Foal Health

Biomarker Shows Prognostic Promise for NMS

By Paul Basilio

Neonatal maladjustment syndrome (NMS) is a rare yet serious condition characterized by neurologic dysfunction and an increased risk for mortality. Many theories have been proposed for the pathophysiologic mechanism underlying this disorder, such as perinatal asphyxia, metabolic derangements and maladaptation to extrauterine light.

“To date, none of these have been validated as a mechanism for this disorder,” said Javier Perez
Quesada, DVM, a resident at North Carolina State University. “We don’t have an objective way to look at the foal in front of us and say, ‘This foal has NMS.’ We’re left with a purely clinical diagnosis.”

Prior investigations have looked at several biomarkers for the condition, but none have proven to be entirely helpful. Dr. Quesada and his team aimed to further the biomarker push by incorporating findings from human neonatal medicine. He described the team’s findings here at the 2024 ACVIM Forum in Minneapolis, Minn.

“We focused on astroglial biomarkers, centering on glial fibrillary acid protein, or GFAP, and the astrocytic protein S100B,” he explained. “We know that astroglia are important because they play a role in the formation of the blood barrier and in neurodevelopment of the fetal brain. They also provide metabolic and structural support for the neurons, as well as help with neurosteroid formation.”

The team also evaluated brain-derived neurotrophic factor (BDNF) as a marker of neuronal damage, and whether there was an association between the various markers and survival, clinical diagnosis of NMS, and disease severity.

The study involved 8 healthy foals, plus 11 foals with NMS and 22 sick horses with other diseases that were presented to the hospital during the study period. Between the foals with NMS and the other sick horses, the team ended up with 24 survivors and 9 non-survivors. Blood samples were obtained on admission and at 24 and 48 hours.

The team’s initial hypothesis was that foals with NMS would have higher blood concentrations of biomarkers of neurological damage versus healthy foals, and that biomarkers of neurological damage would be increased in foals that did not survive.

After analyzing the blood samples, however, results showed that GFAP concentrations were higher in healthy foals at all time points.

“It was the complete opposite of what we expected,” Dr. Quesada said.

When the admission samples were compared between survivors and non-survivors, there was a higher concentration of GFAP in survivor animals. No statistically significant findings were found for S100B between the 2 groups.
The team then evaluated BDNF concentrations in all groups at all points and found that BDNF was decreased from baseline in foals with NMS. There was also a decrease in NMS foals versus healthy foals.

“When we compared the BDNF concentration in survivors and non-survivors, we found that plasma BDNF concentration was higher in non-survivor foals on admission,” he explained. “These preliminary results suggest that reduced GFAP concentrations in NMS foals and in sick foals indicate astroglial dysfunction or delayed postnatal astroglial genesis. GFAP could be a potential biomarker for glial dysfunction in foals, as well as a biomarker for predicting outcomes.”

Dr. Quesada explained that this research is ongoing, and that his team hopes to continue studying this biomarker in foals with NMS to make the statistical analysis more powerful. A point-of-care plasma GFAP test is already available, which makes this potential biomarker an even more appealing target.

“It would be an advantage for us to discuss the foal with the owner and have them make a more informed decision toward management,” he concluded. MeV