MRI characteristics of MOG-Ab associated disease in adults: An update.

Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.

How much progress has there been in the second-line treatment of multiple sclerosis: A 2017 update.

In 1993, the US Food and Drug Administration (FDA) approved the first drug specifically for treating multiple sclerosis (MS). More than two decades later, a dozen such treatments are now available. Of these, four are considered second-line treatments for use in escalation strategies and two new drugs are currently undergoing accreditation procedures. Soon, they will provide clinicians with a range of six effective disease-modifying treatments (DMTs) to thwart the inflammatory processes in MS patients with active disease. However, while such a large number of DMTs for MS can help to control early inflammation, any decisions to be made by clinicians have also been made substantially more complex. This complexity is increased by the lack of head-to-head studies comparing these second-line therapies and the benefit-risk profiles for each of these drugs, which are likely to vary among patients. Ultimately, good awareness of the benefits and, more important, the risks of each MS DMT is crucial for the effective management of inflammation in MS.

Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders

There is growing evidence of a preventive effect of Rituximab (RTX) in neuromyelitis optica spectrum disorders (NMO-SD). This monoclonal antibody against CD20 is becoming the most widely used preventive therapy in NMO-SD, as a first-line therapy or as a rescue therapy. Nevertheless, considerable heterogeneity still exists concerning the pre-treatment work-up, the vaccinations required before and under treatment, the number and dosage of infusions, prevention of the risk of infusion-related reactions, prevention of infections under treatment, and frequency of therapeutic cycles. Thanks to a collaborative work among NMO-SD experts belonging to the NOMADMUS project, we provide here recommendations for all these topics concerning RTX use in NMO-SD.

Efficacy of rituximab in refractory neuromyelitis optica.

BACKGROUND: Despite a growing use of rituximab (RTX) in neuromyelitis optica (NMO), data are lacking in patients with refractory NMO (RNMO), defined as cases with at least one relapse during immunosuppressive therapy. OBJECTIVE: The purpose of this study was to assess RTX as a maintenance therapy in RNMO. METHODS: Out of a total of 305 NMO cases from a population-based cohort, 21 RNMO patients received RTX during a mean follow-up period of 31 months. RESULTS: After RTX, 11 patients (52.3%) were relapse free, meaning that 47.7% were refractory to RTX. The mean annualized relapse rate decreased from 1.3 to 0.4 (p<0.001) and median EDSS from 5 to 3 (p=0.02). Body mass index (BMI) was predictive of EDSS worsening. CONCLUSIONS: RTX is an effective and well-tolerated treatment in RNMO. BMI could be a predictive factor for efficacy.

In-line femtosecond common-path interferometer in reflection mode.

An innovative method to perform femtosecond time-resolved interferometry in reflection mode is proposed. The experiment consists in the combined use of a pump-probe setup and of a fully passive in-line femtosecond common-path interferometer. The originality of this interferometer relies on the use of a single birefringent crystal first to generate a pair of phase-locked pulses and second to recombine them to interfere. As predicted by analytical modeling, this interferometer measures the temporal derivative of the ultrafast changes of the complex optical reflection coefficient of the sample. Working conditions are illustrated through picosecond opto-acoustic experiments on a thin film.

Picosecond time resolved opto-acoustic imaging with 48 MHz frequency resolution.

A compact femtosecond dual-oscillator pump-probe setup with 48 MHz-repetition rate, relying on asynchronous optical sampling, is presented. The relative timing jitter between both lasers over the whole pump-probe delay range is of the order of or lower than 500 fs. We demonstrate that both a picosecond temporal resolution and a 48 MHz spectral resolution combined with the fast acquisition rate inherent to the asynchronous optical sampling allow performing broadband opto-acoustic imaging with a spectrum covering more than two decades from 300 MHz to 150 GHz. As an illustration, the opto-acoustic response of a supported thin film is investigated, revealing high frequency acoustic echoes close to the epicenter as well as low GHz surface acoustic waves propagating up to 40µm away from the epicenter. Semi-analytical calculations have been carried out and perfectly reproduce the dispersion of the surface acoustic waves experimentally observed.

[Nosology and etiologies of acute longitudinally extensive transverse myelitis]. / Cadre nosologique et stratégie diagnostique de la myélite aiguë transverse longitudinalement étendue.

Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment.

Contribution of the MP2RAGE 7T Sequence in MS Lesions of the Cervical Spinal Cord.

BACKGROUND AND PURPOSE: The detection of spinal cord lesions in patients with MS is challenging. Recently, the 3D MP2RAGE sequence demonstrated its usefulness at 3T. Benefiting from the high spatial resolution provided by ultra-high-field MR imaging systems, we aimed to evaluate the contribution of the 3D MP2RAGE sequence acquired at 7T for the detection of MS lesions in the cervical spine. MATERIALS AND METHODS: Seventeen patients with MS participated in this study. They were examined at both 3T and 7T. The MR imaging examination included a Magnetic Imaging in MS (MAGNIMS) protocol with an axial T2*-WI gradient recalled-echo sequence ("optimized MAGNIMS protocol") and a 0.9-mm isotropic 3D MP2RAGE sequence at 3T, as well as a 0.7-mm isotropic and 0.3-mm in-plane-resolution anisotropic 3D MP2RAGE sequences at 7T. Each data set was read by a consensus of radiologists, neurologists, and neuroscientists. The number of lesions and their topography, as well as the visibility of the lesions from one set to another, were carefully analyzed. RESULTS: A total of 55 lesions were detected. The absolute number of visible lesions differed among the 4 sequences (linear mixed effect ANOVA, P = .020). The highest detection was observed for the two 7T sequences with 51 lesions each (92.7% of the total). The optimized 3T MAGNIMS protocol and the 3T MP2RAGE isotropic sequence detected 41 (74.5%) and 35 lesions (63.6%), respectively. CONCLUSIONS: The 7T MP2RAGE sequences detected more lesions than the 3T sets. Isotropic and anisotropic acquisitions performed comparably. Ultra-high-resolution sequences obtained at 7T improve the identification and delineation of lesions of the cervical spinal cord in MS.

High-risk syndrome for neuromyelitis optica: a descriptive and comparative study.

BACKGROUND: Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies. OBJECTIVE: To describe HRS patients and compare them with NMO patients. METHODS: We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database. RESULTS: Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup. CONCLUSION: The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.

Experimental and theoretical study of acoustic waves generated by a laser line pulse in an optically absorptive isotropic cylinder.

The generation of acoustic waves by a line-focused laser pulse in an optically absorptive cylinder is studied experimentally and theoretically. Experiments are performed on a 5 mm diameter NG5 colored glass rod using Nd:yttrium aluminum garnet laser, which delivers 5 ns pulses. The numerical simulation is based on the semi-analytical model of a radially distributed thermoelastic source, which takes into account penetration of laser energy into the bulk of the sample. Good agreement between the experimental and calculated wave forms is observed. Comparison of these wave forms with an auxiliary simulation, which assumes the model of a dipole source located at the cylinder surface, reveals the effect of optical penetration on the shape of the wave form and also on the relative amplitude of bulk and surface waves.

Improved Cervical Cord Lesion Detection with 3D-MP2RAGE Sequence in Patients with Multiple Sclerosis.

Spinal cord lesions have a real diagnostic and prognostic role in multiple sclerosis. Thus, optimizing their detection on MR imaging has become a central issue with direct therapeutic impact. In this study, we compared the 3D-MP2RAGE sequence with the conventional Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) set for cervical cord lesion detection in 28 patients with multiple sclerosis. 3D-MP2RAGE allowed better detection of cervical lesions (+62%) in this population, with better confidence, due to optimized contrast and high spatial resolution.

Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The inhomogeneous magnetization transfer technique has demonstrated high specificity for myelin, and has shown sensitivity to multiple sclerosis-related impairment in brain tissue. Our aim was to investigate its sensitivity to spinal cord impairment in MS relative to more established MR imaging techniques (volumetry, magnetization transfer, DTI). MATERIALS AND METHODS: Anatomic images covering the cervical spinal cord from the C1 to C6 levels and DTI, magnetization transfer/inhomogeneous magnetization transfer images at the C2/C5 levels were acquired in 19 patients with MS and 19 paired healthy controls. Anatomic images were segmented in spinal cord GM and WM, both manually and using the AMU40 atlases. MS lesions were manually delineated. MR metrics were analyzed within normal-appearing and lesion regions in anterolateral and posterolateral WM and compared using Wilcoxon rank tests and z scores. Correlations between MR metrics and clinical scores in patients with MS were evaluated using the Spearman rank correlation. RESULTS: AMU40-based C1-to-C6 GM/WM automatic segmentations in patients with MS were evaluated relative to manual delineation. Mean Dice coefficients were 0.75/0.89, respectively. All MR metrics (WM/GM cross-sectional areas, normal-appearing and lesion diffusivities, and magnetization transfer/inhomogeneous magnetization transfer ratios) were observed altered in patients compared with controls (P < .05). Additionally, the absolute inhomogeneous magnetization transfer ratio z scores were significantly higher than those of the other MR metrics (P < .0001), suggesting a higher inhomogeneous magnetization transfer sensitivity toward spinal cord impairment in MS. Significant correlations with the Expanded Disability Status Scale (ρ = -0.73/P = .02, ρ = -0.81/P = .004) and the total Medical Research Council scale (ρ = 0.80/P = .009, ρ = -0.74/P = .02) were observed for inhomogeneous magnetization transfer and magnetization transfer ratio z scores, respectively, in normal-appearing WM regions, while weaker and nonsignificant correlations were obtained for DTI metrics. CONCLUSIONS: With inhomogeneous magnetization transfer being highly sensitive to spinal cord damage in MS compared with conventional magnetization transfer and DTI, it could generate great clinical interest for longitudinal follow-up and potential remyelinating clinical trials. In line with other advanced myelin techniques with which it could be compared, it opens perspectives for multicentric investigations.

[Cognitive impairment]. / Les troubles cognitifs.

Cognitive impairment is common in multiple sclerosis (MS), occurring at all stages of the disease, even at the earliest, and can be a major source of disability, social impairment, and impoverished quality of life. Cognitive dysfunction is mainly focused on working memory, conceptual reasoning, verbal fluency, speed of information processing, attention and executive function. Measures of information-processing speed appear to be the most robust and sensitive markers of cognitive impairment in MS patients. Cognitive testing in MS patients is complex and cognitive screening tests are time- and cost-saving test instruments. A comprehensive and sensitive cognitive test procedure should be administered to detect cognitive dysfunction, and recent studies demonstrate that single, predominantly speed-related cognitive tests may be superior to extensive and time-consuming test batteries in screening cognitive decline. Additional clinical factors, including disease course, fatigue, and affective disturbance, can impact the degree of MS-related cognitive impairment. Despite weak correlation with disease duration and physical disability status, the degree of cognitive impairment in MS has been related to the extent of topographically specific neuronal tissue damage and loss. Numerous studies have applied conventional and quantitative magnetic resonance imaging (MRI) techniques to correlate the profile and degree of cognitive impairment with various MRI-detectable abnormalities. The burden of MRI-visible lesions does not fully account for the degree of MS-related cognitive impairment. Nonconventional MRI findings suggest the extent of subtle tissue damage in normal-appearing white and grey matter to correlate best with the severity of cognitive impairment in MS patients. Structural MRI approaches have recently been extended by functional MRI studies scrutinizing the brain's ability for adaptive functional reorganization in the presence of widespread tissue damage. Cognitive impairment in MS seems to be not simply the result of tissue destruction, but also a balance between tissue destruction, tissue repair, and adaptive functional reorganization. These findings highlight the need to screen for cognitive deficits in MS patients to conduct potential cognitive rehabilitation intervention.

[Future of non conventional MR techniques in MS]. / Qu'attendre des nouvelles techniques IRM dans l'étude de la sclérose en plaques.

Although conventional magnetic resonance imaging (MRI) is used for diagnosing multiple sclerosis (MS) and monitoring disease activity and course, the correlation between conventional MRI data and clinical findings remains weak. This "clinical-MRI paradox" could be partly due to the lack of MRI specificity related to the heterogeneous pathological substrates of MS and to its inability to quantify the extent of damage in the normal-appearing tissue. Recently, non-conventional MRI techniques, including magnetization transfer MRI, diffusion tensor MRI, and proton MR spectroscopy have been applied to improve our understanding of the pathophysiology of MS. These techniques may provide information about structural and biochemical changes occurring within and outside macroscopic MS lesions (inflammation, demyelination, axonal loss), in particular in the normal-appearing white and grey matter. These techniques could also significantly improve our ability to monitor inflammatory demyelination and axonal injury. In the same way, functional MRI gives us the potential substrate to assess the mechanisms of adaptive cortical reorganization, which may limit the irreversible consequences of MS tissue injury.

Monitoring CD27+ memory B-cells in neuromyelitis optica spectrum disorders patients treated with rituximab: Results from a bicentric study.

BACKGROUND: Rituximab (RTX) is increasingly used in the treatment of neuromyelitis optica spectrum disorder (NMO-SD). Administration regimen is not consensual as there is no reliable biomarker of RTX efficacy. In most cases, after induction, RTX is administered systematically every 6months. OBJECTIVE: To assess efficacy and safety of a maintenance regimen based on CD19+ CD27+ memory B-cell (mBc) detection. METHODS: We conducted a study in two French centers, including patients with NMO-SD who received an induction therapy with RTX. We compared the number of administered infusions, relapses and EDSS depending on two maintenance schemes (S1: administration of 1g RTX infusion every 6months or S2: a scheme based on regular mBc detection. 1g RTX was administered if mBc was >0.05%) RESULTS: 40 patients were included (mean age: 40.2years, F/M sex ratio: 5/1). Aquaporin-4 antibodies were positive in 75% patients. Under S1 regimen, all patients received 2 infusions per year, whereas under S2, they received 1.62 infusion per year. The mean interval between infusions under S2 was 7.4months, without decrease of clinical efficacy. CONCLUSION: In our study, mBc-based administration of RTX allowed personalizing treatment administration and in several cases to lower the cumulative dose without loss of efficacy.

New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study.

OBJECTIVE: In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions. METHODS: EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected). RESULTS: At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0-3] at Year 1 to 2.5 [range: 0-6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression. CONCLUSION: The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.

All-optical broadband ultrasonography of single cells.

Cell mechanics play a key role in several fundamental biological processes, such as migration, proliferation, differentiation and tissue morphogenesis. In addition, many diseased conditions of the cell are correlated with altered cell mechanics, as in the case of cancer progression. For this there is much interest in methods that can map mechanical properties with a sub-cell resolution. Here, we demonstrate an inverted pulsed opto-acoustic microscope (iPOM) that operates in the 10 to 100 GHz range. These frequencies allow mapping quantitatively cell structures as thin as 10 nm and resolving the fibrillar details of cells. Using this non-invasive all-optical system, we produce high-resolution images based on mechanical properties as the contrast mechanisms, and we can observe the stiffness and adhesion of single migrating stem cells. The technique should allow transferring the diagnostic and imaging abilities of ultrasonic imaging to the single-cell scale, thus opening new avenues for cell biology and biomaterial sciences.

Isolated tumefactive demyelinating lesions: diagnosis and long-term evolution of 16 patients in a multicentric study.

Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study (n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event.

Non-destructive evaluation of composite materials with ultrasonic waves generated and detected by lasers.

Measurement of the stiffness properties of composite materials with laser generated and detected ultrasound requires proper understanding of waves emanating from a line or point source in anisotropic and viscoelastic media. The paper briefly presents calculation results of waves radiated by such a source through or at the surface of a composite plate. Dispersion is represented as well as the multiple wave arrivals connected with the folded shape of the quasi-shear ray surface. Moreover, internal diffraction at the cusp edges is properly depicted. An identification method with specific signal processing have been used to measure the stiffness coefficients of composite materials. From group velocity data, the stiffness tensor of materials showing an orthorhombic symmetry can be identified. The stiffness tensor changes induced by elevated temperatures in a composite material were then measured. An alternative approach was developed which allows to measure the phase velocities of waves generated with laser line sources. The material characterisation reliability is then improved. Moreover, the method can be used in practical cases where the front side of the structure only is accessible with the experimental devices. Despite reflection at the rear interface of transient divergent waves which ray surfaces may contain caustics, this inverse problem can be solved in a simple and efficient manner.