Study points to neuroproteins as diagnostic clues in foals with NMS

Bottom line

North Carolina State University researchers report that several blood-based neuroproteins, alongside neurosteroids, may help identify neonatal maladjustment syndrome, or NMS, in newborn foals. The study, published September 22, 2026, in the Journal of Veterinary Internal Medicine, evaluated 14 healthy foals and 58 hospitalized foals younger than 7 days, including 19 with NMS. Investigators found that pregnane neurosteroids stayed elevated in NMS foals, while neuroprotein patterns also differed: BDNF fell over the first day of hospitalization in NMS foals, S100B was higher in septic foals with NMS than in septic foals without NMS, and GFAP was lower in NMS and other sick foals than in healthy foals. The team says BDNF and S100B, in particular, could become useful biomarkers for NMS, prematurity, and sepsis, though more work is needed before routine clinical use. (news.ncsu.edu)

Why it matters: NMS can be difficult to distinguish from other causes of neonatal illness because signs such as poor nursing, abnormal behavior, seizures, and altered mentation overlap with sepsis, prematurity, and other critical conditions. For equine veterinarians, a more objective blood-based tool could improve early triage, sharpen diagnostic confidence, and potentially help monitor neurologic injury in foals that currently rely heavily on clinical assessment and supportive care. The findings also build on prior work linking persistent neurosteroid elevations to NMS pathophysiology, suggesting that biomarker panels, rather than a single analyte, may eventually be more clinically useful. (merckvetmanual.com)

What to watch: The next step is validation in larger cohorts and development of practical testing thresholds that can distinguish NMS from sepsis, prematurity, and other neonatal ICU presentations. (news.ncsu.edu)

Key facts

Study type
Prospective study
Publication date
September 22, 2026
Journal
Journal of Veterinary Internal Medicine
Institution
North Carolina State University
Sample size
72 foals total
Healthy foals
14
Hospitalized foals younger than 7 days
58
NMS foals
19
Main finding
Pregnane neurosteroids stayed elevated in NMS foals
Biomarkers
BDNF, GFAP, and S100B
Key biomarker result
BDNF fell over the first day in NMS foals
Key biomarker result
S100B was higher in septic foals with NMS than in septic foals without NMS
Key biomarker result
GFAP was lower in NMS and other sick foals than in healthy foals
Clinical takeaway
BDNF and S100B may help identify NMS, prematurity, and sepsis
Limitation
More research is needed before routine clinical use

A new NC State study suggests that blood-based neuroproteins could give equine clinicians a more objective way to identify neonatal maladjustment syndrome in newborn foals. In findings published September 22, 2026, in the Journal of Veterinary Internal Medicine, researchers linked circulating concentrations of BDNF, GFAP, and S100B, along with persistent neurosteroid elevations, to NMS and related neonatal illness patterns. (news.ncsu.edu)

That matters because NMS remains one of the more challenging neonatal equine syndromes to diagnose cleanly at the bedside. The condition, also described as neonatal encephalopathy or “dummy foal” syndrome, can present with poor nursing, lack of affinity for the mare, wandering, lethargy, seizures, or coma. Clinical signs often overlap with sepsis, prematurity, and other causes of critical illness, and there is still no widely adopted antemortem diagnostic test. Earlier work has already pointed to neurosteroid dysregulation as part of the syndrome’s biology, while older biomarker research explored UCHL1 as another possible indicator of brain injury. (merckvetmanual.com)

In the new prospective study, the NC State team measured serum and plasma markers in 72 foals total: 14 healthy foals, 19 foals with NMS, and 39 hospitalized foals with other diseases, all younger than 7 days. Samples were collected at admission and again over the next two days of hospitalization. According to the university’s release and the journal abstract, pregnane neurosteroids remained high in NMS foals compared with both healthy and other sick foals. Among the neuroproteins, BDNF decreased over the first day in NMS foals, S100B was higher in septic foals with NMS than in septic foals without NMS, and GFAP concentrations were lower in NMS and other sick foals than in healthy foals. Of the 58 hospitalized foals, 48 survived and 10 did not. (news.ncsu.edu)

The work builds on a longer NC State research thread around neonatal neurosteroids and maladjustment syndrome. Prior studies from the group and related investigators have shown that neuroactive steroid concentrations are normally high around birth but fall quickly in healthy foals, whereas affected foals can retain elevated concentrations for longer. In earlier reporting, resident researcher Javier Perez Quesada said the biomarker work may reflect astroglial damage or underdevelopment, offering a possible window into why some foals show neurologic dysfunction despite the absence of obvious traumatic brain injury. (news.ncsu.edu)

Direct outside commentary on the newly published paper appears limited so far, but the topic has drawn attention in specialty forums. Perez Quesada presented related findings at the 2024 ACVIM Forum, where the project received a resident research award in the equine category, and the study was also listed in European equine internal medicine meeting materials. That conference interest suggests clinicians see a real need for better diagnostic tools in this space, even if the evidence is still early and not yet practice-changing. (cvm.ncsu.edu)

Why it matters: For veterinary professionals, the practical value here is less about an immediate new test and more about the direction of travel. A reliable biomarker panel could help separate NMS from sepsis or nonspecific critical illness earlier in the course of hospitalization, inform prognosis, and support decisions around monitoring intensity, nutritional support, and referral. It may also help frame NMS as a syndrome with measurable biologic signatures rather than a diagnosis based largely on exclusion and behavior. Because S100B and BDNF also showed signals in septic or premature foals, the eventual clinical utility may lie in interpreting these markers alongside neurosteroids and the full clinical picture, not in relying on a single standalone result. (news.ncsu.edu)

There are still important caveats. The study cohort was relatively small, especially within the NMS subgroup, and the investigators themselves say more research is needed to establish clinical applications. Assay availability, turnaround time, cost, and reference intervals for different ages and disease states will all matter before these biomarkers can move from research settings into routine equine neonatal care. (news.ncsu.edu)

What to watch: The next milestones will be larger validation studies, clearer cutoffs for differentiating NMS from sepsis and prematurity, and evidence that serial biomarker testing improves outcomes or clinical decision-making in foal ICUs. If those pieces fall into place, this could become one of the more useful additions to equine neonatology’s diagnostic toolkit. (news.ncsu.edu)

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