Progressive kidney diseases are often associated with scarring of the kidney’s filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This scarring is due to loss of ...podocytes, cells critical for glomerular filtration, and leads to proteinuria and kidney failure. Inherited forms of FSGS are caused by Rac1-activating mutations, and Rac1 induces TRPC5 ion channel activity and cytoskeletal remodeling in podocytes. Whether TRPC5 activity mediates FSGS onset and progression is unknown. We identified a small molecule, AC1903, that specifically blocks TRPC5 channel activity in glomeruli of proteinuric rats. Chronic administration of AC1903 suppressed severe proteinuria and prevented podocyte loss in a transgenic rat model of FSGS. AC1903 also provided therapeutic benefit in a rat model of hypertensive proteinuric kidney disease. These data indicate that TRPC5 activity drives disease and that TRPC5 inhibitors may be valuable for the treatment of progressive kidney diseases.
Modeling blood flow in aneurysms treated with coils could be used to understand the complete embolization of the aneurysm, through thrombus formation that fills the entire sac. Modeling of the ...endovascular coil mass as a porous medium is a technique that allows for study of aneurysm hemodynamics, efficiently for patient-specific treatment outcome predictions. Models in the literature use mean porosity of coils in the aneurysmal volume, proving inadequate for outcome prediction. However, models that consider heterogeneous porosity distribution have shown more accurate hemodynamics. We recently published the porous crown model, considering the heterogeneous coil mass distribution, validated on two patients. This study aims (i) to validate the porous crown model for a larger cohort (eight patients), and (ii) to propose a porous medium model translatable to clinical practice in treatment planning. We analyzed the porosity distribution of the endovascular coils deployed inside the cerebral aneurysm phantoms of eight patients using 3D x-ray synchrotron images. The permeability and inertial factor of the porous crown model are calculated using previously published methodology. We propose a new “bilinear” porous model, that uses the same hypothesis, but the permeability and inertial factor can be defined from just basic information available in the neuro-suite, i.e., the aneurysmal sac volume and the coil volume fraction targeted by the neurosurgeon. These two models are compared to the coil-resolved simulations, considered as the gold standard. The results show that both the porous crown model and the bilinear model produce similarly accurate hemodynamics in the aneurysm. The error in the standard (mean porosity) porous model is 66%, whereas the error of the bilinear model is 26%, compared to the coil-resolved. The bilinear model is promising as a means of treatment outcome prediction at time of intervention.
The COVID-19 pandemic has disrupted established care paths worldwide. Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek ...care for acute conditions in some cases. We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US.
The interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database. We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020.
There were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March). There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period. The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02).
We present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center.
Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate ...electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified in central nervous system disorders. Membrane leakage and electrolyte imbalances, pro-apoptotic pathway activation, and mitophagy are among the mechanisms implicated in the pathogenesis of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, as well as ischemic stroke. In this review, we summarize mitochondrial pathways that contribute to disease progression. Further, we discuss pathological states that damaged mitochondria impose on normal nervous system processes and explore new therapeutic approaches to mitochondrial diseases.
Aneurysmal wall enhancement (AWE) on vessel wall magnetic resonance imaging (VW-MRI) has been described as a new imaging biomarker of unstable unruptured intracranial aneurysms (UIAs). Previous ...studies of symptomatic UIAs are limited due to small sample sizes and lack of AWE quantification. Our study aims to investigate whether qualitative and quantitative assessment of AWE can differentiate symptomatic and asymptomatic UIAs.
Consecutive patients with UIAs were prospectively recruited for vessel wall magnetic resonance imaging at 3T from October 2014 to October 2019. UIAs were categorized as symptomatic if presenting with sentinel headache or oculomotor nerve palsy directly related to the aneurysm. Evaluation of wall enhancement included enhancement pattern (0=none, 1=focal, and 2=circumferential) and quantitative wall enhancement index (WEI). Univariate and multivariate analyses were used to identify the parameters associated with symptoms.
Two hundred sixty-seven patients with 341 UIAs (93 symptomatic and 248 asymptomatic) were included in this study. Symptomatic UIAs more frequently showed circumferential AWE than asymptomatic UIAs (66.7% versus 17.3%,
<0.001), as well as higher WEI (median interquartile range, 1.3 1.0-1.9 versus 0.3 0.1-0.9,
<0.001). In multivariate analysis, both AWE pattern and WEI were independent factors associated with symptoms (odds ratio=2.03 across AWE patterns 95% CI, 1.21-3.39,
=0.01; odds ratio=3.32 for WEI 95% CI, 1.51-7.26,
=0.003). The combination of AWE pattern and WEI had an area under the curve of 0.91 to identify symptomatic UIAs, with a sensitivity of 95.7% and a specificity of 73.4%.
In a large cohort of UIAs with vessel wall magnetic resonance imaging, both AWE pattern and WEI were independently associated with aneurysm-related symptoms. The qualitative and quantitative features of AWE can potentially be used to identify unstable intracranial aneurysms.
Flow in sidewall cerebral aneurysms can be ideally modelled as the combination of flow over a spherical cavity and flow in a curved circular pipe, two canonical flows. Flow in a curved pipe is known ...to depend on the Dean number $De$, combining the effects of Reynolds number $\textit {Re}$ and of the curvature along the pipe centreline, $\kappa$. Pulsatility in the flow introduces a dependence on the Womersley number $Wo$. Using stereo particle image velocimetry measurements, this study investigated the effect of these three key non-dimensional parameters, by modifying pipe curvature ($De$), flow rate ($Re$) and pulsatility frequency ($Wo$), on the flow patterns in a spherical cavity. A single counter-rotating vortex was observed in the cavity for all values of pipe curvature $\kappa$ and Reynolds number $\textit {Re}$, for both steady and pulsatile inflow conditions. Increasing the pipe curvature impacted the flow patterns in both the pipe and the cavity, by shifting the velocity profile towards the cavity opening and increasing the flow rate in to the cavity. The circulation in the cavity was found to collapse well with only the Dean number, for both steady and pulsatile inflows. For pulsatile inflow, the counter-rotating vortex was unstable and the location of its centre over time was impacted by the curvature of the pipe, as well as $\textit {Re}$ and $Wo$ in the free stream. The circulation in the cavity was higher for steady inflow than for the equivalent average Reynolds number and Dean number pulsatile inflow, with very limited impact of the Womersley number in the range studied. A second part of this study, that focuses on the changes in fluid dynamics when the intracranial aneurysm is treated with a flow-diverting stent, can be found in this issue (Barbour et al., J. Fluid Mech., vol. 915, 2021, A124).
Stenting with flow diverter devices (FDDs) has increasingly emerged as a treatment for intracranial aneurysms. The use of FDDs in the developing world has not been described.
A retrospective review ...was performed of a cohort of patients who underwent flow diversion at 4 tertiary-care centers in Lima, Peru between January 2017 and June 2021. Demographics, clinical features, and aneurysm morphology were evaluated. Clinical outcomes were observed 3 months after discharge and occlusion rates were assessed 12 months after treatment.
Sixty-nine patients (mean age, 46 ±14.5 years; 17% female) were treated with FDDs; 4% (n = 3) of the treated aneurysms were ruptured. Most aneurysms were saccular (n = 65; 94%), <10 mm in maximum size (n = 60; 87%), and located in the anterior circulation (n = 67; 97%). Minor complications, such as groin hematoma, occurred in 7 cases. No serious complications or deaths occurred. Patients' functional status was excellent (modified Rankin Scale score 0–1) in 99% (n = 66) at discharge and 100% (n = 67) at 3 months. Although some patients were lost to follow-up, complete occlusion was seen in 76% (n = 31) of 41 treated patients at 12 months.
We report the largest multicenter experience of FDDs for cerebral aneurysm treatment in Peru, with reasonable outcomes that are comparable to other settings despite various challenges, suboptimal circumstances, and lack of resources.
Idiopathic Intracranial Hypertension Anderson, Matthew; Baird-Daniel, Eliza; Meyer, Raymond Michael ...
Neurosurgery clinics of North America
35, Številka:
3
Journal Article
Recenzirano
Idiopathic intracranial hypertension is defined by headaches and a decline in visual acuity due to increased intracranial pressure. Treatment options historically included weight loss, acetazolamide, ...and/or cerebrospinal fluid diversion surgery. Recent understanding of the contributions of dural venous sinus hypertension and stenosis has led to venous sinus stenting as a treatment option.
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