Comparison of two corticosteroid regimens on brain volumetrics in patients with Duchenne muscular dystrophy

ObjectiveDuchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI).MethodsIn a cross-sectional, two-center study, T1-weighted MRI scans were obtained from three age-matched groups (9–18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel-based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate.ResultsBoth patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume.InterpretationVolumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently.Neurological Motor Disorder

The frontotemporal syndrome of ALS is associated with poor survival

Thirty percent of ALS patients have a frontotemporal syndrome (FS), defined as behavioral changes or cognitive impairment. Despite previous studies, there are no firm conclusions on the effect of the FS on survival and the use of non-invasive ventilation (NIV) in ALS. We examined the effect of the FS on survival and the start and duration of NIV in ALS. Behavioral changes were defined as >22 points on the ALS-Frontotemporal-Dementia-Questionnaire or ≥3 points on ≥2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on ≥2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom ons

The frontotemporal syndrome of ALS: Clinical progression & changing brain networks

The frontotemporal syndrome of amyotrophic lateral sclerosis (ALS) consists of cognitive and behavioural impairment. Approximately 50% of the ALS patients have mild cognitive and/or behavioural impairment and around 10% of the ALS patients have a concomitant diagnosis of the behavioural variant of frontotemporal dementia (bvFTD). The combination of ALS and bvFTD negatively influences survival and interferes with the initiation and compliance of life-prolonging therapies. In the first part of the thesis the course of cognitive and behavioural impairment and the impact on survival of ALS patients were examined. We showed that 30% of early symptomatic ALS patients (disease duration <12 months) had a progressive course of cognitive and behavioural impairment over a 6-month period. We also investigated survival in a large cohort of ALS patients and found evidence for a reduced survival in ALS patients with cognitive and/or behavioural impairment, which persisted after initiation of non-invasive ventilation. In the second part of this thesis we described the electrophysiological processes of ALS patients compared to healthy controls and bvFTD patients. For this study, we used magnetoencephalography (MEG), a method to measure brain signals in both cortical and subcortical regions. We showed an overlap in resting-state functional connectivity changes in cortical and subcortical brain regions between ALS and bvFTD patients compared to healthy controls. Additionally, we demonstrated that brain networks of ALS patients with cognitive and/or behavioural impairment move along the ALS-bvFTD spectrum over time and become closer to bvFTD like topology

Cortical and subcortical changes in resting-state neuronal activity and connectivity in early symptomatic ALS and advanced frontotemporal dementia

The objective of this study was to examine if patterns of resting-state brain activity and functional connectivity in cortical and subcortical regions in patients with early symptomatic amyotrophic lateral sclerosis (ALS) resemble those of behavioural variant frontotemporal dementia (bvFTD). In a cross-sectional design, eyes-closed resting-state magnetoencephalography (MEG) data of 34 ALS patients, 18 bvFTD patients and 18 age- and gender-matched healthy controls (HCs) were projected to source-space using an atlas-based beamformer. Group differences in peak frequency, band-specific oscillatory activity and functional connectivity (corrected amplitude envelope correlation) in 78 cortical regions and 12 subcortical regions were determined. False discovery rate was used to correct for multiple comparisons. BvFTD patients, as compared to ALS and HCs, showed lower relative beta power in parietal, occipital, temporal and nearly all subcortical regions. Compared to HCs, patients with ALS and patients with bvFTD had a higher delta (0.5–4 Hz) and gamma (30–48 Hz) band resting-state functional connectivity in a high number of overlapping regions in the frontal lobe and in limbic and subcortical regions. Higher delta band connectivity was widespread in the bvFTD patients compared to HCs. ALS showed a more widespread higher gamma band functional connectivity compared to bvFTD. In conclusion, MEG in early symptomatic ALS patients shows resting-state functional connectivity changes in frontal, limbic and subcortical regions that overlap considerably with bvFTD. The findings show the potential of MEG to detect brain changes in early symptomatic phases of ALS and contribute to our understanding of the disease spectrum, with ALS and bvFTD at the two extreme ends

Minor Planet Observations [244 Geocentic Occultation Observations]

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