Secondary paroxysmal dyskinesia is a rare but life-quality-compromising symptom in multiple sclerosis (MS) and might be associated with particular MS lesions. The present study intended to determine associations between paroxysmal dyskinesia and the MS-associated lesion site using a voxelwise lesion analysis. We conducted a retrospective study and sought MS patients with documented paroxysmal dyskinesia and controls without paroxysmal dyskinesia matched for age, disease severity, and disease duration in a local database. The MS lesions were analysed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T), manually outlined, and transformed into stereotaxic space. We determined the lesion overlap and compared the absence or presence of paroxysmal dyskinesia voxelwise between patients with and without lesions in a given voxel using the Liebermeister test with 4000 permutations. From 15,869 MS patient records screened, we identified 25 patients with paroxysmal dyskinesia. The voxelwise analysis in 22 subjects yielded associations between paroxysmal dyskinesia and MS lesions in the internal capsule, the basal ganglia, and another prominent lesion cluster in the posterior periventricular white matter. Our voxelwise analysis shows associations between paroxysmal dyskinesia and MS lesions in the internal capsule and basal ganglia, areas contributing to motor sequence programming. This association in another lesion site located in the posterior thalamic radiation suggests that lesions in subcortical sensory pathways may also contribute to paroxysmal dyskinesia in MS.

BackgroundIn acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome.PurposeTo evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity.MethodsClinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days.ResultsBoth length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02).ConclusionOrbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival, regeneration, and plasticity. Emerging evidence also indicates an essential role for BDNF outside the nervous system, for instance in immune cells. We therefore investigated the impact of BDNF on T cells using BDNF knockout (KO) mice and conditional KO mice lacking BDNF specifically in this lymphoid subset. In both settings, we observed diminished T-cell cellularity in peripheral lymphoid organs and an increase in CD4 + CD44 + memory T cells. Analysis of thymocyte development revealed diminished total thymocyte numbers, accompanied by a significant increase in CD4/CD8 double-negative (DN) thymocytes due to a partial block in the transition from the DN3 to the DN4 stage. This was neither due to increased thymocyte apoptosis nor defects in the expression of the TCR-β chain or the pre-TCR. In contrast, pERK but not pAKT levels were diminished in DN3 BDNF-deficient thymocytes. BDNF deficiency in T cells did not result in gross deficits in peripheral acute immune responses nor in changes of the homeostatic proliferation of peripheral T cells. Taken together, our data reveal a critical autocrine and/or paracrine role of T-cell-derived BDNF in thymocyte maturation involving ERK-mediated TCR signaling pathways. Keywords: BDNF Neurotrophins T cells Thymus developmentAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNeurotrophins and other neurotrophic factors play an essential role in the development and maintenance of the peripheral and central nervous systems (CNS). They are involved in neuronal survival, axonal growth, generation of new synaptic connections, regulation of neuronal activity as well as synaptic and dendritic plasticity. Moreover, they exert profound effects in a wide variety of neuropsychiatric conditions including (de)myelination, pain, aggression, and depression as well as drug abuse [1][2][3][4][5][6][7][8] and modulate food intake [9]. Furthermore, neurotrophic factors are essential for axonal maintenance [10] and are thought to contribute to regenerative processes after traumatic injury [11][12][13]. These functions could be correlated with the expression and secretion of neurotrophic factors, not only in the CNS but also in immune cells (reviewed in [14]). In particular, mRNA of all known neurotrophins and their receptors were detected in the thymus, spleen, and other lymphoid organs [15][16][17], where they probably act in an autocrine and/or paracrine manner. However, the neurotrophin action on immune cells is much less well defined.The most widely studied neurotrophin, nerve growth factor, has been reported to impact on thymic epithelium differentiation and organogenesis [18], to influence the function of activated CD4 + T cells [19] and B cells [20,21] and to regulate cytokine expression [22]. In addition, nerve growth factor acts on cells of the myeloid-cell lineage by influencing microglial expression of costimulatory and MHC class II molecules [23,...