Review: Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: Clinical, pathological and neuroimaging evidence

Tai, Xin You; Bernhardt, Boris C.; Thom, Maria; Thompson, Pamela J.; Baxendale, Sallie; Koepp, Matthias J.; Bernasconi, Neda

doi:10.1111/nan.12458

Cited by 103 publications

(71 citation statements)

References 134 publications

(152 reference statements)

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“…These findings, together with recent evidence of an association between chronic TLE, memory impairment/decline, and tau-related proteins, 38,39 have led to speculation that hippocampal sclerosis-related TLE may represent a novel tauopathy. 40…”

Section: Discussionmentioning

confidence: 99%

Verbal memory dysfunction is associated with alterations in brain transcriptome in dominant temporal lobe epilepsy

et al. 2020

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Objective: Memory dysfunction is prevalent in many neurological disorders and can have a significant negative impact on quality of life. The genetic contributions to memory impairment in epilepsy, particularly temporal lobe epilepsy (TLE), remain poorly understood. Here, we compare the brain transcriptome between TLE patients with and without verbal memory impairments to identify genes and signaling networks important for episodic memory. Methods: Brain tissues were resected from 23 adults who underwent dominant temporal lobectomy for treatment of pharmacoresistant epilepsy. To control for potential effects of APOE on memory, only those homozygous for the APOE ε3 allele were included. A battery of memory tests was performed, and patients were stratified into two groups based on preoperative memory performance. The groups were well matched on demographic and disease-related variables. Total RNA-Seq and small RNA-Seq were performed on RNA extracted from the brain tissues. Pathway and integrative analyses were subsequently performed. Results: We identified 1092 differentially expressed transcripts (DETs), with the majority (71%) being underexpressed in brain tissues from patients with impaired memory compared to those from patients with intact memory. Enrichment analysis revealed overrepresentation of genes in pathways pertaining to brain-related neurological dysfunction, including a subset associated with neurodegenerative diseases, memory, and cognition (APP, MAPT, PINK1). Despite including patients with identical APOE genotypes, we identify APOE as a differentially expressed gene associated with memory status. Small RNA-Seq identified four differentially expressed microRNAs (miRNAs) that were predicted to target a subset (22%) of all DETs. Integrative analysis showed that these miRNA-predicted DET targets impact brainrelated pathways and biological processes also pertinent to memory and cognition. Significance: TLE-associated memory status may be influenced by differences in gene expression profiles within the temporal lobe. Upstream processes influencing 2204 | BUSCH et al.

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Section: Discussionmentioning

confidence: 99%

Verbal memory dysfunction is associated with alterations in brain transcriptome in dominant temporal lobe epilepsy

et al. 2020

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“…Cognitive abnormalities may develop in people with epilepsy and significantly impact their quality of life, especially in patients who are drug-resistant. 4 Hyperphosphorylated tau is an important feature in several neurodegenerative disorders, including Alzheimer disease (AD), several of the frontotemporal dementias including Pick disease, progressive supranuclear palsy, and corticobasal degeneration, and chronic traumatic encephalopathy (CTE). 3 Tau is a microtubule-associated protein that is involved in microtubule assembly and axonal transport.…”

Section: Introductionmentioning

confidence: 99%

“…3 Tau is a microtubule-associated protein that is involved in microtubule assembly and axonal transport. 4 Hyperphosphorylated tau is an important feature in several neurodegenerative disorders, including Alzheimer disease (AD), several of the frontotemporal dementias including Pick disease, progressive supranuclear palsy, and corticobasal degeneration, and chronic traumatic encephalopathy (CTE). CTE is a poorly understood progressive neurodegenerative disorder that develops following recurrent concussive and subconcussive head trauma.…”

Section: Introductionmentioning

confidence: 99%

Tau deposition in young adults with drug‐resistant focal epilepsy

et al. 2019

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Abstract 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 drugresistant 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. K E Y W O R D Schronic traumatic encephalopathy, epilepsy surgery, neuropathology | 2399 SMITH eT al.

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“…This review draws together the intriguing links between network hyperexcitability and tau , brain injury in epilepsy and the enhanced epileptiform activity noted in Alzheimer's disease . Furthermore, the power of modern MRI approaches to monitor progressive changes and disease involvement of extra‐temporal networks and subcortical regions is overviewed .…”

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confidence: 99%