Efforts to determine the factors responsible for reversing malignancy in the central nervous system may not only increase our understanding of the growth of primary human brain tumors, but may eventually prove to be of therapeutic benefit as well. We therefore devised a model system to study the effects of extracellular matrix (ECM) proteins on the malignant phenotype of an anaplastic glioma line, U-343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The pia-arachnoid cells were then removed with detergent and base, leaving behind an ECM enriched in laminin, fibronectin, types I and IV collagen, and procollagen III. U-343 MG-A tumor cells planted on top of this normal ECM were profoundly growth inhibited, developed multiple slender cytoplastic processes similar to those of normal astrocytes, and expressed more GFAP per cell than did tumor cells growing on plastic alone. The growth of U-343 MG-A tumor cells in flasks coated with purified fibronectin or laminin was not significantly inhibited. However, U-343 MG-A cultures grown in flasks coated with type I or IV collagen showed decreased cellular proliferation and altered cell morphology. Conditioned medium from U-343 MG-A tumor cells growing on plastic alone contained a 64 kD activated metalloprotease. U-343 MG-A tumor cells growing on the pia-arachnoid ECM do not demonstrate such proteolytic activity. We conclude that the tumor cell microenvironment is extremely important in modulating the growth and differentiation of an anaplastic glioma cell line. It is hoped that an increased knowledge of the production of ECM components and their effects on malignant glioma cell growth, migration and differentiation will lead to the development of new approaches to improve the prospects of patients with primary malignant brain tumors.

Fourteen pure oligodendrogliomas were studied by light- and electronmicroscopy and immunohistochemistry to examine glial fibrillary acidic protein (GFAP) positivity in the tumors. To compare the immunohistochemical staining patterns of neoplastic oligodendroglia and immature oligodendroglia, myelination glia in the white matter of eight normal brains from children under 6 months of age were studied. The tumors possessed light microscopic and ultrastructural features characteristic of oligodendrogliomas. Microtubules were found in the cytoplasm of nine tumors on electronmicroscopy. In one, intermediate filaments and microtubules were observed in occasional tumor cells with polygonal crystalline structures in the cytoplasm. Using the peroxidase-antiperoxidase technique, all specimens were stained for GFAP, vimentin, S-100 and neuron-specific enolase (NSE). In nine tumors, variable numbers of cells with an oligodendroglial morphology reacted positively for GFAP. All tumors were positive for S-100 and negative for vimentin and NSE. The myelination glia in the eight normal brains stained positively for GFAP but not for vimentin. Vimentin is expressed by developing, reactive and neoplastic astrocytes. Thus, GFAP positivity combined with vimentin negativity in both neoplastic and immature oligodendroglia suggests that GFAP positivity in oligodendrogliomas may reflect the transient expression of this intermediate filament by immature oligodendroglia.

The cause of idiopathic Parkinson's Disease (PD) is not known but it is believed to be related to some environmental agent(s). Given a long preclinical interval and onset of symptomatology around age 60 years, it becomes impossible to identify and analyze all prior environmental factors satisfactorily. To circumvent these difficulties we evaluated the childhood environment in those PD patients whose symptoms began at age 40 years or earlier. Twenty-one such cases were born and raised in the province of Saskatchewan. Nineteen of these 21 patients spent the first 15 years of life exclusively in rural Saskatchewan. Detailed population analysis indicates a strong predisposition to early onset idiopathic Parkinson's Disease (EPD) in those raised in rural areas (p = 0.0154). All but one case utilized exclusively well water for the first 15 years of life — a trait significantly different from that expected in the provincial population. It is concluded that rural Saskatchewan environments contribute to EPD and that well water used in childhood should be considered as a potential vehicle for the etiological agent.

We have conducted a hospital-based survey of the age-specific prevalence of Parkinson's disease in 551 patients from Helsinki and Vancouver. We conclude that the disorder may be starting earlier than previously and we discuss the implications of this finding for the etiology of Parkinson's disease.

Pattern reversal visual, brain-stem auditory, and short latency median nerve somatosensory evoked potentials (EPs) were evaluated in a prospective study over 4 years in 20 patients with clinically definite sclerosis (MS). Standardized neurological examinations were done at regular intervals and correlated with EP findings. The highest incidence of EP abnormalities occurred in the visual system followed by the somatosensory and auditory systems. Clinical relapse was usually accompanied by EP deterioration, but clinical improvement often occurred without parallel EP recovery. EP changes were not always related to clinical symptoms and often took place during remission periods in the absence of clinical changes. There was no significant correlation between clinical and electrophysiological progression within any given sensory modality. The progression of clinical disability, however, showed a fairly good correlation with the overall progression of EP abnormalities. We conclude that EPs complement the neurological exam in the evaluation of MS and may have a place in the investigation of the effects of therapeutic agents on the neurological status in MS.

Prolonged electroencephalographic and video monitoring of ictal events is useful in aiding the diagnosis of complicated seizure disorders. Forty eight patients admitted to a neurology service were assessed with this technique. Twenty five (54%) had their diagnoses changed, six (14%) had their diagnoses confirmed and the remaining patients had inconclusive studies. Therapy is modified by the results and in addition both patient and staff education is enhanced through the use of this equipment.

Vigabatrin (ɣ-vinyl GABA; GVG), an irreversible inhibitor of GABA-transaminase, at a daily dose of 2-4 g, and a placebo were each administered orally for 4 months to 14 patients with cerebellar ataxia (9 with Friedreich's ataxia, 5 with olivopontocerebellar atrophy), in a double-blind, placebo-controlled crossover study. For the group as a whole, there was no significant difference between the GVG and placebo periods in any of the parameters of cerebellar symptomatology measured. Individually, one patient showed some improvement after 3 months of treatment with 2 g/day GVG. Tolerance to 4 g/day GVG was poor, whereas 2 g/day was well tolerated. The results suggest that agents which increase central GABA concentrations are not likely to be of benefit to patients with Friedreich's ataxia or olivopontocerebellar atrophy.

We report an autopsy study of a 64-year-old female with systemic sarcoidosis. In addition many muscles showed typical light and electron microscopic features of inclusion body myositis. To our knowledge this association has not been previously reported.

In 1949, amphetamine sulfate was replaced by propylhexedrine in the nasal decongestant agent Benzedrex® because of psychosis, sudden death, and widespread abuse. Propylhexedrine is not without risks, and reported cases of psychosis, myocardial infarction, pulmonary vascular disease and pulmonary hypertension, and sudden death are well documented in the medical literature. We are reporting 2 cases of definite brainstem dysfunction and 5 cases of transient diplopia secondary to IV abuse of Benzedrex®. This widely abused drug is prepared by heating Benzedrex® and hydrochloric acid, and the resulting crystals are dissolved in water for injection. This agent is called “stove-top speed”. All 7 patients had transient diplopia, within seconds after injection. One patient had evidence of a right-internuclear opthalmoplegia, and another had a depressed right gag reflex and paralysis of the right half of the tongue. The deficits in these two patients, persisted for many months. In young adults with history of drug abuse, the IV use of Benzedrex® should be considered in the differential diagnosis of transient or permanent focal brainstem deficits.

Bilateral facial weakness, diminished hearing and dysphagia developed in a patient with a large overdose of ethylene glycol. Our case and two others previously reported draw attention to the fact that cranial nerve dysfunction, especially bilateral facial palsy, may occur in addition to encephalopathy, coma and renal failure with ethylene glycol ingestion.

A nine-year-old girl presented with right hemifacial spasm (HFS) of 27 months duration. Stimulation of the right supraorbital nerve produced synkinesis of the ipsilateral facial muscles. Latency and amplitude of the blink reflex were equal bilaterally. Other investigations including computerized tomography (CT) were negative. Treatment with carbamazepine was not helpful. This is the third reported case of HFS in childhood.

Two French-Canadian families with seven cases of hydrocephalus in two generations are presented. The pattern of inheritance is consistent with an X-linked recessive transmission. The clinical and pathologic characteristics of this entity are reviewed. The anomaly of adducted thumbs was present in one patient and its cause is considered. The hypothesis of primary hydrocephalus and secondary compression of the aqueduct as the mechanism for aqueductal stenosis is discussed.