Depression is associated with disconnection of neurotransmitter-related nuclei in multiple sclerosis.

BACKGROUND: Depression is frequently associated with multiple sclerosis (MS). However, the biological background underlying such association is poorly understood. OBJECTIVE: Investigating the functional connections of neurotransmitter-related brainstem nuclei, along with their relationship with white matter (WM) microstructure, in MS patients with depressive symptomatology (MS-D) and without depressive symptomatology (MS-nD). METHODS: Combined resting-state functional magnetic resonance imaging (fMRI) and diffusion-weighted MRI (dMRI) study on 50 MS patients, including 19 MS-D and 31 MS-nD patients, along with 37 healthy controls (HC). Main analyses performed are (1) comparison between groups of raphe nuclei (RN)-related functional connectivity (FC); (2) correlation between RN-related FC and whole brain dMRI-derived fractional anisotropy (FA) map; and (3) comparison between groups of FA in the RN-related WM area. RESULTS: (1) RN-related FC was reduced in MS-D when compared to MS-nD and HC; (2) RN-related FC positively correlated with FA in a WM cluster mainly encompassing thalamic/basal ganglia regions, including the fornix; and (3) FA in such WM area was reduced in MS-D. CONCLUSION: Depressive symptomatology in MS is specifically associated to a functional disconnection of neurotransmitter-related nuclei, which in turn may be traced to a distinct spatial pattern of WM alterations mainly involving the limbic network.

Sensory-motor network topology in multiple sclerosis: Structural connectivity analysis accounting for intrinsic density discrepancy.

Graph theory and network modelling have been previously applied to characterize motor network structural topology in multiple sclerosis (MS). However, between-group differences disclosed by graph analysis might be primarily driven by discrepancy in density, which is likely to be reduced in pathologic conditions as a consequence of macroscopic damage and fibre loss that may result in less streamlines properly traced. In this work, we employed the convex optimization modelling for microstructure informed tractography (COMMIT) framework, which, given a tractogram, estimates the actual contribution (or weight) of each streamline in order to optimally explain the diffusion magnetic resonance imaging signal, filtering out those that are implausible or not necessary. Then, we analysed the topology of this 'COMMIT-weighted sensory-motor network' in MS accounting for network density. By comparing with standard connectivity analysis, we also tested if abnormalities in network topology are still identifiable when focusing on more 'quantitative' network properties. We found that topology differences identified with standard tractography in MS seem to be mainly driven by density, which, in turn, is strongly influenced by the presence of lesions. We were able to identify a significant difference in density but also in network global and local properties when accounting for density discrepancy. Therefore, we believe that COMMIT may help characterize the structural organization in pathological conditions, allowing a fair comparison of connectomes which considers discrepancies in network density. Moreover, discrepancy-corrected network properties are clinically meaningful and may help guide prognosis assessment and treatment choice.

Unique case of atraumatic splenic rupture in a patient with chronic lymphocytic leukaemia with Richter's transformation.

Though rare, atraumatic rupture of the spleen can be a complication in certain leukaemias and lymphomas. We present a unique case of atraumatic rupture of the spleen in a patient with chronic lymphocytic leukaemia. The patient presented to the emergency department with abdominal pain; he had been on ibrutinib therapy but stopped taking the medication abruptly 6 days prior. On evaluation, he was found to have a ruptured spleen with a haemoperitoneum. Pathology of the excised spleen showed infiltration of the spleen with hyperproliferated CD5+ intermediate-to-large cells, consistent with B-cell lymphoma and favouring Richter's transformation. There are only a few available reports of patients with similar presentations identified in our literature review.