Tau deposition in young adults with drug-resistant focal epilepsy.
Open accessAbstract
OBJECTIVE: To evaluate the presence of tau deposition and pathologic features of chronic traumatic encephalopathy (CTE) in young adult patients treated with focal cortical resections for drug-resistant epilepsy. METHODS: Sixty consecutive patients who had undergone surgical treatment for drug-resistant focal epilepsy between 18 and 45 years of age were identified (2010-2017). Medical records were reviewed to determine clinical factors, including history of head trauma, age at seizure onset, age at surgical resection, seizure type(s) and frequency, imaging findings, and surgical outcome. All formalin-fixed, paraffin-embedded blocks from the surgical specimens from each subject were sectioned and stained with hematoxylin and eosin and antibodies to tau (Thermo Fisher Scientific Clone AT8), and examined blindly for tau pathology, including lesions characteristic of CTE. RESULTS: The median age at resection was 29.5 years (range = 19-45). A history of head trauma was reported in 19 patients. Although none of the patients had pathological findings characteristic of CTE, 23 patients (38%) demonstrated tau-immunoreactive lesions, including neurites, neurofibrillary pretangles, neurofibrillary tangles, subpial tau, and/or glial tau. In 4 of the 23 patients (7% of the cohort; 17% of those with tau pathology), substantial tau burden was identified. Three of these 4 patients had no significant history of head trauma; 1 patient had multiple sports-related concussions. No specific clinical factors correlated with the presence of tau pathology. SIGNIFICANCE: Tau-immunoreactive lesions were found in 38% of 60 patients who underwent a focal cortical resection for drug-resistant focal epilepsy. Diagnostic features of CTE were not detected in any patient; however, the pathological evaluation for CTE was limited to a surgical specimen. The prominent and excessive tau deposition in 23 patients (38%) is abnormal in this age group and warrants further investigation.
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The presence of tau pathology in childhood or adolescent-onset epilepsies and in relatively younger temporal lobe epilepsy patient cohorts suggests a causal link between seizure activity and p-tau accumulation.
“However, the presence of tau pathology in childhood or adolescent-onset epilepsies, such as Dravet syndrome, Nodding syndrome, Lafora disease, NPC, TSC, and ASD, and in relatively younger TLE patient cohorts (Puvenna et al., 2016; Smith et al., 2019; Gourmaud et al., 2020) suggest a causal link between seizure activity and p-tau accumulation.”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Smith et al., 2019
The Discussion (page not provided) reports tau deposition in 38% of a younger cohort with drug-resistant focal epilepsy, supporting the younger-patient portion of the claim. It does not establish a causal link between seizures and p-tau accumulation: the authors say further study is needed to determine whether tau contributes to epilepsy, follows seizure activity, or develops in parallel. This study did not examine the listed childhood-onset syndromes. (LLM, conf=0.87)
Experimental — accuracy not yet measuredObservations of subpial bands formed by cortical p-tau depositions have been made across separate studies, providing evidence for a novel pattern of tau pathology in temporal lobe epilepsy that may result from seizure-induced reorganization of temporal lobe networks.
“Interestingly, observations of subpial bands formed by cortical p-tau depositions have been made across separate studies (Puvenna et al., 2016; Tai et al., 2016; Smith et al., 2019), providing evidence for a novel pattern of tau pathology in TLE that may result from seizure-induced reorganization of temporal lobe networks (Tai et al., 2018).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Smith et al., 2019
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McKee, A. C., Stein, T. D., Huber, B. R., Crary, J. F., Bieniek, K., Dickson, D., Alvarez, V. E., Cherry, J. D., Farrell, K., Butler, M., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02540-w · Cited by 244 · see citing works
Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms
Hwang, K., Vaknalli, R. N., Addo-Osafo, K., Vicente, M., & Vossel, K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903973 · Cited by 35 · see citing works
- Authors
- Smith, K. M., Blessing, M. M., Parisi, J. E., Britton, J. W., Mandrekar, J., & Cascino, G. D.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Cascino, Gregory D.
- ORCID
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2019-10-29
- Volume
- 60
- Issue
- 12
- Pages
- 2398-2403
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- PMC
- PMC6973032
- OpenAlex
- W2982423301
- Cited by
- 42
- References
- 4
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 3
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Epilepsia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- tau deposition, drug-resistant focal epilepsy, chronic traumatic encephalopathy, neurofibrillary tangles, young adults, head trauma, sports-related concussion
- MeSH terms
- Drug Resistant Epilepsy, Adult, Brain, Brain Chemistry, Epilepsies, Partial, Humans, Middle Aged, tau Proteins, Young Adult
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