Citations

Spontaneous intracerebral hemorrhage is an uncommon but recognized first presentation of both primary and metastatic brain tumors. The rate of tumor‐related intracranial hemorrhage is variably reported from less than 1% to 14.6%. Hemorrhage in primary gliomas occurs in 3.7 to 7.2% of cases, mainly in glioblastoma and oligodendroglioma with low‐grade astrocytomas accounting for less than 1%. Hemorrhage associated with pilocytic astrocytomas is only sporadically reported. A series of pilocytic astrocytomas presenting as a hemorrhages prompted us to examine the incidence of bleeding in these tumors. Cases with a confirmed tissue diagnosis of pilocytic astrocytoma from 1994–2005 were reviewed retrospectively. Only subjects with radiographic evidence of hemorrhage on CT and/or MRI occurring prior to biopsy or resection and in the absence of trauma or specific vascular pathologies were included. Of 138 patients with histological pilocytic astrocytoma, the average age at diagnosis was 23 years. Eleven (8%) patients (5M, 6F) had evidence of hemorrhage at presentation. Its occurrence was independent of tumor location. Hemorrhage in pilocytic astrocytoma is likely related to the frequently observed abnormal vasculature seen in these tumors, occurs with a greater frequency than previously thought, and should be considered in the differential diagnosis of spontaneous intracerebral hemorrhage.

ObjectiveTo investigate β‐amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients.MethodsPatients with MS (n = 16) and controls (n = 80) matched for age, sex, andAPOEε4 status from the population‐based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age.ResultsAD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98],p= 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99],p= 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90],p= 0.040) were lower in MS than controls. Although AD‐signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35],p= 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006],p= 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005],p= 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls.InterpretationAlthough both β‐amyloid and tau are biomarkers of cognitive aging and AD, cortical β‐amyloid deposition was lower in MS than age‐matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β‐amyloid but not the accumulation of tau.ANN NEUROL 2020;87:556–567

Abstract The concentrations of five essential elements and six potentially toxic elements were determined in seven organs collected at autopsy from 30 human subjects. Elemental analyses were carried out by graphite furnace atomic absorption spectroscopy, and inductively coupled plasma emission spectroscopy, and inductively coupled plasma mass spectroscopy, and concentrations in fresh and formalin-fixed tissues were compared. Formalin-fixation long-term storage has little effect on most element concentrations in tissue, except for Al and Mn, which changed with prolonged storage in formalin. The kidney and liver contained the greatest concentrations of toxic elements compared with other organs, whereas the essential elements were uniformly distributed among all organs. There was no more than a 10-fold difference in the tissue concentration of the elements studied among the organs, except for the concentration of Fe in liver, and Ca and Mg in bone. We also demonstrate that these elements are homogeneously distributed in tissues.

Background: Transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with hippocampal atrophy in Alzheimer’s disease (AD), but whether the association is modified by other factors is unknown. Objective: To evaluate whether the associations between TDP-43 and hippocampal volume and atrophy rate are affected by age, gender, apolipoprotein E ( APOE) ɛ4, Lewy bodies (LBs), amyloid-β (Aβ), or Braak neurofibrillary tangle (NFT) stage. Methods: In this longitudinal neuroimaging-clinicopathological study of 468 cases with AD neuropathological changes (Aβ-positive) that had completed antemortem head MRI, we investigated how age, gender, APOE ɛ4, presence of LBs, Aβ, TDP-43, and Braak NFT stages are associated with hippocampal volumes and rates of atrophy over time. We included field strength in the models since our cohort included 1.5T and 3T scans. We then determined whether the associations between hippocampal atrophy and TDP-43 are modified by these factors using mixed effects models. Results: Older age, female gender, APOE ɛ4, higher field strength, higher TDP-43, and Braak NFT stages were associated with smaller hippocampi. Rate of atrophy was greater with higher TDP-43 and Braak NFT stage, but lower in older patients. The association of TDP-43 with greater rate of atrophy was enhanced in APOE ɛ4 carriers ( p = 0.04). Conclusion: Neurodegenerative effects of TDP-43 seem to be independent of most factors except perhaps APOE in cases with AD neuropathological changes. TDP-43 and tau appear to behave independently of one another.

AbstractObjectiveTo 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.MethodsSixty 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.ResultsThe 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.SignificanceTau‐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.