Abstract Bi‐allelic loss‐of‐function variants in LAMC3 , encoding extracellular matrix protein laminin gamma 3, represent a rare cause of occipital polymicrogyria with epilepsy, developmental delay and cognitive impairment. So far, only five families have been reported. We now identified a novel, homozygous splice variant in LAMC3 in an individual with an unusual manifestation of cortical malformation. She presented with polymicrogyria in the frontal but not the occipital lobes, with adult‐onset seizures and normal psychomotor development and cognition. Additionally, ictal asystole, requiring implantation of a pacemaker, and nonepileptic seizures occurred. This case expands the spectrum of LAMC3 ‐associated cortical malformation phenotypes to frontal only polymicrogyria and adult‐onset of epilepsy.
Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the blood oxygen level dependent (BOLD) response to distinct neuronal processes continues to be challenging. Here, we investigated the characteristics of 7 T-fMRI compared to 3 T-fMRI in the human brain beyond the effect of increased SNR and verified the benefits of 7 T-fMRI in the detection of tiny, highly specific modulations of functional connectivity in the resting state following a motor task.18 healthy volunteers underwent two resting state and a stimulus driven measurement using a finger tapping motor task at 3 and 7 T, respectively. The SNR for each field strength was adjusted by targeted voxel size variation to minimize the effect of SNR on the field strength specific outcome. Spatial and temporal characteristics of resting state ICA, network graphs, and motor task related activated areas were compared. Finally, a graph theoretical approach was used to detect resting state modulation subsequent to a simple motor task.Spatial extensions of resting state ICA and motor task related activated areas were consistent between field strengths, but temporal characteristics varied, indicating that 7 T achieved a higher functional specificity of the BOLD response than 3 T-fMRI. Following the motor task, only 7 T-fMRI enabled the detection of highly specific connectivity modulations representing an "offline replay" of previous motor activation. Modulated connections of the motor cortex were directly linked to brain regions associated with memory consolidation.These findings reveal how memory processing is initiated even after simple motor tasks, and that it begins earlier than previously shown. Thus, the superior capability of 7 T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.
Abstract Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the BOLD response to distinct neuronal processes continues to be challenging. Here, we performed 3T and 7T-fMRI analysis of motor-task activation and resting-state connectivity with adjusted SNR. We then applied graph theory to analyze resting-state neuronal networks detected by fMRI after a simple motor task. Despite adjusted SNR, 7T achieved a higher functional specificity of the BOLD response than 3T-fMRI. Following the motor task, 7T-fMRI therefore enabled the detection of an ‘offline replay’ that was directly linked to brain regions associated with memory consolidation. These findings reveal how memory processing is initiated even after simple motor tasks and begins earlier than previously shown. Thus, the superior capability of 7T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.
Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as one third of patients do not respond adequately to TNFi.
Objectives
We investigated whether brain activity associated to arthritis measured by functional magnetic resonance imaging (fMRI) can function as a predictor of response to TNFiin RA patients.
Methods
This is an interim analysis of the first 50 patients of the PreCePRA trial, a multi-center, double-blind, placebo-controlled fMRI trial on patients with RA. [1] [2] Active RA patients failing csDMARDs with a DAS28-ESR >3.2 and at least three tender and/or swollen joints received a baseline brain BOLD fMRI scan upon joint compression at screening. Patients werethen randomized into a 12-week double-blinded treatment phase with placebo (arm 1) or 200mg certolizumab-pegol eow (arm 2; fMRI Bold signal>2000 voxel i.e. 2cm3, arm 3; fMRI Bold signal <2000 voxel). LDA 3mo. Primary end point was DAS28-ESR low disease activity at 12 weeks. A 12 weeks follow-up phase in which patients were switched from the placebo to the treatment arm folowed the blinded phase. fMRIwas carried out at baseline as well as after 12 and 24 weeks of or placebo.
Results
In 31 patients (responders) baseline signal volume i.e. sum of significantly coupled voxels after the FDR thresholding was significatly higher compared to 19 patients (non-responders) (p<0.001) allowing discrimination between the two groups prior to treatment. In responders we detected an persitent decrease of the BOLD volume from baseline to week 12 and week 24 (r2=0.561) whereas the BOLD volume in non-responders persitently increased (r2=0.589).
Conclusions
Based on this interim analysis we conclude that high BOLD volumes in fMRI, indicating high-level brain representation of pain in arthritis. These data represent the first encouring signal of the PreCePRA brain fMRI study supporting the concept that increased RA-related brain activity is related to response to TNFi.
References
Rech, J., et al., Association of brain functional magnetic resonance activity with response to tumor necrosis factor inhibition in rheumatoid arthritis. Arthritis Rheum, 2013.65(2): p. 325–33. Hess, A., et al., Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A, 2011.108(9): p. 3731–6.
Vasoplegia as a frequent complication after cardiac surgery often requires catecholamine therapy. The guanylate cyclase inhibitor methylene blue is dicussed controversially as alternative treatment in catecholamine-refractory vasoplegia. The aim of this study is to examine the results of methylene blue therapy for norepinephrine-refractory vasoplegia and to analyze follow up and survival.
Objectives: Operative correction of the sinus venosus atrial septal defect can either be performed using a rotation advancement Z-flap method or using an intra-superior vena cava baffle and is associated with low morbidity and mortality. The aim of this retrospective study was to analyze occurrence of rhythm disturbances postoperatively undergoing one of these surgical procedures.
