Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders

Hannah Dobson; Said Al Maawali; Charles Malpas; Alexander F Santillo; Matthew Kang; Marian Todaro; Rosie Watson; Nawaf Yassi; Kaj Blennow; Henrik Zetterberg; Emma Foster; Andrew Neal; Dennis Velakoulis; Terence John O'Brien; Dhamidhu Eratne; Patrick Kwan

doi:10.1111/epi.18065

Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders

Epilepsia. 2024 Sep;65(9):2751-2763. doi: 10.1111/epi.18065. Epub 2024 Jul 20.

Authors

Hannah Dobson^{1

2}, Said Al Maawali³, Charles Malpas^{4

5}, Alexander F Santillo⁶, Matthew Kang^{1

2

7}, Marian Todaro^{3

5

8

9}, Rosie Watson^{5

10}, Nawaf Yassi^{5

10

11}, Kaj Blennow^{12

13

14

15}, Henrik Zetterberg^{12

13

16

17

18}, Emma Foster^{3

9}, Andrew Neal^{3

9}, Dennis Velakoulis^{2

7}, Terence John O'Brien^{3

11}, Dhamidhu Eratne^{2

7}, Patrick Kwan^{3

9

11}

Affiliations

¹ Department of Psychiatry, Alfred Health, Melbourne, Victoria, Australia.
² Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
³ Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
⁴ Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
⁶ Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund/Malmö, Sweden.
⁷ Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁹ Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
¹⁰ Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
¹¹ Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
¹² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
¹³ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁴ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
¹⁵ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, China.
¹⁶ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁷ UK Dementia Research Institute at UCL, London, UK.
¹⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 39032019
DOI: 10.1111/epi.18065

Abstract

Objective: Research suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood in response to neuroaxonal damage, and they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic nonepileptic seizures (PNES) and other nonepileptic disorders.

Methods: We recruited consecutive adults admitted for video-electroencephalographic monitoring and formal neuropsychiatric assessment. NfL and GFAP levels were quantified and compared between different patient groups and an age-matched reference cohort (n = 1926) and correlated with clinical variables in patients with epilepsy.

Results: A total of 138 patients were included, of whom 104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p = .04, GFAP p = .04). A high proportion of patients with epilepsy (20%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%). NfL levels above the 95th percentile of the reference cohort had a 95% positive predictive value for epilepsy. Patients with epilepsy who had NfL levels above the 95th percentile were younger than those with lower levels (37.5 vs. 43.8 years, p = .03).

Significance: An elevated NfL or GFAP level in an individual patient may support an underlying epilepsy diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.

Keywords: biomarker; epilepsy; glial fibrillary acidic protein; neurofilament light chain; nonepileptic seizures.

MeSH terms

Adult
Aged
Biomarkers* / blood
Diagnosis, Differential
Electroencephalography
Epilepsy* / blood
Epilepsy* / diagnosis
Female
Glial Fibrillary Acidic Protein* / blood
Glial Fibrillary Acidic Protein* / cerebrospinal fluid
Humans
Male
Middle Aged
Neurofilament Proteins* / blood
Neurofilament Proteins* / cerebrospinal fluid
Seizures* / blood
Seizures* / cerebrospinal fluid
Seizures* / diagnosis
Young Adult

Substances

Glial Fibrillary Acidic Protein
Neurofilament Proteins
neurofilament protein L
GFAP protein, human
Biomarkers

Abstract

MeSH terms

Substances

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