Peter T. Ostrow

Correlation of Endothelin-1 and Transforming Growth Factor β1 with Malignancy and Vascularity in Human Gliomas

Because the prominent neovascularization characteristic of high grade primary brain tumors is composed mostly of vascular smooth muscle cells (VSMC), we studied the expression of the potent smooth muscle mitogen endothelin-1 (ET-1) and one of its secretagogues, transforming growth factor β1 (TGF-β1) in a series of astrocytic tumors. TGF-β1 is also of interest due to its known activity as an angiogenic factor. Using immunohistochemical methods, we examined 30 surgical cases: 10 glioblastoma multiforme, 10 anaplastic astrocytomas, and 10 low-grade astrocytomas. Using a monoclonal antibody to TGF-β1 and a polyclonal antibody to ET-1, we detected both growth factors in all cases of glioblastoma examined. In cases of anaplastic astrocytoma, 4 tumors were positive for both factors; 2 contained only ET-1; 2 contained only TGF-β1; and 2 exhibited no tumor cell immunoreactivity for either factor. In low-grade astrocytoma, 4 of 10 tumors showed weak ET-1 immunoreactivity; 2 of those contained TGF-β1 immunopositive tumor astrocytes; 6 tumors were negative for both factors. In all tumors that expressed both factors, serial sections showed that regions of ET-1 immunopositivity also tended to be positive for TGF-β1. Endothelial cells within all tumors were positive for ET-1. ET-1 and TGF-β1 are present in human astrocytomas and their expression correlates with tumor vascularity and malignancy. These results suggest roles for both ET-1 and TGF-β1 in the growth and progressive angiogenesis of the human glioma.

Acute hemorrhagic leukoencephalitis vs ADEM: FLAIR MRI and neuropathology findings

Acute hemorrhagic leukoencephalitis (AHL) is characterized by an acute, rapidly progressive, monophasic, fulminant inflammatory hemorrhagic demyelination of white matter, usually postinfectious and associated with death or severe morbidity within a few days.1-3⇓⇓ We report MRI and neuropathology in a case of AHL. A 19-year-old white man was admitted with acute onset of fever, headache, and progressive lethargy. He had developed mild upper respiratory symptoms and cough 2 weeks earlier. Examination showed lethargy and meningismus, but he was arousable and oriented to person, place, and time. Brainstem responses were intact. Serum white blood count was 17.9 cells/uL. Head CT (not shown) revealed a left parietal hypodensity with mild mass effect. He was started on levofloxacin, ceftriaxone, and dexamethasone treatment. Brain MRI (figure, A) was performed while the patient was able to communicate and brainstem function was intact. Six hours later, he had a cardiopulmonary arrest and required resuscitation, intubation, and mechanical ventilation, after which he lost all brainstem function. He was treated with mannitol and hyperventilation, yet he was declared brain dead 12 hours after resuscitation and pronounced dead another 3 hours later. Blood cultures were negative. Nasopharyngeal cultures and serum …

AGE-RAGE in multiple sclerosis brain.

This pilot study used immunohistochemical techniques to investigate the advanced glycation end-product (AGE) Nepsilon-(carboxymethyl)lysine (CML) and its receptor (RAGE) in the brains of multiple sclerosis (MS) patients, comparing them with the brains of patients with Alzheimers disease (AD) (positive controls) and with age-matched control subjects (negative controls). Postmortem slides derived from the hippocampi of MS patients, AD patients, and controls were stained with monoclonal antibodies for CML and human RAGE. Results showed increased AGE and RAGE immunostaining in the hippocampi of MS patients, similar to AD patients.

Primary central nervous system lymphoma masquerading as herpes encephalitis: clinical, magnetic resonance imaging and pathologic findings

An 84-year-old man presented with acute confusion, global aphasia, and fever. Magnetic resonance imaging (MRI) showed hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images predominantly affecting the cortical gray matter of the left mesial temporal and inferior frontal lobes, and insula. Acyclovir was prescribed for presumed viral encephalitis. Clinical and MRI worsening prompted a left temporal lobe biopsy that revealed primary central nervous system lymphoma (PCNSL). This case adds to the MRI spectrum of PCNSL and illustrates that it may mimic the clinical and MRI presentation of herpes simplex encephalitis.