Arteriolar neuropathology in cerebral microvascular disease.

Cerebral microvascular disease (MVD) is an important cause of vascular cognitive impairment. MVD is heterogeneous in aetiology, ranging from universal ageing to the sporadic (hypertension, sporadic cerebral amyloid angiopathy [CAA] and chronic kidney disease) and the genetic (e.g.

Mechanisms of Cerebral Microbleeds.

Cerebral microbleeds (CMB) are a common MRI finding, representing underlying cerebral microhemorrhages (CMH). The etiology of CMB and microhemorrhages is obscure. We conducted a pathological investigation of CMH, combining standard and immunohistological analyses of postmortem human brains.

Intracranial meningioma with carcinoma tumor-to-tumor metastasis: two case reports.

Meningiomas have been implicated as the most common primary intracranial tumor to contain tumor-to-tumor metastasis. In the following two case reports, we describe cases of adenocarcinoma and breast carcinoma that metastasized into an intracranial meningioma. The first patient was a 64-year-old man presenting to the emergency department with seizures and loss of consciousness.

Intracranial Myeloid Sarcoma Metastasis Mimicking Acute Subdural Hematoma.

Myeloid sarcoma, a rare consequence of myeloproliferative disorders, is rarely seen in the central nervous system, most commonly in the pediatric population. Although there are a handful of case reports detailing initial presentation of CNS myeloid sarcoma in the adult population, we have been unable to find any reports of CNS myeloid sarcoma presenting as a large mass lesion in a herniating patient. Here, we present the case of a patient transferred to our facility for a very large subdural hematoma.

Cerebrovascular pathology in Down syndrome and Alzheimer disease.

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology.

Case of glioblastoma patient treated with tumor treating fields therapy at recurrence degenerating to sarcoma.

Optune treatment is a US FDA-approved treatment for glioblastoma (GBM) that employs alternating electric fields. Tumor treating field (TTF) therapy can exert its effects on GBM via cell cycle mitosis disruption and cytokinesis. We describe a patient with recurrent GBM who had disease progression following standard surgical treatment and concomitant chemoradiotherapy, and was found to have sarcomatous transformation after initiation of TTF therapy with bevacizumab.

Microinfarcts are common and strongly related to dementia in the oldest-old: The 90+ study.

Introduction: We estimated the prevalence of microinfarcts and their association with dementia in a cohort of oldest-old participants.

Methods: Participants were from The 90+ Study, a population-based study of people 90 years and older. Dementia diagnoses were assigned postmortem during a consensus conference.

Impact of interventions to reduce Alzheimer's disease pathology on the prevalence of dementia in the oldest-old.

Introduction: The number of persons aged >90 years will grow significantly in coming decades. This group has the highest rates of dementia, most commonly Alzheimer's disease (AD).

Methods: Using The 90+ Study, we developed a statistical model for dementia risk based on brain pathologies.

Multiple pathologies are common and related to dementia in the oldest-old: The 90+ Study.

Objective: The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old.

Methods: A total of 183 participants of The 90+ Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized.

Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer's disease.

Mild cognitive impairment (MCI) represents a cognitive state intermediate between normal aging and early Alzheimer's disease (AD). To investigate if the molecular signature of MCI parallels the clinical picture, we use microarrays to extensively profile gene expression in 4 cortical brain regions (entorhinal cortex, hippocampus, superior frontal gyrus, post-central gyrus) using the postmortem tissue from cognitively normal aged controls, MCI, and AD cases. Our data reveal that gene expression patterns in MCI are not an extension of aging, and for the most part, are not intermediate between aged controls and AD.

Bapineuzumab alters aβ composition: implications for the amyloid cascade hypothesis and anti-amyloid immunotherapy.

The characteristic neuropathological changes associated with Alzheimer's disease (AD) and other lines of evidence support the amyloid cascade hypothesis. Viewing amyloid deposits as the prime instigator of dementia has now led to clinical trials of multiple strategies to remove or prevent their formation. We performed neuropathological and biochemical assessments of 3 subjects treated with bapineuzumab infusions.

Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration.

RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1.

Frontal cortex neuropathology in dementia pugilistica.

Dementia pugilistica (DP) is associated with chronic traumatic brain injury (CTBI), and leads to a "punch drunk" syndrome characterized by impairments in memory and executive function, behavioral changes, and motor signs. Microscopic features include the accumulation of neurofibrillary tangles (NFTs), beta-amyloid (Aβ), and TAR DNA binding protein 43 (TDP-43) pathology. Here we describe detailed clinical and neuropathological data about a 55-year-old retired boxer (ApoE3/4), who presented with executive dysfunction and behavioral impairments.

Primary leptomeningeal plasmablastic lymphoma.

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity.

Cerebral microbleeds in the elderly: a pathological analysis.

Background And Purpose: Cerebral microbleeds in the elderly are routinely identified by brain MRI. The purpose of this study was to better characterize the pathological basis of microbleeds.

Methods: We studied postmortem brain specimens of 33 individuals with no clinical history of stroke and with an age range of 71 to 105 years.

Altered white matter integrity in temporal lobe epilepsy: association with cognitive and clinical profiles.

Purpose: Diffusion tensor imaging (DTI) studies have reported substantial white matter abnormalities in patients with temporal lobe epilepsy (TLE). However, limited data exist regarding the extent of white matter tract abnormalities, cognitive effects of these abnormalities, and relationship to clinical factors. The current study examined these issues in subjects with chronic TLE.

Isolated amygdala neurocysticercosis in a patient presenting with déjà vu and olfactory auras. Case report.

Neurocysticercosis is the most common parasitic infection in the CNS and a leading cause of epilepsy. Since it is a circumscribed lesional cause of epilepsy, specific locations of neurocysticercal lesions may lead to specific clinical presentations. The authors describe a 17-year-old Hispanic boy who had a single enhancing bilobar mass in the right amygdala.

Primary leptomeningeal oligodendrogliomatosis.

Primary leptomeningeal oligodendrogliomas (PLOs) are rare intracranial malignancies where tumors grow in the subarachnoid space without an obvious connection to the brain or spinal cord parenchyma. Adding to the three previously reported cases of PLO with no parenchymal involvement we report a fourth case of the same in this paper in a 50-year-old woman presenting with unrelenting headaches. CT scan of her head revealed hydrocephalus and MRI revealed diffuse enhancement of her leptomeninges throughout her brain and spine, prominent over the basilar region.

Synaptic proteins, neuropathology and cognitive status in the oldest-old.

An increasing number of individuals in our population are surviving to over 90 years and a subset is at risk for developing dementia. However, senile plaque and neurofibrillary tangle pathology do not consistently differentiate individuals with and without dementia. Synaptic protein loss is a feature of aging and dementia and may dissociate 90+ individuals with and without dementia.

Relapsing polychondritis with features of dementia with Lewy bodies.

We describe a 72-year old man with clinical features suggestive of dementia with Lewy bodies (DLB) who proved neuropathologically to have degeneration induced by relapsing polychondritis (RP), an autoimmune inflammatory disorder of cartilaginous tissues. There was lymphocytic infiltration of the leptomeninges, perivascular cuffing, reactive astrocytosis, and activation of microglia in multiple brain areas all consistent with an immunologically mediated process. There was widespread neuronal loss within the hippocampus, entorhinal cortex, and amygdala as well as diffuse myelin pallor of cortical pathways.

Acute toxicity pilot evaluation of proliferol in rats and swine.

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.

Acute hemorrhagic leukoencephalitis: neuroimaging features and neuropathologic diagnosis.

A case of biopsy-proven acute hemorrhagic leukoencephalitis is reported. The early computed tomography scans showed extensive bilateral hypodensities with mass effects and foci of microhemorrhages. Bilateral asymmetric hyperintensities in the mesiotemporal and frontal lobes and massive edema were found on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images in a pattern classic for herpes simplex encephalitis.

Caspase-cleaved tau accumulation in neurodegenerative diseases associated with tau and alpha-synuclein pathology.

Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or alpha-synuclein. In AD, beta-amyloid (Abeta)-associated caspase activation and cleavage of tau at Asp421 (DeltaTau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether DeltaTau accumulates in other diseases not characterized by extracellular Abeta accumulation, we examined PiD, PSP, and CBD cases in comparison to those without extensive tau accumulation including frontotemporal lobar degeneration without Pick bodies (FTLD) and control cases.

Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a "paraptosis"-induced pathway that promotes systemic immunity against intracranial T9 gliomas.

Cloned T9-C2 glioma cells transfected with membrane macrophage colony-stimulating factor (mM-CSF) never formed subcutaneous tumors when implanted into Fischer rats, whereas control T9 cells did. The T9-C2 cells were completely killed within 1 day through a mechanism that resembled paraptosis. Vacuolization of the T9-C2 cell's mitochondria and endoplasmic reticulum started within 4 hours after implantation.