Longitudinal Retinal Changes in MOGAD.

OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N = 66 and HCs: N = 103) and (2) Cirrus high-definition OCT (MOGAD: N = 14 and HCs: N = 36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HCs (p < 0.001). MOGAD-NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow-up up to 3 years), MOGAD-ON with ON within the last 6-12 months before baseline exhibited greater pRNFL thinning than MOGAD-ON with an ON greater than 12 months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort. INTERPRETATION: Our study suggests the absence of attack-independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476-485.

Long-term effect of natalizumab in patients with RRMS: TYSTEN cohort.

BACKGROUND: Data are needed on long-term effect of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To evaluate the time of onset of secondary progressive phase in patients with an RRMS treated with NTZ and to investigate predictive factors. METHODS: TYSTEN is an observational study. Patients starting NTZ between 2007 and 2012 were included and followed up until October 2018. Relapses, Expanded Disability Status Scale (EDSS) scores, and results of brain magnetic resonance imaging (MRI) were collected each year. Data were used to estimate the cumulative probability of several poor outcomes such as secondary progressive multiple sclerosis (SPMS) conversion, EDSS worsening, EDSS 4.0, and EDSS 6.0. RESULTS: 770 patients were included. The mean follow-up duration was 97 months and the mean time exposure to NTZ was 66 months. At 10 years, the cumulative probability of SPMS was 27.7%. Predictive factors for poor outcomes were a ⩾1-point increase in EDSS score from baseline, new T2 lesion or T1 gadolinium-enhancing lesion, the occurrence of relapse at 1 or 2 years and No Evidence of Disease Activity (NEDA-3; no relapse, no new T2 or T1 gadolinium-enhancing lesions, no progression) was a protective factor. CONCLUSION: In our cohort of patients treated with NTZ, poor outcomes were infrequent and are driven by disease activity.

Patterns of use, effectiveness and safety of gadolinium contrast agents: a European prospective cross-sectional multicentre observational study.

BACKGROUND: The EU gadolinium-based contrast agents (GBCA) market has changed in recent years due to the European Medicines Agency decision to suspend the marketing authorisation of linear GBCA and the marketing authorisation of new generic macrocyclic GBCA. The study aims to understand the patterns of (GBCA) use, and to study the effectiveness and safety of GBCA in routine practice across Europe. METHODS: Prospective, cross-sectional, multicentre, observational study in patients undergoing contrast-enhanced magnetic resonance. Reported usage patterns included indication, referral and examination details. Assessment of effectiveness included changes in radiological diagnosis, diagnostic confidence and image quality. Safety data were collected by spontaneous patient adverse event (AE) reporting. RESULTS: 2118 patients were included from 8 centres across 5 European countries between December 2018 and November 2019. Clariscan, Dotarem (gadoteric acid), Gadovist (gadobutrol) and ProHance (gadoteridol) were utilised in 1513 (71.4%), 356 (16.8%), 237 (11.2%) and 12 (0.6%) patients, respectively. Most were performed in CNS-related indications (46.2%). Mean GBCA doses were 0.10 mmol/kg body weight, except for Gadovist (mean 0.12 mmol/kg). GBCA use increased confidence in diagnosis in 96.2% of examinations and resulted in a change in radiological diagnosis in 73.9% of patients. Image quality was considered excellent or good in 96.1% of patients and across all GBCA. Four patients reported AEs (0.19%), with only 1 (0.05%) considered serious. CONCLUSIONS: This European study confirmed that GBCAs are used appropriately in Europe for a wide range of indications. The study demonstrated a significant increase in diagnostic confidence after GBCA use and confirmed the good safety profile of GBCAs, with comparable results for all agents used.

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.

A Fully Automatic Method for Optic Radiation Tractography Applicable to Multiple Sclerosis Patients.

The optic radiations (OR) are white matter tracts forming the posterior part of the visual ways. As an important inter-individual variability exists, atlases may be inefficient to locate the OR in a given subject. We designed a fully automatic method to delimitate the OR on a magnetic resonance imaging using tractography. On 15 healthy subjects, we evaluated the validity of our method by comparing the outputs to the Jülich post-mortem histological atlas, and its reproducibility. We also evaluated its feasibility on 98 multiple sclerosis (MS) patients. We correlated different visual outcomes with the inflammatory lesions volume within the OR reconstructed with different methods (our method, atlas, TractSeg). Our method reconstructed the OR bundle in all healthy subjects (< 2 h for most of them), and was reproducible. It demonstrated good classification indexes: sensitivity up to 0.996, specificity up to 0.993, Dice coefficient up to 0.842, and an area under the receiver operating characteristic (ROC) curve of 0.981. Our method reconstructed the OR in 91 of the 98 MS patients (92.9%, < 6 h for most of patients). Compared to an atlas-based approach and the TractSeg method, the inflammatory lesions volume in the OR measured with our method better correlated with the visual cortex volume, visual acuity and mean peripapillar retinal nerve fiber layer thickness. Our method seems to be efficient to reconstruct the OR in healthy subjects, and seems applicable to MS patients. It may be more relevant than an atlas based approach.

Optical coherence tomography in myelin-oligodendrocyte-glycoprotein antibody-seropositive patients: a longitudinal study.

BACKGROUND: Serum antibodies against myelin-oligodendrocyte-glycoprotein (MOG-IgG) are detectable in a proportion of patients with acute or relapsing neuroinflammation. It is unclear, if neuro-axonal damage occurs only in an attack-dependent manner or also progressively. Therefore, this study aimed to investigate longitudinally intra-retinal layer changes in eyes without new optic neuritis (ON) in MOG-IgG-seropositive patients. METHODS: We included 38 eyes of 24 patients without ON during follow-up (F/U) [median years (IQR)] 1.9 (1.0-2.2) and 56 eyes of 28 age- and sex-matched healthy controls (HC). The patient group's eyes included 18 eyes without (EyeON-) and 20 eyes with history of ON (EyeON+). Using spectral domain optical coherence tomography (OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIP), inner nuclear layer (INL), and macular volume (MV). High-contrast visual acuity (VA) was assessed at baseline. RESULTS: At baseline in EyeON-, pRNFL (94.3 ± 15.9 µm, p = 0.36), INL (0.26 ± 0.03 mm3, p = 0.11), and MV (2.34 ± 0.11 mm3, p = 0.29) were not reduced compared to HC; GCIP showed thinning (0.57 ± 0.07 mm3; p = 0.008), and VA was reduced (logMAR 0.05 ± 0.15 vs. - 0.09 ± 0.14, p = 0.008) in comparison to HC. Longitudinally, we observed pRNFL thinning in models including all patient eyes (annual reduction - 2.20 ± 4.29 µm vs. - 0.35 ± 1.17 µm, p = 0.009) in comparison to HC. Twelve EyeON- with other than ipsilateral ON attacks ≤ 6 months before baseline showed thicker pRNFL at baseline and more severe pRNFL thinning in comparison to 6 EyeON- without other clinical relapses. CONCLUSIONS: We observed pRNFL thinning in patients with MOG-IgG during F/U, which was not accompanied by progressive GCIP reduction. This effect could be caused by a small number of EyeON- with other than ipsilateral ON attacks within 6 months before baseline. One possible interpretation could be a reduction of the swelling, which could mean that MOG-IgG patients show immune-related swelling in the CNS also outside of an attack's target area.

Optic nerve double inversion recovery hypersignal in patients with clinically isolated syndrome is associated with asymptomatic gadolinium-enhanced lesion.

BACKGROUND: Optic nerve involvement is not considered in dissemination in space (DIS) or time (DIT) of multiple sclerosis (MS) lesions. OBJECTIVES: To evaluate frequency of optic nerve involvement using three-dimensional (3D)-double inversion recovery (DIR) sequence in clinically isolated syndrome (CIS) and to measure its relationship with DIS and DIT (2010 and 2017 McDonald criteria). METHODS: From November 2013 to August 2016, 57 CIS patients underwent 3T-magnetic resonance imaging (3T-MRI) including 3D-DIR sequence and optical coherence tomography (OCT) at 3 months after CIS. We assessed signal abnormalities of the optic nerves on DIR sequence and collected data for DIS and DIT criteria according to 2010 and 2017 McDonald criteria. RESULTS: Among the 57 recruited patients, the presence of ⩾1 DIR hypersignal in optic nerve was observed in 36 (63%; 48 optic nerves) including asymptomatic hypersignal in 22 (38.5%; 25 optic nerves). Optic nerve involvement was significantly associated with DIT (p = 0.006) and MS according to 2010 criteria (p = 0.01) but was not significantly associated with presence of DIS criteria according to 2010 and 2017 McDonald criteria. We identified a significant (p < 0.001) temporal peripapillary retinal nerve fiber layer thinning on eyes with optic nerve involvement versus healthy controls. CONCLUSIONS: Optic nerve involvement is very frequent at the earliest clinical stage of MS. It is associated with the presence of asymptomatic gadolinium-enhancement and retinal axonal loss and may reflect the inflammatory disease activity level.

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

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.

Magnetic resonance imaging changes following natalizumab discontinuation in multiple sclerosis patients with progressive multifocal leukoencephalopathy.

BACKGROUND: Detecting early progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant. OBJECTIVE: Evaluating magnetic resonance imaging (MRI) changes following natalizumab (NTZ) discontinuation and preceding PML-IRIS. METHODS: MRIs (including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were performed every week following PML diagnosis in 11 consecutive NTZ-PML patients. PML expansion, punctate lesions, contrast-enhancement, and mass-effect/edema were evaluated on each MRI sequence, following NTZ discontinuation. RESULTS: PML-IRIS occurred from 26 to 89 days after NTZ discontinuation. MRI changes prior to early PML-IRIS appeared significantly more pronounced using DWI compared to T2-FLAIR imaging (p < 0.003). Two DWI features (marked PML expansion, punctate lesions) systematically preceded contrast-enhancement. CONCLUSION: Subtle changes may occur on DWI preceding contrast-enhancement.

Altered signal intensity of active enhancing inflammatory lesions using post-contrast double inversion recovery MR sequence.

OBJECTIVES: We aimed at establishing the impact upon gadolinium administration on the conspicuity of active enhancing multiple sclerosis (MS) lesions using double inversion recovery (DIR) at 3T. METHODS: 15 consecutive patients with MS (n=8) or a clinically isolated syndrome (n=7) underwent pre and post-contrast DIR in addition to T2-weighted, FLAIR, pre and post-contrast T1-weighted sequences. First, two neuroradiologists located and marked all the enhancing MS lesions visible in consensus. Second, two other neuroradiologists, blinded to other sequences than DIR, independently assessed the SI changes from pre to post-contrast DIR images for each enhancing lesion, according to a 4-point-scale: increased SI (grade 1), absence of change (grade 2), lesion being partially (grade 3) or completely masked on post-contrast DIR images (grade 4). RESULTS: 246 MS lesions were detected including 26 enhancing on post-contrast T1-weighted images in 9 patients. The two blinded readers concluded to a decreased signal-intensity on post-contrast DIR images for all the 26 enhancing MS lesions (14 of grade 3 and 12 of grade 4). Inter-observer agreement was excellent, Kappa=0.85 (0.75 - 0.94). Using DIR post-contrast leads to altered signal-intensity of enhancing active MS lesions, ranging from partial to complete signal-loss. CONCLUSION: Our study strongly suggests the use of DIR before gadolinium administration. KEY POINTS: • DIR has gained widespread use in MS. • MRI protocols for MS patients usually contain several post-contrast sequences. • Signal-intensity of enhancing MS lesions is altered using DIR post-contrast. • Our study strongly suggests the use of DIR before gadolinium administration.

Asymptomatic Progressive Multifocal Leukoencephalopathy Associated with Natalizumab: Diagnostic Precision with MR Imaging.

PURPOSE: To determine diagnostic precision with magnetic resonance (MR) imaging of the brain, the most predictive MR imaging features, and the added value of comparison with previous data for the diagnosis of asymptomatic progressive multifocal leukoencephalopathy (PML) associated with natalizumab (NTZ). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and written informed consent was obtained. Eleven consecutive patients with multiple sclerosis (MS) who had received a definitive diagnosis of asymptomatic NTZ-associated PML (NTZ PML, 18 brain lesions) underwent 3-T MR imaging. The control group included 40 patients with MS but without PML who were treated with NTZ. Three readers independently performed blinded analysis of MR images. First, the readers were asked to detect NTZ PML lesions without comparing current images with previously obtained MR imaging data by evaluating MR images for the following features: U fiber and/or cortex involvement, lesion signal intensity and borders, and occurrence of punctate lesions. Second, they reassessed NTZ PML lesions with all the previous MR imaging data available. Diagnostic precision with MR imaging was assessed with and without comparison with previously obtained data. Logistic regression analyses were performed to identify the association of MR imaging features with NTZ PML. RESULTS: Overall interobserver agreement was good (κ = 0.76; 95% confidence interval [CI]: 0.71, 0.81). Hyperintensity on diffusion-weighted images and involvement of U fibers were the most predictive features (odds ratio, 33.7; 95% CI: 4.9, 229.7 [P < .0001] and odds ratio, 8.7; 95% CI: 1.2, 61.4 [P = .03], respectively), while punctate lesions were exclusively observed in patients with NTZ PML. Comparison with previous MR imaging data improved specificity of MR imaging for the detection of NTZ PML lesions (from 88% to 100%, P = .05). CONCLUSION: Recognition of the most predictive imaging features and comparison with previous MR imaging data may facilitate the detection of asymptomatic NTZ PML.

Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.

A comparative optical coherence tomography study in neuromyelitis optica spectrum disorder and multiple sclerosis.

OBJECTIVES: The aim of this study was to find, using spectral domain-optical coherence tomography (SD-OCT), retinal imaging biomarkers differentiating neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS) and healthy controls (HCs). MATERIALS AND METHODS: The population was composed of patients with NMOSD (n=23) or MS (n=110) and of HCs (n=75). Evaluation criteria were retinal thickness/volume, visual acuity, low contrast vision acuity and Expanded Disability Status Scale score. RESULTS: Considering all eyes and after statistical adjustments including the number of optic neuritis (ON) episodes, we found that NMOSD patients did not have significantly more retinal atrophy than MS patients; whereas MS non-optic neuritis (NON) eyes had thinner temporal (p=0.032) and temporo-superior peripapillary retinal nerve fibre layer (pRNFL; p=0.011) thicknesses than NMOSD NON eyes; in addition, NMOSD NON eyes presented significant naso-inferior pRNFL (p=0.024), temporal pRNFL (p=0.039), macular ganglion cell complex (p=0.004) and ganglion cell layer (p=0.002) atrophy vs HC eyes. We identified significant correlations between visual and clinical disability and retinal thicknesses in both diseases. CONCLUSION: OCT may help to differentiate NMOSD and MS by focusing on the NON eyes (temporal pRNFL atrophy more severe in MS). Moreover, we discuss the possibility of a retinal degenerative process independent of ON in NMOSD.

JC-virus seroconversion in multiple sclerosis patients receiving natalizumab.

AIM: The objectives of this study were to evaluate the rate of JC virus (JCV) seroconversion/seroreversion in a French cohort of multiple sclerosis (MS) patients receiving natalizumab (NTZ), describe the characteristics of this population, identify risk factors for JCV seropositivity and analyse the additional value of quantitative JCV serology results in this context. METHODS: MS patients from two French MS centres, whose JCV serological status in 2011 while receiving NTZ was known (n=357; first-generation enzyme-linked immunosorbent assay (ELISA) test (Gen1)), were proposed for inclusion in this study. We evaluated the rate of JCV seroconversion over a period of one year with a second-generation ELISA test (Gen2; n=303) and analysed the quantitative results. Multivariate analysis was performed to identify risk factors for JCV seropositivity. RESULTS: Among the patients with Gen2 JCV serology (n=303) that had been JCV-seronegative one year before (n=165), the rate of JCV seroconversion was 26.67% (44/165). We observed a higher proportion of anti-JCV antibody seroconverters (14.5%) than expected (≤3%) but also increasing index values of anti-JCV antibody over time. CONCLUSION: Our data suggest that JCV reactivation occurs during NTZ therapy and leads to an increase in the anti-JCV antibodies titre, thus making them more easily detectable by the second-generation ELISA test.

Comparison of 3D double inversion recovery and 2D STIR FLAIR MR sequences for the imaging of optic neuritis: pilot study.

OBJECTIVES: We compared the three-dimensional (3D) double inversion recovery (DIR) magnetic resonance imaging (MRI) sequence with the coronal two-dimensional (2D) short tau inversion recovery (STIR) fluid-attenuated inversion recovery (FLAIR) for the detection of optic nerve signal abnormality in patients with optic neuritis (ON). METHODS: The study group consisted of 31 patients with ON (44 pathological nerves) confirmed by visual-evoked potentials used as the reference. MRI examinations included 2D coronal STIR FLAIR and 3D DIR with 3-mm coronal reformats to match with STIR FLAIR. Image artefacts were graded for each portion of the optic nerves. Each set of MR images (2D STIR FLAIR, DIR reformats and multiplanar 3D DIR) was examined independently and separately for the detection of signal abnormality. RESULTS: Cisternal portion of optic nerves was better delineated with DIR (p < 0.001), while artefacts impaired analysis in four patients with STIR FLAIR. Inter-observer agreement was significantly improved (p < 0.001) on 3D DIR (κ = 0.96) compared with STIR FLAIR images (κ = 0.60). Multiplanar DIR images reached the best performance for the diagnosis of ON (95% sensitive and 94% specific). CONCLUSIONS: Our study showed a high sensitivity and specificity of 3D DIR compared with STIR FLAIR for the detection of ON. These findings suggest that the 3D DIR sequence may be more useful in patients suspected of ON. KEY POINTS: 3D DIR is increasingly used in neuroradiology. Compared with STIR FLAIR, 3D DIR improves detection of optic neuritis. Multiplanar analysis had the best diagnostic performance for optic nerve signal abnormalities. Sensitivity was 95% and specificity 94%. Findings support the use of 3D DIR instead of 2D sequences.

3D mapping of cerebrospinal fluid local volume changes in patients with hydrocephalus treated by surgery: preliminary study.

OBJECTIVE: To develop automated deformation modelling for the assessment of cerebrospinal fluid (CSF) local volume changes in patients with hydrocephalus treated by surgery. METHODS: Ventricular and subarachnoid CSF volume changes were mapped by calculating the Jacobian determinant of the deformation fields obtained after non-linear registration of pre- and postoperative images. A total of 31 consecutive patients, 15 with communicating hydrocephalus (CH) and 16 with non-communicating hydrocephalus (NCH), were investigated before and after surgery using a 3D SPACE (sampling perfection with application optimised contrast using different flip-angle evolution) sequence. Two readers assessed CSF volume changes using 3D colour-encoded maps. The Evans index and postoperative volume changes of the lateral ventricles and sylvian fissures were quantified and statistically compared. RESULTS: Before surgery, sylvian fissure and brain ventricle volume differed significantly between CH and NCH (P = 0.001 and P = 0.025, respectively). After surgery, 3D colour-encoded maps allowed for the visual recognition of the CSF volume changes in all patients. The amounts of ventricle volume loss of CH and NCH patients were not significantly different (P = 0.30), whereas readjustment of the sylvian fissure volume was conflicting in CH and NCH patients (P < 0.001). The Evans index correlated with ventricle volume in NCH patients. CONCLUSION: 3D mapping of CSF volume changes is feasible providing a quantitative follow-up of patients with hydrocephalus. KEY POINTS: • MRI can provide helpful information about cerebrospinal fluid volumes. • 3D CSF mapping allows quantitative follow-up in communicating and non-communicating hydrocephalus. • Following intervention, fissures and cisterns readjust in both forms of hydrocephalus. • These findings support the hypothesis of suprasylvian block in communicating hydrocephalus. • 3D mapping may improve shunt dysfunction detection and guide valve pressure settings.

Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness z Scores.

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted z scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS). METHODS: We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted z scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests. RESULTS: In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], p = 3.82e-5). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], p = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], p = 0.04). Compared with raw values with arbitrary cutoffs, applying the z score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score). DISCUSSION: In conclusion, our work demonstrated reference cohort-based z scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.

Fluid-attenuated inversion recovery vascular hyperintensities are not visible using 3D CUBE FLAIR sequence.

OBJECTIVE: Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH), initially described on 2D FLAIR images, are a useful imaging marker in patients with acute ischaemic stroke. We aimed to compare the sensitivity of the 3D CUBE FLAIR sequence with 2D FLAIR for the detection of FVH. METHODS: Forty-seven consecutive patients admitted for a suspected stroke were explored by 2D and 3D CUBE FLAIR MR sequences at 1.5 and 3 T. Three blinded readers assessed FVH defined as hyperintensities within cerebral arteries. Location of FVH, acute brain infarct and arterial stenosis were also assessed. 2D images were compared with 3D images for the detection of FVH. Agreement between readers was assessed. RESULTS: Of the 47 patients, 21 FVHs were observed on 2D FLAIR images of 15 patients (11 with acute brain infarct and 11 with an arterial stenosis). No FVH was visualised on 3D CUBE FLAIR images for either proximal or distal locations. Agreement between readers was excellent. CONCLUSION: FVHs are not visible using 3D CUBE FLAIR images. This study suggests that, in suspected acute ischaemic stroke, the assessment of FVH should only be performed on conventional 2D FLAIR images. KEY POINTS: • Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are of neuroradiological importance. • FVHs are useful imaging markers in patients with an acute ischaemic stroke. • FVHs are not visible using 3D CUBE FLAIR images. • Assessment of FVH should be performed on conventional 2D FLAIR images.

Extensive myelitis associated with anti-NMDA receptor antibodies.

BACKGROUND: Encephalitis with anti-N-methyl-D-aspartate receptor antibodies (anti-NMDAR-Ab) is a rapid-onset encephalitis including psychosis, seizures, various movement disorders and autonomic system disturbances. CASE PRESENTATION: We report a very unusual case of extensive myelitis associated with anti-NMDAR-Ab. MRI also revealed a hyperintense T2 lesion, non-suggestive of MS, which progressively extended, associated with periventricular gadolinium enhancement visualized on brain MRI. Ophthalmological evaluation showed subclinical right optic neuritis. The absence of anti-AQP4 antibody argued against neuromyelitis optica spectrum disorder. A slight psychomotor slowing prompted us to search for various causes of autoimmune encephalitis. Anti-NMDAR-Ab was found in cerebrospinal fluid. CONCLUSION: In patients with extensive myelitis who are seronegative for anti-AQP4 antibodies, and after other classical causes have been excluded, the hypothesis of atypical anti-NMDAR-Ab encephalitis should also be considered.

Relation between retina, cognition and brain volumes in MS: a consequence of asymptomatic optic nerve lesions.

INTRODUCTION: Asymptomatic optic nerve lesions are frequent in multiple sclerosis (MS) and their impact on cognition and/or brain volume has never been taken into account. PATIENTS AND METHODS: We used the data from the cross-sectional Visual Ways in MS (VWIMS) study including relapsing remitting MS. All patients underwent brain and optic nerve Magnetic Resonance Imaging (MRI) including Double Inversion Recuperation (DIR) sequence, retinal OCT, and cognitive evaluation with the Brief International Cognitive Assessment in MS (BICAMS). We measured the association between OCT findings (thickness/volume of retinal layers) and extra-visual parameters (cerebral volumes and BICAMS scores) in optic nerves with and/or without the presence of DIR asymptomatic optic nerve hypersignal. RESULTS: Between March and December 2017, we included 98 patients. Two patients were excluded. Over the 192 eyes, 73 had at least one clinical history of optic neuritis (ON-eyes) whereas 119 were asymptomatic (NON-eyes). Among the 119 NON-eyes, 58 had 3D-DIR optic nerve hypersignal (48.7%). We confirmed significant associations between some retinal OCT measures and some extra-visual parameters (cerebral volumes, cognitive scores) in NON-eyes. Unexpectedly, these associations were found when an asymptomatic optic nerve DIR-hypersignal was present on MRI, but not when it was absent. CONCLUSION: Our study showed a relation between OCT measures and extra-visual parameters in NON-eyes MS patients. As a confusion factor, asymptomatic optic nerve lesions may be the explanation of the relation between OCT measures and extra-visual parameters. Retinal OCT seems to be far more a "window over the optic nerve" than a "window over the brain".