbon dioxide (32 mmHg [4.3 kPa]; normal range, 38-42 mmHg [5.1-5.6 kPa]). A second contrast-enhanced chest CT examination and initial brain magnetic resonance (MR) imaging were performed. Femoral fracture was stabilized with external fixation, and the patient was admitted to the intensive care unit, with progressive neurologic recovery at day 3 and respiratory improvement at day 4. Treatment included intubation with mechanical ventilation and intravenous administration of steroids and noradrenaline. Afterward, the femoral fracture was stabilized with an intramedullary nail. The patient made a full neurologic recovery 1 month after the accident.
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http://dx.doi.org/10.1148/radiol.2018160233DOI Listing
June 2018