Use of gadolinium-based contrast agents in multiple sclerosis: a review by the ESMRMB-GREC and ESNR Multiple Sclerosis Working Group.

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

OBJECTIVES: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). METHODS: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. RESULTS: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. CONCLUSIONS: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. CLINICAL RELEVANCE STATEMENT: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. KEY POINTS: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Editorial Comment: Free water corrected diffusion tensor imaging discriminates between good and poor outcome of comatose patients after cardiac arrest.

KEY POINTS: • Prediction of neurological outcome after cardiac arrest is a major ethical challenge. • Diffusion tensor imaging (DTI) is a promising prognostic tool in comatose patients assessing brain microstructural damages. • The combination of clinical data with whole-brain fractional anisotropy and mean diffusivity values appears more accurate to predict poor outcome.

3-T MR neurography of lumbo-sacral plexus in hereditary transthyretin-related amyloidosis with polyneuropathy.

OBJECTIVES: Our aim was to evaluate the ability of magnetic resonance neurography (MRN) of the lumbo-sacral plexus (LSP) to distinguish patients with hereditary transthyretin-related amyloidosis with polyneuropathy (ATTRv-PN) from asymptomatic variant carriers (AVC) and healthy controls and to assess its prognostic value. METHODS: Three-Tesla MRN was performed in 25 consecutive ATTRv-PN patients, 18 AVC, and 10 controls including T2-w DIXON and DWI MR sequences. Two blinded readers independently assessed LSP root diameter and intraneural signal on the MRN images of each subject. MRN findings were compared between groups and correlated with clinical impairment scored on the Neuropathy Impairment Score (NIS) and the modified Polyneuropathy Disability score (mPND). RESULTS: The agreement between readers on MRN images was excellent (Cohen's kappa = 0.82). LSP root enlargement was significantly more frequent in ATTRv-PN patients compared to AVC (ratio = 4.38, p = 0.038). Increased LSP root intraneural signal on T2-w images was significantly more frequent in ATTRv-PN patients compared to AVC (ratio = 3.4, p = 0.016). In contrast, there were no MRN abnormalities in controls. In ATTRv-PN patients, LSP root enlargement was associated with higher mPND scores (p = 0.03) and increased intraneural signal on T2-w images was associated with significantly higher NIS and mPND scores (p = 0.004 and 0.02, respectively). CONCLUSIONS: MRN of the LSP can help differentiate ATTRv-PN patients from AVC. LSP root enlargement and increased intraneural signal are significantly associated with clinical impairment, suggesting potential implications for patient care. KEY POINTS: • ATTRv-PN patients showed abnormal LSP changes on MRN. • MRN of the LSP can help to differentiate ATTRv-PN patients from AVC and healthy controls. • LSP root enlargement and increased intraneural signal were significantly associated with clinical impairment in ATTRv-PN patients.

Diffusion tensor imaging MR neurography in patients with acute or chronic plexopathy.

The nerve plexus is susceptible to various pathological processes. In addition to clinical and electrophysiological findings, magnetic resonance neurography (MRN) may contribute to characterize plexus involvement. Diffusion tensor imaging (DTI) was reported feasible for the nerve plexuses imaging but its value in the clinical practice remains uncertain. From 2014 to 2020, we routinely performed MRN including DTI at 3T in patients with acute or chronic plexopathy. DTI images were co-registered with conventional MRN images. MRN images including DTI were reviewed by consensus by two neuroradiologists and one neurologist. They retrospectively identified cases for whom the use of DTI had a potential impact on the diagnostic workup, seven of these clinical cases are presented here. Compared to conventional MRN, the added value of DTI consisted in: (i) improved detection of signal/morphological abnormalities of the plexus (due to removal of background structures, multiplanar reformatted views and large field of view), (ii) additional information regarding the microarchitecture of nerve fibers provided by DTI metrics, (iii) potential alternative for the use of gadolinium. This case series supports the implementation of DTI in MRN protocols.

Mild encephalopathy with reversible splenial lesion: Description of nine cases and review of the literature.

Mild encephalopathy/encephalitis with reversible splenial lesion (MERS) is a transient clinico-radiological syndrome characterized by non-specific encephalopathy and specific magnetic resonance imaging (MRI) pattern. MRI shows an ovoid lesion in the mid-splenium of the corpus callosum (SCC), with signal-intensity anomaly similar to stroke but vanishing within few weeks. Although there are a lot of child MERS cases descriptions, there are just a few adult-onset reported. Our goal is to provide a better clinical and radiological description of this entity. We reported nine adult-onset cases of MERS managed in our stroke unit between 2017 and 2019. The study of our adult series suggests that epilepsy and the context of an infection are very common in MERS. Adult cases show frequent focal neurological deficits and few encephalopathies compared to children. The measurement of very low ADC values in SCC lesion is a new radiological feature of MERS that should be systematically assessed in suspected cases to differentiate this complex syndrome from SCC strokes.

High effector-memory CD8+ T-cell levels correlate with high PML risk in natalizumab-treated patients.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab (NTZ) treatment in multiple sclerosis (MS) patients. Based on the analysis of cryopreserved cells, several reports have showed that CD62L+ CD4+ T-cells percentage drops before PML onset. OBJECTIVE: To analyze CD62L and CD45RA expression on fresh-blood CD4+ and CD8+ T-cells from NTZ-treated patients, according to their estimated PML risk. METHODS: We prospectively enrolled 74 MS patients, including 62 NTZ-treated, and stratified them into low, intermediate and high PML risk groups. Circulating naïve and memory T-cell subsets were analyzed by flow cytometry. RESULTS: We found no correlation between the percentage of CD62L+ CD4+ T-cells and PML risk. In contrast, the repartition of CD8+ T-cells subpopulations was altered in the high risk group: both the percentage and absolute count of CD8+ CD62L- CD45RA- effector memory T- cells (TEM) was significantly higher compared to patients at lower risk despite similar CD3+ and CD8+ T-cell counts. One high-risk patient with elevated CD8+ TEM and CD62L+ CD4+ T-cell levels developed PML six months after sampling. CONCLUSION: Our results suggest that CD8+ TEM cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients.

Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis.

Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and further investigations are required to better understand and manage this complaint. A new imaging modality-the phosphorous magnetic resonance spectroscopy (31P-MRS)-might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores [i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS)] were collected. 31P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and ß-adenosine triphosphate (ß-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal ß-ATP % (p < 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.

Non-COVID-19 emergencies: where have all the patients gone?

KEY POINTS: • Early in the pandemic, numbers of patients undergoing non-COVID-19 emergent CTs dropped sharply but diagnostic yield did not increase, suggesting potentially undiagnosed emergencies in patients not seen in healthcare institutions.

Deciphering the neural underpinnings of alexithymia in multiple sclerosis.

OBJECTIVES: Alexithymia is a personality construct that could occur in up to 53 % of patients with multiple sclerosis (MS). It entails difficulties in identifying and describing one's feelings and an externally oriented thinking. The current work aims to assess the neural underpinnings of alexithymia in this population. METHODS: Forty-five patients with MS filled in the Toronto Alexithymia Scale (n = 17 with high alexithymia and n = 28 with low alexithymia). Brain magnetic resonance imaging was obtained for each patient and a morphometry algorithm (MorphoBox) was applied to calculate regional brain volumes. All patients underwent a clinical and neuropsychological evaluation which included measures for anxiety, depression, fatigue, daytime sleepiness, and basic and social cognition. RESULTS: Compared to patients with low alexithymia, patients with high alexithymia had significantly higher fatigue and depression ratings, and lower empathy scores. In addition, they had lower volumes of corpus callosum, deep white matter, pallidum bilaterally, and left thalamus. In the whole cohort, alexithymia scores were inversely correlated with gray matter (thalamus and pallidum bilaterally) and white matter volumes (corpus callosum and bilateral deep white matter) after controlling for covariates (ps<0.05). CONCLUSION: This study offers insights on the neuropsychological and neural substrates of alexithymia in MS. The current findings are consistent with alexithymia reports in other clinical populations, and suggest an association between alexithymia and atrophy of thalami, pallidum, corpus callosum and deep white matter in MS. Further research is needed to enhance the understanding of alexithymia mechanisms in this clinical context.

Post-contrast 3D T1-weighted TSE MR sequences (SPACE, CUBE, VISTA/BRAINVIEW, isoFSE, 3D MVOX): Technical aspects and clinical applications.

Post-contrast three-dimensional T1-weighted imaging of the brain is widely used for a broad range of vascular, inflammatory or tumoral diseases. The variable flip angle 3D TSE sequence is now available from several manufacturers (CUBE, General Electric; SPACE, Siemens; VISTA/BRAINVIEW, Philips; isoFSE, Itachi; 3D MVOX, Canon). Compared to gradient-echo (GRE) techniques, 3D TSE offers the advantages of useful image contrasts and reduction of artifacts from static field inhomogeneity. However, the respective role of 3D TSE and GRE MR sequences remains to be elucidated, particularly in the setting of post-contrast imaging. The purpose of this review was (1) to describe the technical aspects of 3D TSE sequences, (2) to illustrate the main clinical applications of the post-contrast 3D T1-w TSE sequence through clinical cases, (3) to discuss the respective role of post-contrast 3D TSE and GRE imaging in the field of neuroimaging.

Jugular venous reflux may mimic type I dural arterio-venous fistula on arterial spin labeling magnetic resonance images.

PURPOSE: Previous studies have shown that arterial spin-labeling (ASL) has high sensitivity and specificity for detecting dural arteriovenous fistulas (DAVFs). However, in case of jugular venous reflux (JVR), the labeled protons in the jugular vein may lead to a venous hypersignal in the jugular vein, sigmoid, and transverse sinus on ASL images and mimic DAVF. METHODS: To ascertain this hypothesis, two blinded senior neuroradiologists independently and retrospectively reviewed randomized ASL images and graded the likelihood of DAVF on a 5-point Likert scale in 2 groups of patients: (i) 13 patients with angiographically proven type I DAVF; and (ii) 11 patients with typical JVR diagnosed on the basis of clinical and MR imaging data, first using ASL alone, and second using ASL together with all of the sequences including 4D CE MRA. RESULT: A dural venous ASL signal was seen in 11 patients with type I DAVF and in all the 11 patients with JVR, with no distinctive pattern between the two. The mean Likert score was "very likely" in DAVF and JVR patients when using ASL alone (k = 0.71), and "very unlikely" for JVR versus "very likely" for DAVF when using all the sequences available (k = 0.92). CONCLUSION: Our study shows that JVR can mimic DAVF on ASL images with potential implications for patient care. The detection of DAVFs should be based on additional MR sequences such as TOF-MRA and 4D CE MRA to exclude JVR and to avoid unnecessary DSAs.

Intracranial aneurysms in sickle cell disease: Aneurysms characteristics and modalities of endovascular approach to treat these patients.

INTRODUCTION: The neurological complications of Sickle Cell Disease (SCD) include cerebral infarction and haemorrhage with rarely subarachnoid haemorrhage due to cerebral aneurysms. MATERIALS AND METHODS: In our interventional department, working with SCD referral department, we reported our experience concerning management of adult's patients with cerebral aneurysms. We identified 26 adults with 48 intracranial aneurysms documented by imaging. RESULTS: 18 patients, with 26 cerebral aneurysms were treated by endovascular approach for their aneurysms. No patient was treated by surgical way in our institution. 50% of patients had multiple aneurysms. Locations of aneurysms treated were typical with 70% of cerebral anterior artery and 30% of posterior artery. Three patients suffered from subarachnoid haemorrhage. Two procedure-related complications occurred during the treatment: one thrombo-embolic event with good recovery after medical treatment and one aneurismal perforation leading to the death of patient. Hypercoagulability is a major specific risk in SCD and use of permanent device as stent of flow diverter should be discussed to prevent complications. CONCLUSION: Endovascular management of these aneurysms seems to be a good alternative to treat these patients, with stability of occlusion at follow-up.

Acute Hippocampal Encephalopathy in Heavy Cannabis Users: About 2 Cases.

BACKGROUND: Cannabis use is increasing worldwide despite the various health effects of this substance. METHODS: We report 2 cases of acute hippocampal encephalopathy in heavy cannabis users (>10 joints/d). RESULTS: In both male patients, acute encephalitis was suspected. Brain magnetic resonance imaging (MRI) diffusion-weighted sequences showed bilateral high signal abnormalities in hippocampal regions. Patients had renal dysfunction, rhabdomyolysis, and inflammatory syndrome. Investigations showed no evidence of infectious or autoimmune encephalitides. Repeated electroencephalograms revealed no epileptic activity. Clinical, biological, and magnetic resonance imaging acute abnormalities improved within weeks. New exposure to cannabis yielded a new episode of encephalopathy. In both patients, severe long-lasting episodic memory impairment associated with hippocampal atrophy were observed several months later. CONCLUSIONS: Health professionals should be aware of this cannabis-related syndrome given its severe and long-lasting effects.

Idiopathic Normal-Pressure Hydrocephalus: Diagnostic Accuracy of Automated Sulcal Morphometry in Patients With Ventriculomegaly.

BACKGROUND: Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of gait and cognitive impairment. iNPH should be differentiated from ventriculomegaly secondary to brain atrophy to choose the best therapeutic option (ventriculoperitoneal shunt vs medical management). OBJECTIVE: To determine the diagnostic accuracy of automated sulcal morphometry to differentiate patients with iNPH from patients with ventriculomegaly of neurodegenerative origin. METHODS: Thirty-eight consecutive patients with iNPH (shunt responsive n = 31, nonresponsive n = 7), 35 with vascular cognitive disorder, and 25 age- and sex-matched healthy controls were prospectively included and underwent cognitive evaluation and 3T brain magnetic resonance imaging. Sulcal opening of 10 sulci of interest was retrospectively measured using an automated surface-based approach from the 3-dimensional T1-weighted images. Receiver-operating characteristic curve analyses determined the best parameter to identify iNPH patients. RESULTS: The best parameter to discriminate shunt-responsive iNPH from patients with vascular cognitive disorder and healthy controls was the ratio between calcarine sulcus and cingulate sulcus opening with an area under the curve of 0.94 (95% CI: 0.89, 0.99). A cut-off value of 0.95 provided the highest sensitivity (96.8%) and specificity (83.3%). CONCLUSION: This preliminary study showed that automated sulcal morphometry may help the neurosurgeon to identify iNPH patients and to exclude other causes of ventriculomegaly.

Optical coherence tomography: a window to the optic nerve in clinically isolated syndrome.

In this study, we aimed to evaluate the association of asymptomatic optic nerve demyelinating lesion in patients presenting a clinically isolated syndrome with the asymptomatic retinal neuro-axonal loss previously reported at clinically isolated syndrome. We prospectively recruited 66 patients presenting a clinically isolated syndrome and 66 healthy control subjects matched according to age and gender. All patients underwent brain magnetic resonance imaging including 3D-double inversion recovery (DIR) sequence, optical coherence tomography examination and visual function evaluation, at 2.5-4.5 months after CIS. Evaluation criteria were presence and length of optic nerve DIR hypersignal, retinal layers (including ganglion cell inner plexiform layer and inner nuclear layer) thickness/volume, and low contrast monocular vision acuity (number of letters correctly identified). All clinically isolated syndrome eyes with past history of optic neuritis (CIS-ON) presented an optic nerve DIR hypersignal. We observed asymptomatic optic nerve DIR hypersignal in 22.2% of clinically isolated syndrome eyes without optic neuritis (CIS-NON). In comparison with healthy control, GCIPL volume (in mm3) was significantly lower in CIS-ON eyes [ß (95% confidence interval, CI) = -0.121 (-0.168 to -0.074); P < 0.0001], and to a lesser extent in CIS-NON [ß (95% CI) = -0.023 (-0.039 to -0.008); P = 0.004]. In comparison to healthy controls, eyes with asymptomatic optic nerve DIR hypersignal presented significantly lower macular ganglion cell inner plexiform layer volume [ß (95% CI) = -0.043 (-0.068 to -0.019); P = 0.001], and eyes without did not [ß (95% CI) = -0.016 (-0.034 to 0.003); P = 0.083]. Among CIS-NON, macular ganglion cell inner plexiform layer volume decrease was associated with asymptomatic optic nerve DIR hypersignal independently of optic radiations T2 lesions and primary visual cortex volumes (P = 0.012). Symptomatic optic nerve DIR hypersignal were significantly longer (13.8 ± 6.7 mm) than asymptomatic optic nerve hypersignal (10.0 ± 5.5 mm; P = 0.047). Length of optic nerve DIR hypersignal was significantly associated with thinner inner retinal layers (P ≤ 0.001), thicker inner nuclear layer (P = 0.017) and lower low contrast monocular vision acuity (P < 0.05). Compared to healthy control, low contrast monocular vision acuity was significantly lower in CIS-ON eyes (P < 0.0001) and CIS-NON eyes with (P = 0.03) or without asymptomatic optic nerve DIR hypersignal (P = 0.0005). Asymptomatic demyelinating optic nerve DIR hypersignal at the earliest clinical stage of multiple sclerosis is frequent and associated with asymptomatic retinal neuro-axonal loss reported at clinically isolated syndrome stage. Length of optic nerve DIR hypersignal is a biomarker of retinal neuro-axonal loss and visual disability at clinically isolated syndrome stage. Visual disability of clinically isolated syndrome eyes without clinical and subclinical optic nerve involvement might be due to missed optic nerve lesions on MRI. At the earliest clinical stage of multiple sclerosis, our results support considering optical coherence tomography as a window to the optic nerve rather than to the brain.