Forty adult patients (average age 40 years), with the clinical and radiological features of the Chiari malformations, were seen at the Toronto Western Hospital between 1967 and 1984. Surgical confirmation of the diagnosis was obtained in 32 cases; of these, 23 were classified as Chiari I malformation while 9 fulfilled the anatomic criteria of Chiari II. The patient population consisted of 22 males and 18 females. Common presenting symptoms included head and neck pain (60%), sensory complaints (60%), upper extremity weakness (42%), and gait disturbance (40%). Neurological findings included signs of central cord dysfunction (73%), long-tract motor and/or sensory findings (58%), brainstem signs (38%), cerebellar dysfunction (18%), and increased intracranial pressure (15%). The majority of patients underwent myelography with or without computed tomography of the cervical-medullary junction. Two recent patients had 0.15T MRI scans which helped demonstrate an intramedullary syrinx. Thirty-three patients underwent 47 operative procedures (discounting spinal fusion and CSF shunt revisions). Open surgical management was performed in 32 patients, with CSF shunting along in one patient. Five patients (15%) incurred surgical complications within a six week postoperative period. Follow-up to date, ranges from one month to 11 years. In the 33 surgically treated patients, 18 are improved (55%), 10 are neurologically stable (30%), and five have worsened clinically (15%), including one death. Based on this study it appears that the Chiari II malformation maybe more common in adults than previously recognized. Surgical intervention has a favourable outcome in the majority of patients but a significant proportion continue to deteriorate.

Physostigmine, oxotremorine, RS-86, and a combination of piracetam and lecithin, have all been studied in patients with Alzheimer's disease. Intravenous physostigmine produced a significant improvement in patients' ability to recognize words and particularly to distinguish words they had never seen before from words previously presented. A subgroup of Alzheimer's patients had a clinically meaningful improvement to treatment with oral physostigmine, with the degree of improvement correlating with the ability of oral physostigmine to increase the nocturnal secretion of Cortisol. No statistically significant differences of piracetam or piracetam and lecithin, compared to placebo were noted, however, the ratio of red cell to plasma choline might be associated with treatment responsivity. The potential therapeutic efficacy of oxotremorine proved all but impossible to assess due to concomitant adverse effects, particularly dysphoria. Results with another cholinergic agonist, RS-86, will be reported. This drug appeared to be better tolerated than oxotremorine.

Animals with a kianic acid induced cortical depletion of choline acetyltransferase were found to have a significant impairment in retention of a passive avoidance task, an abnormality that was readily reversible by physostigmine, oxotremorine and 4-amino-pyridine. Cysteamine, a depletor of somatostatin, also produced a comparable deficit.

This paper reports two children who had mental retardation as the predominant manifestation of vein of Galen malformations. C.T. scans demonstrated extensive intracerebral calcification. Surgery reversed the progressive downhill course in one patient and may have arrested further deterioration in the other. The pathophysiological mechanisms underlying the clinical and radiographic features are discussed.

Clinical exacerbations of multiple sclerosis (MS) are characterized by elevated levels of cerebrospinal fluid (CSF) myelin basic protein (MBP). The purposes of this study were to determine whether anti-MBP antibodies are present in increased titer in CSF of MS patients with exacerbations, and whether they can be suppressed by the administration of immunosuppressive dosages of methylprednisolone (MP). A solid phase radio-immunoassay (RIA) was used to detect free and total anti-MBP antibodies before and after acid hydrolysis of CSF. In MS exacerbations, the majority of elevated anti-MBP is in the free form. With the exception of subacute sclerosing panencephalitis (SSPE) and some cases of post infectious encephalomyelitis, anti-MBP antibodies are not present in either MS patients in remission or in non-MS controls. Anti-MBP levels remained elevated over a 10 day period when patients are managed by bed rest only or when treated with intravenous (IV) ACTH. IV administration of MP in “high” (160 mg/day) or “mega” (2 g/day) dosages produces a highly significant reduction of both MBP (p<0.01) and anti-MBP (p<0.001) levels. Total intrathecal IgG synthesis is also significantly suppressed by IV-MP but not by ACTH.

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.

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

We analysed the charts of 131 consecutive cases of spontaneous subarachnoid hemorrhage — without arteriovenous malformations — for seizures. Convulsions occurred in 31 patients (24%) and most often within 24 hours of bleeding. Motor manifestations of partial seizures were of no lateralizing value to aneurysm site. Early mortality, rebleeding and intracerebral hematoma were similar in both seizure and non-seizure groups. Late seizures were infrequent in survivors who had suffered seizures in the acute stage — thus questioning the necessity for routine, long term prophylactic anticonvulsants in these patients.

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.

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. Minimal AO-RNA fluorescence was seen in 8 cerebellar medulloblastomas and in a retinoblastoma; strong AO-RNA fluorescence occurred in one cerebellar medulloblastoma and in 3 primitive neuroectodemal tumours of the cerebral cortex. Intermediate intensity of fluorescence was found in neuroblastomas, and strong fluorescence was shown in well differentiated ganglioneuroma cells and in cells of chromaffin tumours. Among glial tumours, by contrast, the most anaplastic cells displayed the most RNA fluorescence, while better differentiated astrocytoma cells showed much less. Gradients also were found within some astrocytomas, corresponding to zones of relative anaplasia. Minimal or no fluorescence was detected in reactive gemistocytes or in oligodendroglioma cells. Ependymomas were weakly fluorescent and choroid plexus papillomas showed more fluorescence, similar to the findings in normal ependyma and choroid plexus. Several non-neuroepithelial tumours of the nervous system and Schwannomas also were studied. The acridine orange technique applied to either frozen or paraffin sections of nervous system tumours, has value as an adjunct in the diagnosis and grading of these neoplasms and perhaps in distinguishing reactive gliosis from benign astrocytoma.

We report a case of intermittent compression of the lingual nerve due to sialolithiasis and presenting with episodic unilateral numbness of the tongue. Removal of the obstruction has relieved the patient of symptoms over a 21 month period to date.

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.

Embolic and thrombotic infarction in the territory of the posterior cerebral artery (PCA) is described with emphasis on the stroke and cerebrovascular features rather than special neurological syndromes. Of 47 cases of obstruction at the distal bifurcation of the basilar artery, 43 (95%) were consistent with embolism. The clinical categories and pathological findings are presented. Local embolism, vertebral distal-stump embolism, the dynamics of hemorrhagic infarction and embolus-in-transit are briefly described. The prodromal manifestations of PCA thrombotic occlusion include photopsias, hemianopic blackouts, headache, transient episodes of numbness, episodic lightheadedness, spells of bewilderment and rarely tinnitus. Recognition of these may allow prevention of a stroke. Prodromal photopsias did not closely resemble the scintillating displays of migraineurs. When the stroke occurred, visual complaints ususally predominated. A sensory deficit occurred in one-third of cases. In 25 cases of memory impairment the dominant hemisphere was involved in 24. The kinds of visual hallucinations, simple and formed, are described.

Forty-four adult patients with various forms of dystonia were treated with anticholinergics slowly increased to maximum tolerated doses. Thirty-seven per cent of the 35 idiopathic dystonia patients had a moderate to marked improvement with an average dosage of 21.5 mg of trihexyphenidyl. Younger patients with a shorter duration of dystonia and those who tolerated higher doses tended to benefit most. However there were exceptions to all of these factors. None of the nine patients with symptomatic dystonias improved more than mildly and most had no benefit despite the use of dosages similar to those resulting in improvement in idiopathic dystonia patients. Side effects were common. These often forced drug withdrawal at lower doses than those which might have resulted in improvement. These results suggest that high dose anticholinergics should be the first line of therapy for disabling dystonia.

A patient with a submandibular gland carcinoma was found clinically to have a unilateral chorda tympani, lingual and hypoglossal nerve deficit. This unique neurological entity of loss of taste sensation of one-half of the tongue (hemiageusia), hemianaesthesia and hemiatrophy of the tongue, has not previously been reported.

Abnormal findings on neurological examination were evaluated in 165 patients with a clinical diagnosis of Alzheimer's disease who attended a memory disorders clinic. Severity of dementia was measured by the Blessed Dementia Scale, and associations of abnormalities with dementia severity were evaluated using logistic regression. Presence of aphasia, apraxia, and primitive reflexes on neurological examination were strongly associated with severity, and weak associations were observed for abnormalities of muscle tone and gait. Among these associated neurological features, only aphasia and apraxia were present in mildly demented cases with sufficient frequency to suggest utility as diagnostic signs early in the course of the disease.

A province wide prevalence study on multiple sclerosis (MS) was conducted in British Columbia (B.C.). The prevalence date was July 1, 1982. The major portion of this study was a review of all the files of neurologists practicing in B.C. as this was judged to be the most accurate source for identifying MS patients. 239,412 neurologists' files were hand searched by one researcher using modified Schumacher criteria for classification. Other sources used during the study for identifying MS patients were the MS Clinic, general practitioners, ophthalmologists, urologists, specialized facilities such as long term care facilities and rehabilitation centres, and patient self-referrals.

A total of 4,620 non-duplicated cases were identified and classified. 4,112 of these (89%) were classified according to information contained in neurologists' records.

The prevalence estimate for definite/probable MS in B.C. was 93.3/100,000 population. This increased to 130.5/100,000 population if possible MS and optic neuritis were also included. These rates are among the highest reported in Canada or elsewhere. The cooperation of B.C. neurologists made this study unique in its scope and accuracy of diagnosis.

This paper reports neuropsychologic and pathologic data for eleven patients with a clinical diagnosis of probable Alzheimer disease (AD) according to recently proposed NINCDS criteria. In all cases, the clinical diagnoses were verified by cortical biopsy using histopathologic criteria for definite AD. Similar tissue samples from nine non-demented autopsied patients were also evaluated and none received an histopathologic diagnosis of AD. Correlations between cortical plaque counts and neuropsychologic test scores are also presented. These data have important implications for 1) the accuracy of clinical diagnosis in AD; 2) the validity of NINCDS criteria for the clinical and pathologic diagnosis of AD; and 3) the utility of cognitive test scores as indicators of disease severity.

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.

Multimodal evoked potentials were analyzed from 58 possible, 62 probable and 100 definite (total 220) multiple sclerosis (MS) patients. Visual evoked potentials (VEP) were most frequently abnormal yielding 39%, 69%, 84% in the three diagnostic groups respectively. Median nerve sensory evoked potentials (SEP) yielded abnormalities in 26%, 65%, 79% respectively. Brainstem auditory evoked responses (BAER) were abnormal in 17%, 39%, 66% respectively. We measured the combined amplitude (CA) of waves III, IV, V in the BAER of these patients as an objective measure of amplitude asymmetry. The CA was considered abnormal if it was 1SD below the lowest CA value in the control group. The CA was abnormal in 9.2% of BAER with normal central conduction time. The BAER diagnostic yield in MS patients increased 11% by using CA analysis.

A case of motor neuron disease with clinical and pathological resemblance to amyotrophic lateral sclerosis (ALS) in a woman who was severely bitten on the ankle by a cat is described. Weakness first appeared at the ankles and relentlessly advanced proximally, terminating in death from pulmonary failure in a year. A number of unusual features that are uncharacteristic of ALS were found that included a markedly elevated antinuclear antibody titre in the serum and the presence of prominent oligoclonal bands in the cerebrospinal fluid. The spinal cord showed loss of anterior horn cells and pyramidal degeneration that are characteristic of ALS, but an extraordinary finding was the presence of transmural granulomatous inflammation of numerous small and medium sized vessels, especially veins, in the subarachnoid space around the cord. There were also inflammatory changes in the brainstem and spinal cord consisting of microglial and astrocytic nodules and perivenous cuffing by mononuclear cells. Ill-defined hyaline eosinophilic cytoplasmic inclusions were seen in some remaining anterior horn cells. No viral particles were found by electron microscopy despite an extensive search. Virological studies were inconclusive but there is reason to believe that this patient's illness was caused by an as yet unidentified virus.