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Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

Background and Purpose: The Boston criteria for cerebral amyloid angiopathy (CAA) need validation by neuropathological examination in patients with lobar cerebral haematomas (LCHs). In "vivo" 1.5-tesla magnetic resonance imaging (MRI) is unreliable to detect the age-related signal changes in LCHs. This post-mortem study investigates the validity of the Boston criteria in brains with LCHs and the signal changes during their time course with 7.0-tesla MRI., Materials and Methods: Seventeen CAA brains including 26 LCHs were compared to 13 non-CAA brains with 14 LCHs. The evolution of the signal changes with time was examined in 25 LCHs with T2 and T2* 7.0-tesla MRI., Results: In the CAA group LCHs were predominantly located in the parieto-occipital lobes. Also white matter changes were more severe with more cortical microinfarcts and cortical microbleeds. On MRI there was a progressive shift of the intensity of the hyposignal from the haematoma core in the acute stage to the boundaries later on. During the residual stage the hyposignal mildly decreased in the boundaries with an increase of the superficial siderosis and haematoma core collapse., Conclusions: Our post-mortem study of LCHs confirms the validity of the Boston criteria for CAA. Also 7.0-tesla MRI allows staging the age of the LCHs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To evaluate the usefulness of the punctate pattern (PP) for the diagnosis and follow-up of patients with progressive multifocal leukoencephalopathy (PML)., Methods: A cohort of 20 consecutive patients with PML, related to natalizumab (NTZ) (n = 14) or not (n = 6), underwent 3T MRI (147 MRI examinations). MRI was available at presymptomatic (n = 9 patients), symptomatic (n = 15), immune reconstitution inflammatory syndrome (IRIS), and chronic stages (n = 20). A pathologic control group of patients without PML (n = 80), with clinically definitive multiple sclerosis or a clinically isolated syndrome suggestive of CNS demyelination, underwent the same MRI protocol. Number and appearance of punctate lesions were assessed by 3 blinded readers using T2-weighted, fluid-attenuated inversion recovery (FLAIR), and postcontrast T1-weighted images., Results: Interobserver agreement was good (κ = 0.79) (0.72-0.87). Of the 20 patients with PML, 18 had PP, including the 14 patients with NTZ-PML; none in the pathologic control group. Of the 9 presymptomatic patients with NTZ-PML, PP was observed in 7 (78% sensitive and 100% specific). Nonenhancing PP on T2-weighted/FLAIR images was detected in 13 patients with PML, exclusively at the presymptomatic or symptomatic stages (including 7 NTZ-PML), whereas enhancing PP occurred in 16 patients with PML, including 13 of the 14 patients with NTZ-PML at the IRIS stage., Conclusions: PP is a highly specific feature of PML and may be the first imaging feature at the presymptomatic stage with potential implications in patient care., Classification of Evidence: This study provides Class II evidence that a PP on MRI accurately identifies patients with NTZ-PML., (© 2016 American Academy of Neurology.)

Background: Until recently cortical microinfarcts (CMIs) were considered as the invisible lesions in clinical-radiological correlation studies that rely on conventional structural magnetic resonance imaging. The present study investigates the presence of CMIs on 7.0-T magnetic resonance imaging (MRI) in post-mortem brains with different neurodegenerative and cerebrovascular diseases., Materials and Methods: One hundred-seventy five post-mortem brains, composed of 37 with pure Alzheimer's disease (AD), 12 with AD associated to cerebral amyloid angiopathy (AD-CAA), 38 with frontotemporal lobar degeneration, 12 with amyotrophic lateral sclerosis, 16 with Lewy body disease (LBD), 21 with progressive supranuclear palsy, 18 with vascular dementia (VaD) and 21 controls were examined. According to their size several types of CMIs were detected on 3 coronal sections of a cerebral hemisphere with 7.0-T MRI and compared to the mean CMI load observed on histological examination of one standard separate coronal section of a cerebral hemisphere at the level of the mamillary body., Results: Overall CMIs were significantly prevalent in those brains with neurodegenerative and cerebrovascular diseases associated to CAA compared to those without CAA. VaD, AD-CAA and LBD brains had significantly more CMIs compared to the controls. While all types of CMIs were increased in VaD and AD-CAA brains, a predominance of the smallest ones was observed in the LBD brains., Conclusions: The present study shows that 7.0-T MRI allows the detection of several types of MICs and their contribution to the cognitive decline in different neurodegenerative and cerebrovascular diseases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Purpose: Accumulation of iron (Fe) is often detected in brains of people suffering from neurodegenerative diseases. However, no studies have compared the Fe load between these disease entities. The present study investigates by T2*-weighted gradient-echo 7.0 T magnetic resonance imaging (MRI) the Fe content in post-mortem brains with different neurodegenerative and cerebrovascular diseases., Methods: One hundred and fifty-two post-mortem brains, composed of 46 with Alzheimer's disease (AD), 37 with frontotemporal lobar degeneration (FTLD), 11 with amyotrophic lateral sclerosis, 13 with Lewy body disease, 14 with progressive supranuclear palsy, 16 with vascular dementia (VaD) and 15 controls without a brain disease, were examined. The Fe load was determined semi-quantitatively on T2*-weighted MRI serial brain sections in the claustrum, caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, hippocampus, mamillary body, lateral geniculate body, red nucleus, substantia nigra and dentate nucleus. The disease diagnosis was made on subsequent neuropathological examination., Results: The Fe load was significantly increased in the claustrum, caudate nucleus and putamen of FTLD brains and to a lesser degree in the globus pallidus, thalamus and subthalamic nucleus. In the other neurodegenerative diseases no Fe accumulation was observed, except for a mild increase in the caudate nucleus of AD brains. In VaD brains no Fe increase was detected., Conclusions: Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity., (© 2014 The Author(s) European Journal of Neurology © 2014 EAN.)

Introduction: Progressive supranuclear palsy (PSP) is a degenerative disease affecting mainly the brain stem, basal ganglia and cerebellum. Associated cerebrovascular lesions, mainly small cerebral bleeds, are frequently observed in some neurodegenerative diseases such as Alzheimer dementia and rare in others such as frontotemporal lobar degeneration. The present post-mortem study investigates the prevalence and distribution of small cerebral bleeds in PSP brains., Material and Methods: Nineteen brains of PSP patients were compared to 12 age-matched controls. The prevalence and distribution of mini-bleeds were investigated on a coronal section of a cerebral hemisphere at the level of the mamillary bodies and on a horizontal section through the pons and cerebellum. In addition, out of these series T2*-weighted gradient-echo 7.0-Tesla magnetic resonance imaging (MRI) of 3 coronal sections of a cerebral hemisphere and of a brain stem and cerebellum was performed in 14 PSP and 11 control brains., Results: Although the total number of mini-bleeds was the same on neuropathological examination of both groups, they prevailed around the dentate nucleus of the cerebellum (p = 0.05) and in the tegmentum pontis (p = 0.05) of the PSP brains. On MRI the small bleeds were also more frequent around the dentate nucleus of the cerebellum (p = 0.02) and in the pons (p = 0.04) of PSP brains., Discussion: In PSP brains, mini-bleeds only prevail in the regions affected by the neurodegenerative process, similarly to what happens in frontotemporal lobar degeneration. They should be considered as the result of increased angiogenesis and microglial activation, leading to associated disturbances of the blood-brain barrier in the most affected regions of PSP. They are not indicative of cerebrovascular disease.

This study aims to determine the distribution and to quantify microbleeds (MBs) in postmortem brains of patients with Alzheimer disease (AD) on T2*-weighted gradient-echo 7.0 T magnetic resonance imaging. Twenty-eight AD brains were compared with 5 controls. The AD brains were subdivided further: 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central, and the occipital level of a cerebral hemisphere. MBs prevailed in the central sections (P=0.005) of AD brains without CAA, whereas in AD-CAA brains, they were more frequent in all coronal sections (P≤0.002). They prevailed in the deep cortical layers of the AD brains and of the controls (P≤0.03). They were significantly increased in all cortical layers of the AD-CAA brains (P≤0.04), compared with the controls. MBs prevalence in brains of AD patients had a different topographic distribution according to the absence or presence of severe CAA.

Background: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions., Materials and Methods: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases., Results: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03)., Conclusions: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.

Background: In view of the increasing recognition of cerebral microbleeds (MCBs) with MRI, there is a need to validate their detection in post-mortem brains in patients with cerebrovascular diseases and dementia., Materials and Methods: Out of 20 post-mortem brains of patients with Alzheimer dementia and with different cerebrovascular lesions, 45 large sections of the cerebral hemispheres, brainstem and cerebellum were submitted to a 7.0-T T₂*-weighted MRI, and afterwards compared to the histological detection of haematomas, MCBs and mini-bleeds (MNBs)., Results: The sensitivity, specificity, predictive positive value and predictive negative value of the T₂* imaging to detect MCBs and MNBs were excellent for those in the cortico-subcortical regions. There was a significant overestimation of MNBs in the striatum due to iron deposits unrelated to old haemorrhages. Also in the deep white matter, 42% of MNBs were not detected, while 31% of T₂* hyposignals were not due to MNBs but to vessels filled with post-mortem thrombi., Conclusions: When evaluating the 'bleeding load' with 7.0-T T₂*-weighted MRI in post-mortem brain sections of patients with dementia and vascular risk factors, only quantification of small cerebral bleeds in the cortico-subcortical regions is reliable., (Copyright © 2011 S. Karger AG, Basel.)

Cortical microbleeds (CMBs) detected on T2*-weighted gradient-echo (GRE) magnetic resonance imaging (MRI) are considered as a possible hallmark of cerebral amyloid angiopathy (CAA). The present post-mortem 7.0-tesla MRI study investigates whether topographic differences exist in Alzheimer's brains without (AD) and with CAA (AD-CAA). The distribution of CMBs in thirty-two post-mortem brains, consisting of 12 AD, 8 AD-CAA and 12 controls, was mutually compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean numbers of CMBs were determined in twenty-two different gyri. As a whole there was a trend of more CMBs on GRE MRI in the prefrontal section of the AD, the AD-CAA as well as of the control brains. Compared to controls AD brains had significantly more CMBs in the superior frontal, the inferior temporal, the rectus and the cinguli gyrus, and in the insular cortex. In AD-CAA brains CMBs were increased in all gyri with exception of the medial parietal gyrus and the hippocampus. AD-CAA brains showed a highly significant increase of CMBs in the inferior parietal gyrus (p value: 0.001) and a significant increase in the precuneus and the cuneus (p value: 0.01) compared to the AD brains. The differences in topographic distribution of CMBs between AD and AD-CAA brains should be further investigated on MRI in clinically suspected patients. [ABSTRACT FROM AUTHOR]

Background Microbleeds ( MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration ( FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging ( MRI) in post-mortem FTLD brains. Patients and methods The neuropathological and MRI findings in 12 FTLD brains were compared with eight age-matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, the distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central and the occipital level of a cerebral hemisphere. Results Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls ( P = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers ( P < 0.01) and borderline increased in the middle cortical layers ( P = 0.07) of the frontal section. Conclusions Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood-brain barrier. [ABSTRACT FROM AUTHOR]

Background: In view of the increasing recognition of cerebral microbleeds (MCBs) with MRI, there is a need to validate their detection in post-mortem brains in patients with cerebrovascular diseases and dementia. Materials and Methods: Out of 20 post-mortem brains of patients with Alzheimer dementia and with different cerebrovascular lesions, 45 large sections of the cerebral hemispheres, brainstem and cerebellum were submitted to a 7.0-T T2*-weighted MRI, and afterwards compared to the histological detection of haematomas, MCBs and mini-bleeds (MNBs). Results: The sensitivity, specificity, predictive positive value and predictive negative value of the T2* imaging to detect MCBs and MNBs were excellent for those in the cortico-subcortical regions. There was a significant overestimation of MNBs in the striatum due to iron deposits unrelated to old haemorrhages. Also in the deep white matter, 42% of MNBs were not detected, while 31% of T2* hyposignals were not due to MNBs but to vessels filled with post-mortem thrombi. Conclusions: When evaluating the 'bleeding load' with 7.0-T T2*-weighted MRI in post-mortem brain sections of patients with dementia and vascular risk factors, only quantification of small cerebral bleeds in the cortico-subcortical regions is reliable. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]