What is a newer biomarker for diagnosing seizures, aside from electroencephalogram (EEG)?

Newer Biomarker for Seizure

Serum neurofilament light chain (NfL) is the most promising newer blood biomarker for seizures, particularly in status epilepticus, where it correlates with seizure severity, duration, treatment response, and clinical outcomes.

Serum Neurofilament Light Chain (NfL) as a Seizure Biomarker

Clinical Utility in Status Epilepticus

• Serum NfL levels are significantly elevated in patients with status epilepticus (median 26.15 pg/mL) compared to drug-resistant epilepsy patients (median 7.35 pg/mL) and healthy controls (median 6.81 pg/mL) 1

• NfL levels correlate strongly with cerebrospinal fluid (CSF) NfL (τ = 0.68) and CSF total tau levels (τ = 0.627), validating its accuracy as a peripheral biomarker of neuronal injury 1

Prognostic Value

• Serum NfL levels >28.8 pg/mL predict 30-day clinical worsening or death with an odds ratio of 10.83 and status epilepticus refractoriness with an odds ratio of 9.33 1

• Higher NfL levels are associated with prolonged status epilepticus (>24 hours), refractory/superrefractory status epilepticus, and worse clinical outcomes 1

Advantages Over Traditional Biomarkers

• NfL provides a quantitative, objective measure of seizure-related neuronal damage that overcomes the invasiveness of CSF sampling 2

• Blood NfL can be measured repeatedly for longitudinal monitoring, unlike single-time CSF sampling 2, 3

• New ultrasensitive immunoassays can detect NfL at attomolar levels (as low as 0.012 pg/mL), making it feasible for clinical use 4

Important Caveats

Non-Specificity

• NfL is not specific to seizures and increases in any condition causing neuronal injury, including multiple sclerosis, traumatic brain injury, stroke, and neurodegenerative diseases 2, 3

• Peripheral tissue injury from surgery or trauma can elevate plasma NfL independent of brain injury, potentially confounding interpretation 5

Temporal Considerations

• NfL accumulates over days following neuronal injury and remains elevated for months, making it difficult to determine peak levels or normalization with a single measurement 2

• This temporal profile limits its utility for acute seizure diagnosis but makes it valuable for monitoring chronic seizure-related damage 2

Clinical Application Algorithm

For patients with status epilepticus or refractory seizures:

1. Obtain baseline serum NfL measurement during acute presentation 1
2. Use NfL >28.8 pg/mL as a threshold to identify high-risk patients requiring aggressive treatment 1
3. Repeat measurements at intervals to monitor treatment response and ongoing neuronal injury 2, 3
4. Interpret results in context of seizure duration, refractoriness, and clinical trajectory 1

For routine seizure evaluation:

• EEG remains the primary diagnostic tool for distinguishing epileptic from non-epileptic seizures 6, 7
• MRI is superior to CT for identifying epileptogenic structural lesions (70-80% vs 30% sensitivity) 5, 7
• Serum NfL should be considered an adjunctive biomarker for assessing cumulative neuronal damage rather than a primary diagnostic test 1, 2

Future Directions

• Standardized protocols for blood sample collection, processing, and storage are essential for reliable NfL measurement 8
• Clinical-grade assays with high precision are critical for widespread implementation 8
• Further research is needed to establish seizure-specific NfL thresholds and optimal timing of measurements 1, 2