Publications by authors named "Damien Galanaud"

107 Publications

Simultaneously acquired PET and ASL imaging biomarkers may be helpful in differentiating progression from pseudo-progression in treated gliomas.

Eur Radiol 2021 Mar 31. Epub 2021 Mar 31.

Service de Neuroradiologie Diagnostique et Fonctionnelle, Groupe Hospitalier Pitié-Salpêtrière C. Foix, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.

Objectives: The aim of this work was investigating the methods based on coupling cerebral perfusion (ASL) and amino acid metabolism ([F]DOPA-PET) measurements to evaluate the diagnostic performance of PET/MRI in glioma follow-up.

Methods: Images were acquired using a 3-T PET/MR system, on a prospective cohort of patients addressed for possible glioma progression. Data were preprocessed with statistical parametric mapping (SPM), including registration on T1-weighted images, spatial and intensity normalization, and tumor segmentation. As index tests, tumor isocontour maps of [F]DOPA-PET and ASL T-maps were created and metabolic/perfusion abnormalities were evaluated with the asymmetry index z-score. SPM map analysis of significant size clusters and semi-quantitative PET and ASL map evaluation were performed and compared to the gold standard diagnosis. Lastly, ASL and PET topography of significant clusters was compared to that of the initial tumor.

Results: Fifty-eight patients with unilateral treated glioma were included (34 progressions and 24 pseudo-progressions). The tumor isocontour maps and T-maps showed the highest specificity (100%) and sensitivity (94.1%) for ASL and [F]DOPA analysis, respectively. The sensitivity of qualitative SPM maps and semi-quantitative rCBF and rSUV analyses were the highest for glioblastoma.

Conclusion: Tumor isocontour T-maps and combined analysis of CBF and [F]DOPA-PET uptake allow achieving high diagnostic performance in differentiating between progression and pseudo-progression in treated gliomas. The sensitivity is particularly high for glioblastomas.

Key Points: • Applied separately, MRI and PET imaging modalities may be insufficient to characterize the brain glioma post-therapeutic profile. • Combined ASL and [F]DOPA-PET map analysis allows differentiating between tumor progression and pseudo-progression.
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http://dx.doi.org/10.1007/s00330-021-07732-0DOI Listing
March 2021

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.

JAMA Netw Open 2021 03 1;4(3):e211489. Epub 2021 Mar 1.

Sorbonne Université, Paris Brain Institute, Institut du Cerveau, Institut National de la Santé et de la Recherche Médicale U 1127, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7225, Paris, France.

Importance: There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management.

Objectives: To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19-related encephalopathy.

Design, Setting, And Participants: This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020.

Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest.

Main Outcomes And Measures: Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records.

Results: Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter-enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions.

Conclusions And Relevance: The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19-related encephalopathy and guide treatment strategy.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.1489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961310PMC
March 2021

Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: a new gold standard?

J Neurol 2021 Jan 30. Epub 2021 Jan 30.

Sorbonne Université, AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière Charles Foix, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Service de Maladies Infectieuses et Tropicales, INSERM 1136, 47-83 Bd de l'Hôpital, 75651, Paris Cedex, France.

Objectives: Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML.

Methods And Results: We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14-33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML.

Conclusions: Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
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http://dx.doi.org/10.1007/s00415-021-10414-yDOI Listing
January 2021

Global mean diffusivity: A radiomarker discriminating good outcome long term after traumatic brain injury.

Ann Phys Rehabil Med 2021 Mar 8;64(2):101433. Epub 2021 Feb 8.

AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, Neurosurgical Department, NeuroIntensive Care Unit, Paris, France; Sorbonne Université, Groupe de Recherche Clinique Biosfast, Paris, France.

Background: Traumatic brain injury (TBI) is a chronic pathology responsible for cognitive disorders impacting outcome. Global clinical outcome several years after TBI may be associated with anatomical sequelae. Anatomical lesions are not well described because characterizing diffuse axonal injury and brain atrophy require using specific MRI sequences with quantitative measures. The best radiologic parameter to describe the lesions long term after TBI is not known.

Objective: We aimed to first, assess the global volumetric and diffusion parameters related to long-term outcome after TBI and second, define the most discriminating parameter.

Methods: In this observational study, we included 96 patients with severe TBI and 22 healthy volunteers. The mean delay after TBI was 63.2 months [range 31-119]. The Glasgow Outcome Scale Extended (GOS-E) was used to assess the global long-term clinical outcome. All patients underwent multimodal MRI with measures of brain volume, ventricle volume, global fractional anisotropy (FA) and global mean diffusivity (MD).

Results: All 96 participants had significant impairment in global FA, global MD, brain volume and ventricle volume as compared with the 22 controls (P<0.01). Only global MD significantly differed between the "good recovery" group (GOS-E score 7-8) and the other two groups: GOS-E scores 3-4 and 5-6. Brain volume significantly differed between the GOS-E 7-8 and 3-4 groups. Global MD was the most discriminating radiological parameter for the "good recovery" group versus other patients, long term after TBI. FA appeared less relevant at this time. Global atrophy was higher in patients than controls but lacked reliability to discriminate groups of patients.

Conclusion: Global mean diffusivity seems a more promising radiomarker than global FA for discriminating good outcome long term after TBI. Further work is needed to understand the evolution of these long-term radiological parameters after TBI.
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http://dx.doi.org/10.1016/j.rehab.2020.08.002DOI Listing
March 2021

Central nervous system involvement in Erdheim-Chester disease: An observational cohort study.

Neurology 2020 11 4;95(20):e2746-e2754. Epub 2020 Sep 4.

From Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares et Histiocytoses (F.C.A., Z.A., J.H.), Service de Neuroradiologie (D.G., B.L.-Y.), Service d'Anatomopathologie (F.C.), Service de Médecine Nucléaire (P.M.), Service de Neuropathologie (D.S.), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne Université; Service de Neurologie 2-Mazarin (A.I., K.H.-Z.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Sorbonne Université, Paris; Département de Pathologie (J.-F.E.), EA4340, Université Versailles-Saint Quentin, Assistance Publique Hôpitaux de Paris, Hôpital Ambroise Paré, Boulogne; and Service d'Hématologie Pédiatrique, Centre de Référence National Histiocytoses (J.D.), Hôpital Trousseau, Sorbonne Université, Paris, France.

Objective: CNS involvement in Erdheim-Chester disease (ECD) leads to substantial morbidity and mortality. To assess CNS manifestations in a French cohort of 253 patients with ECD, we determined clinical characteristics and outcomes, including those under targeted therapies.

Methods: This was a retrospective longitudinal study. CNS manifestations were determined by clinical examination and brain or spine MRI. Targeted therapy efficacy was assessed using global assessment from a physician and a radiologist. The study was approved by the ethics committee Comité de Protection des Personnes Ile de France III.

Results: Ninety-seven of 253 patients (38%) with ECD had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptom onset (mean 50.5 years), as well as with the presence of the mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than that of patients with ECD without CNS involvement (124 months vs 146 months, = 0.03). Seventy-four CNS MRIs were centrally reviewed, which showed 3 patterns: tumoral in 66%, pseudo-degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF or MEK inhibitors) was associated with improved symptoms in 43% of patients and MRI improvement in 45%.

Conclusions: CNS manifestations are typically associated with poor prognosis in patients with ECD. Three distinct patterns can be recognized: tumoral, pseudodegenerative, and vascular.

Classification Of Evidence: This study provides Class III evidence that targeted therapy leads to clinical or imaging improvement in almost 50% of patients.
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http://dx.doi.org/10.1212/WNL.0000000000010748DOI Listing
November 2020

Retrospective Observational Study of Brain MRI Findings in Patients with Acute SARS-CoV-2 Infection and Neurologic Manifestations.

Radiology 2020 12 17;297(3):E313-E323. Epub 2020 Jul 17.

From the Sorbonne Université, Inserm, CNRS, Institut du Cerveau-Paris Brain Institute (ICM), F-75013 Paris, France (L.C., D.G., B.M., C.R., D.D., J.C.C., S.L., N.P.); Sorbonne Université, INSERM 75013 Paris, France (L.C., N.S., N.W., D.G., B.M., S. Burrel, D.B., A.D., C.R., D.S., D.D., E.M., M.R., T.S., V.D., J.C.C., S.L., N.P.); Paris Brain Institute - ICM, Movement Investigations and Therapeutics Team (MOV'IT), Paris, France (L.C., S.L., N.P.); ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France (L.C., D.G., S.L., N.P.); Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Neuroradiologie (L.C., N.S., D.G., D.L., S. Belkacem, S.S., D.D., S.G., S.T., S.L., N.P.), Médecine Intensive Réanimation Neurologique (N.W.), Service de Neurochirurgie (B.M.), Service de Virologie, Centre d'Investigation Clinique Neurosciences (S. Burrel, D.B.), Service de Pneumologie, Médecine Intensive et Réanimation (A.D., E.M., T.S.), Urgences Cérébro-Vasculaires (C.R.), Département de Neurologie, Centre d'Investigation Clinique Neurosciences (C.D., J.C.C.), Département de Neuropathologie (D.S.), Department of Anesthesia, Critical Care and Peri-Operative Medicine (M.R., V.D.), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, INSERM UMR S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (N.W., S.D.); CNR Herpèsvirus (laboratoire associé HSV), SU-INSERM UMR_S 1136 Team 3 THERAVIR IPLESP (S. Burrel, D.B.); ICM, Stroke Network, STAR Team, Paris, France (C.R.); Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière,; ICM, INRIA, ARAMIS project-team, Paris, France (D.D., M.R.); Clinical Research Group ARPE, Sorbonne University, Paris, France (V.D.); INSERM UMR 1141, Paris France (V.D.); and Assistance Publique Hôpitaux de Paris, DMU ESPRIT, Paris, France (P.R.).

Background This study provides a detailed imaging assessment in a large series of patients infected with coronavirus disease 2019 (COVID-19) and presenting with neurologic manifestations. Purpose To review the MRI findings associated with acute neurologic manifestations in patients with COVID-19. Materials and Methods This was a cross-sectional study conducted between March 23 and May 7, 2020, at the Pitié-Salpêtrière Hospital, a reference center for COVID-19 in the Paris area. Adult patients were included if they had a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and referral for brain MRI. Patients with a prior history of neurologic disease were excluded. The characteristics and frequency of different MRI features were investigated. The findings were analyzed separately in patients in intensive care units (ICUs) and other departments (non-ICU). Results During the inclusion period, 1176 patients suspected of having COVID-19 were hospitalized. Of 308 patients with acute neurologic symptoms, 73 met the inclusion criteria and were included (23.7%): thirty-five patients were in the ICU (47.9%) and 38 were not (52.1%). The mean age was 58.5 years ± 15.6 [standard deviation], with a male predominance (65.8% vs 34.2%). Forty-three patients had abnormal MRI findings 2-4 weeks after symptom onset (58.9%), including 17 with acute ischemic infarct (23.3%), one with a deep venous thrombosis (1.4%), eight with multiple microhemorrhages (11.3%), 22 with perfusion abnormalities (47.7%), and three with restricted diffusion foci within the corpus callosum consistent with cytotoxic lesions of the corpus callosum (4.1%). Multifocal white matter-enhancing lesions were seen in four patients in the ICU (5%). Basal ganglia abnormalities were seen in four other patients (5%). Cerebrospinal fluid analyses were negative for SARS-CoV-2 in all patients tested ( = 39). Conclusion In addition to cerebrovascular lesions, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and intensive care unit-related complications, we identified two patterns including white matter-enhancing lesions and basal ganglia abnormalities that could be related to severe acute respiratory syndrome coronavirus 2 infection. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020202422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370354PMC
December 2020

Orbitofrontal involvement in a neuroCOVID-19 patient.

Epilepsia 2020 08 23;61(8):e90-e94. Epub 2020 Jul 23.

Neurology Department, Neurological Intensive Care Unit, Pitié-Salpêtrière Hospital, AP-HP.Sorbonne Université, Paris, France.

Neurological manifestations of coronavirus disease 19 (COVID-19) such as encephalitis and seizures have been reported increasingly, but our understanding of COVID-19-related brain injury is still limited. Herein we describe prefrontal involvement in a patient with COVID-19 who presented prior anosmia, raising the question of a potential trans-olfactory bulb brain invasion.
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http://dx.doi.org/10.1111/epi.16612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361605PMC
August 2020

Habituation of auditory startle reflex is a new sign of minimally conscious state.

Brain 2020 07;143(7):2154-2172

Institut du Cerveau et de la Moelle épinière - ICM, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.

Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined unresponsive wakefulness syndrome (UWS)-and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15-20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.
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http://dx.doi.org/10.1093/brain/awaa159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364741PMC
July 2020

Low ADC in CNS Lymphoma.

Clin Nucl Med 2020 Jul;45(7):545-546

Département d'Oncologie Médicale-Hématologie, CLCC Hôpital René Huguenin-Institut Curie, Saint-Cloud.

Patients with primary central nervous system lymphomas (PCNSLs) present with nonspecific clinical symptoms, which makes correct imaging evaluation essential for diagnostic and therapeutic management. In this work, we examined an 81-year-old man with recently discovered PCNSL using F-FDG PET/MRI, and we were able to differentiate between 2 lesions-PCNSL lymphoma extension and a recent ischemia. Our work shows that ischemia should be considered as a differential diagnosis for lymphoma progression. Although F-FDG PET or MRI alone cannot always give unambiguous solution, PET/MRI can greatly improve the diagnosis accuracy and help decide on the appropriate patient management.
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http://dx.doi.org/10.1097/RLU.0000000000003067DOI Listing
July 2020

Neuropsychological and neuroanatomical phenotype in 17 patients with cystinosis.

Orphanet J Rare Dis 2020 02 26;15(1):59. Epub 2020 Feb 26.

Centre de référence des maladies rénales rares - Néphrogones - Filière ORKiD, Bron, France.

Background: Cystinosis is a rare autosomal recessive disorder caused by intracellular cystine accumulation. Proximal tubulopathy (Fanconi syndrome) is one of the first signs, leading to end-stage renal disease between the age of 12 and 16. Other symptoms occur later and encompass endocrinopathies, distal myopathy and deterioration of the central nervous system. Treatment with cysteamine if started early can delay the progression of the disease. Little is known about the neurological impairment which occurs later. The goal of the present study was to find a possible neuroanatomical dysmorphic pattern that could help to explain the cognitive profile of cystinosis patients. We also performed a detailed review of the literature on neurocognitive complications associated with cystinosis.

Methods: 17 patients (mean age = 17.6 years, [5.4-33.3]) with cystinosis were included in the study. Neuropsychological assessment was performed including intelligence (Intelligence Quotient (IQ) with Wechsler's scale), memory (Children Memory Scale and Wechsler Memory Scale), visuo-spatial (Rey's figure test) and visuo-perceptual skills assessments. Structural brain MRI (3 T) was also performed in 16 out of 17 patients, with high resolution 3D T1-weighted, 3D FLAIR and spectroscopy sequences.

Results: Intellectual efficiency was normal in patients with cystinosis (mean Total IQ = 93). However the Perceptual Reasoning Index (mean = 87, [63-109]) was significantly lower than the Verbal Comprehension Index (mean = 100, [59-138], p = 0.003). Memory assessment showed no difference between visual and verbal memory. But the working memory was significantly impaired in comparison with the general memory skills (p = 0.003). Visuospatial skills assessment revealed copy and reproduction scores below the 50th percentile rank in more than 70% of the patients. Brain MRI showed cortical and sub-cortical cerebral atrophy, especially in the parieto-occipital region and FLAIR hypersignals in parietal, occipital and brain stem/cerebellum. Patients with atrophic brain had lower Total IQ scores compared to non-atrophic cystinosis patients.

Conclusions: Patients with cystinosis have a specific neuropsychological and neuroanatomical profile. We suggest performing a systematic neuropsychological assessment in such children aiming at considering adequate management.
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http://dx.doi.org/10.1186/s13023-019-1271-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045592PMC
February 2020

Pseudo-continuous arterial spin labelling shows high diagnostic performance in the detection of postoperative residual lesion in hyper-vascularised adult brain tumours.

Eur Radiol 2020 May 21;30(5):2809-2820. Epub 2020 Jan 21.

Neuroradiology Department, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, F-75013, Paris, France.

Objectives: Our aim was to evaluate the contribution of pseudo-continuous arterial spin labelling (pCASL) in the detection of a postoperative residual lesion in adult brain tumours.

Methods: Seventy-five patients were prospectively included. Following the results of preoperative DSC-PWI assessment, intra-axial lesions, including high-grade gliomas (n = 43) and certain metastases (n = 14), were classified as hyper-vascular (HV+ group, n = 57); other lesions, including low-grade gliomas and certain metastases, were classified as non-hyper-vascular (HV- group, n = 18). To confirm the absence/presence of a residual lesion or disease progression, postoperative MRI including pCASL sequence and follow-up-MRI were performed within 72 h and 1-6 months after the resection, respectively. Two raters evaluated the images. Mean and maximal ASL cerebral blood flow (CBF) values were measured in the perioperative region and normalised to the contralateral tissue. The pCASL-CBF maps and post-contrast T1WI were visually assessed for residual lesion. Quantitative data were analysed with unpaired Student t and Mann-Whitney U tests and the visual diagnostic performance with the McNemar test.

Results: In the HV+ group, the mean normalised CBF was 1.97 ± 0.59 and 0.97 ± 0.29 (p < 0.0001, AUC = 0.964, cut-off = 1.27) for patients with or without residual tumours, respectively. The mean normalised CBF was not discriminative for assessing residual tumours in the HV- group (p = 0.454). Visual CBF evaluation allowed 92.98% patients belonging to the HV+ group to be correctly classified (sensitivity 93.02%, specificity 92.86%, p < 0.001). Visual evaluation was correlated with contrast enhancement evaluation and with the mean normalised CBF values (r = 0.505, p < 0.0001 and 0.838, p < 0.0001, respectively).

Conclusion: Qualitative and quantitative ASL evaluation shows high diagnostic performance in postoperative assessment of hyper-perfused tumours. In this case, postoperative pCASL may be useful, especially if contrast injection cannot be performed or when contrast enhancement is doubtful.

Key Points: • Evaluation of postoperative residual lesion in the case of brain tumours is an imaging challenge. • This prospective monocentric study showed that increased normalised cerebral blood flow assessed by pseudo-continuous arterial spin labelling (pCASL) correlates well with the presence of a residual tumour in the case of hyper-vascular tumour diagnosed on preoperative MRI. • Qualitative and quantitative pCASL is an informative sequence for hyper-vascular residual tumour, especially if acquired more than 48 h after brain tumour surgery, when contrast enhancement can give ambiguous results due to blood-brain barrier disruption.
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http://dx.doi.org/10.1007/s00330-019-06474-4DOI Listing
May 2020

Potential effect of fetal origin of posterior cerebral artery on the arterial spin labeling sequence.

J Neuroradiol 2020 May 6;47(3):238-241. Epub 2019 Nov 6.

Service de neuroradiologie, hôpital Pitié-Salpêtrière, Assistance publique Hôpitaux de Paris, 75013 Paris, France.

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http://dx.doi.org/10.1016/j.neurad.2019.08.006DOI Listing
May 2020

The eclipse sign as a radiological presentation of neurosarcoidosis.

Int J Neurosci 2020 May 1;130(5):435-437. Epub 2019 Dec 1.

Service de Médecine Interne 2, Institut e3m, Hôpital de la Pitié-Salpêtrière, Centre National de Référence Maladies Systémiques Rares, Lupus, Syndrome des anticorps antiphospholipides, Sorbonne Université, Assistance Publique Hôpitaux de Paris, Paris, France.

Neurosarcoidosis is a rare inflammatory neurological condition. We describe a challenging radiological presentation of neurosarcoidosis. The eclipse sign refers to hypo T1-weighted parenchymal or leptomeningeal images surrounded by circular gadolinium enhancement. The eclipse sign was identified in 3 out of 46 patients with histologically-proven neurosarcoidosis. The eclipse sign may correspond to necrotizing parenchymal or leptomeningeal granuloma. This sign expands the spectrum of radiological presentations of neurosarcoidosis.
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http://dx.doi.org/10.1080/00207454.2019.1688807DOI Listing
May 2020

Magnetic resonance spectroscopy: A surrogate marker of hepatic encephalopathy?

J Hepatol 2019 11 26;71(5):1055-1057. Epub 2019 Sep 26.

Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Département de Neurologie, Unité de réanimation neurologique, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2019.07.008DOI Listing
November 2019

Long-term cognitive disability after traumatic brain injury: Contribution of the DEX relative questionnaires.

Neuropsychol Rehabil 2020 Dec 22;30(10):1905-1924. Epub 2019 May 22.

Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Paris, France.

Executive functions are high-level cognitive processes commonly impaired after severe traumatic brain injury (sTBI), which may be associated with persistent anosognosia. The dysexecutive questionnaire (DEX) was designed to assess different domains of executive functioning in daily life. Two versions of the DEX exist (DEX-S completed by the patient, DEX-O completed by a relative) to compare cognitive complaints and patient's awareness. This work was aimed at studying the relevance of DEX-O for assessing daily-life limitations, the persistence of anosognosia and its association with global disability (GOSE) and magnetic resonance imaging (MRI) markers of brain alterations. Sixty-three patients (and relatives) were included within 63.4 months (±20.7) after sTBI. DEX-S and DEX-O scores were significantly positively correlated. We obtained significant correlations between DEX-S and episodic memory and phasic alert but not with executive assessment, GOSE and diffusion MRI markers. DEX-O was significantly correlated with executive function, episodic memory, attention (phasic alert sustained and divided attention), with the GOSE and the volume of the body of the corpus callosum (MRI marker). Anosognosia score (DEX-O minus DEX-S) correlated with mean diffusivity measure. These results highlight the clinical interest of DEX-O in assessing long-term disability.
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http://dx.doi.org/10.1080/09602011.2019.1618345DOI Listing
December 2020

Editorial: predicting hepatic encephalopathy after TIPSS-is multimodal cerebral MRI the answer? Authors' reply.

Aliment Pharmacol Ther 2018 11;48(9):1020-1021

Service d'hépatogastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France.

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http://dx.doi.org/10.1111/apt.14993DOI Listing
November 2018

First European case of Creutzfeldt-Jakob disease with a PRNP G114V mutation.

Cortex 2019 08 1;117:407-413. Epub 2018 Sep 1.

Department of Neurology, Pitié-Salpêtrière Hospital, APHP, Paris, France; Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, CIC-1422, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Genetic Creutzfeldt-Jakob disease is due to mutations in the PRNP gene. Only two families with a PRNP G114V mutation have been described around the world. We report the first European case, who had no family history and initially presented with isolated deficit in hippocampus-dependent memory. Initial investigations were normal except for elevated total tau protein in the cerebrospinal fluid. He died 4 years after disease onset. This case highlights the diagnostic difficulties posed by genetic Creutzfeldt-Jakob disease, and shows that genetic analyses should be considered even in sporadic cases.
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http://dx.doi.org/10.1016/j.cortex.2018.08.014DOI Listing
August 2019

Combined diffusion tensor imaging and magnetic resonance spectroscopy to predict neurological outcome before transjugular intrahepatic portosystemic shunt.

Aliment Pharmacol Ther 2018 10 4;48(8):863-874. Epub 2018 Sep 4.

Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Paris, France.

Background: Hepatic encephalopathy (HE) may occur after transjugular intrahepatic portosystemic shunt (TIPSS) placement. Multimodal magnetic resonance imaging (MRI), combining anatomical sequences, diffusion tensor imaging (DTI) and H magnetic resonance spectroscopy, is modified in cirrhotic patients.

Aims: To describe multimodal MRI images before TIPSS, to assess if TIPSS induces changes in multimodal MRI, and to find predictors of HE after TIPSS in patients with cirrhosis.

Methods: Consecutive cirrhotic patients with an indication for TIPSS were prospectively screened. Diagnosis of minimal HE was performed using psychometric HE test score. Multimodal MRI was performed before and 3 months after TIPSS placement.

Results: Twenty-five consecutive patients were analysed (median age = 59, male gender 76%, median Child-Pugh score = 8 [5-8], MELD score = 12 [9-17], indication for TIPSS placement: ascites/secondary prophylaxis of variceal bleeding/other 20/3/2), no HE/minimal HE/overt HE: 21/4/0. 8/25 patients developed HE after TIPSS. Before TIPSS placement, metabolite concentrations were different in patients with or without minimal HE (lower myo-inositol, mI, higher glutamate/glutamine), but there were no differences in DTI data. TIPSS placement induced changes in metabolite concentrations even in asymptomatic patients, but not in DTI metrics. Baseline fractional anisotropy was significantly lower in patients who developed HE after TIPSS in five regions of interest.

Conclusions: TIPSS placement induced significant changes in cerebral metabolites, even in asymptomatic patients. Patients who developed HE after TIPSS displayed lower fractional anisotropy before TIPSS. Brain MRI with DTI acquisition may help selecting patients at risk of HE.
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http://dx.doi.org/10.1111/apt.14938DOI Listing
October 2018

Increased 18F-FDG Uptake in Lhermitte-Duclos Disease With Cowden Syndrome Revealed by PET-MRI.

Clin Nucl Med 2018 Oct;43(10):e355-e356

From the Departments of Nuclear Medicine, and.

A 62-year-old woman, with the history of breast and colorectal cancer, presented intermittent diplopia. A cerebellar lesion was revealed by F-FDG PET-MRI without post-gadolinium enhancement, but with increased perfusion and strong F-FDG uptake. The diagnosis of Cowden syndrome with PTEN gene mutation, linked to higher risk of neoplasia and occurrence of hamartomatous lesions characteristic of the Lhermitte-Duclos disease (LDD), was confirmed by genetic investigation.
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http://dx.doi.org/10.1097/RLU.0000000000002248DOI Listing
October 2018

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

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.

Lancet Neurol 2018 04 27;17(4):317-326. Epub 2018 Feb 27.

CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Sorbonne Université, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France. Electronic address:

Background: Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome.

Methods: This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954.

Findings: Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome.

Interpretation: In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI.

Funding: French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.
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http://dx.doi.org/10.1016/S1474-4422(18)30027-9DOI Listing
April 2018

Quantitative neuroimaging biomarkers in a series of 20 adult patients with POLG mutations.

Mitochondrion 2019 03 21;45:22-28. Epub 2018 Feb 21.

Sorbonne Université, UPMC-Paris 6, UMR S 1127 and Inserm U 1127, and CNRS UMR 7225, and Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France. Electronic address:

Mutations in the gene encoding polymerase gamma (POLG) are a common cause of mitochondrial diseases in adults. We retrospectively analyzed volumetric and diffusion tensor imaging data from 20 adult POLG-mutated patients compared to healthy controls. We used an original clinical binary load score and electroneuromyography to evaluate disease severity. Patients showed atrophy in the basal ganglia, amygdala, and brainstem (p < 0.05) compared to controls, as well as decreased fractional anisotropy (FA) in the cingulate gyrus, the internal capsule and the corona radiata (p < 0.05). Clinical scores correlated with decreased FA and increased radial diffusivity in several brain regions (p < 0.05).
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http://dx.doi.org/10.1016/j.mito.2018.02.001DOI Listing
March 2019

Case 251: Nontraumatic Drug-associated Rhabdomyolysis of Head and Neck Muscles.

Radiology 2018 03;286(3):1088-1092

From the Departments of Maxillofacial and Oral Surgery (A.D., R.H.K.) and Neuroradiology (D.G.) and the Medical Intensive Care Unit (D.B.), AP-HP, Pitiè-Salpêtrière University Hospital, Université Pierre-et-Marie-Curie, Sorbonne Universités, 47-83 boulevard de l'Hôpital, Paris 75013, France.

History A 21-year-old man with a history of abuse of multiple drugs and mild cognitive impairment who initially underwent treatment for excited delirium developed respiratory arrest shortly after admission and was successfully resuscitated. Unenhanced computed tomography (CT) of the head and neck and contrast material-enhanced CT of the chest, abdomen, pelvis, and complete spine were performed shortly after the initial treatment. Head and neck magnetic resonance (MR) imaging was performed 24 hours after admission. No other abnormalities were noted. There were no fractures, and there was no vascular injury in the head and neck region. The patient had no external neck injuries, congestion, or petechiae suggesting neck compression. He had no history of chronic or recurrent pain or skin rash. Urine testing was positive for cocaine, cannabis, and methamphetamine. Serum creatine kinase level was initially high (31 117 U/L [520 μkat/L]; normal, 1000 U/L [16.7 μkat/L]). Corrected calcium level was 2.22 mmol/L, and ionized calcium level was 1.09 mmol/L (lower end of the normal range). There was no acute renal failure at the initial phase, but serum creatinine levels reached 180 µmol/L 24 hours after admission, and creatine kinase peaked at 61 000 U/L [1019 μkat/L]. Urine was initially red, but the patient was not tested for myoglobinuria.
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http://dx.doi.org/10.1148/radiol.2018152594DOI Listing
March 2018

Survival and consciousness recovery are better in the minimally conscious state than in the vegetative state.

Brain Inj 2018 20;32(1):72-77. Epub 2017 Nov 20.

a AP-HP, Groupe hospitalier Pitié-Salpêtrière , Department of Neurology , Paris , France.

Background: The prognosis value of early clinical diagnosis of consciousness impairment is documented by an extremely limited number of studies, whereas it may convey important information to guide medical decisions.

Objective: We aimed at determining if patients diagnosed at an early stage (<90 days after brain injury) as being in the minimally conscious state (MCS) have a better prognosis than patients in the vegetative state/Unresponsive Wakefulness syndrome (VS/UWS), independent of care limitations or withdrawal decisions.

Methods: Patients hospitalized in ICUs of the Pitié-Salpêtrière Hospital (Paris, France) from November 2008 to January 2011 were included and evaluated behaviourally with standardized assessment and with the Coma Recovery Scale-Revised as being either in the VS/UWS or in the MCS. They were then prospectively followed until 1July 2011 to evaluate their outcome with the GOSE. We compared survival function and outcomes of these two groups.

Results: Both survival function and outcomes, including consciousness recovery, were significantly better in the MCS group. This difference of outcome still holds when considering only patients still alive at the end of the study.

Conclusions: Early accurate clinical diagnosis of VS/UWS or MCS conveys a strong prognostic value of survival and of consciousness recovery.
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http://dx.doi.org/10.1080/02699052.2017.1364421DOI Listing
July 2018

Lesions in deep gray nuclei after severe traumatic brain injury predict neurologic outcome.

PLoS One 2017 2;12(11):e0186641. Epub 2017 Nov 2.

Department of Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France.

Purpose: This study evaluates the correlation between injuries to deep gray matter nuclei, as quantitated by lesions in these nuclei on MR T2 Fast Spin Echo (T2 FSE) images, with 6-month neurological outcome after severe traumatic brain injury (TBI).

Materials And Methods: Ninety-five patients (80 males, mean age = 36.7y) with severe TBI were prospectively enrolled. All patients underwent a MR scan within the 45 days after the trauma that included a T2 FSE acquisition. A 3D deformable atlas of the deep gray matter was registered to this sequence; deep gray matter lesions (DGML) were evaluated using a semi-quantitative classification scheme. The 6-month outcome was dichotomized into unfavorable (death, vegetative or minimally conscious state) or favorable (minimal or no neurologic deficit) outcome.

Results: Sixty-six percent of the patients (63/95) had both satisfactory registration of the 3D atlas on T2 FSE and available clinical follow-up. Patients without DGML had an 89% chance (P = 0.0016) of favorable outcome while those with bilateral DGML had an 80% risk of unfavorable outcome (P = 0.00008). Multivariate analysis based on DGML accurately classified patients with unfavorable neurological outcome in 90.5% of the cases.

Conclusion: Lesions in deep gray matter nuclei may predict long-term outcome after severe TBI with high sensitivity and specificity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186641PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667824PMC
December 2017

Case 251.

Radiology 2017 11;285(2):681-682

From the Departments of Maxillofacial and Oral Surgery (A.D., R.H.K.) and Neuroradiology (D.G.) and the Medical Intensive Care Unit (D.B.), AP-HP, Pitiè-Salpêtrière University Hospital, Université Pierre-et-Marie-Curie, Sorbonne Universités, 47-83 boulevard de l'Hôpital, Paris 75013, France.

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http://dx.doi.org/10.1148/radiol.2017152593DOI Listing
November 2017

Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.

Radiology 2018 Apr 18;287(1):247-255. Epub 2017 Oct 18.

From the Departments of Radiology and Radiological Science (H.I.S., R.D.S.), Anesthesiology and Critical Care Medicine (Y.H., R.D.S.), Neurology (Y.H., R.D.S.), and Neurosurgery (R.D.S.), Johns Hopkins University School of Medicine, 600 N Wolfe St, Phipps 455, Baltimore, MD 21287; Department of Biostatistics, Indiana University Fairbanks School of Public Health, Indianapolis, Ind (S.L.); Department of Neurology, Tufts University School of Medicine, Boston, Mass (J.K.); Institut du Cerveau et de la Moelle Épinière, Groupe Hospitalier Pitié-Salpêtrière, Paris, France (A.D.); Coma Science Group and Department of Neurology, University of Liège, Liège, Belgium (C.D.P., S.L.); Departments of Anesthesia Resuscitation (R.C.) and Neuroradiology (B.J.), Centre Hospitalier Universitaire, Clermont-Ferrand, France; Functional Imaging Laboratory U678, Faculté de Médecine Pierre et Marie Curie, Paris, France (H.B., V.P.); F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Md (J.P.); Medical Resuscitation Service (C.E.L.), Department of Neuroradiology (D.G.), and Neurosurgical Resuscitation Service (L.V., L.P.), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, and Université Pierre et Marie Curie, Paris, France; and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md (B.C.).

Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. RSNA, 2017.
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http://dx.doi.org/10.1148/radiol.2017162161DOI Listing
April 2018

Peak hyperammonemia and atypical acute liver failure: The eruption of an urea cycle disorder during hyperemesis gravidarum.

J Hepatol 2017 Sep 20. Epub 2017 Sep 20.

Brain Liver Pitié-Salpêtrière (BLIPS) study group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France; Université Pierre et Marie Curie Paris 6, Sorbonne Universités, INSERM UMR_S 938, CDR Saint-Antoine Maladies métaboliques, biliaires et fibro-inflammatoires du foie, & Institut de Cardiométabolisme et Nutrition, ICAN, Paris, France; UF de Soins Intensifs d'Hépato-gastroentérologie, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France. Electronic address:

Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected. We performed emergency metabolic analyses, stopped all protein intake and started with intravenous (i.v.) high caloric intake, nitrogen scavenger drugs and haemodialysis. The neurological and hepatic status of the patient quickly improved together with normalisation of her ammonemia levels. High plasma glutamine and urinary orotic acid, alongside low plasma arginine, citrulline and ornithine were suggestive of an ornithine transcarbamylase deficiency, later confirmed by molecular analyses. Foetal sex was female, as determined by foetal DNA analysis in maternal blood, and foetal development was unremarkable throughout the pregnancy. Delivery was induced at 39 weeks with a close monitoring of ammonemia levels and i.v. perfusion of carbohydrates and lipids during labour and immediately post-partum to avoid hypercatabolism. Delivery was uneventful and the patient delivered a healthy female baby. Urea cycle disorders should be contemplated in non-jaundiced patients with ALI or ALF, severe hyperammonemia and normal serum creatinine regardless of serum aminotransferase levels. The prompt recognition of this rare condition and the rapid initiation of adequate metabolic therapy are mandatory to prevent irreversible neurological sequelae and to avoid liver transplantation.
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http://dx.doi.org/10.1016/j.jhep.2017.09.009DOI Listing
September 2017

Cerebral pseudo-tumoral neuro-Behcet: Histological demonstration of an inflammatory and vascular disease.

Clin Neurol Neurosurg 2017 10 12;161:48-50. Epub 2017 Aug 12.

Internal Medicine Department, French Reference Centre for Rare Autoimmune Systemic Diseases, e3 m Institute, Assistance-Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France; Paris VI University (UPMC), Sorbonnes Universités, Paris, France.

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http://dx.doi.org/10.1016/j.clineuro.2017.08.004DOI Listing
October 2017

Probing consciousness in a sensory-disconnected paralyzed patient.

Brain Inj 2017 28;31(10):1398-1403. Epub 2017 Jun 28.

b INSERM, U 1127 , Paris , France.

Background: Diagnosis of consciousness can be very challenging in some clinical situations such as severe sensory-motor impairments.

Case Study: We report the case study of a patient who presented a total "locked-in syndrome" associated with and a multi-sensory deafferentation (visual, auditory and tactile modalities) following a protuberantial infarction.

Result: In spite of this severe and extreme disconnection from the external world, we could detect reliable evidence of consciousness using a multivariate analysis of his high-density resting state electroencephalogram. This EEG-based diagnosis was eventually confirmed by the clinical evolution of the patient.

Conclusion: This approach illustrates the potential importance of functional brain-imaging data to improve diagnosis of consciousness and of cognitive abilities in critical situations in which the behavioral channel is compromised such as deafferented locked-in syndrome.
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http://dx.doi.org/10.1080/02699052.2017.1327673DOI Listing
June 2018