MRI features of intra-axial histiocytic brain mass lesions.

AIM: To describe MRI features, including diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and perfusion-weighted imaging (PWI), of intra-axial tumour-like presentations of four different subtypes of histiocytosis. MATERIAL AND METHODS: The brain MRI findings of 23 patients with histologically proven histiocytosis were reviewed retrospectively (11 Langerhans cell histiocytosis [LCH], eight Erdheim-Chester disease [ECD], one overlap form LCH/ECD, two Rosai-Dorfman disease [RDD], and one haemophagocytic lymphohistiocytosis [HLH]) with single or multiple enhancing intraparenchymal brain lesions. RESULTS: Histiocytic brain mass lesions show some similar MRI features including Supra and/or infratentorial and/or paraventricular subcortical well-delineated masses, linear ependymal enhancement along the ventricles and brain stem lesions. Masses always present with mixed hyper- and hypointense signal on T2-weighted imaging (WI). Their enhancement is often homogeneous. Apparent diffusion coefficient (ADC) values are often normal or elevated. CONCLUSION: The presence of multiple periventricular and subcortical enhancing lesions with mixed signal intensity on T2WI and normal or high ADC values should lead radiologists to consider the diagnosis of histiocytic lesions and search for associated systemic lesions.

Clinical, imaging and follow-up study of optic neuritis associated with myelin oligodendrocyte glycoprotein antibody: a multicentre study of 62 adult patients.

BACKGROUND AND PURPOSE: There are few clinico-radiological data on optic neuritis (ON) with myelin oligodendrocyte glycoprotein antibody (MOG-IgG). The objective was to characterize the clinico-radiological phenotype and outcome of patients with MOG-IgG-related ON. METHODS: The records of all adult patients admitted in three medical centres with MOG-IgG-associated ON who underwent orbital and brain magnetic resonance imaging (MRI) at the acute phase were reviewed. Spinal cord MRI within 1 month from the ON and all of the follow-up MRI were reviewed. RESULTS: Of 62 patients, 41.9% had bilateral ON and 66.2% optic disc swelling. On initial MRI, lesions were anterior (92%), extensive (63%) and associated with optic perineuritis (46.6%). Silent brain lesions were found in 51.8% of patients but were mainly non-specific (81%). Of 39 individuals with spinal MRI at onset, nine had abnormal findings (four were asymptomatic). Two symptomatic patients had longitudinally extensive myelitis with concurrent H-sign. At last follow-up, 5% of patients had visual acuity ≤0.1. Brain MRI remained unchanged in 41 patients (87%). CONCLUSIONS: Our study supports a mostly benign ophthalmological course of MOG-IgG-associated ON, despite initially longitudinally extensive lesions and development of optic nerve atrophy on orbital MRI. Spinal MRI could be of interest in detecting silent suggestive lesions.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PURPOSE: Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. METHODS: Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. RESULTS: Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. CONCLUSION: Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI.

Multimodal assessment improves neuroprognosis performance in clinically unresponsive critical-care patients with brain injury.

Accurately predicting functional outcomes for unresponsive patients with acute brain injury is a medical, scientific and ethical challenge. This prospective study assesses how a multimodal approach combining various numbers of behavioral, neuroimaging and electrophysiological markers affects the performance of outcome predictions. We analyzed data from 349 patients admitted to a tertiary neurointensive care unit between 2009 and 2021, categorizing prognoses as good, uncertain or poor, and compared these predictions with observed outcomes using the Glasgow Outcome Scale-Extended (GOS-E, levels ranging from 1 to 8, with higher levels indicating better outcomes). After excluding cases with life-sustaining therapy withdrawal to mitigate the self-fulfilling prophecy bias, our findings reveal that a good prognosis, compared with a poor or uncertain one, is associated with better one-year functional outcomes (common odds ratio (95% CI) for higher GOS-E: OR = 14.57 (5.70-40.32), P < 0.001; and 2.9 (1.56-5.45), P < 0.001, respectively). Moreover, increasing the number of assessment modalities decreased uncertainty (OR = 0.35 (0.21-0.59), P < 0.001) and improved prognostic accuracy (OR = 2.72 (1.18-6.47), P = 0.011). Our results underscore the value of multimodal assessment in refining neuroprognostic precision, thereby offering a robust foundation for clinical decision-making processes for acutely brain-injured patients. ClinicalTrials.gov registration: NCT04534777 .

Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Imaging findings of intraventricular and ependymal lesions.

Intraventricular and ependymal lesions comprise a wide spectrum of tumoral, cystic, vascular, infectious and inflammatory disorders. With respect to tumoral and cystic diseases, the location, age and CT and MRI patterns are the main factors for diagnosis. The MRI findings of infectious diseases are supported by the clinical history, immune status and laboratory findings. Intracranial associated lesions may be very helpful for the diagnosis of Sturge-Weber, subependymal giant cell astrocytoma and systemic diseases, such as sarcoidosis and histiocytosis. Intraventricular vascular lesions are rare but present typical features on neuroimaging. The aim of this review is to provide a detailed description of these disorders with an emphasis on the key imaging findings and to generate a narrow differential diagnosis. We present a diagnostic approach based on the solid or cystic aspect of the intraventricular focal mass, its origin from the ventricular wall or choroid plexus and its location within the ventricular system. We also propose a differential diagnosis for ependymal dissemination: the ependymal enhancement may be due to ventriculitis from adjacent parenchymal lesions, the ependymal spread of tumors or infectious or inflammatory/systemic diseases.

A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is associated with regulatory T cells (Tregs) insufficiency while low-dose interleukin-2 (IL2LD) activates Tregs and reduces disease activity in autoimmune diseases. METHODS: We aimed at addressing whether IL2LD improved Tregs from MS patients. MS-IL2 was a single-center double-blind phase-2 study. Thirty patients (mean [SD] age 36.8 years [8.3], 16 female) with relapsing-remitting MS with new MRI lesions within 6 months before inclusion were randomly assigned in a 1:1 ratio to placebo or IL-2 at 1 million IU, daily for 5 days and then fortnightly for 6 months. The primary endpoint was change in Tregs at day-5. RESULTS: Unlike previous trials of IL2LD in more than 20 different autoimmune diseases, Tregs were not expanded at day-5 in IL2LD group, but only at day-15 (median [IQR] fold change from baseline: 1.26 [1.21-1.33] in IL2LD group; 1.01 [0.95-1.05] in placebo group, p < 0.001). At day-5, however, Tregs had acquired an activated phenotype (fold change of CD25 expression in Tregs: 2.17 [1.70-3.55] in IL2LD versus 0.97 [0.86-1.28] in placebo group, p < 0.0001). Regulator/effector T cells ratio remained elevated throughout treatment period in the IL2LD group (p < 0.001). Number of new active brain lesions and of relapses tended to be reduced in IL2LD treated patients, but the difference did not reach significance in this trial not powered to detect clinical efficacy. CONCLUSION: The effect of IL2LD on Tregs in MS patients was modest and delayed, compared to other auto-immune diseases. This, together with findings that Tregs improve remyelination in MS models and recent reports of IL2LD efficacy in amyotrophic lateral sclerosis, warrants larger studies of IL2LD in MS, notably with increased dosages and/or modified modalities of administration. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02424396; EU Clinical trials Register: 2014-000088-42.

A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency.

OBJECTIVE: To identify a consistent pattern of brain MRI imaging in primary complex I deficiency. Complex I deficiency, a major cause of respiratory chain dysfunction, accounts for various clinical presentations, including Leigh syndrome. Human complex I comprises seven core subunits encoded by mitochondrial DNA (mtDNA) and 38 core subunits encoded by nuclear DNA (nDNA). Moreover, its assembly requires six known and many unknown assembly factors. To date, no correlation between genotypes and brain MRI phenotypes has been found in complex I deficiencies. DESIGN AND SUBJECTS: The brain MRIs of 30 patients carrying known mutation(s) in genes involved in complex I were retrospectively collected and compared with the brain MRIs of 11 patients carrying known mutations in genes involved in the pyruvate dehydrogenase (PDH) complex as well as 10 patients with MT-TL1 mutations. RESULTS: All complex I deficient patients showed bilateral brainstem lesions (30/30) and 77% (23/30) showed anomalies of the putamen. Supratentorial stroke-like lesions were only observed in complex I deficient patients carrying mtDNA mutations (8/19) and necrotising leucoencephalopathy in patients with nDNA mutations (4/5). Conversely, the isolated stroke-like images observed in patients with MT-TL1 mutations, or the corpus callosum malformations observed in PDH deficient patients, were never observed in complex I deficient patients. CONCLUSION: A common pattern of brain MRI imaging was identified with abnormal signal intensities in brainstem and subtentorial nuclei with lactate peak as a clue of complex I deficiency. Combining clinico-biochemical data with brain imaging may therefore help orient genetic studies in complex I deficiency.

[MRI in diagnosis and follow-up of patients with adult metabolic disease: contribution of new techniques]. / Place de l'IRM dans l'orientation diagnostique et le suivi des maladies métaboliques: intérêt des nouvelles techniques.

INTRODUCTION: Conventional MRI allows diagnostic and prognosis approaches for patients with suspected metabolic disease. BACKGROUND: Bilateral and symmetrical abnormalities are the most suggestive aspects. Signal characteristics (intensity, difference of signal on various sequences), lesion extension and location provide important etiological information. Non-conventional MRI techniques are particularly interesting for pathophysiology. Different MRI modalities offer promising techniques for monitoring treatments and patient follow-up. CONCLUSION: Combining different MRI modalities can contribute to the diagnosis and help improve understanding of the pathogenic mechanisms of adult metabolic diseases; they offer promising options for the prognosis and treatment follow-up.

[Infection associated cerebral vasculitis]. / Vascularites cérébrales associées aux infections.

Infections are a frequent cause of cerebral vasculitis, important to diagnose because a specific treatment may be required. Infection-associated vasculitis can be caused by angiotropic pathogens (varicella zoster virus, syphilis, aspergillus). They can be associated with subarachnoidal meningitis (tuberculosis, pyogenic meningitis, cysticercosis). They can appear contiguously to sinuses or orbital infection (aspergillosis, mucormycosis). Finally, they also may be due to an immune mechanism in the context of chronic infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Cerebral vasculitis are severe conditions and their prognosis is directly linked to early recognition and diagnosis. Infectious causes must therefore be systematically considered ahead of cerebral vasculitis, and the appropriate investigations must be determined according to the patient's clinical context. We propose here an update on the infectious causes of cerebral vasculitis, their diagnosis modalities, and therapeutic options.

Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase.

BACKGROUND AND PURPOSE: In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. MATERIALS AND METHODS: Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MDz). Through linear regression, we evaluated the relation between microbleed concentration and MDz in predefined structures. RESULTS: In the cerebral hemispheres, MDz at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5-69.3], P = .017; right: B = 26.3 [95% CI 5.7-47.0], P = .014). No such relation was demonstrated in the central brain. MDz in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8-75.2], P < .000). MDz in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9-47.5], P = .023). CONCLUSIONS: SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

Reliability of the ECASS radiological classification of postthrombolysis brain haemorrhage: a comparison of CT and three MRI sequences.

BACKGROUND: Postthrombolysis brain haemorrhagic transformations (HT) are often categorized with the CT-based classification of the European Cooperative Acute Stroke Study (ECASS). However, little is known about the reliability of this classification and its extension to MRI. Our objective was to compare the inter- and intraobserver reliability of this classification on CT and 3 MRI sequences. METHODS: Forty-three patients with postthrombolysis HT on CT or at least 1 of the 3 MRI sequences: fluid-attenuation inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2* gradient recalled echo (T2*GRE) were selected. Twelve control patients without any bleeding were added to avoid a bias based on a pure HT-positive cohort. Each series of images were independently classified with the ECASS method by 6 blinded observers. Inter- and intraobserver reproducibility was categorized from poor to excellent depending on kappa values. RESULTS: The inter- and intraobserver overall concordance of the classification was good for T2*GRE, DWI and CT (kappa > 0.6) and moderate for FLAIR (kappa < 0.6). The interobserver concordance for parenchymal haematomas was excellent for T2*GRE (kappa > 0.8) and moderate for CT, FLAIR and DWI. CONCLUSION: The T2*GRE sequence is the most reproducible method to categorize postthrombolysis HT and has an excellent reliability for the severe parenchymal haematoma category, suggesting that this sequence should be used to assess HT in thrombolytic therapy trials.

Characterization of Skull Base Lesions Using Pseudo-Continuous Arterial Spin Labeling.

PURPOSE: Pseudo-continuous arterial spin labeling (pCASL) is a non-invasive magnetic resonance (MR) perfusion technique. Our study aimed at estimating the diagnostic performance of the pCASL sequence in assessing the perfusion of skull base lesions both qualitatively and quantitatively and at providing cut-off values for differentiation of specific skull base lesions. METHODS: In this study 99 patients with histopathologically confirmed skull base lesions were retrospectively enrolled. Based on a pathological analysis, the lesions were classified as hypervascular and non-hypervascular. Patients were divided into two subgroups according to the anatomical origin of each lesion. The MRI study included pCASL and 3D T1-weighted fat-saturated post-contrast sequences. Of the patients seven were excluded due to technical difficulties or patient movement. The lesions were classified by two raters, blinded to the diagnosis as either hyperperfused or non-hyperperfused, based on the pCASL sequence. The normalized tumor blood flow (nTBF) of each lesion was determined. Qualitative and quantitative characteristics of hypervascular and non-hypervascular lesions were compared. RESULTS: Visual assessment enabled correct classification of 98% of the lesions to be performed. Quantitatively, we found significant differences between the nTBF values for hypervascular and non-hypervascular lesions (p < 0.001) and provided cut-off values, allowing meningioma and schwannoma to be distinguished from meningioma and adenoma. Significant differences were also found within the hypervascular group, namely, paraganglioma was more hyperperfused than meningioma (p = 0.003) or metastases (p = 0.009). CONCLUSION: The present study demonstrates the high diagnostic performance of pCASL in characterizing skull base lesions by either visual assessment or nTBF quantification. Adding the pCASL sequence to the conventional protocol of skull base assessment can be recommended.

MRI and FDG PET/CT findings in a case of probable Heidenhain variant Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disease caused by the accumulation of a pathogenic isoform of a prion protein in neurons that is responsible for subacute dementia. The Heidenhain variant is an atypical form of CJD in which visual signs are predominant. This is a report of the case of a 65-year-old man with probable CJD of the Heidenhain variant, with topographical concordance between findings on magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) photopenic areas on positron emission tomography (PET)/computed tomography (CT) for cortical parietooccipital lesions.

[Myelin and nuclear magnetic resonance]. / Myéline et résonance magnétique nucléaire.

MRI is one of the most important tools for the investigation of white matter diseases of the central nervous system. Other techniques based on the magnetic resonance phenomena (magnetization transfer imaging, diffusion imaging, magnetic resonance spectroscopy) have joined MRI to better caracterize certain diseases, understand their pathophysiology and follow their evolution.

[Indications for cerebral MR proton spectroscopy in 2007]. / Spectroscopie par résonance magnétique du proton. Quelles indications neurologiques en 2007?

Magnetic resonance spectroscopy (MRS) is being increasingly performed alongside the more conventional MRI sequences in the exploration of neurological disorders. It is however important to clearly differentiate its clinical applications aiming at improving the differential diagnosis or the prognostic evaluation of the patient, from the research protocols, when MRS can contribute to a better understanding of the pathophysiology of the disease or to the evaluation of new treatments. The most important applications in clinical practice are intracranial space occupying lesions (especially the positive diagnosis of intracranial abscesses and gliomatosis cerebri and the differential diagnosis between edema and tumor infiltration), alcoholic, hepatic, and HIV-related encephalopathies and the exploration of metabolic diseases. Among the research applications, MRS is widely used in multiple sclerosis, ischemia and brain injury, epilepsy and neuro degenerative diseases.

[Brain magnetic resonance spectroscopy]. / Spectroscopie par résonance magnétique cérébrale.

MR spectroscopy (MRS) sequences allow noninvasive exploration of brain metabolism during a MRI examination. Their day-to-day use in a clinical setting has recently been improved by simple programming of sequences and automated quantification of metabolites. However, a few simple rules should be observed in the choice of sequences and the location of the voxels so as to obtain an informative, high-quality examination. The research applications of MR spectroscopy, where use of this examination seeks to better understand the pathophysiology of the disease, must be distinguished from its clinical indications, where MRS provides information that can be used directly in patient management. The most significant of the clinical uses are imaging intracranial tumors (positive and differential diagnosis, extension, treatment follow-up), diffuse brain injury, encephalopathies (especially hepatic and HIV-related), and the diagnosis of metabolic disorders.

Capecitabine-induced acute toxic leukoencephalopathy.

A 45-year-old woman was treated by Capecitabine (Xeloda®) during 6days for breast cancer with metastatic bone lesions when she presented with nausea, headaches, muscle cramps, dysarthria and swallowing disorders. A stroke was first suspected. Brain CT was normal. MRI showed bilateral and symmetric high signal intensities of deep white matter, corpus callosum and corticospinal tracts on diffusion-weighted imaging and T2 fluid-attenuated inversion recovery (FLAIR) sequence, similar to 5-FU acute leukoencephalopathy. An acute toxic leukoencephalopathy was diagnosed prompting to discontinue capecitabine, which allowed a regression of the symptoms. Though acute toxic leukoencephalopathies with pseudo-stroke presentation have been reported with other chemotherapy agents such as methotrexate or 5-fluorouracil (5-FU), cases of leukoencephalopathy induced by capecitabine are less reported and less well known. This oral precursor of 5-FU is commonly used to treat colorectal, stomach or breast cancers. Neurotoxicity of other 5-FU derivates like cormafur and tergafur have rarely been depicted as well. Although 5-FU-induced leukoencephalopathy is known, the potential toxicity of its precursor should be acknowledged as well. Early detection of chemotherapy-induced toxicity by MRI is crucial as symptoms may be reversible to the condition that chemotherapy is immediately discontinued.

[Neurosarcoidosis: Diagnosis and therapeutic issues]. / Les atteintes neurologiques au cours de la sarcoïdose : diagnostic et traitement.

Neurological localizations of sarcoidosis are heterogeneous and may affect virtually every part of the central or peripheral nervous system. They are often the inaugural manifestation of sarcoidosis. The diagnosis may be difficult due to the lack of extra-neurological localization. Diagnosis may be discussed in the presence of an inflammatory neurological disease, in particular in case of suggestive radiological or biological pattern. Cerebrospinal fluid analysis shows lymphocytic pleiocytosis, often with low glucose level. The diagnosis relies on a clinical, biological and radiological presentation consistent with neurosarcoidosis, the presence of non-caseating granuloma and exclusion of differential diagnoses. Screening for other localizations of sarcoidosis, in particular cardiac disease may be obtained during neurosarcoidosis. The treatment of neurosarcoidosis relies on corticosteroids although immunosuppressive drugs are usually added because of the chronic course of this condition and to limit the side effects of steroids. Treatments and follow-up may be prolonged because of the high rate of relapses.