Acute cerebral microbleeds detected on high resolution head CT presenting with transient neurologic events.

Introduction: Cerebral microbleeds (CMBs) are deposits of hemosiderin-laden macrophages that can be visualized on T2-weighted MRI sequences as small, ovoid areas of signal void. These markers represent hemorrhagic cerebral small vessel disease and are usually subclinical and asymptomatic. In these cases, we present two patients who presented with symptomatic, acute CMBs. Case description: Case 1 involves a 70-year-old male with history of diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea. Five days prior to presentation, this patient reported a transient period of left upper extremity weakness. CT was performed and demonstrated a lesion on CT imaging consistent with an acute CMB in the R centrum semiovale.Case 2 describes an 82-year-old female with history of hypertension, remote large ischemic stroke, and post-stroke epilepsy. Patient described an episode of prolonged left sided shaking consistent with prior seizures despite her consistently taking anti-epileptic drugs. On CT, a small hyperdensity was seen in the R thalamus/internal capsule region consistent with acute CMB. Discussion: These two examples demonstrate acute CMBs causing patients to demonstrate symptoms mirroring those of a TIA and experience breakthrough seizures. A TIA would normally be an indication for antiplatelet therapy. Though prior reasoning warns against anticoagulation in patients with CMBs, recent works including the SPS3 (Shoamanesh et al., 2017) and WAKE-UP (Schlemm et al., 2022) trials both showed that the presence of CMB did not significantly affect outcomes after initiating antiplatelet therapy. One should adopt a more personalized approach when deciding the therapeutic intervention of choice in patients with prior CMB.

Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

Correction to: Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD.

An amendment to this paper has been published and can be accessed via the original article.

Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD.

Ever since a GGGGCC hexanucleotide repeat expansion mutation in C9ORF72 was identified as the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), three competing but nonexclusive hypotheses to explain how this mutation causes diseases have been proposed and are still under debate. Recent studies in the field have tried to understand how the repeat expansion disrupts cellular physiology, which has suggested interesting convergence of these hypotheses on downstream, functional defects in cells, such as nucleocytoplasmic transport disruption, membrane-less organelle defects, and DNA damage. These studies have not only provided an integrated view of the disease mechanism but also revealed novel cell biology implicated in neurodegeneration. Furthermore, some of the discoveries have given rise to new ideas for therapeutic development. Here, we review the research progress on cellular pathophysiology of C9ORF72-mediated ALS and FTD and its therapeutic implication. We suggest that the repeat expansion drives pathogenesis through a combination of downstream defects, of which some can be therapeutic targets.

Pharmacokinetic Evaluation of Two Paclitaxel-Coated Balloons with Different Drug Load in a Short-Term Porcine Study.

PURPOSE: The aim of the study was to evaluate the pharmacokinetics and tissue absorption of 2 paclitaxel (PTX) drug-coated balloons (DCB) using different drug loads in a porcine-injured iliac artery model. MATERIALS AND METHODS: Twenty-eight pigs were randomized into 2 groups. In group B1, angioplasty was performed with a 1.0 µg/mm(2) DCB with PTX and in group B3, with a 3.0 µg/mm(2) DCB with PTX. An overstretched model of the iliac artery was used for angioplasty under fluoroscopy. Blood and vessel wall PTX were measured with liquid-chromatography mass spectrometry at 1, 5, 30 min, 1, 7, and 28 days. Remaining drug in the balloon was analyzed. RESULTS: Mean PTX in blood was significantly higher in the group B3 0.269 ± 0.085 µg/ml compared with the B1 0.218 ± 0.085 µg/ml; p = 0.01. Peak blood PTX concentration was detected at 1 min, and PTX was undetectable 24 h post-angioplasty. There were no statistically significant differences in the mean arterial wall concentration from the treated iliac artery between group-B1 (15.24 ± 21.29 ng/mg) and B3 (15.68 ± 16.33 ng/mg), or in the PTX wall concentration measured at different time points. Mean remaining drug in assayed balloons was lower for group-B1 and represented 8 % of the initial dose. CONCLUSIONS: Blood PTX was higher when using 3.0 µg/mm(2) DCB, with a peak drug concentration at 1-min, although the drug was undetectable at 24 h, independently of the loading dose. This study demonstrates no difference in arterial wall uptake of a low dose DCB (1.0 µg/mm(2)), when compared to a common dose DCB (3.0 µg/mm(2)) suggesting that the dose of drug in the DCB could be reduced obtaining a similar clinical effect.