FLAIR MRI biomarkers of the normal appearing brain matter are related to cognition.

A novel biomarker panel was proposed to quantify macro and microstructural biomarkers from the normal-appearing brain matter (NABM) in multicentre fluid-attenuation inversion recovery (FLAIR) MRI. The NABM is composed of the white and gray matter regions of the brain, with the lesions and cerebrospinal fluid removed. The primary hypothesis was that NABM biomarkers from FLAIR MRI are related to cognitive outcome as determined by MoCA score. There were three groups of features designed for this task based on 1) texture: microstructural integrity (MII), macrostructural damage (MAD), microstructural damage (MID), 2) intensity: median, skewness, kurtosis and 3) volume: NABM to ICV volume ratio. Biomarkers were extracted from over 1400 imaging volumes from more than 87 centres and unadjusted ANOVA analysis revealed significant differences in means of the MII, MAD, and NABM volume biomarkers across all cognitive groups. In an adjusted ANCOVA model, a significant relationship between MoCA categories was found that was dependent on subject age for MII, MAD, intensity, kurtosis and NABM volume biomarkers. These results demonstrate that structural brain changes in the NABM are related to cognitive outcome (with different relationships depending on the age of the subjects). Therefore these biomarkers have high potential for clinical translation. As a secondary hypothesis, we investigated whether texture features from FLAIR MRI can quantify microstructural changes related to how "structured" or "damaged" the tissue is. Based on correlation analysis with diffusion weighted MRI (dMRI), it was shown that FLAIR MRI texture biomarkers (MII and MAD) had strong correlations to mean diffusivity (MD) which is related to tissue degeneration in the GM and WM regions. As FLAIR MRI is routinely collected for clinical neurological examinations, novel biomarkers from FLAIR MRI could be used to supplement current clinical biomarkers and for monitoring disease progression. Biomarkers could also be used to stratify patients into homogeneous disease subgroups for clinical trials, or to learn more about mechanistic development of dementia disease.

Integrating New Staff into Endovascular Stroke-Treatment Workflows in the COVID-19 Pandemic.

A health care crisis such as the coronavirus disease 2019 (COVID-19) pandemic requires allocation of hospital staff and resources on short notice. Thus, new and sometimes less experienced team members might join the team to fill in the gaps. This scenario can be particularly challenging in endovascular stroke treatment, which is a highly specialized task that requires seamless cooperation of numerous health care workers across various specialties and professions. This document is intended for stroke teams who face the challenge of integrating new team members into endovascular stroke-treatment workflows during the COVID-19 pandemic or any other global health care emergency. It discusses the key strategies for smooth integration of new stroke-team members in a crisis situation: 1) transfer of key knowledge (simple take-home messages), 2) open communication and a nonjudgmental atmosphere, 3) strategic task assignment, and 4) graded learning and responsibility. While these 4 key principles should generally be followed in endovascular stroke treatment, they become even more important during health care emergencies such as the COVID-19 pandemic, when health care professionals have to take on new and additional roles and responsibilities in challenging working environments for which they were not specifically trained.

Emergency noninvasive angiography for acute intracerebral hemorrhage.

Spontaneous ICH is a devastating condition and is associated with significant mortality in the acute phase due to ongoing hemorrhage and hematoma expansion. A growing body of evidence suggests that there may be considerable utility in performing noninvasive vascular imaging during the acute-to-early phase of ICH. CTA has become widely available and is sensitive and specific for detecting vascular causes of secondary ICH such as aneurysms, arteriovenous malformations, dural arteriovenous fistulas, intracranial dissections, and neoplasm. CT venography can also diagnose dural sinus thrombosis presenting as hemorrhagic infarction. Recent data from stroke populations demonstrate a relatively low risk to patients when contrast is administered in the absence of a known serum creatinine. Detection of acute contrast extravasation within the hematoma ("spot sign") with CT angiography is predictive of subsequent hematoma expansion and is associated with increased morbidity and mortality. Risk stratification based on acute CTA can inform and expedite decision-making regarding intensive care unit admission, blood pressure control, correction of coagulopathy, and neurosurgical consultation. Noninvasive vascular imaging should be considered as an important component of the initial diagnostic work-up for patients presenting with acute ICH.

Antiepileptic efficacy of topiramate: assessment in two in vitro seizure models.

The antiepileptic efficacy of topiramate (TPM) has been demonstrated in both whole animal seizure models and clinical trials; however, there is no consensus concerning its mechanism of action. We determined first whether the antiepileptic effect of TPM generalized to in vitro seizure models. Epileptiform discharges, recorded extracellularly, were evoked by repeated tetanic stimulation of Schaffer collaterals and layer III association fibers in entorhinal cortex/hippocampus and piriform cortex slices, respectively. TPM was applied at concentrations of 20 or 100 microM. Whole cell recordings were made from CA1 pyramidal neurons and the effect of TPM was assessed on a variety of intrinsic membrane properties including resting membrane potential, input resistance and postspike potentials. TPM (20 microM) was without effect in entorhinal cortex/hippocampus (N=6); however, 100 microM TPM decreased significantly the Coastline Burst Index from 358.3+/-65.8 to 225. 5+/-77.1 (N=4), the frequency of spontaneous epileptiform discharges to 44.6+/-21.8 (N=5) and the duration of primary afterdischarge (PAD) to 65.9+/-10.1 (N=10) percent of control. In contrast, phenytoin (50 microM, N=7; 100 microM, N=8) reduced PAD to 96.9+/-14. 8 and 86.5+/-17.3 percent of control, respectively. TPM (100 microM) did not reduce significantly the frequency of spontaneous discharges in piriform cortex (85.4+/-12.3 percent of control; N=5). TPM (100 microM) was without significant effect on intrinsic membrane properties in CA1 pyramidal neurons. Likely candidate mechanisms underlying the antiepileptic effect produced by TPM include enhancement of chloride-mediated GABA(A) currents and reduction of kainate and L-type calcium currents.

Type III intermittency in human partial epilepsy.

A rigorous characterization of the dynamic regimes underlying human seizures is needed to understand, and possibly control, the transition to seizure. Intra- or extracranial brain electrical activity was recorded in five patients with partial epilepsy, and the interictal and ictal activity analysed to determine the dynamics of seizures. We constructed first-return one-dimensional maps by fitting the scatter plots of interpeak intervals. The features of the mapping indicated that type III intermittency is the dynamic characteristic of the ictal events. This was confirmed using histograms of the durations of the regular phases during seizures. The intermittent regime explains the abrupt transitions observed during ictal events in terms of transient stabilization of the unstable steady state.