Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study

Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome

Motional and relaxational processes in amorphous and crystalline phases of methoxy-benzyldene-butylaniline. I. Study of the dynamical behaviour of MBBA in its solid phases by incoherent inelastic neutron scattering

From time-of-flight incoherent inelastic neutron scattering, the density of vibrational states of methoxy-benzylidene-butylaniline (MBBA) was measured in its different phases. In the low frequency range, the density of states of the amorphous phases is enhanced with respect to the crystalline phases. The precise shape of these densities of states is analysed and compared in the different amorphous and crystalline phases and noticeable differences are evidenced. In addition, the analysis of the quasielastic part of the spectra at highest temperatures permits to get some information about the dynamics of the molecules in the crystalline phases and in the nematic phase

Localized Relaxational Dynamics of Succinonitrile

Succinonitrile (N&equiv;C&mdash;CH2&mdash;CH2&mdash;C&equiv;N) is a good ionic conductor, when doped with an ionic compound, at room temperature, where it is in its plastic crystalline phase (Long et al. Solid State Ionics 2003, 161, 105; Alarco et al. Nat. Mater. 2004, 3, 476). We report on the relaxational dynamics of the plastic phase near the two first-order phase transitions and on the effect of dissolving a salt in the plastic matrix by quasi-elastic neutron scattering. At 240 K, the three observed relaxations are localized and we can describe their dynamics (&tau; &asymp; 1.7, 17, and 140 ps) to a certain extent from a model using a single molecule that was proposed by B&eacute;e et al. allowing for all conformations in its unit cell (space group IM3M). The extent of the localized motion as observed is however larger than that predicted by the model and suggests that the isomerization of succinonitrile is correlated with a jump to the nearest neighbor site in the unit cell. The salt containing system is known to be a good ionic conductor, and our results show that the effect of the ions on the succinonitrile matrix is homogeneous. Because the isomerizations and rotations are governed by intermolecular interactions, the dissolved ions have an effect over an extended range. Due to the addition of the salt, the dynamics of one of the components (&tau; &asymp; 17 ps) shows more diffusive character at 300 K. The calculated upper limit of the corresponding diffusion constant of succinonitrile in the electrolyte is a factor 30 higher than what is reported for the ions. Our results suggest that the succinonitrile diffusion is caused by nearest neighbor jumps that are localized on the observed length and time scales.<br /

Randomized phase II–III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†

International audienceBACKGROUND:This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC).PATIENTS AND METHODS:Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle.RESULTS:In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers.CONCLUSION:Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.TRIAL REGISTRATION:ClinicalTrials.gov NCT00930891