Genomic tool may predict MS severity
Monash University researchers have used data from the MSBase registry to develop a genome-based tool that can predict the course of multiple sclerosis.
Led by Dr Vilija Jokubaitis (PhD) of the Department of Neuroscience, an international team used a genome-wide association study and machine learning approaches to assess the genetic contribution to longitudinally defined MS severity phenotypes in 1,813 people with relapse-onset MS.
No variants with moderate to large effect sizes were identified, but clinical outcomes in MS were found to be associated with multiple genetic loci of small effect sizes.
Using a machine learning approach incorporating over 62,000 variants and demographic variables available at MS disease onset, they could predict severity with an area under the receiver operator curve (AUROC) of 0.87 (95% CI 0.83 – 0.91). The classification algorithm had 86% sensitivity and 88% specificity, with a positive predictive value (PPV) of 89% and negative predictive value (NPV) of 85%.
“This approach, if externally validated, could quickly prove useful for clinical stratification at MS onset,” they wrote in a paper published on the preprint server medRxiv.
The analysis also found evidence to support CNS and mitochondrial involvement in determining MS severity, they added, with an overrepresentation of genes expressed in the cerebellum relating to mitochondrial function, synaptic plasticity, cellular senescence, calcium and the g-protein receptor signalling pathway.
Antiseizure medication adjustment needed in pregnancy
Some women with epilepsy may need dose adjustments of their antiseizure medications during pregnancy to counter declines in plasma levels that can occur from the first trimester, US researchers say.
A University of Pittsburg study of 430 women with epilepsy found that those taking lamotrigine, levetiracetam, lacosamide, oxcarbazepine, and zonisamide experienced significant decreases in dose-normalised concentrations during pregnancy.
Dose-normalised concentrations also decreased for carbamazepine but remained stable for unbound carbamazepine and carbamazepine-10,11-epoxide, according to findings published in JAMA Neurology.