Oligodendrogliomas respond to nitrosourea-based chemotherapy and are induced in rats following transplacental exposure to ethylnitrosourea, observations suggesting that neoplastic and normal cells of the oligodendrocyte lineage are “sensitive” to nitrosoureas. Nitrosoureas alkylate DNA at O6-guanine with repair mediated by O6-methyIguanine-DNA methyltransferase (MGMT). The cytotoxic and carcinogenic properties of the nitrosoureas appear related to MGMT activity.

To explore why oligodendrogliomas respond to chemotherapy, we measured MGMT activity in five chemosensitive human oligodendrogliomas and in rat oligodendrocyte lineage cells. We also measured MGMT activity in rat astrocytes and compared the cytotoxic effects of carmustine (BCNU) on oligodendrocyte lineage cells and astrocytes.

Low levels of MGMT activity were found in five of five human oligodendrogliomas. Cultures of neonatal rat glia enriched for oligodendrocyte lineage cells also had low levels of MGMT activity, approximately one-third that found in astrocytes (p < 0.02), and oligodendrocyte lineage cells were more sensitive to BCNU than astrocytes.

Low MGMT activity may contribute to the chemosensitivity of some human oligodendrogliomas and rat oligodendrocyte lineage cells also have low levels. If drug resistance mechanisms in tumors reflect the biochemical properties of their cells of origin, then normal glia may serve as a laboratory substitute for human glioma.

Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain.

Carbachol was injected directly into the brain in a dose of 1 or 3 (jg. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe.

Injections of high dose carbachol (3 (jg) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 ug) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta.

Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.

Genetic factors may be important in the etiology of subarachnoid hemorrhage (SAH) and intracranial aneurysm (IA) formation. Several studies have reported the familial occurrence of SAH and IA, although in most cases asymptomatic family members were not studied with elective angiography. The examination of data from large sibships could provide important information about the frequency of IA occurrence in at-risk individuals and the mode of inheritance for familial SAH/1A.

We reviewed published case series of sibships with SAH and at least four siblings, in which at least one sibling underwent elective angiography. Data were collected on age-of-onset, clinical events, presence of hypertension, angiographic findings, and outcome. Patients were classified as “affected” if they had a SAH or if an IA was detected by elective angiography, and “unaffected” if they were asymptomatic and had a negative angiogram.

Seven case series with 52 individuals (26 men and 26 women) met our inclusion criteria. The sibships ranged from 6 to 13 members. Most of the siblings (32 of 52, 61%) were asymptomatic, 18 (35%) had a SAH, and 2 (4%) had focal symptoms but no SAH. Elective angiography of 34 siblings showed an IA in 11 (32%) and was negative in 23 (68%). The overall rate of affecteds (SAH or IA) was 56%.

Based on data from these sibships, angiography of asymptomatic at-risk siblings demonstrated an IA in almost one-third of cases. Familial SAH/IA segregated with a pattern that was consistent with an autosomal dominant trait in this selected series of sibships, although other factors could produce these findings.

Postural instability is a common problem in patients with Parkinson’s disease. This paper reports results of a study undertaken to investigate some of the possible mechanisms responsible for this instability.

Preparatory postural adjustments associated with a lateral leg raising task were studied in five parkinsonian patients and four age-matched controls. Recordings included ground reaction forces, kinematics, and surgace EMG activity from multiple leg muscles.

In normal subjects there was a well-defined sequence of events preceding the onset of leg elevation, beginning with a transfer of centre of foot pressure (CP), initially toward the moving leg and then back to the support side, followed by displacement of the trunk toward the support side. In the more severely affected parkinsonian patients, the amplitude of the the initial displacement of CP was markedly reduced. The interval between the earliest force changes and the onset of leg elevation was prolonged and the relative timing of the kenematic adjustments during this interval was disrupted. In addition the alternating burst and periods of inhibition observed in the EMG recordings from the normal subjects were replaced by continuous tonic EMG activity.

These observations suggest that abnormalities in programming preparatory postural adjustments may contribute to postural instability in some patients with advanced Parkinson’s disease.

To review the clinical characteristics and associated features found in patients with psychogenic dystonia.

A 10 year retrospective chart review of all patients diagnosed by the author as having psychogenic dystonia.

Eighteen patients fulfilled diagnostic criteria for “Documented” or “Clinically Established” psychogenic dystonia. Clinical characteristics of the dystonia were inconsistent or incongruous with established forms of organic dystonia. Fourteen of the 18 patients had a known precipitant. In most, the onset was abrupt and progression occurred rapidly, often to fixed dystonic postures. In contrast to idiopathic dystonia, involvement of the legs was common (12 patients), despite onset in adult life. Although cases of isolated paroxysmal dystonia were excluded in the review, 10 patients had paroxysmal worsening of dystonia or other abnormal movements. Pain was a prominent feature in 14 of 16 patients with the complaint and 1 patient with documented psychogenic dystonia also had well established reflex sympathetic dystrophy (RSD). Other psychogenic movement disorders, psychogenic neurological signs and multiple somatizations were common. Long-term follow up was available for less than one-half of the patients. Outcome varied considerably; some patients had complete resolution of symptoms (including 1 who had undergone 2 previous thalamotomies) and others remained disabled by persistent dystonia.

Dystonia is uncommonly due to primary psychological factors. At times this is an extremely difficult diagnosis to make and even when the diagnosis is confirmed, management remains very challenging. Future studies are required in hopes of providing more efficient means of distinguishing psychogenic dystonia from other dystonic syndromes especially those which rarely follow peripheral injury or accompany RSD/causalgia syndromes.

Here we assess the ability of patients with cerebellar disease to execute a simple visually-guided movement task involving tracking of a target with the index finger.

Spontaneous microdisplacements in index finger position are compared in patients with cerebellar deficits (ischemia [n = 3], multiple sclerosis [n = 3], degenerative cerebellar disease [n = 3]) and age-matched healthy subjects. Subjects were required to maintain a constant finger position relative to a stationary baseline displayed on an oscilloscope.

Unusual transient abrupt movements (saccadic or myoclonic-like) directed with or against gravity were seen in patients whose neurological deficits were the most severe (7/9 patients). These abrupt myoclonic-like movements occurred independently of visual input, were not associated with clinically observable myoclonus, and were not detected previously in patients with Parkinson’s disease. These abrupt myoclonic-like movements were not associated with abnormalities in either physiological tremor, or oscillations in finger microdisplacements induced by insertion of a delay (300–1400 ms) into the visual feedback of this finger “holding” experiment. An unexpected finding is that the results obtained for patients with cerebellar deficits by insertion of an experimental delay are not significantly different from those obtained with their age-matched controls.

These observations suggest that abrupt myoclonic-like movements are a characteristic abnormality of patients with a variety of cerebellar deficits and emphasize the value of this simple motor tracking task for characterizing movement disorders.

Some patients with reflex sympathetic dystrophy (RD) develop intractable symptoms unresponsive to conventional therapy. Recently, intrathecal morphine therapy has been used with some success in such patients.

The clinical course of two patients with intractable reflex sympathetic dystrophy (RSD) is described. Both patients developed intractable leg pain, swelling and autonomic changes after a leg injury. Numerous medical treatments and surgical sympathectomies failed to provide long term relief.

Relatively satisfactory symptom control was achieved only with the use of long term intrathecal morphine therapy delivered by subcutaneously implanted infusion pumps. Exacerbations of the RSD continued to occur, at times in association with further leg trauma, but these could be controlled by a temporary escalation of the intrathecal morphine dose. Complications of morphine therapy were relatively minor. A red rash appearing over the pump site was the first sign that a drug catheter break had occurred, necessitating surgical catheter revision.

Long term intrathecal morphine therapy is a useful treatment option for patients with intractable severe RSD who have failed other therapies and remain markedly disabled.

In animals and in humans, stress is known to be accompanied by increased β-endorphin secretion.

Blood samples from 47 patients in a state of stress induced by multiple trauma were assessed for β-endorphin concentration by radioimmunoassays.

We show that there is a clearcut correlation (Spearman’s R = 0.72, P = 2.1 x 10”-6) between the level of consciousness evaluated with the Glasgow score and levels of circulating β-endorphin. In addition, β-endorphin levels are higher than normal in patients with Glasgow coma with scores higher than seven, and lower than normal in those with Glasgow coma scores of seven or less. Finally, in the complete absence of stress (shown by the lack of brain activity in six irreversible coma patients), there is a severe drop in the level of circulating β-endorphin.

β-endorphin serum levels correlate with the state of consciousness of multiple trauma patients.

We have searched for amyloid substance in 41 consecutive samples of tissue taken during laminectomies performed to relieve spinal canal stenoses. We also evaluated the relation between the occurrence of deposits and the age of patients.

Tissue sections were stained with Congo red; positive areas had to show green dichroism under polarized light.

Small amyloid deposits were found in fibrous and fibro-elastic (ligamentum flavum) tissues in 14 subjects (34%). After age 60, the frequency was close to 50%. It reached 58% in those aged 70 or over. Our 3 patients aged 80 or more all had deposits. There was also a relation between age and importance of the infiltration. Both sexes appeared evenly involved. Systemic amyloidosis (multiple myeloma) was demonstrated in a single patient. In this case infiltration was slightly more abundant and exceeded ligamentary structures, also involving vascular walls.

Small amyloid deposits were frequent in our material. Their presence and their abundance were closely related to the age of patients. Rarely, a more important infiltration, exceeding ligamentary structures will perhaps suggest a systemic form of amyloidosis. A few other rare amyloid conditions (amyloidosis associated with prolonged dialysis, amyloid tumour) have been reported to induce spinal canal stenosis. The occurrence of amyloid in vertebral ligaments of non-stenosed elderly persons is not documented; it may represent a new localization of senile amyloidosis.

Neurenteric cysts are rare spinal lesions of congenital origin. They usually present insidiously with a long history of local spinal pain, radiculopathy and myelopathy. We report a 14-year-old male with a high cervical neurenteric cyst who developed a progressive myelopathy after minor neck trauma. Full recovery followed a partial cyst excision and decompressive procedure.

The possible pathogenic mechanisms for this unusual presentation include hemorrhage into the cyst, sudden mechanical compression from abnormal spinal movement of a chronically distorted and compressed spinal cord, or an increase in the size of the cyst secondary to accumulation of cyst fluid. In this case a small increase in the cyst size may have resulted in increased mechanical distortion and spinal cord dysfunction on a compressive and ischemic basis.