By Lucy Piper, medwireNews Reporter
medwireNews: Elevated total (t)-tau in cerebral spinal fluid (CSF) may indicate initial brain injury in patients with cryptogenic new-onset refractory status epilepticus (cNORSE) and predict subsequent hippocampal atrophy, suggest study findings.
“The identification of acute phase biomarkers that reflect neuronal damage, and possibly, prognosticate functional outcomes, represents a gap in the understanding of cNORSE”, write Soon-Tae Lee (Seoul National University College of Medicine, South Korea) and co-investigators in the Annals of Clinical and Translational Neurology.
To address this, they studied potential biomarkers in CSF samples collected from 19 adults within 7 days of the onset of NORSE that had no identifiable structural, toxic or metabolic cause and was refractory to at least two appropriately dosed antiseizure medications including benzodiazepines. The participants had a median age of 35 years and 52.6% were women.
The researchers used two proteomic neurology panels to identify CSF proteins that were at least twofold higher in the patients with cNORSE, compared with 21 controls (median age 40.7 years) with other neurological diseases including atypical parkinsonism (n=5), postural orthostatic hypotension syndrome (n=6), epilepsy (n=7) and cerebellar ataxia (n=3).
Of these, t-tau and nicotinamide/nicotinic acid mononucleotide adenylyltransferase were the only proteins that significantly correlated with changes in modified Rankin Scale score for neurological disability at 4 weeks, as a measure of clinical outcome, and only t-tau also had a significant association with hippocampal atrophy in unadjusted analysis.
Lee and colleagues therefore concentrated on t-tau and found that median CSF levels were significantly elevated in patients with cNORSE compared with controls (2.134 vs 0.552 NPX).
“The marked increase in CSF t-tau levels in the cNORSE cohort could reflect significant axonal injury that occurs in the acute phase of cNORSE, to a much greater extent than that in chronic stable neurological conditions, such as epilepsy or atypical parkinsonism,” the study authors suggest.
They then compared nine patients with high t-tau levels (≥2.2 NPX) and 10 patients with lower levels and found hippocampal atrophy on magnetic resonance imaging scans 2 months after diagnosis in 88.9% versus 37.5%, respectively. This translated to a significant odds ratio for hippocampal atrophy of 13.33 among patients with high t-tau levels relative to those with low levels.
In terms of disease severity, the study showed a significantly higher need for antiseizure medications among patients with elevated CSF t-tau levels versus low levels, both within the first month (6 vs 4 agents) and during the entire clinical course (7 vs 5 agents).
The researchers note, however, that “as this is an uncontrolled study with no defined treatment protocols, [antiseizure medication] usage in this cohort could be affected by physician preference.”
The patients with high t-tau levels also had significantly worse Clinical Assessment Scale in Autoimmune Encephalitis scores at 1 month than those with low levels, at 24 versus 14 points. There was a trend for longer duration of anaesthetic infusion duration among those with high t-tau levels, “potentially reflecting greater clinical severity,” note Lee and team, but it did not reach statistical significance.
Despite the small number of study participants, they say that “[e]arly detection of t-tau in patients with cNORSE can help identify patients at higher risk of greater clinical severity and subsequent hippocampal atrophy.” They add: “This may facilitate family discussions to prepare for adverse outcomes and inform therapeutic decisions.”
The team concludes that “[f]urther studies are required to determine if earlier and more aggressive immunotherapy in cNORSE patients with high CSF t-tau can improve long-term clinical and cognitive outcomes.”
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Ann Clin Transl Neurol 2025; doi:10.1002/acn3.70043