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Chronic traumatic encephalopathy-neuropathologic change in a routine neuropathology service: 7-year follow-up.

ABSTRACT: To follow our 2016 study of chronic traumatic encephalopathy neuropathologic change (CTE-NC) in our forensic autopsy service, we prospectively screened all cases with clinical histories of multiple concussions, persistent post-head injury symptoms, or ≥3 hospital investigations for head injuries from 2016 to 2022 inclusive using hyperphosphorylated tau (p-tau) immunostaining. The cases had routine brain sampling plus 4-6 additional lateral hemisphere samples. When "pathognomonic" CTE-NC lesions were identified, additional p-tau immunostaining was done for CTE-NC staging. Of ∼1100 adult brains aged 18-65 years examined, 85 were screened, and 16 were positive for CTE-NC (2 women, 14 men, ages 35-61 years, median 47 years). Alcohol abuse was documented in 14 of 16 (8 in combination with other substances); 5 had developmental brain anomalies (2 presumed genetic, 3 from acquired perinatal insults). Widespread p-tau deposits (high CTE-NC) were found in 7 of 16. Old brain contusions were present in 9 of 16, but CTE-NC did not colocalize. Of particular interest were (1) a man with FGFR3 mutation/hypochondroplasia and life-long head banging, (2) a woman with cerebral palsy and life-long head banging, and (3) a man with bilateral peri-Sylvian polymicrogyria, alcohol abuse, and multiple head injuries. Thus, CTE-NC occurs in association with repeated head trauma outside contact sports. Substance abuse is a common determinant of risk behavior. The utility of diagnosing mild-/low-stage CTE-NC in this population remains to be determined.

SUBMITTER: Del Bigio MR

PROVIDER: S-EPMC10588000 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Chronic traumatic encephalopathy-neuropathologic change in a routine neuropathology service: 7-year follow-up.

Del Bigio Marc R MR Krawitz Sherry S Sinha Namita N

Journal of neuropathology and experimental neurology 20231001 11

To follow our 2016 study of chronic traumatic encephalopathy neuropathologic change (CTE-NC) in our forensic autopsy service, we prospectively screened all cases with clinical histories of multiple concussions, persistent post-head injury symptoms, or ≥3 hospital investigations for head injuries from 2016 to 2022 inclusive using hyperphosphorylated tau (p-tau) immunostaining. The cases had routine brain sampling plus 4-6 additional lateral hemisphere samples. When "pathognomonic" CTE-NC lesions ...[more]

PMID: 37846159

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Project description:IntroductionWe examined postmortem brain tissue from men, over the age of 50, for chronic traumatic encephalopathy neuropathologic change (CTE-NC). We hypothesized that (i) a small percentage would have CTE-NC, (ii) those who played American football during their youth would be more likely to have CTE-NC than those who did not play contact or collision sports, and (iii) there would be no association between CTE-NC and suicide as a manner of death.MethodsBrain tissue from 186 men and accompanying clinical information were obtained from the Lieber Institute for Brain Development. Manner of death was determined by a board-certified forensic pathologist. Information was obtained from next of kin telephone interviews, including medical, social, demographic, family, and psychiatric history. The 2016 and 2021 consensus definitions were used for CTE-NC. Two authors screened all cases, using liberal criteria for identifying "possible" CTE-NC, and five authors examined the 15 selected cases.ResultsThe median age at the time of death was 65 years (interquartile range = 57-75; range = 50-96). There were 25.8% with a history of playing American football and 36.0% who had suicide as their manner of death. No case was rated as definitively having "features" of CTE-NC by all five authors. Ten cases were rated as having features of CTE-NC by three or more authors (5.4% of the sample), including 8.3% of those with a personal history of playing American football and 3.9% of those who did not play contact or collision sports. Of those with mood disorders during life, 5.5% had features of CTE-NC compared to 6.0% of those who did not have a reported mood disorder. Of those with suicide as a manner of death, 6.0% had features of CTE-NC compared to 5.0% of those who did not have suicide as a manner of death.DiscussionWe did not identify a single definitive case of CTE-NC, from the perspective of all raters, and only 5.4% of cases were identified as having possible features of CTE-NC by some raters. CTE-NC was very uncommon in men who played amateur American football, those with mood disorders during life, and those with suicide as a manner of death.

Project description:Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma and is characterised by the perivascular accumulation of hyperphosphorylated tau (p-tau) in the depths of cortical sulci. CTE can only be diagnosed postmortem and the cellular mechanisms of disease causation remain to be elucidated. Understanding the full scope of the pathological changes currently identified in CTE is necessary to identify areas requiring further research. This systematic review summarises the current literature on CTE pathology from postmortem human tissue histology studies published until 31 December 2021. Publications were included if they quantitively or qualitatively compared postmortem human tissue pathology in CTE to neuropathologically normal cases or other neurodegenerative diseases such as Alzheimer's disease (AD). Pathological entities investigated included p-tau, beta-amyloid, TDP-43, Lewy bodies, astrogliosis, microgliosis, axonopathy, vascular dysfunction, and cell stress. Of these pathologies, p-tau was the most frequently investigated, with limited reports on other pathological features such as vascular dysfunction, astrogliosis, and microgliosis. Consistent increases in p-tau, TDP-43, microgliosis, axonopathy, and cell stress were reported in CTE cases compared to neuropathologically normal cases. However, there was no clear consensus on how these pathologies compared to AD. The CTE cases used for these studies were predominantly from the VA-BU-CLF brain bank, with American football and boxing as the most frequent sources of repetitive head injury exposure. Overall, this systematic review highlights gaps in the literature and proposes three priorities for future research including: 1. The need for studies of CTE cases with more diverse head injury exposure profiles to understand the consistency of pathology changes between different populations. 2. The need for more studies that compare CTE with normal ageing and AD to further clarify the pathological signature of CTE for diagnostic purposes and to understand the disease process. 3. Further research on non-aggregate pathologies in CTE, such as vascular dysfunction and neuroinflammation. These are some of the least investigated features of CTE pathology despite being implicated in the acute phase response following traumatic head injury.

Project description:Limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC) and microvascular pathologies, including microinfarcts, cerebral amyloid angiopathy (CAA), and arteriolosclerosis are common in old age. A relationship between LATE-NC and arteriolosclerosis has been reported in some but not all studies. The objectives of this study were to investigate the frequency of co-occurring LATE-NC and microvascular pathologies and test the hypothesis that arteriolosclerosis, specifically, is related to LATE-NC in brains from community-dwelling older persons. Analyses included 749 deceased participants with completed data on LATE-NC and microvascular pathology from 3 longitudinal clinical pathologic studies of aging. Given the specific interest in arteriolosclerosis, we expanded the examination of arteriolosclerosis to include not only the basal ganglia but also two additional white matter regions from anterior and posterior watershed territories. Ordinal logistic regression models examined the association of microvascular pathology with LATE-NC. LATE-NC was present in 409 (54.6%) decedents, of which 354 (86.5%) had one or multiple microvascular pathologies including 132 (32.3%) with moderate-severe arteriolosclerosis in basal ganglia, 195 (47.6%) in anterior watershed, and 144 (35.2%) in posterior watershed; 170 (41.5%) with moderate-severe CAA, and 150 (36.6%) with microinfarcts. In logistic regression models, only posterior watershed arteriolosclerosis, but not other regions of arteriolosclerosis was associated with a higher odds of more advanced LATE-NC stages (Odds Ratio = 1.12; 95% Confidence Interval = 1.01-1.25) after controlling for demographics, AD, and other age-related pathologies. Capillary CAA, but not the severity of CAA was associated with an increased odds of LATE-NC burden (Odds Ratio = 1.71; 95% Confidence Interval = 1.13-2.58). Findings were unchanged in analyses controlling for APOE ε4, vascular risk factors, or vascular diseases. These findings suggest that LATE-NC with microvascular pathology is a very common mixed pathology and small vessel disease pathology may contribute to LATE-NC in the aging brain.

Dataset Information

Chronic traumatic encephalopathy-neuropathologic change in a routine neuropathology service: 7-year follow-up.

Publications

Chronic traumatic encephalopathy-neuropathologic change in a routine neuropathology service: 7-year follow-up.

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