Background: Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) has been extensively studied and characterized in normal mammalian tissues; however very little is known about this enzyme in human brain tumors. It has been established that high levels of this enzyme exist in non-central nervous system tumors, PDE inhibitors or cAMP analogues have been used to treat them. This study has examined the levels of CaMPDE in glioblastoma multiforme from six patients and has compared these to the levels of CaMPDE in four patients with normal cerebral tissue. In addition, an enzyme immune assay method (EIA) was developed in this study for the detection of CaMPDE in human cerebral tissue. This method is proposed to be used as an adjunct to the spectrophotometric method presently utilized. This would be beneficial in cases where small tissue samples, for example in stereotactic biopsy, are available. Methods: The CaMPDE activity and corresponding levels of expression in cerebral tissue from temporal lobectomies and both surgical extraction or stereotactic biopsy in patients with primary tumors were determined by spectophotometric and EIA, respectively. The EIA was developed from the production of a polyclonal antibody against bovine brain 60 kDa CaMPDE isozyme. Cross reactivity of the antibody with human was confirmed using transblot and immunohistochemistry. Results: Utilising the EIA, there was found to be significant reduction in both catalytic activity (p < 0.001) and in quantitative protein expression (p < 0.001) in glioblastoma multiforme from patients when compared to normal cerebral cortex. Immunoblotting experiments and immunohistochemistry demonstrated that CaMPDE in glioblastoma multiforme failed to react with a polyclonal antibody raised against bovine brain 60 kDa CaMPDE isozyme, whereas the enzyme from normal tissue reacted with antibody. Conclusions: Contrary to other studies on non-CNS tumors, the catalytic activity and the protein expression of CaMPDE is reduced in glioblastoma multiforme. The EIA method is a more sensitive in detecting CaMPDE than in the spectrophotometric method, especially when a small amount of tissue is available. Immunohistochemistry and the EIA may be useful in the future to use as markers for other types of brain tumors and not for glioblastoma multiforme as demonstrated.

Background: Thirty-one gliosarcomas (25 nonirradiated and 6 postirradiated tumors) were selected based on the presence of two distinctive areas: a malignant gliomatous and a sarcomatous component. In all cases, the sarcomatous component appears like fibrosarcoma or malignant fibrous histiocytoma. Two tumors showed additional areas consisting of osteochondroid differentiation. Methods: All tumors were examined using antibodies against Ulex europaeus agglutinin I (UEA), glial fibrillary acidic protein (GFAP), vimentin (VM), epithelial membrane antigen (EMA), desmin, collagen IV, alpha-1-antitrypsin (a-l-AT) and smooth muscle actin (SMA). Results: While the VM highlighted the sarcomatous areas of all tumors there were only scattered spindle cells that were GFAP-positive in the same areas. The a-l-AT was diffusely reactive in the sarcomatous areas in 20 cases. Focal immunoreactivity was seen with SMA (20 tumors), UEA (8 tumors), EMA (5 tumors), collagen IV (5 tumors) and desmin (4 tumors) in the nonvascular sarcomatous cells. Conclusions: The range of immunophenotypical expression is likely to be a reflection of the capacity of a multipotential progenitor to undergo divergent differentiation. There is very little morphological difference between the postirradiated and nonirradiated tumors except that a higher proportion of postirradiated tumors are immunoreactive to SMA and desmin.

Objective: We report three patients with malignant rhabdoid tumor (MRT) of the brain, two children and an adult. There were three purposes to this report: to describe the clinical course in an adult with MRT; to describe the interesting histopathological metamorphosis of one of the tumors; and to report the outcome of the treatment regimens we used in order to help guide future treatment. Since these tumors are quite rare it is important to continue to try new regimens in the search for effective therapy rather than to repeat ineffective ones. Method: Report of three patients. Results: The clinical course in all three patients was typical of these aggressive neoplasms in that chemotherapy and radiotherapy were ineffective in modifying the rapid deterioration leading to death. Conclusions: MRT can occur in adults. Autopsy in one patient showed that the tumor seemed to undergo an evolution in appearance when compared with the original pathology specimen from craniotomy. Administration of systemic therapy should be prompt and include intrathecal chemotherapy.

Background: When H-reflexes are recorded during movement in human subjects, the stimulator current output is not a good indicator of sensory stimulation efficacy because of unavoidable nerve movement relative to the stimulus electrodes. Therefore, the M-wave amplitude has been used by researchers as an indicator of the efficacy of the stimulus. In this study we have examined the general validity of the hypothesis that the M-wave amplitude is directly proportional to the group I sensory afferent volley evoked by the stimulus. Methods: A nerve recording cuff, stimulating electrodes, and EMG recording electrodes were implanted in cats. Nerve cuff recordings of centrally propagating volleys evoked by electrical stimuli were directly compared to M-waves produced by the same stimuli. Compound action potentials (CAPs) recorded in the sciatic nerve were compared with soleus M-waves during either tibial nerve or soleus muscle nerve stimulation. CAPs in the ulnar nerve were correlated with flexor carpi ulnaris M-waves during ulnar nerve stimulation. Results and Conclusions: Our findings indicate that for mixed nerve stimulation (e.g., tibial or ulnar nerve) the M-wave can be a reliable indicator of the centrally propagating sensory volley. Due to the high correlation between CAP and M-wave amplitude in these nerves, a small number of M-waves can give a good estimate of the size of the group I sensory volley. On the other hand, when nerves with only partially overlaping fibre diameter populations are stimulated (e.g., the soleus muscle nerve), the M-wave is not well correlated with the group I sensory volley and thus may not be used as a measure of the size of the input volley for H-reflex studies.

Objective: To quantify the performance of patients with Parkinson’s disease (PD) in incentive learning, or learning to respond to stimuli that signal the imminent presentation of a reinforcer, and in paired-associate learning, or learning of word associations. Methods: The performance of 32 patients with idiopathic PD was compared to that of 25 healthy control subjects, and 32 subjects suffering from arthritis, matched for age and education. The PD and arthritic groups were comparable on a self-report measure of physical disability. All subjects were physically capable of satisfying the contingencies of the incentive learning task. The avoidance task that quantified incentive learning used money loss as an aversive stimulus. The word paired-associate learning task was presented on a computer and feedback was not given on performance. Results: The normal and arthritic groups performed equally well on the avoidance task, whereas the PD group was impaired despite dopaminergic replacement therapy. The groups did not differ significantly in paired-associate learning. Conclusions: These findings are among the first to suggest that the nigrostriatal dopamine dysfunction associated with PD may play a role in incentive learning but not in paired-associate learning and are consistent with a role for dopamine in certain forms of learning and memory. The findings may highlight differences between tonic and modulated function in the nigrostriatal system.

Background and Objective: In preparation for analytic study we undertook to describe areas of relative excess and deficit of Parkinson’s Disease (PD) in Nebraska and tested two methodologic tools for inexpensive assessment of descriptive epidemiology of PD. Methods: In lieu of large-scale population screening and diagnosis, we obtained sales information of anti-PD drugs in the state in 1988 – 1990 as well as listings of all people dying from 1984 to 1993 who had Parkinson’s Disease mentioned anywhere on their death certificate. The anti-PD drug sales data are intended as a proxy for prevalence, while the death certificate data are intended as a proxy for incidence. Results: Sales divided by population over age 54 indicates where anti-PD drug sales differ from expected. We found high correlation of drug sales rates with several farming exposures. Age-adjusted death rates, however, showed a low degree of association with sales or farming variables. This may be attributable to differences in death certificate completion or in underlying incidence versus prevalence. Conclusions: These techniques provide a useful tool for delineating possible differences in incidence and prevalence. While not as accurate as full community survey with expert diagnosis, they are not as expensive, and can be followed by local cluster investigations and individual-level etiologic studies to test hypotheses resulting from the initial study.

Objective: The interactions between sleep, neck muscle activity, and cervical spinal pain were examined in a controlled study with nine patients suffering from idiopathic cervical dystonia (ICD; also referred to as spasmodic torticollis), and nine gender- and age-matched controls. Methods: From each participant, two all-night polysomnograms with additional electromyographic recordings from the sternocleidomastoid and upper trapezius muscles were obtained. The first night was for habituation to the laboratory environment; the second night for experimental data collection. Visual analogue scales were used to collect intensity and unpleasantness ratings of cervical spinal pain before and after the second sleep recording. Results: None of the standard sleep variables showed statistically significant differences between average values of both groups of participants. However, a significantly larger variance in sleep latency was obtained for the ICD patients. In general, abnormal cervical muscle activity decreased immediately when lying down without the intention to go to sleep. Subsequently, abnormal muscle contractions were gradually abolished in all ICD patients during the transition from relaxed wakefulness to light NREM sleep. Following this transition phase, no more abnormal EMG activity was found in any of our patients. Finally, cervical spinal pain intensity and unpleasantness were reduced by about 50% overnight. Conclusions: Both supine position and sleep can be associated with an improvement of symptoms of ICD, and this disorder does not induce any sleep perturbations.

Objective: To report the occurrence, clinical characteristics and genealogical analysis of multiple sclerosis in the Hutterites of North-Western United States and Western Canada. Background: The incidence of multiple sclerosis is reported to be lower or rare in certain ethnic groups and genetic isolates and was previously observed to be absent in the Hutterite population. Methods: After long-term surveillance, six patients were identified and clinical examinations and laboratory investigations including VER and MRI were completed. Results: The six cases included two brothers, two first cousins, male and female, another male and female, all representing two of the three endogamous groups of Hutterites, are linked to two common ancestors through lines of descent dating to 1723. The individual pedigrees were analyzed from extensive genealogical records covering eight generations. Conclusion: The incidence of multiple sclerosis in Hutterites is low in a high risk area of North America. A specific mode of inheritance pattern has not been established and a common founder effect may play a role in the development of multiple sclerosis. The genetic contribution of the Hutterites seems greater than previously recognized.

Background: We report experience with patients presenting with a specific combination of symptoms: unilateral sciatica, unilateral sensibility loss in the dermatomes SI to S5 (hemi-saddle) and subjective micturation problems secondary to ruptured lumbar disc. Because of its similarities with a cauda equina syndrome, this combination of symptoms was thought to be a unilateral cauda equina syndrome and it was called hemi-cauda equina syndrome. Consequently, it was treated as an emergency. Methods: Ten patients were evaluated. They compromised 2.3% of all patients undergoing lumbar discectomy. Results: Outcome is good with only 10% persisting minor neurologic deficit (sensibility loss in dermatomes S3 to S5). With the exception of urinary retention or incontinence, duration of symptoms and signs does not seem to influence outcome. Comparing signs, symptoms and radiographic findings with those of a cauda equina syndrome which were recently and thoroughly studied, they were found to be more severe in cases of cauda equina syndrome. Especially, the good outcome, (apparently unrelated to the duration of symptoms in cases of hemi-cauda equina syndrome) contrasted with the treatment results of cauda equina syndrome. Conclusions: We defined the hemi-cauda equina syndrome from ruptured disc as a combination of unilateral leg pain, unilateral sensibility loss in dermatomes SI to S5 and sphincter paralysis (proven urinary retention or incontinence). Motor deficit is not necessarily present. Emergency surgery is warranted. Patients presenting with micturation complaints other than urinary retention or incontinence do not suffer from a hemi-cauda equina syndrome.

Background: Neoplastic metastases to the cerebellum are a frequent complication in patients with carcinoma. However, the co-existence of an abscess within a CNS metastasis is a rare event. Methods: We report the case of a 79-year-old woman with two cerebellar abscesses within metastatic lesions in the cerebellum. She presented with a rapidly progressing syndrome characterized by elevated intracranial pressure and cerebellar findings. Results: At surgery, a purulent exudate within discrete metastatic tumours was identified. Pathological and microbiological examinations confirmed the coexistence of an abscess within a metastatic carcinoma. Significance and Conclusion: The radiological diagnosis of intracranial abscesses and metastases can be non-specific and brain imaging may not reliably identify both processes when they coexist. Furthermore, brain metastases often contain liquefied material which can be mistaken for tissue necrosis rather than an infectious process. It is important to be aware that a brain metastasis can also be infected. Therefore, acquisition of lesionai tissue for both pathological and microbiological examinations is essential for accurate diagnosis and to direct optimal therapy in situations where the intracranial lesion could be either an abscess or a metastatic deposit.

In 1909, in an isolated community hospital, on the northern tip of the Province of Newfoundland and Labrador, Canada, Dr. John Mason Little, Jr. performed electrical stimulation of the cerebral cortex, prior to cortical excision, as treatment of recurrent cerebral seizures in three patients. Extracts from Dr. Little’s written records of the clinical features, the neurosurgical procedures and cerebral cortical stimulation are summarised. A brief review of the contemporaneous history of neurosurgical procedures for epilepsy provides a prospective of Dr. Little’s remarkable surgical virtuosity.

It is particularly fitting that at this reception of members of the Canadian Neurological and Clinical Neurophysiologists Societies at the American Academy of Neurology we should honour Dr. Herbert Jasper. He is, at the age of 90, a living legend in the neurosciences. It is a rare opportunity for the young people who have followed him to meet a pioneer of his generation, let alone somebody who continues to this day to exercise his wise counsel and his extraordinary grasp of the working of the human brain.

Herbert Jasper, like Wilder Penfield, was born in the west of the United States, and, like his friend and colleague, became a Canadian and a founder of Canadian Neuroscience.

Jasper started his career as a psychologist of physiological persuasion and studied with Lapique who is remembered for his studies on chronaxie, in Paris. He became aware of Berger’s writings on the electroencephalogram and realized early the enormous potential of being able to record the electrical activity generated by the human brain. In the 30s, two schools of epilepsy developed in North America: the medical with William Lennox in Boston, and the surgical with Wilder Penfield in Montreal.