Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype

Background: Antibodies against myelin oligodendrocyte glycoprotein (MOG) have been identified in a subgroup of pediatric patients with inflammatory demyelinating disease of the central nervous system (CNS) and in some patients with neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to examine the frequency, clinical features, and long-term disease course of patients with anti-MOG antibodies in a European cohort of NMO/NMOSD. Findings: Sera from 48 patients with NMO/NMOSD and 48 patients with relapsing-remitting multiple sclerosis (RR-MS) were tested for anti-aquaporin-4 (AQP4) and anti-MOG antibodies with a cell-based assay. Anti-MOG antibodies were found in 4/17 patients with AQP4-seronegative NMO/NMOSD, but in none of the AQP4-seropositive NMO/NMOSD (n = 31) or RR-MS patients (n = 48). MOG-seropositive patients tended towards younger disease onset with a higher percentage of patients with pediatric (<18 years) disease onset (MOG+, AQP4+, MOG-/AQP4-: 2/4, 3/31, 0/13). MOG-seropositive patients presented more often with positive oligoclonal bands (OCBs) (3/3, 5/29, 1/13) and brain magnetic resonance imaging (MRI) lesions during disease course (2/4, 5/31, 1/13). Notably, the mean time to the second attack affecting a different CNS region was longer in the anti-MOG antibody-positive group (11.3, 3.2, 3.4 years). Conclusions: MOG-seropositive patients show a diverse clinical phenotype with clinical features resembling both NMO (attacks mainly confined to the spinal cord and optic nerves) and MS with an opticospinal presentation (positive OCBs, brain lesions). Anti-MOG antibodies can serve as a diagnostic and maybe prognostic tool in patients with an AQP4-seronegative NMO phenotype and should be tested in those patients

Assessing autophagy in sciatic nerves of a rat model that develops inflammatory autoimmune peripheral neuropathies

The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP) and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199) peptide develop a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology and several typical features of CIDP. We have set up a series of techniques that led us to examine the failures of autophagy pathways in the sciatic nerve of these model rats and to follow the possible improvement of these defects after treatment. Based on these newly introduced methods, a novel area of investigation is now open and will allow us to more thoroughly examine important features of certain autophagy pathways occurring in sciatic nerves

Spin-Glass State in CuGa2O4\rm CuGa_2O_4

Magnetic susceptibility, magnetization, specific heat and positive muon spin relaxation (\musr) measurements have been used to characterize the magnetic ground-state of the spinel compound $\rm CuGa_2O_4$. We observe a spin-glass transition of the S=1/2 $\rm Cu^{2+}$ spins below $\rm T_f=2.5K$ characterized by a cusp in the susceptibility curve which suppressed when a magnetic field is applied. We show that the magnetization of $\rm CuGa_2O_4$ depends on the magnetic histo Well below $\rm T_f$, the muon signal resembles the dynamical Kubo-Toyabe expression reflecting that the spin freezing process in $\rm CuGa_2O_4$ results Gaussian distribution of the magnetic moments. By means of Monte-Carlo simulati we obtain the relevant exchange integrals between the $\rm Cu^{2+}$ spins in this compound.Comment: 6 pages, 16 figure

Antibody to aquaporin-4 in the long-term course of neuromyelitis optica

Neuromyelitis optica (NMO) is a severe inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the spinal cord and optic nerves. Recently, a highly specific serum reactivity to CNS microvessels, subpia and Virchow–Robin spaces was described in patients with NMO [called NMO–IgG (NMO–immunoglobulin G)]. Subsequently, aquaporin-4 (AQP4), the most abundant water channel in the CNS, was identified as its target antigen. Strong support for a pathogenic role of the antibody would come from studies demonstrating a correlation between AQP4-Ab (AQP4-antibody) titres and the clinical course of disease. In this study, we determined AQP4-Ab serum levels in 96 samples from eight NMO–IgG positive patients (median follow-up 62 months) in a newly developed fluorescence-based immunoprecipitation assay employing recombinant human AQP4. We found that AQP4-Ab serum levels correlate with clinical disease activity, with relapses being preceded by an up to 3-fold increase in AQP4-Ab titres, which was not paralleled by a rise in other serum autoantibodies in one patient. Moreover, AQP4-Ab titres were found to correlate with CD19 cell counts during therapy with rituximab. Treatment with immunosuppressants such as rituximab, azathioprine and cyclophosphamide resulted in a marked reduction in antibody levels and relapse rates. Our results demonstrate a strong relationship between AQP4-Abs and clinical state, and support the hypothesis that these antibodies are involved in the pathogenesis of NMO

Une approche a contrario pour la détection de changements dans des images IRM multimodales 3D

La détection de changements significatifs entre deux images demeure un problème délicat. Dans ce contexte, une méthodologie récemment proposée dans [DMM03] émerge : l'approche a contrario. Il s'agit d'une approche non paramétrique présentant l'avantage de prendre en compte dans le processus de décision l'information contextuelle et différentes valeurs de seuil de détection. Nous étendons ici cette approche de manière à traiter des images multimodales desquelles sont extraites différentes images de mesure. Pour cela, deux règles de fusion sont développées de manière à combiner l'information provenant des images de mesure et celle provenant des différents seuils de détection. De plus, une nouvelle règle de décision, basée sur des tests de permutation, est proposée. La méthodologie a contrario est décrite dans la Section 1. Nous proposerons ensuite un nouveau cadre statistique dans la section 2. Enfin, la section 3 illustre l'application de la méthode pour de la détection de changements dans des images IRM dans le contexte de la sclérose en plaques

Magnetic properties of the frustrated AFM spinel ZnCr_2O_4 and the spin-glass Zn_{1-x}Cd_xCr_2O_4 (x=0.05,0.10)

The $T$-dependence (2- 400 K) of the electron paramagnetic resonance (EPR), magnetic susceptibility, $\chi (T)$, and specific heat, $C_{v}(T)$, of the $normal$ antiferromagnetic (AFM) spinel ZnCr$_{2}$O$_{4}$ and the spin-glass (SG) Zn$_{1-x}$Cd$_{x}$Cr$_{2}$O$_{4}$ ($x=0.05,0.10$) is reported. These systems behave as a strongly frustrated AFM and SG with $$ $\approx T_{G}\approx 12$ K and -400 K $\gtrsim \Theta_{CW}\gtrsim -500$ K. At high-$T$ the EPR intensity follows the $\chi (T)$ and the $g$-value is $T$-independent. The linewidth broadens as the temperature is lowered, suggesting the existence of short range AFM correlations in the paramagnetic phase. For ZnCr$_{2}$O$_{4}$ the EPR intensity and $\chi (T)$ decreases below 90 K and 50 K, respectively. These results are discussed in terms of nearest-neighbor Cr$^{3+}$ (S $=3/2$%) spin-coupled pairs with an exchange coupling of $| J/k| \approx$ 50 K. The appearance of small resonance modes for $T\lesssim 17$ K, the observation of a sharp drop in $\chi (T)$ and a strong peak in $C_{v}(T)$ at $T_{N}=12$ K confirms, as previously reported, the existence of long range AFM correlations in the low-$T$ phase. A comparison with recent neutron diffraction experiments that found a near dispersionless excitation at 4.5 meV for $T\lesssim T_{N}$ and a continuous gapless spectrum for $T\gtrsim T_{N}$, is also given.Comment: 17 pages, 8 figures, 1 Table. Submitted to Physical Review

Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

$\textbf{Objective:}$ To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. $\textbf{Methods:}$ Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. $\textbf{Results:}$ Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores ($p$ < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a ($p$ = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores ($p$ = 0.0014) and MSFC + SLCLA composite scores ($p$ = 0.0097) than SC IFN-β-1a-treated patients. $\textbf{Conclusions:}$ In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities. $\textbf{Classification of evidence:}$ This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.Sanofi Genzyme, Bayer HealthCare Pharmaceutical

MOG encephalomyelitis: international recommendations on diagnosis and antibody testing

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ('red flags') that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation

The effect of antenna polarization and body morphology on the measurement uncertainty of a wearable multi-band distributed exposure meter

This paper studies the effect of antenna polarization on measurement uncertainty of a multi-band body-worn distributed exposure meter (BWDM). The BWDM is a device for assessing electromagnetic fields in real environments accurately. The BWDM consists of 8 nodes and is calibrated on the body for simultaneous measurement of the incident power density in four frequency bands. Each node contains an antenna that can have two potential antenna polarizations.The BWDM is calibrated on four human subjects in an anechoic chamber to determine its measurement uncertainty in terms of 68% confidence interval (CI68) of the on-body antenna aperture. The results show that using a fixed polarization of the antennas on body can lead to a different CI68 up to maximum 4.9 dB when worn by another person which is still 9.6 dB lower than the measurement uncertainty of commercial exposure meters