Cerebrovascular Lesions in Mixed Neurodegenerative Dementia: A Neuropathological and Magnetic Resonance Study.

BACKGROUND: In elderly brains of demented patients, Alzheimer and Lewy body pathology (LBP) are frequently associated. Cortical microinfarcts (CoMIs) are more observed in Lewy body disease, even in the absence of cerebral amyloid angiopathy (CAA). The present neuropathological and 7.0-tesla MRI studies investigate whether CoMIs are also more frequent in mixed neurodegenerative dementia syndromes. SUMMARY: Both examinations revealed that CoMIs are increased to different degrees in mixed dementia syndromes according to the severity of the LBP. They were mainly associated with a trend of older age and arterial hypertension in the patients with the most severe LBP. Messages: The increased number of CoMIs in mixed dementia syndromes with LBP is mainly due to the associated cerebrovascular pathology, even in the absence of CAA.

The Topography of Cortical Microinfarcts in Neurodegenerative Diseases and in Vascular Dementia: A Postmortem 7.0-Tesla Magnetic Resonance Imaging Study.

BACKGROUND: Cortical microinfarcts (CoMIs) are considered as barely visible lesions in clinical-neuroradiological correlation studies. On postmortem 7.0-tesla MRI, however, CoMIs of different size are easily detected. SUMMARY: The present MRI study investigates 84 postmortem brains with different neurodegenerative diseases and vascular dementia (VaD) for their topographic distribution and the prevalence of CoMIs. The mean numbers of CoMIs were determined on 6 hemispheric coronal sections and in 22 different gyri with a 7.0-tesla MRI Bruker BioSpin SA. A large coronal section at the level of the mammillary body was also used for neuropathological evaluation. CoMIs were predominantly observed in the prefrontal and postcentral sections of VaD brains. The mean number of CoMIs was significantly increased in the inferior frontal and in the cingulate gyri of VaD brains compared to the controls. No topographic differences were observed in the neurodegenerative diseases. KEY MESSAGES: As the inferior frontal and the cingulated gyri are areas frequently involved in VaD, CoMIs in those strategic locations must have an impact on the evolution of the vascular cognitive decline in those patients.

The significance of cortical cerebellar microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases. A post-mortem 7.0-tesla magnetic resonance study with neuropathological correlates.

BACKGROUND: As cortical microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases have been studied predominantly at the level of the cerebral hemispheres and linked to the presence of cerebral amyloid angiopathy (CAA), we aimed at determining with 7.0-tesla magnetic resonance imaging (MRI) whether the causes and the frequency of cortical cerebellar microbleeds (CCeMBs) and microinfarcts (CCeMIs) are the same. MATERIALS AND METHODS: Hundred and four postmortem brains, composed of 29 with pure Alzheimer's disease (AD), 9 with AD associated to CAA, 10 with frontotemporal lobar degeneration, 9 with amyotrophic lateral sclerosis, 10 with Lewy body disease, 12 with progressive supranuclear palsy, 9 with vascular dementia (VaD), and 16 controls, were examined. On a horizontal section of a cerebellar hemisphere examined with 7.0-tesla MRI, the number CCeMBs and CCeMIs were compared between the different disease groups and the control group. The MRI findings were also compared with the corresponding mean values observed on histological examination of a separate standard horizontal section of a cerebellar hemisphere, used for diagnostic purpose. RESULTS: CCeMBs and CCeMIs were only significantly increased in the VaD group. When comparing the diseased patients with and without CAA mutually and with those with arterial hypertension and severe atherosclerotic cerebrovascular disease, only in the latter an increase of CCeMBs and CCeMIs was observed. There was an excellent correlation between the MRI and the neuropathological findings. CONCLUSIONS: CCeMBs and CCeMIs are mainly due to atherosclerotic cerebrovascular disease and not due to CAA. Their increased presence cannot be included to the Boston diagnostic criteria for CAA.

Detection of Cortical Microbleeds in Postmortem Brains of Patients with Lewy Body Dementia: A 7.0-Tesla Magnetic Resonance Imaging Study with Neuropathological Correlates.

BACKGROUND: It is unclear whether associated cerebrovascular pathology contributes to the clinical spectrum of Lewy body dementia (LBD). SUMMARY: The present postmortem 7.0-tesla MRI study investigates the anatomical distribution of cortical microbleeds (CoMBs) in LBD brains with and without associated Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). CoMBs predominated in the frontal section of the LBD brains and were associated to severe white matter lesions. No differences were observed when LBD brains with and without AD and CAA were compared. KEY MESSAGES: In LBD, there is a specific distribution of CoMBs that is different from that in other neurodegenerative diseases. The increase of frontal CoMBs is not due to the frequently associated AD and CAA features but due to the LBD itself.

Microbleeds in postmortem brains of patients with Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study.

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.

Cerebrovascular lesions in patients with frontotemporal lobar degeneration: a neuropathological study.

BACKGROUND: Cerebrovascular lesions are frequently observed in Alzheimer brains. Not all of them are due to cerebral amyloid angiopathy. Some of them are related to the severity of the degenerative process itself, implying additional vascular factors in the pathogenesis of Alzheimer's dementia. The aim of the study was to investigate the impact of cerebrovascular pathology on brains with frontotemporal lobar degeneration (FTLD). PATIENTS AND METHODS: Twenty-two brains with autopsy-proven FTLD were compared to 15 brains of age-matched patients without evident cognitive decline, who died from an illness not related to a brain disease. The prevalence and the severity of small ischaemic and haemorrhagic lesions were determined. Vascular risk factors and the use of antithrombotic agents were also recorded. RESULTS: The patients with FTLD were heterogeneous concerning age of onset, disease duration, clinical presentation, genetic background and neuropathological typing. Cerebrovascular risk factors and lesions were overall rare in FTLD brains without differences in their prevalence and severity compared to the controls. Only white matter changes were more prevalent in the FTLD group (p = 0.04) and showed a trend to greater severity (p = 0.08). CONCLUSIONS: Cerebrovascular pathology is not contributing to the evolution of the disease process of patients with FTLD. The isolated prevalence of white matter changes should not be considered as a vascular indicator.

Seizures and epilepsy in patients with a posterior circulation infarct.

Seizures occur mainly in patients with cortical infarcts in the anterior circulation. Those related to a posterior circulation infarct (POCI) are considered rare. This study investigated the characteristics of patients with seizures related to a POCI. A total of 180 consecutive patients admitted with a POCI had a 2- to 7-year follow-up; 24 of them (13.6%) developed seizures. Vascular risk factors, etiology and extension of the infarct, degree of neurologic impairment, and outcome were compared in the patients with and without seizures. Complex partial type seizure was the most common presentation. Stroke characteristics were largely the same in the patients with and without seizures. History of a previous stroke was noted in 62.5% of the seizure group and in 17.9% of the nonseizure group (P < .001). Clinical outcome was worse in the seizure group (P = .004). The relative incidence of seizures in patients with a POCI was not lower than that in the overall stroke population. The high incidence of recurrent stroke is the main risk factor for seizures in patients with a POCI. The seizures themselves are responsible for the increased dependence rate.

Stroke-related seizures and epilepsy.

No guidelines exist concerning risk factors, diagnosis, management and treatment of stroke-related seizures. Seizures related to intracerebral haemorrhages occur in 10.6%, while those related to ischaemic stroke appear in 8.6%. Early-onset seizures have a poor prognosis with a high in-hospital mortality rate. They occur significantly more often in patients with haemorrhagic strokes. The recurrence rate is low. Late-onset seizures occur mainly between 6 months and 2 years after stroke with a high recurrence rate. Patients with a partial anterior circulation syndrome, a large cortical infarct with irregular borders, located in the parieto-temporal regions, are mainly at risk. Post-stroke seizures are harmful and require treatment with antiepileptic drugs. Post-stroke EEG can help to predict those patients who are at risk of developing seizures. The difference between early- and late-onset seizures is arbitrary as 20% of seizures occurring in patients with a previous cerebral infarct are the clinical expression of a new stroke.

Diabetic ketoacidosis presenting as a cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis is an uncommon condition with a variable clinical presentation, often resulting in a delayed diagnosis. The most common risk factors are pregnancy and puerperium, oral contraceptive use, head injury, dehydration, blood dyscrasias, malignancies, and systemic diseases. We present a nineteen-year-old female in whom a superior sagittal sinus thrombosis was caused by dehydration during diabetic ketoacidosis and led to the diagnosis of new-onset type 1 diabetes mellitus. To our knowledge this is the first published report of a cerebral venous sinus thrombosis in association with diabetic ketoacidosis in an adult.

Semiquantification of the peripheral-type benzodiazepine ligand [11C]PK11195 in normal human brain and application in multiple sclerosis patients.

OBJECTIVES: [11C]PK11195 is a peripheral-benzodiazepine-receptor radioligand used for detection of microglial inflammation. Normal uptake by means of semiquantification was measured in order to establish reference data. The applicability of this semiquantitative approach was tested in three multiple sclerosis patients. MATERIALS AND METHODS: Seven controls and three patients underwent MR and PET scanning. Coregistered static scans 40 minutes postinjection of [11C]PK11195 were used for assessment of relative ligand uptake by comparison to whole-brain uptake. RESULTS: For static scans acquired in near steady-state, the relative ligand uptake was significantly higher in gray matter structures as compared to the whole brain (ratio: 1.041 +/- 0.06, p = 0.036) whereas it was comparable in white matter (1.010 +/- 0.035). Intersubject reproducibility was 11.4% and 12.9% for white and grey matter. Intrasubject reproducibility was of the same order: 14.0% and 14.5% respectively. In two clinically active patients with Gadolinium-positive T1-weighted lesions on MRI the focal ligand uptake was significantly increased (1.36 and 1.14, p = 0.001). In one clinically stable patient, the uptake value corresponding with a T2-weighted MR lesion was not different from normal brain measurements. CONCLUSION: The current investigations show that normal brain uptake of [11C]PK11195 is very low and shows the feasibility of a semiquantitative method which can be applied to larger cohorts of patients subgroups.

The significance of small cerebral bleeds in neurodegenerative dementia syndromes.

Small cerebral bleeds are frequently observed in brains of patients with Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). However, they are also observed in patients with other neurodegenerative dementias and in persons without cognitive impairment. The aim of this survey is to compare the bleeding load in brains with different dementia syndromes and in age-matched controls. Hundred sixty-five brains were examined. The prevalence and the severity of the different cerebrovascular lesions were examined. Quantification of the number of mini-bleeds allowed to determinate the bleeding load in different cerebral regions. Micro-bleeds were considered as small macroscopically visible lesions while mini-bleeds were defined as small perivascular accumulations of red blood cells or siderophages only visible on microscopic examination. Several types of cerebrovascular lesions prevailed in AD brains with CAA, compared to the controls. White matter changes prevailed in frontotemporal lobar degeneration. Mini-bleeds were significantly more frequent in the cerebral cortex of AD and Lewy body dementia brains. They also prevailed around the dentate nucleus of the cerebellum and in the tegmentum pontis of patients with progressive supranuclear palsy. On the other hand the bleeding load in frontotemporal lobar degeneration and in corticobasal degeneration was similar to that in age-matched control brains. Cerebrovascular lesions, including micro-bleeds, predominated in AD brains with CAA. Mini-bleeds, on the other hand, were more related to the neurodegenerative process itself and reflected associated disruption of the blood-brain barrier.

Histopathological stainings and definitions of vascular disruptions in the elderly brain.

Post-mortem neuropathological examination still remains an important tool not only to confirm the clinical diagnosis of the neurodegenerative dementia but also for research purposes. Cerebrovascular lesions are more and more suspected to be involved in the pathogenesis of Alzheimer dementia (AD). In particular the occurrence of small cerebral bleeds becomes a main topic of interest. Post-mortem brain examination, using standard quantification techniques, allows to determine its bleeding load. In AD amyloid angiopathy is not the only cause of small bleeds, while in other neurodegenerative dementias the bleeding load is low and mainly related to associated disturbances of the blood-brain barrier.