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Various surgical strategies have been developed to alleviate elevated intraspinal pressure (ISP) following acute traumatic spinal cord injury (tSCI). Surgical decompression of either the dural (durotomy) or the dural and pial (myelotomy) lining of the spinal cord has been proposed. However, a direct comparison of these two strategies is lacking. Here, we compare the histological and functional effects of durotomy alone and durotomy plus myelotomy in a rodent model of acute thoracic tSCI. Our results indicate that tSCI causes local tissue edema and significantly elevates ISP (7.4 ± 0.3 mmHg) compared with physiological ISP (1.7 ± 0.4 mmHg; p

Background: Obesity is a risk factor for atrial fibrillation (AF) and strongly influences the response to treatment. Atrial fibrosis shows similar associations. Left atrial epicardial fat (LAEF) may be a link to these associations. Objective: We sought to assess whether LAEF is associated with atrial fibrosis and BMI (Body Mass Index). Methods: Patients with atrial fibrillation undergoing catheter ablation were assessed with cardiac MRI for overall epicardial fat, LAEF, and fibrosis quantification. Epicardial fat was imaged using a 3-dimensional Dixon sequence and quantified by contouring regions of fat on axial images (Panel A; Blue regions represent LAEF). Atrial fibrosis was quantified from the Late Gadolinium Enhancement (LGE) MRI. Image registration was used to assess the relationship between left atrial epicardial fat and left atrial fibrosis. Results: 45 patients underwent the imaging protocol (64±10 years; 76% male). BMI was 29.3±6.1 kg/m 2 , LAEF was 248±155 cm 2 , and LA fibrosis was 17.4±8.4%. LAEF was significantly correlated with both LA fibrosis (Fig B; P=0.017; R 2 =0.125) and BMI (y[BMI] = 0.093x[LAEF] + 5.37; p=0.01, R 2 =0.155). Total epicardial fat was also correlated with BMI (y[BMI] = 0.014x[total epicardial fat] + 9.01; p2 =0.33). The overlap of LAEF and fibrosis was moderate with a Dice coefficient ranging from 0.26 to 0.49. (Fig C). Conclusion: LAEF is associated with obesity (BMI) and LA fibrosis with a moderate degree of colocalization. These findings support a role for LAEF as a contributor to atrial fibrosis and a link between obesity and atrial fibrillation.

Introduction: Late-gadolinium enhanced (LGE)-MRI has revealed atrial fibrotic remodeling in embolic stroke of undetermined source (ESUS) patients. Curiously, fibrosis levels in ESUS patients are the same as those observed in AF. A potential explanation is that ESUS patients have pre-clinical arrhythmic substrate, but lack the triggers needed to initiate AF. Hypothesis: Simulations in computational models reconstructed from LGE-MRI scans can determine if the fibrotic substrate of a particular ESUS patient has the capacity to sustain reentry. Methods: ESUS (per standard criteria) was verified by a neurologist. 45 ablation-naïve AF patients and 45 ESUS patients within three months of stroke underwent LGE-MRI for fibrosis assessment. Left atrial (LA) models were built from LGE-MRI scans. Fiber orientations were mapped into each LA model using universal atrial coordinates. Burst pacing from 15 sites was used to test inducibility of arrhythmia sustained by reentry (Fig A). Results: In 23/45 (51%) ESUS and 29/45 (64%) AF models, we observed sustained reentry. Fibrosis burden was significantly higher for patients in whom simulations suggested the existence of pre-clinical arrhythmic substrate; however, within the inducible and non-inducible sub-groups, there was no significant difference in fibrosis burden for ESUS vs. AF patients (Fig B). This suggests that the presence of pre-clinical substrate in ESUS is correlated with fibrosis burden, although exceptions to this supposition were not uncommon (i.e., inducible low-fibrosis and non-inducible high-fibrosis models; Fig C). Conclusions: In this modeling study, pro-arrhythmic properties of fibrosis in ESUS and AF are indistinguishable. This suggests that some ESUS patients have pre-clinical fibrotic substrate, but do not have AF due to a lack of suitable triggers. Ongoing clinical follow-up will test whether abundance of pre-clinical substrate is predictive of incident AF.

Cardiac magnetic resonance imaging (MRI) has revealed fibrosis in embolic stroke of undetermined source (ESUS) patients comparable to levels seen in atrial fibrillation (AFib). We used computational modeling to understand the absence of arrhythmia in ESUS despite the presence of putatively pro-arrhythmic fibrosis. MRI-based atrial models were reconstructed for 45 ESUS and 45 AFib patients. The fibrotic substrate’s arrhythmogenic capacity in each patient was assessed computationally. Reentrant drivers were induced in 24/45 (53%) ESUS and 22/45 (49%) AFib models. Inducible models had more fibrosis (16.7 ± 5.45%) than non-inducible models (11.07 ± 3.61%; p, eLife digest The heart usually beats with a regular rhythm to pump the blood that carries oxygen and nutrients to different organs. Sometimes, alterations in the heart’s rhythm known as arrhythmias can occur. Atrial fibrillation, also called AFib, is a type of arrhythmia in which the heart beats rapidly and irregularly, causing abnormal blood-flow that can lead to the formation of blood clots. If one of these blood clots travels to the brain, it can block a blood vessel, causing a stroke. However, many strokes occur without any evidence of AFib. One subset of strokes that are not associated with AFib are embolic strokes of undetermined source (ESUS), which account for 25% of all strokes. By definition ESUS and AFib do not occur together, but both are associated with similar elevated levels of disease-related remodeling (i.e., fibrosis) in the heart tissue, which appears when the heart is injured. Fibrosis impairs the heart’s normal electrical activity. Bifulco et al. wanted to determine whether there is some fundamental difference in fibrosis between people with AFib and those who have had an ESUS event. To do this, they used a computational approach to model the geometries and patterns of fibrosis of the hearts of 45 ESUS patients and 45 patients with AFib, essentially producing a virtual version of each patient’s heart. Bifulco et al. then applied a virtual pace-maker (working in overdrive mode) to each heart model to determine whether electrical inputs that can lead to AFib had different effects on ESUS and AFib patients. The results showed that the electrical inputs had similar effects in all of the heart models. This led Bifulco et al. to conclude that ESUS and AFib patients have indistinguishable patterns of fibrosis. The key difference is that ESUS patients are missing the trigger to initiate the fibrillation process – if atrial fibrosis is the proverbial tinderbox, these triggers are the spark needed to ignite a fire. Further research, including confirmation of Bifulco et al.’s findings in live patients, will be needed to confirm the hypothesis that ESUS patients lack AFib primarily due to an absence of triggers. If this is indeed the case, these findings may make it easier to identify ESUS patients at higher risk for AFib or further strokes. Additionally, a better understanding of fibrosis as a link between stroke and AFib will help clinicians provide better, more personalized treatments, for example guiding whether a patient should take blood thinners or undergo more rigorous cardiac monitoring.

Background: Lateral recess stenosis is a common pathology causing de-novo or residual radicular pain following lumbar spine surgery. Diagnostic criteria and treatment strategies for symptomatic lateral recess stenosis are not well established. Methods: We identified ten patients in our prospective patient database (n=146) who underwent endoscopic interlaminar decompression for unilateral symptomatic lateral recess stenosis. Lateral recess height and angle were measured on axial T2-weighted MRI. Values from the symptomatic side were compared to the contralateral side which served as asymptomatic control. Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) for back and leg pain were collected preoperatively, postoperatively and at last follow-up. Results: Preoperative MRI revealed that both lateral recess angle and height were significantly smaller on the symptomatic compared to the asymptomatic side (angle: 19.3˚ vs . 35.7˚; height: 2.9 vs . 5.7 mm; P vs . postoperatively 1.7±0.9, P Conclusions: Lateral recess height and angle correlate with symptomatic lateral recess stenosis which is effectively treated utilizing interlaminar endoscopic lateral recess decompression.

The inhibition of excitatory (pyramidal) neurons directly dampens their activity resulting in a suppression of neural network output. The inhibition of inhibitory cells is more complex. Inhibitory drive is known to gate neural network synchrony, but there is also a widely held view that it may augment excitability by reducing inhibitory cell activity, a process termed disinhibition. Surprisingly, however, disinhibition has never been demonstrated to be an important mechanism that augments or drives the activity of excitatory neurons in a functioning neural circuit. Using voltage sensitive dye imaging (VSDI) we show that 20-80 Hz stimulus trains, (beta-gamma) activation, of the olfactory cortex pyramidal cells in layer II leads to a subsequent reduction in inhibitory interneuron activity that augments the efficacy of the initial stimulus. This disinhibition occurs with a lag of about 150-250 ms after the initial excitation of the layer 2 pyramidal cell layer. In addition activation of the endopiriform nucleus also arises just before the disinhibitory phase with a lag of about 40-80 ms. Preventing the spread of action potentials from layer II stopped the excitation of the endopiriform nucleus, abolished the disinhibitory activity and reduced the excitation of layer II cells. After the induction of experimental epilepsy the disinhibition was more intense with a concomitant increase in excitatory cell activity. Our observations provide the first evidence of feed forward disinhibition loop that augments excitatory neurotransmission, a mechanism that could play an important role in the development of epileptic seizures.