Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS). We aimed to assess relationships between cerebral arterial blood flow (CABF) and serum neurofilament light chain (sNfL) as neuronal damage biomarkers. METHODS AND MATERIALS: Total CABF was measured in 137 patients (86 with clinically isolated syndrome/relapsing-remitting (RR) MS and 51 with progressive MS [PMS]) and 48 healthy controls using Doppler ultrasonography. sNfL was quantitated using a single-molecule assay (Simoa). Examination using 3.0-T magnetic resonance imaging (MRI) allowed quantification of T2 lesions and whole-brain volume (WBV). Multiple linear regression models determined the sNfL association with CABF after correction for demographic and MRI-derived variables. RESULTS: After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained an additional 2.6% of the sNfL variance (ß = -0.167, p = 0.044). CABF also remained significant in a stepwise regression model (ß = 0.18, p = 0.034) upon the inclusion of T2 lesion burden and WBV effects. Patients in the lowest CABF quartile (CABF ≤ 761 ml/min) had significantly higher sNfL levels (34.6 vs. 23.9 pg/ml, age and BMI-adjusted-p = 0.042) when compared to the highest quartile (CABF ≥ 1130 ml/min). CONCLUSION: Lower CABF is associated with increased sNfL in MS patients, highlighting the relationship between cerebral hypoperfusion and axonal pathology.

Six logical steps that connect the introduction of the Nernst equation to its clinical application.

The Nernst equation is key to understanding the electrophysiology of the cell membrane and the pathophysiology of K+ imbalances (i.e., hyperkalemia and hypokalemia). However, in our experience teaching medical students over the years, many students struggle to make connections between a brief introduction of the Nernst equation and its clinical application to K+ imbalances. This article aims to connect the introduction of the equation to its clinical application to understand K+ imbalances using six logical steps with detailed visual illustrations that make the connection explicit and cohesive. In addition, we highlight a few common areas related to the six steps that are often overlooked by both teachers and students. Students who are able to thoroughly demonstrate an understanding of all the six steps highlighted in this article will achieve mastery of this topic.NEW & NOTEWORTHY This article fills the gaps in teaching about the Nernst equation, which is important in medical physiology. Six logical steps are presented that connect the introduction of the equation to its clinical applications to hyperkalemia and hypokalemia, two conditions that can be life-threatening if left untreated. Only when students know how to apply the equation will their learning transition from surface to mastery.