From July 1989 to February 1996, 130 patients underwent sterotactic radiosurgery. We report the results of the first 50 patients eligible for a minimum of three years of follow-up.

Twenty women and 30 men, (mean age: 37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior treatment was embolization in seventeen, surgery in three and embolization and surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty-seven treatments used a single isodose. Restricting eloquent normal tissue to 15 Gy, margin doses (at 50 - 90% isodose) were 12 Gy (one patient); 15 Gy (sixteen patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: <1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0 cm (thirteen patients; 3.0 cm (four patients).

Forty-five patients were evaluable at three years, with thirty-nine having angiography. Twenty-five had angiographically confirmed obliterations; two had parenchymal AVMs obliterated but with residual dural components; four had MRI evidence of obliteration (refused angiography). One patient acutely had a seizure; one patient (with hemorrhages, resection, and embolizations preceding two applications of radiosurgery, separated by 3.5 years) had worsening of memory.

Our uncorrected (five patients unevaluable at three years) and corrected angiographically confirmed obliteration rates are 54% and 60% respectively. Our follow-up (98% accounting of cohort; 78% angiographic rate) and explicit derivation of denominators help delineate the efficacy of radiosurgery at these doses.

To describe the response to single dose photon stereotactic radiosurgery of arteriovenous malformations (AVMs) so that the probability of success or failure of treatment may be predicted for the individual patient.

The obliteration prediction index (OPI) was calculated for AVMs by dividing the marginal dose of radiation in Gray (Gy) by the lesion diameter in centimetres in cohorts of 42 patients treated with the modified linear accelerator at Toronto-Sunnybrook Regional Cancer Centre and 394 patients treated with the gamma unit at the Royal Hallamshire Hospital, Sheffield, United Kingdom. Patients were grouped into ranges by OPI and the proportion of success and failure was calculated for each group. An exponential function [P = 1-A•e(-B-OPI)] was fitted to the data by the least squares method.

Despite systematic differences in radiation treatment, that is, marginal doses of 15 and 20 Gy in Toronto and most Sheffield patients with a marginal dose of 25 Gy, the resultant data points exhibited similar behaviour.

The function [P = 1-A•e(-B-OPI)] partly describes the biological effect of radiation and is independent of the radiation device used. Radiosurgery centres can use this model to facilitate predictions of successful treatment for individual patients.

To assess the feasibility, toxicity, and local control of stereotactic radiosurgery followed by accelerated external beam radiotherapy (AEBR) for patients with glioblastoma multiforme.

Six males and eight females, with a median age of 67.5 years (range 45-78 years), entered the study. Karnofsky performance status was 90 for five, 80 for six, and 60 for three patients. Following surgery, the patients were left with a residual mass 4 cm. Radiosurgery was delivered with a single dose of 20 Gy to the 90% isodose surface corresponding to the contrast-enhancing edge of the tumour. A total AEBR dose of 60 Gy in 30 fractions was delivered using a concomitant boost technique over four weeks.

Median survival time was 40 weeks (range 17-80 weeks). Actuarial survivals at 12 and 18 months were 43% and 14%, respectively. The median time to progression was 25 weeks (range 2-77 weeks). One patient developed a seizure on the day of stereotactic radiosurgery. Two patients experienced somnolence at 47 and 67 days post-radiotherapy. Eight patients remained steroid-dependent. Radiological evidence of leukoencephalopathy was observed in one patient, and brain necrosis in two additional patients at 30 and 63 weeks. One of these two patients with brain necrosis developed complete loss of vision in one eye, and decreased vision in the contralateral eye at 63 weeks.

Stereotactic radiosurgery followed by AEBR was feasible but was associated with late complications. The use of such radiosurgical boost for patients with glioblastoma multiforme should be reserved for those patients entering controlled clinical trials.

To assess the ease and reliability of routine use of somatosensory evoked potentials (SSEPs) for identification of sensorimotor cortex in brain tumour removal and to document its influence on the performance and outcome of surgery.

SSEPs in response to contralateral median nerve stimulation were recorded from the cortical surface by means of a four lead electrode strip. Polarity reversal of short latency SSEP waves was used to identify the position of the central sulcus in 46 consecutive craniotomies for removal of metastases, gliomas, or meningiomas located in, near, or overlying sensorimotor cortex.

SSEPs were successfully recorded in 43/46 cases (94%) with demonstration of polarity reversal in 42/43 (98%). SSEP localization led to modification of 14/42 (33%) procedures, most frequently because of either displacement or involvement of sensorimotor cortex by tumour. Six patients (14%) developed new neurological deficits but none of these was attributable to incorrect identification of sensorimotor cortex.

SSEP polarity reversal is a simple, reliable, accurate, and inexpensive method of localizing sensorimotor cortex under general anaesthesia. Correct identification is possible when sensorimotor cortex is displaced or when surface anatomy is obscured by tumour. Routine use of this technique should be considered in all procedures for lesions located near the central sulcus.

The cortical changes resulting from chronic hydrocephalus in adults are not well defined.

Retrospective analysis of twenty-one patients (age 64-88 years) with a clinical diagnosis of “normal pressure hydrocephalus” who underwent cortical biopsy at the time of intracranial pressure monitoring or shunt insertion, and eight patients who were biopsied but not shunted. Eleven brains (age 26-92 years), seven from patients who could be considered to have “normal pressure hydrocephalus”, were also examined following autopsy. Age- and sex-matched control brains with small ventricles and no history of dementia were compared to the hydrocephalic brains. Senile plaques and neurofibrillary tangles were assessed semiquantitatively and a non-parametric statistical analysis was employed.

Five biopsies exhibited both senile plaques and rare neurofibrillary tangles, while two had only neurofibrillary tangles. Neurofibrillary tangles were more prevalent in hydrocephalic brains than in controls. There was no difference in the prevalence of senile plaques between the two groups. Grumose bodies in the substantia nigra were identified in five autopsy brains, a prevalence higher than in control brains.

These pathological features are not specific for hydrocephalus; however, they suggest that long-standing ventriculomegaly is associated with degenerative brain changes in sites beyond the periventricular white matter. The presence of senile plaques in cortical biopsies from hydrocephalic patients does not appear to be a contraindication to shunting; however a prospective study in patients undergoing intracranial pressure monitoring would better address the issue.

Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of “familial PD”(fPD).

81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined.

On examination, 8 persons, said to be “normal” by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100 000 versus 1190/100 000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100 000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree.

“Familial parkinsonism” cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a “negative” family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population – regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD.

Pallidotomy helps parkinsonian symptoms. We tested the hypothesis that this might be due to changes in inhibition in the motor cortex.

We examined 15 patients with parkinsonism before and after posteroventral pallidotomy. Magnetic stimuli were delivered over the motor cortex, while subjects maintained a 30% maximum voluntary contraction of the contralateral first dorsal interosseus (FDI).

Weak stimuli inhibited voluntary muscle activity, while slightly stronger stimuli caused short latency facilitation from activation of the corticospinal neurons. After pallidotomy magnetic stimulation, at the threshold for the short latency facilitation, resulted in more inhibition than before.

Pallidotomy increases cortical inhibition. This may be associated with improved control of movements.

We previously showed that Manitoba Hutterites seek physician care for varicella zoster virus infection significantly less than non-Hutterites. The current study was undertaken to measure varicella zoster virus seroprevalence for Hutterite and non-Hutterite controls.

Blood was obtained from 315 Hutterites and 259 similar age and sex controls at the time of blood donations to The Canadian Red Cross Society. The controls were from the same or a contiguous postal code area and were collected at the same time as the Hutterite samples. The immune status of the specimens was determined by the ELISA method (enzyme linked immunosorbent assay).

Twenty-eight per cent of 315 Hutterites had no immunity and an additional 25% had only marginal immunity. Among the 259 controls, 10% had no immunity and an additional 10% had only marginal immunity (p < .0001).

Manitoba Hutterites have significantly decreased seroprevalence to varicella zoster virus infection. This study of serum varicella zoster virus antibodies verifies a previous population based study that demonstrated the relative rarity of varicella and herpes zoster among a particular population group.

We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.

A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.

No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.

This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

Orthochromatic leukodystrophy with pigmented glia and scavenger cells is a rare leukodystrophy of unknown etiology. This report describes a 42-year-old man with a history of depression, dementia and parkinsonism having the pathological features of orthochromatic leukodystrophy with pigmented glia.

We reviewed the clinical history and pathology of autopsy and brain biopsy material.

Imaging revealed bilateral cerebral white matter hypodensities. At autopsy, the brain demonstrated a leukodystrophy affecting predominantly the cerebral hemispheres and characterized by demyelination, and cytoplasmic pigment deposits in oligodendroglia and astrocytes. The pigment had the staining properties of ceroid-lipofuschin and on ultrastructural examination was composed of membrane-bound lipid and electron-dense inclusions which had a fingerprint-like pattern. Similar pigment inclusions were not observed on ultrastructural examination of renal, splenic or hepatic tissue obtained at autopsy. The brain biopsy contained cerebral cortex with sparse subcortical white matter in which a few oligodendroglia and fewer astrocytes at the grey/white junctions showed cytoplasmic pigmentary inclusions identical to those described above. However, due to the paucity of white matter in the specimen a definite diagnosis of orthochromatic leukodystrophy with pigmented glia was not made.

The diagnosis of orthochromatic leukodystrophy with pigmented glia and scavenger cells can only be made antemortem if the brain biopsy contains adequate white matter and although a rare condition, it should be considered in the differential diagnosis of an adult onset leukodystrophy.

Spontaneous dissection of the vertebral artery is uncommon.

Case study.

We report a 49-year-old woman who presented with the rapidly progressing basilar artery syndrome who was given an intravenous dose of tissue plasminogen activator seven hours after the onset of first symptoms. Thirty minutes after the injection, a dramatic recovery of the patient's consciousness and neurological signs was noted.

To our knowledge, this is the first reported case of intravenous tissue plasminogen activator use in acute vertebral artery dissection.

Lhermitte-Duclos disease (LDD) is a rare pathologic entity involving the cerebellum. The fundamental nature of the entity and its pathogenesis remain unknown, and considerable debate has centered on whether it represents a neoplastic, malformative or hamartomatous lesion. The cell or cells of origin remain incompletely defined. Previous reports of cases in the English literature have dealt predominantly with the clinical and pathological aspects yet few address issues of treatment.

A case of Lhermitte-Duclos disease (LDD) in a 54-year-old female leading to local compressive symptoms and obstructive hydrocephalus is presented. A craniectomy, in addition to a CI laminectomy followed by a decompressive duroplasty (using autologous fascia lata graft) was performed.

The patient clinically improved and follow-up MRI 11 months post-operatively revealed improvement in hydrocephalus.

The histological and immunohistochemical features of the lesion are described, emphasizing the role of an abnormal dysplastic granule cell layer. The evidence in favor of each of the major theories of pathogenesis, malformative and neoplastic is discussed. Based on these facts a form of surgical intervention involving decompressive duroplasty is proposed.