Hippocampal T2 hyperintensities on 7Tesla MRI

AbstractHippocampal focal T2 hyperintensities (HT2Hs), also referred to as hippocampal sulcal cavities, are a common finding on Magnetic Resonance (MR) images. There is uncertainty about their etiology and clinical significance. In this study we aimed to describe these HT2Hs in more detail using high resolution 7Tesla MR imaging, addressing 1) the MR signal characteristics of HT2Hs, 2) their occurrence frequency, 3) their location within the hippocampus, and 4) their relation with age. We also performed an explorative post-mortem study to examine the histology of HT2Hs.Fifty-eight persons without a history of invalidating neurological or psychiatric disease (mean age 64±8years; range 43–78years), recruited through their general practitioners, were included in this study. They all underwent 7Tesla MRI, including a T1, T2, and FLAIR image. MR signal characteristics of the HT2Hs were assessed on these images by two raters. Also, the location and number of the HT2Hs were assessed. In addition, four formalin-fixed brain slices from two subjects were scanned overnight. HT2Hs identified in these slices were subjected to histopathological analysis.HT2Hs were present in 97% of the subjects (median number per person 10; range 0–20). All HT2Hs detected on the T2 sequence were hypointense on T1 weighted images. Of all HT2Hs, 94% was hypointense and 6% hyperintense on FLAIR. FLAIR hypointense HT2Hs were all located in the vestigial sulcus of the hippocampus, FLAIR hyperintense HT2Hs in the hippocampal sulcus or the gray matter. Post-mortem MRI and histopathological analysis suggested that the hypointense HT2Hs on FLAIR were cavities filled with cerebrospinal fluid. A hyperintense HT2H on FLAIR proved to be a microinfarct upon microscopy.In conclusion, hippocampal T2Hs are extremely common and unrelated to age. They can be divided into two types (hypo- and hyperintense on FLAIR), probably with different etiology

Histologic characterization of the immune infiltrate in IDH wild type and mutant WHO grade 2 and 3 gliomas

Aim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organization Grade II and III gliomas were defined using next-generation sequencing or multiplex ligation-dependent probe amplification. The immune infiltrates of these tumors (46 mutant IDH, 20 wild-type IDH) were assessed immunohistochemically using a panel of antibodies (CD3, CD4, CD8, FOXP3, CD20, CD68, and CD163). Confirmatory analyses were performed on a cohort of lower grade gliomas from the Cancer Genome Atlas (TCGA). Statistical analyses were performed with Mann–Whitney U-tests and Kaplan–Meier survival estimates. Results: There was no relation between the amount of CD3+, CD4+, CD8+, or CD20+ lymphocyte infiltration and IDH mutation status in the tumors. FOXP3+ T regulatory cell infiltrates were rare, but more frequent in IDH1/2 wild-type tumors (P = 0.046). While the presence of these cells did not correlate with overall survival, FOXP3 messenger RNA expression was associated with survival in a distinct cohort of LGG from the TCGA (P < 0.05). CD4+ lymphocyte infiltrates, on the other hand, tended to prevail in astrocytic tumors as compared to oligodendrogliomas (P = 0.056). While CD68 (M1) microglial/monocytic cells were equally abundant in IDH mutant and wild-type tumors, the presence of round, activated M1 CD68+ microglia significantly associated with a mutant IDH status (P = 0.015). Conclusion: FOXP3+ expression and activated CD68+ M1 cells associated with IDH status in LGG, and might contribute to their differential evolution

Histologic characterization of the immune infiltrate in IDH wild type and mutant WHO grade 2 and 3 gliomas

Aim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organization Grade II and III gliomas were defined using next-generation sequencing or multiplex ligation-dependent probe amplification. The immune infiltrates of these tumors (46 mutant IDH, 20 wild-type IDH) were assessed immunohistochemically using a panel of antibodies (CD3, CD4, CD8, FOXP3, CD20, CD68, and CD163). Confirmatory analyses were performed on a cohort of lower grade gliomas from the Cancer Genome Atlas (TCGA). Statistical analyses were performed with Mann–Whitney U-tests and Kaplan–Meier survival estimates. Results: There was no relation between the amount of CD3+, CD4+, CD8+, or CD20+ lymphocyte infiltration and IDH mutation status in the tumors. FOXP3+ T regulatory cell infiltrates were rare, but more frequent in IDH1/2 wild-type tumors (P = 0.046). While the presence of these cells did not correlate with overall survival, FOXP3 messenger RNA expression was associated with survival in a distinct cohort of LGG from the TCGA (P < 0.05). CD4+ lymphocyte infiltrates, on the other hand, tended to prevail in astrocytic tumors as compared to oligodendrogliomas (P = 0.056). While CD68 (M1) microglial/monocytic cells were equally abundant in IDH mutant and wild-type tumors, the presence of round, activated M1 CD68+ microglia significantly associated with a mutant IDH status (P = 0.015). Conclusion: FOXP3+ expression and activated CD68+ M1 cells associated with IDH status in LGG, and might contribute to their differential evolution

Histological differences of the Vascular wall between sites with high and low prevalence of intracranial aneurysm

Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle ofWillis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA]) using histological sections of 10 CoWs without IAs. Medial defect density in the AcomA was 0.24 medial defects/mm compared with 0.02 for the A1 part and 0.03 for the A2 part of the ACA. In the basilar tip we found 0.15 medial defects/mm compared with 0.14 in the BA. Vascular smooth muscle cells (VSMCs) were more often disorganized in both high-prevalence sites (AcomA: 10/ 10, basilar tip: 5/10) compared with low-prevalence sites (both ACA and BA: 1/10). Intima thickening was more severe in the highprevalence sites. Vascular wall thickness was not significantly different between high- and low-prevalence sites, but had a larger variance in high- compared with low-prevalence sites (AcomA vs ACA: p=6.8E-12, basilar tip vs BA: p=0.02). Disorganized VSMCs at high-prevalence sites likely result in a higher susceptibility to hemodynamic stress, leading to more vascular remodeling (such as intima thickening), which could increase the likelihood of IA formation

Histological differences of the Vascular wall between sites with high and low prevalence of intracranial aneurysm

Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle ofWillis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA]) using histological sections of 10 CoWs without IAs. Medial defect density in the AcomA was 0.24 medial defects/mm compared with 0.02 for the A1 part and 0.03 for the A2 part of the ACA. In the basilar tip we found 0.15 medial defects/mm compared with 0.14 in the BA. Vascular smooth muscle cells (VSMCs) were more often disorganized in both high-prevalence sites (AcomA: 10/ 10, basilar tip: 5/10) compared with low-prevalence sites (both ACA and BA: 1/10). Intima thickening was more severe in the highprevalence sites. Vascular wall thickness was not significantly different between high- and low-prevalence sites, but had a larger variance in high- compared with low-prevalence sites (AcomA vs ACA: p=6.8E-12, basilar tip vs BA: p=0.02). Disorganized VSMCs at high-prevalence sites likely result in a higher susceptibility to hemodynamic stress, leading to more vascular remodeling (such as intima thickening), which could increase the likelihood of IA formation

Elf jaar obducties wegens de ziekte van Creutzfeldt-Jakob in Nederland

OBJECTIVE: To describe our experience with the diagnostics of Creutzfeldt-Jakob disease (CJD) and other prion diseases in the Netherlands over a period of 11 years (1997-2007). DESIGN: Retrospective. METHODS: In the period 1997-2007 autopsies were carried out on 280 patients with probable or possible CJD at the Dutch Surveillance Center for Prion Diseases in Utrecht. We registered clinical details, results of additional investigations such as EEG, MRI and cerebrospinal fluid tests, and outcomes of neurological investigations. The contribution of the different disorders within this group was estimated retrospectively. RESULTS: A prion disease was diagnosed in 146 patients (52%) with probable or possible CJD. 133 (91%) of these had the sporadic form. 2 patients were diagnosed with the 'variant CJD' (caused by bovine spongiform encephalopathy). 5 patients were diagnosed as having an iatrogenic form of CJD and 6 patients had a genetic form of the disease. A different disease was diagnosed in 134 patients (48%), such as Alzheimer disease (40%), multi-infarct dementia (13%), neoplasm (10%) and Lewy body dementia (8%). In this group, periodic sharp wave complexes were observed on EEG in 17 patients (13%), most frequently in those with Alzheimer disease. The 14-3-3 protein test on cerebrospinal fluid was positive in 28 of these patients (21%), most frequently in patients with vascular dementia and Alzheimer disease. CONCLUSION: In all cases of an unclear clinical picture suggestive of neurodegenerative disease, prion disease must be considered. Periodic sharp wave complexes on EEG and a positive 14-3-3 protein test on cerebrospinal fluid alone are not diagnostic of CJ

The spectrum of MR detectable cortical microinfarcts: A classification study with 7-tesla postmortem MRI and histopathology

Cerebral microinfarcts (CMIs) are common neuropathologic findings in aging and dementia. We explored the spectrum of cortical CMIs that can be visualized with 7T magnetic resonance imaging (MRI). Thirty-three coronal brain slices of 11 individuals with neuropathologically confirmed dementia were subjected to a high-resolution postmortem 7T MRI protocol. First, we identified all visible small (≤5 mm) intracortical and juxtacortical lesions on postmortem MRI. Lesions were classified as CMI or nonCMI based on histology, and their MR features were recorded. Thirty lesions were identified on the initial MRI evaluation, of which twenty-three could be matched with histology. Histopathology classified 12 lesions as CMIs, all of which were located intracortically. On the basis of their MR features, they could be classified as chronic gliotic CMIs - with or without cavitation or hemorrhagic components - and acute CMIs. Eleven MRI identified lesions were not of ischemic nature and most commonly enlarged or atypically shaped perivascular spaces. Their MRI features were similar to gliotic CMIs with or without cavitation, but these 'CMI mimics' were always located juxtacortically. 7T postmortem MRI distinguishes different histopathologic types of cortical CMIs, with distinctive MR characteristics. On the basis of our findings, we propose in vivo rating criteria for the detection of intracortical CMIs