Background: Chronic liver failure is associated with high signal abnormalities in the basal ganglia on Tl-weighted magnetic resonance imaging of the brain. These abnormalities are strikingly similar to those seen following manganese intoxication. As dietary manganese is normally cleared by the liver, we hypothesize that hepatic dysfunction could lead to manganese overload and account for the MR1 abnormalities seen in patients with chronic liver disease. Methods: We measured blood manganese concentrations in eleven patients with biopsy-proven hepatic cirrhosis and eleven healthy age and sex-matched controls. We also performed semi-quantitative measures of Tl signal abnormalities on MRI in the patients with chronic liver disease. Results: Patients with cirrhosis had significantly higher blood manganese concentrations (20.6 ± 10.2 mcg/L) than controls (7.2 ± 2.7, p = .0013). In addition, semi-quantitative scores of TI-weighted signal hyperintensity on MRI correlated with blood manganese concentration in patients with cirrhosis (r = .65, p = .029). Conclusions: These findings demonstrate that chronic liver disease is associated with manganese overload and suggest that manganese is responsible for the Tl-weighted signal hyperintensity seen on MRI of patients with liver disease. As manganese intoxication is known to cause parkinsonism and an encephalopathy similar to those which occur with chronic liver disease, it is possible that manganese toxicity contributes to the development of these symptoms in liver damaged patients and that therapies which prevent or reduce manganese overload may have clinical benefit.

Background: Patient outcomes in multiple sclerosis (MS) have generally been measured by their neurological impairment using specific scales such as the Kurtzke Expanded Disability Status Scale (EDSS). However, this scale does not measure the multiple dimensions of health-related quality of life (HRQOL) such as functional status and general well-being, which are also important outcomes along with disease-specific measurements. Methods: HRQOL was measured in a group of 97 MS patients using the RAND 36-item Health Survey 1.0. The EDSS score was assigned by the clinic neurologist. Additional data were collected from the clinical record for each patient. Results: MS patients scored poorly in a number of HRQOL domains such as physical and role functioning and energy or vitality. Disability as quantified by the EDSS correlated only with the physical functioning domain. Regression models were developed to measure the relationship between patient characteristics (independent variables) and HRQOL domains (dependent variables). Discussion: A number of patient characteristics were associated with higher or lower scores on the HRQOL domains. Of particular interest is the finding that a family history of MS was associated with poorer physical and social functioning as well as more pain and less vitality. The occurrence of seizures had a negative impact on role functioning, social functioning and general health perceptions. HRQOL gives caregivers a broader measure of disease burden than the EDSS alone, and should be useful in planning and monitoring interventions.

Background: Neuropsychological studies of the pattern and extent of cognitive impairment in HIV-infected patients have mostly used deviations from control values and/or cut-off scores as criteria for classification of dementia. There is, however, no agreement as to how to define impairment, and classification is imprecise. Method: The current study used a dementia classification matrix, developed with a step-wise linear discriminant analysis of neuropsychological data from patients with primary neurodegenerative dementias, to classify symptomatic HIV patients as demented or non-demented, and further to differentiate cortical and subcortical dementia patterns. Thirty-two male and 2 female patients (mean age 39 ± 2) with symptomatic HIV disease (mean absolute CD4 count 195 ±41) participated in the study. Results: Thirty-five per cent of patients were classified as demented. Of these, 83% showed a subcortical pattern and 17% a cortical profile of deficits. Significant differences between patients classified as subcortically demented and those categorized as normal on neuropsychological measures associated with subcortical integrity further validated the classification. Measures of psychiatric status between subgroups were similar. Conclusion: Since certain treatments may delay or reverse cognitive deficits, the use of an objective classification method based on discriminant analysis may help to identify patients who may benefit from therapy.

Background: We set out to determine whether separable visual and representational components underlie normal subjects’ upward and distal biases in bisecting vertical and radial lines under visual guidance. Methods: Thirty-four normal subjects were asked to bisect lines oriented horizontally, vertically, and radially. Human silhouette figures were placed at either end of each line. These figures were presented upright or upside down in order to pictorially define a “top” to each line independent of the actual top of the visual field. Results: Although subjects erred toward the top of the visual field, they also demonstrated a significant bias toward the heads of the figures for lines in all spatial orientations. Conclusions: This result supports the existence of two biases: one toward the upper visual field, and another toward an internally represented “top” as suggested pictorially. These findings provide further support for the hypothesis that normal subjects’ upward and distal biases on bisection of vertical and radial lines under visual guidance have both representational and visual-based components.

Background: The observation that resection of structural lesions of the frontal lobe provides an effective treatment of intractable epilepsy has been made by surgeons specializing in this field for over sixty years! However, the excellent results achieved when such resections are coupled with the use of modern diagnostic and operative technologies are not fully appreciated by the modern clinician. Methods: We review the results of resection of large post traumatic frontal lesions in six patients with intractable frontal seizures. No invasive EEG recording was required pre-operatively. Results: The imaging characteristics of the underlying lesions, usually due to depressed skull fractures are illustrated. Surgical treatment rendered five patients seizure free and the sixth had over 85% improvement in seizure frequency. Conclusions: Modern imaging permits ready visualization of the post traumatic lesions with cause intractable seizures. It is important to recognize that resection of these post traumatic scars usually leads to excellent seizure control.

Background: Brain tumors comprise more than 20% of all childhood malignancies, and constitute the greatest number of solid pediatric cancers. Incidence rates reported have varied from 2.4 to 3.5/100, 000 children, reflecting the impact of modern imaging techniques, the application of diverse investigative methodologies, and the accessibility of the community to health care. Methods: Material from patients < 18 years of age was collated from the Manitoba Cancer Foundation Tumor Registry, the personal records of Winnipeg pediatric neurologists, and autopsy data. Patient data were also obtained from hospital charts and operating room log books. Histological sections were examined and classified according to the American Cancer Society by a single neuropathologist. The chi-square test was used for statistical evaluation. Results: During the seven-year study period, the diagnosis of brain tumor was made in 89 pediatric patients, of which 88 were diagnosed premortem. The overall average annual incidence rate for both sexes was 4.03/100, 000 child-years, higher than that previously reported. The male and female average annual incidence rates were 4.2 and 3.7/100, 000 child-years, respectively. Tumor type and location were relatively unremarkable, with an expected peak of medulloblastoma occurring in young males. The yearly incidence of tumor occurrence was fairly stable, and the geographic distribution of cases within Manitoba, homogeneous. Conclusion: The highest incidence rates of pediatric brain tumors have been recorded in countries possessing sophisticated universal health care systems, possibly reflecting their efficacy in disease surveillance.

Purpose: To review our experience with pre-radiation chemotherapy for malignant glioma. Methods: Consecutive adults with newly diagnosed glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic mixed glioma with a Karnofsky Performance Score of 60 or greater were treated with one cycle of procarbazine, lomustine and vincristine or lomustine alone, prior to radiation. Computed tomographic scans were obtained soon after surgery, eight weeks later, after radiation, and at regular intervals thereafter. The effects of chemotherapy and subsequent radiation and durations of tumor control and survival were assessed in this single arm, single center, prospective trial. Results: Thirty-seven patients started chemotherapy, 36 were rescanned eight weeks after diagnosis. Five patients (16%) responded to the first cycle of chemotherapy, three had glioblastoma and two anaplastic oligodendroglioma. Seven (19%) progressed during the first cycle, 6 had glioblastoma; with the addition of radiation one progressive case responded, three stabilized, and three continued to progress. Median times to progression and median durations of survival were 26 weeks and 60 weeks for the entire group, 24 weeks and 44 weeks for glioblastoma, and greater than 104 weeks for anaplastic astrocytoma. Conclusions: Most patients with glioblastoma do not respond to one cycle of nitrosourea-based chemotherapy given prior to radiation, but patients with anaplastic oligodendroglioma sometimes do. Patients with anaplastic astrocytoma may not respond to one cycle of chemotherapy, but often respond to subsequent radiation. Judging by survival results, radiation can be delayed eight weeks without appearing to compromise patient outcome. Implications: Pre-radiation chemotherapy with newer agents can be evaluated more fully in the future knowing that brief delays in radiation are unlikely to yield substantially inferior results.

Background: Seizures associated with intracranial neoplasms are occasionally refractory to conventional anti-epileptic drugs. Gabapentin (GBP) is one of several novel anti-epileptic drugs effective as an add-on therapy for intractable seizures but has not been studied in patients with cerebral tumours. Patients and Methods: We used GBP in a open-label add-on fashion to treat 14 patients with intractable seizures associated with intracranial tumours including four glioblastomas, four metastases, three recurrent glioblastomas, and one each of anaplastic and low grade astrocytoma and meningioma. GBP was added if optimization of pre-existing therapy failed and was titrated until seizures were controlled. Results: One patient experienced adverse drowsiness. Follow-up ranged from 3–24 weeks during which time 7 patients died from disease progression. Concurrent therapy included dexamethasone in eight, cranial irradiation in four, and radiosurgery in one. Responder rate (number with at least 50% fewer seizures) was. 100% and persisted throughout follow-up. Complete resolution of seizures occurred in 8/14 patients. Conclusions: GBP was well tolerated in patients with brain tumours. Seizure frequency was reduced in all patients and efficacy persisted over time; however, the mechanism of this improvement is unclear. Concurrent therapy, regression of frequency to the mean, and the lack of controls may account for apparent benefit. In addition, because GBP may interact with a leucine-related neuronal binding site we also speculate that this novel mechanism of action may have been enhanced in our patients due to the abnormal blood-brain barrier associated with cerebral tumours. Further investigation and a controlled trial are warranted.

Introduction: Chondromas are rare intracranial tumors. The authors present two cases of intracranial intradural chondroma, one originating from the falx cerebri and the other from the dura mater of the convexity. Method and Results: Diagnostic procedures, including magnetic resonance imaging, and surgical findings are described. In both cases, pre-operative diagnosis could have been at least suspected, and the tumor was completely removed, without recurrence after a follow-up of many years. The pathogenesis and pathological findings are discussed, and cases from the literature are reviewed. Conclusion: Benign intradural chondroma has a good prognosis, with no recurrence after surgical excision in most cases.

Background: Oat cell carcinoma of the lung is the most common cause of paraneoplastic limbic encephalitis. Association with other malignancies, in particular Hodgkin’s disease, is very rare. Case Report: This 23-year-old male presented with a six month history of progressive alteration in mental status, which consisted of insomnia, short-term memory loss, depression and cognitive impairment. Gadolinium MRI of the head showed intense bilateral contrast enhancement affecting the medial aspects of the temporal lobes in the region of the amygdala and hippocampus. The brain biopsy showed minimal neuronal loss with intense perivascular lymphocytic cuffing and microglia] nodules. Polymerase chain reaction for herpes simplex and cytomegalovirus were negative. With prednisone treatment, the patient’s neurologic status stabilized but did not improve. Four months later, he presented with left axillary lymphadenopathy. Lymph node biopsy was diagnostic of Hodgkin’s disease. During the chemotherapy, his lymphadenopathy subsided and his neurologic and mental status improved. When seen last after completion of his chemotherapy, one year after presentation, he had resumed normal social activities and was enrolled in a university language course. Conclusion: This is the first reported case in the English literature of a biopsy proven paraneoplastic limbic encephalitis associated with Hodgkin’s disease. Hodgkin’s disease should be thought of as a possible cause of paraneoplastic limbic encephalitis in the appropriate clinical setting.

Background: Increased intracranial pressure with encephalopathy has rarely been reported in Addison’s disease. Method: Case Study. Results: A 16-year-old female who presented with cerebral edema of unknown etiology was eventually diagnosed as having Addison’s disease. She had early morning headaches, fatiguability, diarrhea and deterioration in school performance. She was hyponatremic with a serum sodium of 128 mmol/L and hyperkalemic with a serum potassium of 5.9 mmol/L. She had a low serum osmolality (264 mosm), high urine osmolality (533 mosm) and high urine sodium (87 mosm). She had a postural drop in blood pressure and diffuse hyperpigmentation. An ACTH stimulation test revealed a low baseline Cortisol and no response to ACTH. Plasma renin activity was increased. Serum ACTH was elevated. She responded well to intravenous fluids and solu-cortef and was discharged on hydrocortisone and florinef. She remains well 18 months after the acute episode with no neurologic complaints or findings. Conclusion: Addison’s Disease should be considered in the differential diagnosis of symptomatic cerebral edema and idiopathic intracranial hypertension.

Background: A 20-year-old woman with a right occipital condylar fracture and bilateral hypoglossal nerve injury is presented. Only 17 cases of condylar fracture have been reported in the literature. Methods: The patient was evaluated with plain films, coronal and axial cut CT, and MRI. Results: MRI showed a severely distorted but otherwise normal medulla and a displaced condylar bone fragment. Conclusion: Condylar fracture may cause twelfth nerve palsy by injuring the central or peripheral nerve.

In the hope of eventually using replication-competent, neurovirulence-attentuated Herpes simplex type 1 virus in the treatment of brain tumors in humans, we analyzed the effect of such a mutant in human malignant meningioma transplanted into nude mice. Two models were used, one subcutaneous, the other intracranial subdural; nine or ten animals were used in each group. A 1 mm tumor mass was implanted. In the subcutaneous model, after 7 or 12 days, the tumors had reached size of 6 or 10 mm, respectively. At this time either saline or the attenuated, lac Z HSV-1 mutant G207 (5 × 106 PFU/50 μ1) were injected into the tumor; for the 10 mm tumors, the identical dose and 5 × 106 PFU/50 μl were given. Animals were sacrificed up to 28 days later. The ratio of tumor volume between untreated and treated groups was compared by the t-test. For all three treatment groups, tumor growth was markedly inhibited (p < 0.0001). In the intracranial model, either saline or G207 at a dose of 2 × 106 PFU/2 μl was injected into the tumor implant on day 7, with 9 animals in each group. By day 31, all animals in the control group had died; in the treated group, three were still alive at day 66; a significant difference in survival was found (Wilcoxon test, p < 0.01).