Neuropathology in Canada: the first one hundred years.

We describe the evolution of neuropathology in Canada, beginning with William Osler who began working in Montréal in 1874 and finishing with the major period of expansion in the 1970s. Organized services began in the 1930s, in Montréal with the neurosurgeons Wilder Penfield and William Cone, and in Toronto with Eric Linell and Mary Tom, who both began their careers as neuroanatomists. Jerzy Olszewski and Gordon Mathieson, who trained in Montréal and Toronto, drove the creation of the Canadian Association of Neuropathologists in 1960.

Pseudoglandular elements in schwannomas.

Context: Uncommon examples of schwannomas are seen in which a coexisting glandular component is present. The pseudoglandular schwannoma is a relatively recently described variant in which cystic spaces are lined by pseudocolumnar or cuboidal-like neoplastic Schwann cells exhibiting an epithelial-like appearance.

Objectives: To determine the incidence of pseudoglandular elements in schwannomas, to describe the variable morphology of the schwannomas that may contain pseudoglandular elements, and to discuss the potential mechanisms of development and biological significance of these elements.

Efficacy and safety evaluation of human reovirus type 3 in immunocompetent animals: racine and nonhuman primates.

Purpose: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates.

Experimental Design: Racine glioma cells 9L and RG2 were implanted s.

Reovirus as an experimental therapeutic for brain and leptomeningeal metastases from breast cancer.

Brain and leptomeningeal metastases are common in breast cancer patients and our current treatments are ineffective. Reovirus type 3 is a replication competent, naturally occurring virus that usurps the activated Ras-signaling pathway (or an element thereof) of tumor cells and lyses them but leaves normal cells relatively unaffected. In this study we evaluated reovirus as an experimental therapeutic in models of central nervous system (CNS) metastasis from breast cancer.

Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma.

Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus.

How often are nonenhancing supratentorial gliomas malignant? A population study.

The presence of contrast enhancement in a brain tumor is often regarded as a sign of malignancy. The authors identified 314 patients with malignant and low-grade supratentorial glial neoplasms in an unselected population, 58 of which lacked contrast enhancement on preoperative neuroimaging. Nonenhancing gliomas were malignant in approximately one third of cases, especially in older patients.

Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis.

Multiple sclerosis is characterized by the infiltration of leukocytes into the CNS. As matrix metalloproteinases (MMPs) facilitate the passage of leukocytes across matrix barriers, we tested the hypothesis that targeting MMPs could attenuate neuro-inflammation. We report that minocycline, a widely used generic drug with a good safety record, inhibited MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier.

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas.

Studies have suggested that an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to the malignant phenotype of gliomas. In this study, we have undertaken a detailed analysis of expression of the TIMP family in normal human brain and malignant gliomas at both the mRNA and protein level. Reverse transcription-PCR (RT-PCR) analyses of total RNA from surgical tumour specimens revealed unique expression patterns for the 4 members of the TIMP family, with TIMP-1 and -4 showing positive and negative correlations, respectively, with glioma malignancy.

Reovirus as an oncolytic agent against experimental human malignant gliomas.

Background: Reovirus is a naturally occurring oncolytic virus that usurps activated Ras-signaling pathways of tumor cells for its replication. Ras pathways are activated in most malignant gliomas via upstream signaling by receptor tyrosine kinases. The purpose of this study was to determine the effectiveness of reovirus as an experimental treatment for malignant gliomas.

Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas.

Malignant gliomas maintain a poor prognosis and survival rate due to their marked local invasive growth and neovascularization. Matrix metalloproteinases (MMPs) have been implicated in glioma invasion and angiogenesis, but it is unknown whether they are produced by the tumor cells or surrounding stroma. Using in situ hybridization and immunohistochemistry, we found expression of mRNA for both gelatinase-A (MMP2) and gelatinase-B (MMP9) localized to tumor cells and vascular structures in glioma sections.

Acute quadriplegic myopathy unrelated to steroids or paralyzing agents: quantitative EMG studies.

Background: Quadriplegic myopathy (QM) and its variants generally are described in critically ill patients who are exposed to steroids and nondepolarizing muscle blocking agents (NDMBAs).

Methods: A patient with sepsis who was not exposed to steroids or an NDMBA infusion developed QM and was studied using serial quantitative electromyography.

Results: Clinical and electrophysiological studies identified evidence of a severe myopathy and muscle biopsy showed necrosis, calcifications and selective loss of myosin filaments in non-necrotic fibers.

Which glioblastoma multiforme patient will become a long-term survivor? A population-based study.

In this clinical and histopathological study, the frequency of long-term glioblastoma multiforme (GBM) survivors (LTGBMSs) was determined in a population-based study. The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in Alberta between January 1, 1975, and December 31, 1991. Patient charts were reviewed and histology reexamined.

Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340.

Synthetic matrix metalloproteinase (MMP) inhibitors have activity against a variety of tumors in preclinical models but have not been studied in gliomas. We determined the effect of AG3340, a novel synthetic MMP inhibitor with Ki values against gelatinases in the low picomolar range, on the growth of a human malignant glioma cell line (U87) in SCID-NOD mice. Mice were injected s.

Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas.

Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs.

Long-term glioblastoma multiforme survivors: a population-based study.

Background: Long-term glioblastoma multiforme survivors (LTGBMS) are uncommon. The frequency which these occur in an unselected population and factors which produce these unusually long survivors are unknown.

Objectives: To determine in a population-based study 1) the frequency of LTGBMS in a population and 2) identify which patient, treatment or tumor characteristics would predict which glioblastoma (GBM) patient would become a LTGBMS.

High levels of gelatinase-B and active gelatinase-A in metastatic glioblastoma.

Purpose: Extra-neural metastases from glioblastoma multiforme (GBM) are rare. Because gelatinases-A and -B have been implicated in tumor invasion/metastasis in non-neural tumors, we compared the expression of gelatinase-A and -B in 2 patients (both had a prior craniotomy performed) with extraneural metastases from GBM to expression levels in 24 other gliomas; 15 non-metastatic GBMs, 9 other lower grade gliomas, and 7 normal brain tissues.

Methods: The intracerebral tumor from both patients, patient # 1's extraneural metastases, 24 other gliomas, 1 sample of reactive astrocytes and 7 normal brain tissues were studied using gelatin zymography.

Variable morphology of coronary atherosclerosis: characterization of atherosclerotic plaque and residual arterial lumen size and shape by epicardial echocardiography.

The purpose of this study was to evaluate the in vivo characteristics of coronary atherosclerosis by using high frequency epicardial echocardiography. High frequency epicardial echocardiography was used to evaluate residual lumen and wall morphology at the sites of maximal coronary atherosclerosis in 26 patients undergoing coronary artery bypass grafting. The maximal/minimal wall thickness ratio was 3.

Gliosis and glioma distinguished by acridine orange.

Acridine orange fluorochrome of nucleic acids was applied to sections of cerebral tissue from 20 patients showing acute or chronic reactive gliosis. The results were compared with the findings in 39 well differentiated and malignant astrocytomas. The orange cytoplasmic fluorescence of ribonucleic acid is lacking in reactive astrocytes of all ages including gemistocytes, but is uniformly present in astrocytoma cells.

Cytoplasmic RNA in nervous system tumours in children: a fluorochromic histochemical study using acridine orange.

Acridine orange was used as a fluorochromic histochemical stain of nucleic acids, applied to 78 neoplasms of the central and peripheral nervous systems of 60 children. Some cases were compared with 5 adults and 4 other cases of chronic reactive gemistocytic gliosis. Opposite concentration gradients of cytoplasmic ribonucleic acid (RNA) was demonstrated in tumours of the neuronal/neuroectodermal series, and those of the glial/neuroepithelial series.

Pathological findings in a case of hypoxic myoclonus treated with 5-hydroxytryptophan and a decarboxylase inhibitor.

A 72-year-old woman suffered a respiratory arrest following intoxication with barbiturates. Her examination 27 months after the anoxic incident revealed involuntary jerks of trunk and limb muscles triggered by willed movements. On a regimen of 1 g L-5-HTP and 100 mg l-alpha-methyldopa hydrazine (carbidopa), action myoclonus disappeared completely.

Oculoskeletal myopathy with abnormal mitochondria.

A clinical, electrophysiological and pathological review of 14 patients having oculoskeletal myopathy with abnormal mitochondria was undertaken. These patients present with ophthalmoplegia, and mild skeletal muscle weakness. The clinical course is slowly progressive.

Methanol optic neuropathy: a histopathological study.

The histopathologic effects of methanol on the optic nerve were studied in four patients. Circumscribed myelin damage occurred behind the lamina cribrosa in each nerve. Axons were preserved.

Tomographic abnormalities simulating pituitary microadenomas.

False-positive and false-negative interpretations of sellar tomography were found in about one-fifth of cases in a recent autopsy study correlating the presence of pituitary microadenomas with abnormal sellar tomograms. An analysis of minor variations in the bony configuration of the sella disclosed variations due to posterior lobe asymmetry, intercavernous venous channels, bony asymmetry, and an empty sella in 27 of the 120 sellas examined. In some instances, the asymmetry resulted from a combination of these causes.

Rupture of central canal with multisegmental haematomyelia. An unusual complication of rapidly fatal intracranial hypertension.

Acute haematomyelia, an unrecognized sequela of sudden intracranial hypertension is described in 3 patients with massive intracerebral and intraventricular haemorrhage. The presence of a persistent central canal of the spinal cord in communication with the 4th ventricle and acute functional obstruction of the latter allows CSF and blood to pass down into the spinal cord with subsequent rupture into the cord parenchyma.