Advanced intimal hyperplasia without luminal narrowing of leptomeningeal arteries in CADASIL.

Background And Purpose: Leptomeningeal artery abnormalities in Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) have not been extensively characterized. We quantified substructure and diameter of leptomeningeal arteries in CADASIL compared with age-matched controls and the very old; in addition, we characterized intimal thickening in CADASIL using immunohistochemistry.

Methods: Frontal and temporal cortex of 6 genetically proven CADASIL brains (average age, 66 years), 6 controls without symptoms of cerebrovascular disease, and 6 very old brains (average age, 89 years) were examined for leptomeningeal artery intimal, medial, and adventitial thickness; inner diameter; and sclerotic index and for smooth muscle markers.

ABO blood antigens define human cerebral endothelial diversity.

Cerebral endothelial cells participate in the blood-brain barrier and regulate activity-dependent changes in brain blood flow. It has been assumed that all cerebral endothelial cells are similar, but genetic studies in mice suggest that there are heterogeneous populations of endothelial cells in rodent brain. In this study, we tested for molecular heterogeneity of endothelial cells in the human brain.

Von Willebrand Factor permeates small vessels in CADASIL and inhibits smooth muscle gene expression.

Background And Purpose: CADASIL (cerebral autosomal dominant arteriopathy subcortical infarcts and leukoencephalopathy) is a genetic disorder hallmarked by ischemic stroke and vascular dementia. Characteristic pathological changes in the vasculature include thickening of small arteries and accumulation of heterogeneous material within the vessel wall. We tested whether endothelial von Willebrand factor (vWF) accumulates in CADASIL vessels and whether exposure of smooth muscle cells to vWF alters the expression of smooth muscle gene expression.

Bidirectional encroachment of collagen into the tunica media in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Arteries in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are susceptible to smooth muscle loss and fibrosis, but the molecular components underlying these dramatic vascular changes are not well characterized. The purpose of this study was to investigate the distribution of collagen isoforms in the cerebral vessels of North American CADASIL patients with classical NOTCH3 mutations. Expression of types I-VI collagen in brains obtained at autopsy from six CADASIL patients with cysteine-altering mutations in NOTCH3 was compared to control brain expression.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy affecting an African American man: identification of a novel 15-base pair NOTCH3 duplication.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the best characterized genetic cause of vascular dementia and stroke and has been extensively reported in European and Asian populations.

Objective: To report the pathological and genetic analysis of CADASIL in an African American man with a 15-base pair NOTCH3 duplication.

Design: Case report.

Paraspinal malignant ossifying fibromyxoid tumor with spinal involvement.

Ossifying fibromyxoid tumors (OFT), first described in 1989 by Enzinger et al., are rare lesions; malignant OFT (MOFT) are even rarer. We report a large recurrent paraspinal MOFT invading the spine and causing epidural compression in a 70-year-old male, despite prior debulking and radiotherapy.

Radiation-induced meningeal osteosarcoma of tentorium cerebelli with intradural spinal metastases.

Background: Primary meningeal osteosarcomas and radiation-induced extraosseous tumors are extremely rare. We encountered a patient with a radiation-induced meningeal osteosarcoma with metastatic spread.

Case Description: A 54-year-old man presented with a 2-week history of nausea, vomiting, and ataxia.

Autopsy findings in eight patients with fatal H1N1 influenza.

A novel H1N1 influenza A virus emerged in April 2009, and rapidly reached pandemic proportions. We report a retrospective observational case study of pathologic findings in 8 patients with fatal novel H1N1 infection at the University of Michigan Health Systems (Ann Arbor) compared with 8 age-, sex-, body mass index-, and treatment-matched control subjects. Diffuse alveolar damage (DAD) in acute and organizing phases affected all patients with influenza and was accompanied by acute bronchopneumonia in 6 patients.

Localization of blood proteins thrombospondin1 and ADAMTS13 to cerebral corpora amylacea.

Corpora amylacea (CA) have long been described in aging brains and in patients with neurodegenerative conditions, but their origins have been debated. It has been proposed that CA represent collections of nervous system breakdown products that accumulate within astrocytic cytoplasm. In support of this, studies have shown that CA include glycosylated material, ubiquitin, and an assortment of proteins derived from neuronal cytoplasm.

Lymphoplasmacyte-rich meningioma mimicking idiopathic hypertrophic pachymeningitis.

A 24-year-old man presented with long-term headache and progressive visual loss. Neuro-ophthalmic manifestations included finger counting acuity in both eyes, weakly reactive pupils, pale optic discs, and increased deep tendon reflexes. Brain MRI showed meningeal thickening that involved the optic nerves and chiasm and enveloped and displaced the brainstem as far caudally as the foramen magnum.

Extracranial nasopharyngeal craniopharyngioma: case report.

Objective: Craniopharyngiomas (CPs) are benign tumors that almost always occur in a suprasellar location, making complete resection difficult and often necessitating radiotherapy. A case of CP presenting in an unusual location in an 8-year-old boy highlights the goals of CP treatment.

Clinical Presentation: An 8-year-old boy sought treatment for symptoms of nasal obstruction and snoring.

Imaging features of clear-cell ependymoma of the spinal cord.

A 10-year-old girl presented with increasing lower back pain without gait or sphincter disturbances. MRI demonstrated a large, intramedullary tumor at the level of the conus. The imaging findings were unlike those of a classic ependymoma or astrocytoma.

Nontuberculous mycobacterial infection of a metastatic brain neoplasm in an immunocompromised patient.

Background: Nontuberculous mycobacterial infections occur in immunocompromised patients but so rarely involve the central nervous system (CNS) that they may not be included in a differential diagnosis of CNS lesions in such patients.

Objective: To illustrate a putative mechanism for nontuberculous mycobacterial infection of the CNS via breakdown of the blood-brain barrier by metastatic neoplasm.

Results: A 56-year-old man who had undergone renal transplantation in February 2003 and was taking an immunosuppressive regimen of mycophenolate mofetil and cyclosporine was seen in the emergency department after a syncopal episode.

Inhibition of vascular endothelial growth factor (VEGF)-A causes a paradoxical increase in tumor blood flow and up-regulation of VEGF-D.

Purpose: Vascular endothelial growth factor (VEGF)-A is an important mediator of angiogenesis in almost all solid tumors. The aim of this study was to evaluate the effect of VEGF-A expression on tumor growth, perfusion, and chemotherapeutic efficacy in orthotopic 9L gliosarcomas.

Experimental Design: Stable 9L cell lines underexpressing and overexpressing VEGF-A were generated.

Pitfalls in the diagnosis of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes.

We describe a patient with genetically- and biochemically-proven mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) who was initially misdiagnosed as having had multiple ischemic strokes in part because the clinical presentation appeared to be acute, the MRI of lesions showed restricted diffusion, and the brain biopsy showed features suggestive of stroke. This report emphasizes the pitfalls in the diagnosis of MELAS and points out the similarities and differences between MELAS and ischemic stroke.

The second kindred with autosomal dominant distal myopathy linked to chromosome 14q: genetic and clinical analysis.

Background: Distal myopathies (MPDs) are genetically heterogeneous. Genetic causes within this subgroup of muscle disorders remain largely unknown. An MPD linked to chromosome 14q11-q13 (MPD1) is rare, and to our knowledge, only one family with definitive linkage has been described.