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Biomedical subjects

G S Venables

Publications and source records attributed to G S Venables.

At least 19 recordsLinked to original sources

Unilateral leptomeningeal enhancement after carotid stent insertion detected by magnetic resonance imaging.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty combined with vascular stenting is currently being assessed in the treatment of patients with symptomatic, severe carotid stenosis. The immediate cerebral hemodynamic effects resulting from stenting are not fully understood. This article describes a novel finding: abnormal leptomeningeal enhancement after stenting shown by MRI. METHODS: Fourteen patients with symptomatic severe carotid bifurcation stenosis underwent MRI within 4 hours before and within 3 hours after attempted carotid stenting. Twelve patients were successfully stented. Part of the MR investigation consisted of the acquisition of T1-weighted images before and after administration of the contrast agent Gd-DTPA, both before and after the procedure. RESULTS: All 12 patients who underwent successful stenting did not have abnormal enhancement of the leptomeninges before stenting but developed unilateral enhancement following intervention but before the second injection of contrast agent. No contrast enhancement was detected in the 2 patients who had the angiographic procedure but were not stented. CONCLUSIONS: These findings suggest that abnormal changes to the leptomeningeal vasculature occur during carotid stenting which are not associated with sudden development of neurological symptoms. The anatomic distribution of the enhancement suggests that it is a consequence of the sudden change in brain hemodynamics secondary to the improvement in carotid flow after stenting.

Aged↗

Diagnosis and management of transient ischaemic attacks in accident and emergency.

Stroke is an important cause of morbidity and mortality. Often the first presentation of cerebrovascular disease is a TIA which will present to the A&E department. Patients who have had a TIA are at increased risk of stroke, myocardial infarction, and vascular death. The risk of stroke after a TIA is greatest in the first year (approximately 11.6%) with a risk of approximately 5.9% per year over the first five years. As the risk is highest in the first months following a TIA it is important that the patients are diagnosed accurately, investigated promptly, and referred appropriately for treatment in order that valuable time is not lost. For this reason A&E physicians have a valuable role in the initial assessment and management of the patient. It has been advocated that patients should be seen by a neurologist or physician with an interest in cerebrovascular disease within days of their symptoms and be prepared for surgery within two weeks after a TIA. While it is usually not possible to achieve this ideal, improved cooperation between A&E physicians and these neurologists, general physicians, and geriatricians should lead to the implementation of speedy efficient referral procedures which can only improve patient care. When you next see a patient with a TIA in the A&E department remember what they have to lose. Three questions relating to this article are: (1) How are TIAs subdivided and what clinical features allow this differentation? (2) What are the initial investigations that should be performed in A&E? (3) When are the risks of completed stroke greatest after a TIA? Enumerate these risks. How effective is aspirin at reducting this risks?

Anti-Inflammatory Agents, Non-Steroidal↗

Multifocal motor neuropathy.

We present a review of the literature on multifocal motor neuropathy (MMN), a rare neurological disorder which has features in common with both chronic inflammatory demyelinating neuropathy and lower motor neuron disease. Clinically, MMN is characterised by slowly progressive asymmetrical limb weakness, usually most prominent in the forearms. Weakness may be associated with muscle wasting, fasciculations and decreased tendon reflexes. Serum anti-GM1 ganglioside antibody titres may be increased. The diagnostic hallmark of MMN is the electrophysiological demonstration of persistent localised motor conduction blocks, with otherwise normal or near-normal motor and sensory conduction velocities. The pathogenesis of MMN has not been elucidated completely. There is, however, substantial evidence for an autoimmune mechanism. Based on the possible involvement of the immune system in the pathogenesis of MMN the therapeutic efficacy of several immunomodulatory drugs has been tested. Treatment of MMN patients with human immunoglobulin or cyclophosphamide is usually followed by a marked improvement of strength. The finding that MMN is a potentially treatable disorder underscores the importance of distinguishing MMN from lower motor neuron disease, for which no effective therapy is currently available.

Biopsy↗

European carotid angioplasty trial.

The Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) is an international multicenter randomized trial, the primary aims of which are: (1) to determine the risks and benefits of carotid and vertebral artery transluminal angioplasty; and (2) to compare these with surgical treatment (carotid endarterectomy) or best medical treatment. Through the end of October 1995, 193 patients have been randomized (90 at our center). In this article, the rationale for the trial, its design and protocol, and the experience of our institution within the trial will be discussed.

Angioplasty, Balloon↗

Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group.

BACKGROUND AND PURPOSE: The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation (NRAF) varies from 2% to 15% in the first year and is approximately 5% yearly thereafter. Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population. METHODS: We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial. The mean follow-up was 1.6 years. RESULTS: By means of multivariate modeling, six independent variables were identified: history of previous thromboembolism, ischemic heart disease, enlarged cardiothoracic ratio on chest roentgenogram, systolic blood pressure greater than 160 mm Hg at study entry, NRAF for more than 1 year, and presence of an ischemic lesion on CT scan. These variables could also be used to stratify patients in low-, medium-, and high-risk subgroups for the other two arms of the trial, those treated with anticoagulation and aspirin. Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment. CONCLUSIONS: Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke.

Aged↗

The role of magnetic stimulation in the diagnosis of multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck, and head and lumbar region, as well as amplitude of the motor evoked potential (MEP) in normal subjects and patients with multiple sclerosis (MS). Patients with definite MS had significantly longer MCTs and smaller amplitude MEPs than normal subjects when recording from arm and leg muscles. In a comparison with visual evoked potential (VEP) recordings, head to neck MCTs were abnormal less often than VEPs, and VEPs detected more silent lesions. Recording from leg as well as arm muscles significantly increased the yield of abnormal MCT measurements. The detection of silent lesions in the patients with definite MS was improved, but there was no improvement in the non-definite cases. Amplitude measurements provided very little extra diagnostic information over MCT measurements alone and did not improve the detection of silent lesions. Interside MCT differences yielded extra abnormalities when recording from the arms but not the legs. Interside MCT abnormalities increased the detection of silent lesions in both the definite and non-definite categories. It was concluded that the majority of useful diagnostic information in patients with MS should be obtainable from bilateral MCT (head to neck) measurements, together with estimation of interside MCT differences. However, VEP recording is a better diagnostic test for MS than MEP recording as more silent lesions are detected. This may be because MCT abnormalities tend to reflect the degree of pyramidal disability.

Adult↗

The role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck in a prospective longitudinal study of patients with multiple sclerosis (MS) and normal subjects. MCT measurements showed a high degree of reproducibility in normal subjects and patients with stable MS. In patients with definite MS, there was significant positive correlation between MCT and motor disability. In patients treated with steroids for relapse of MS, there was significant shortening of MCT following treatment in those who clinically improved, but not in those who were clinically unchanged. In a smaller group of patients followed for 3 months, MCT changes tended to mirror the clinical pattern. Magnetic stimulation should prove a useful tool for the quantification of motor disability, and monitoring the response to new treatments in MS.

Adrenal Cortex Hormones↗

Abnormalities of central motor conduction in Parkinson's disease.

The new technique of magnetic stimulation was used to measure amplitude of the motor evoked potential (MEP) recorded from abductor digiti minimi whilst stimulating at the head, and motor conduction time (MCT) between head and neck. Bilateral studies were made in 12 normal subjects and 56 patients with Parkinson's disease. The amplitudes of the MEPs were significantly larger (P less than 0.05) in the patients (mean 1.6 mV, SD 1.4) compared with the normal subjects (mean 0.9 mV, SE 0.6). MCTs were significantly shorter (P less than 0.001) in patients (mean 8.1 ms, SD 1.3) compared with the normal subjects (mean 9.4 ms, SD 1.2). Although the pathophysiological basis of these changes has not been determined, they provide objective measurements which may be clinically valuable in monitoring therapy.

Central Nervous System↗

A randomized double-blind controlled trial of naftidrofuryl in acute stroke.

There is evidence to support the use of naftidrofuryl in acute stroke with claims of increased recovery, reduced fatality and reduced bed occupancy in patients treated with either oral or intravenous preparations. One hundred patients presenting with acute hemisphere stroke (less than 72 hours) were randomized to receive either a new oral formulation of naftidrofuryl or placebo on a double-blind basis. Treatment was given for a total of 12 weeks and patients followed for 26 weeks with serial neurological and functional assessments by a single observer. Cumulative fatality and hospital-bed occupancy were determined at each assessment interval. No significant difference was demonstrated in cumulative fatality, hospital-bed occupancy or recovery of motor function in patients treated with either naftidrofuryl or placebo. There is no evidence from this study to support the use of oral naftidrofuryl in acute stroke.

Acute Disease↗

Recovery of visual fields in acute stroke: homonymous hemianopia associated with adverse prognosis.

In a prospective study of 157 patients (median age 73 years) admitted to hospital within 72 hours of acute cerebral hemisphere stroke, there was clinical evidence of homonymous hemianopia (HH) as assessed by confrontation in 99 (63%). Patients were followed with serial neurological examinations for 28 days. Complete recovery of visual fields occurred in 14 (17%) of the 81 patients with a complete HH on admission and in 13 (72%) of the 18 patients with a partial HH on admission. Cumulative fatality at 28 days was greater in patients with a complete HH (49%), compared with patients with a partial HH (11%). These two patterns of recovery and outcome probably reflect the differing extent of cerebral damage in the two groups.

Acute Disease↗

Increasing age, diabetes mellitus and recovery from stroke.

In a prospective study of 200 patients with acute stroke, blood glucose and glycated haemoglobin (HbA1) were measured within 72 hours of onset. Unrecognized hyperglycaemia as defined by a raised stable HbA1 more than two s.d. above the mean reference value and no previous history of diabetes was present in 27%. No correlation existed between patient age and admission blood glucose or HbA1 levels (r = 0.1). Cumulative mortality and recovery of limb function was assessed in the first 136 patients with carotid distribution events. Admission blood glucose greater than or equal to 8 mmol/l was shown to be associated with a significantly greater mortality at 4 and 12 weeks (P less than 0.05). Multivariate analysis with age, glucose, HbA1 as independent variables demonstrated that age was the only significant predictor for death at 4 weeks (P less than 0.05) but at 12 weeks both age and blood glucose were significant (P less than 0.05). In patients less than 65 years blood glucose was a significant predictor for death (P less than 0.05) but in patients less than or equal to 65 years HbA1 and not glucose was significantly (P less than 0.05). Patients greater than or equal to 65 years with HbA1 greater than or equal to 7.5% were significantly more likely to have a raised admission blood glucose. Hyperglycaemia on admission was not shown to influence recovery of limb function. Increasing age is of greatest importance in predicting mortality although blood glucose is of prognostic value especially in the young stroke patient.

Acute Disease↗

Noradrenaline response to edrophonium in primary autonomic failure: distinction between central and peripheral damage.

The effects of intravenous edrophonium on plasma noradrenaline were studied in 12 subjects with primary autonomic failure. 5 had clinical features of central autonomic damage, 4 with parkinsonism (PD) and 1 with multiple system atrophy (MSA); the other 7 had clinical features of progressive autonomic failure without detectable central neurological damage (PAF). After edrophonium all but 1 subject showed falls in heart rate of about 6 beats/min; there were no consistent blood pressure changes. The 5 PD/MSA patients all had normal plasma noradrenaline responses to edrophonium, with rises of 35-66% within 2-8 min of injection. 6 of the 7 PAF patients had no response or very small responses (-6 to +11%), while the other subject had a normal response (70% rise). The noradrenaline response to edrophonium may provide a simple way to differentiate between central and peripheral autonomic damage.

Aged↗

Changes in vascular and metabolic reactivity as indices of ischaemia in the penumbra.

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 +/- 12.9 (SD) ml 100 g-1 min-1 and fell to 19.8 +/- 11.1 following occlusion (p less than 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 +/- 53.6 and fell to 19.9 +/- 29.8 after middle cerebral artery occlusion (p less than 0.01). Steady-state NADH fluorescence rose from 33.5 +/- 10.7 to 40.5 +/- 17.6% full-scale deflection following MCAO (p less than 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 +/- 8.2 to 22.1 +/- 11.9 s (p less than 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.

Animals↗

The effects of etomidate in the cat middle cerebral artery occlusion model of brain ischaemia. An experimental study.

The effects of etomidate on focal cerebral ischaemia following transorbital occlusion of the cat middle cerebral artery were investigated. Etomidate had no effect on CBF before or after onset of ischaemia by comparison with controls, but caused a greater fall in CBF in cats with high preocclusion or initial ischaemic CBF than in those in which CBF was lower. There were more sustained rises in Kp on SG. The established flow threshold for water accumulation was lost; more gyri with CBF above and fewer gyri with CBF below the flow threshold accumulated water. The relationship between mean occlusion CBF and in vitro GABA uptake was lost; uptakes from MG were lower and from SG and EG higher than expected. In the ischaemic penumbra there was a trend towards reduction in CBF, disruption of ion homeostasis and cerebral oedema formation, whilst in areas of lower flow there was some recovery of GABA uptake and less cerebral oedema following administration of etomidate.

Animals↗

Clinical and subclinical nutritional neurological damage in former war prisoners of the Japanese.

Five former war prisoners of the Japanese were clinically evaluated and intensively investigated for evidence of neurological disease. On release from imprisonment 36 years previously they were known to have a single neurological problem each, attributable to nutritional damage to the nervous system (four had optic atrophy and one a peripheral neuropathy). The present assessment confirmed these persisting neurological problems; but in addition two patients were found to have extrapyramidal and one pyramidal disease, one was demented, and two had evidence of non-dominant hemisphere damage on psychometric testing. Nutritional damage to the nervous system may be permanent, and more extensive than usually recognized.

Aged↗

The effects of hyperglycaemia on changes during reperfusion following focal cerebral ischaemia in the cat.

The effects of isosmolar loads of glucose and saline after onset of focal cerebral ischaemia (middle cerebral artery occlusion) were compared in cats. In cats given saline cerebral blood flow (CBF) fell and then rose slightly on the marginal gyrus (infarct penumbra). There was a sustained fall in CBF on the suprasylvian and ectosylvian gyri (infarct core). Reperfusion restored blood flow to preocclusion levels with no overall postischaemic hypoperfusion. Below ischaemic flows of 14 ml/100 g/min brain specific gravity was reduced in a smaller proportion of gyri by contrast with non reperfused cortex, suggesting that in some gyri resolution of cerebral oedema had taken place. GABA uptake was normal in the infarct core, but was reduced within the ischaemic penumbra. In animals given glucose after occlusion, CBF fell on the marginal gyrus during reperfusion. The degree of resolution of cerebral oedema was less than in saline infused cats. GABA uptake showed a pattern of abnormality similar to that seen in saline infused cats, except that uptake values were lower in the infarct core. Pial surface potassium activity remained elevated in the penumbra following reperfusion in glucose infused cats, but returned to normal in saline infused cats. Implications for the management of cerebral ischaemia in man are discussed.

Animals↗

Carotid endarterectomy in patients with transient cerebral ischaemia.

A randomised controlled trial of endarterectomy in patients with carotid artery disease showed that operation significantly reduced the frequency of transient ischaemic attacks (TIA) in the relevant vascular territory. Because of the high post-operative morbidity in the surgical group, the trial was abandoned before conclusions could be drawn as to the influence of endarterectomy on long-term survival or on the incidence of subsequent strokes.

Aged↗

The cortical ischaemic penumbra associated with occlusion of the middle cerebral artery in the cat: 1. Topography of changes in blood flow, potassium ion activity, and EEG.

The gyral topography of the ischaemic penumbra associated with middle cerebral artery occlusion was studied in cats; local blood flow (hydrogen clearance, 2-min initial slope analysis), pial surface potassium activity (Kp), and electroencephalogram (EEG) amplitude were recorded on the ectosylvian, suprasylvian, and marginal gyri. Penumbral conditions were defined as a reduction of EEG amplitude in the absence of a major increase in Kp. Whole hemisphere cerebral blood flow prior to occlusion was 35.6 +/- 11.4 (SD) ml 100 g-1 min-1 (n = 25), and fell significantly (p less than 0.001) to 13.0 +/- 4.7 (SD), 14.1 +/- 6.6, and 23.8 +/- 9.3 on ectosylvian, suprasylvian, and marginal gyri, respectively. Pre-occlusion Kp was 3.0 +/- 0.9 mM (n = 53); sustained, steady-state increases in excess of 11.5 mM occurred in 5 of 7 (71%) experiments on ectosylvian gyrus, in 13 of 22 (59%) experiments on suprasylvian gyrus, and in 2 of 24 experiments on marginal gyrus. Transient increases in Kp occurred at occlusion and resolved to baselines significantly higher than control in 5 (23%) experiments in suprasylvian gyrus and in 15 (63%) on marginal gyrus. In 7 experiments on the marginal gyrus (29%), no increase in Kp greater than 1 mM occurred. In contrast, EEG amplitude on this gyrus was reduced by middle cerebral artery occlusion in 25 of 26 experiments, and it is concluded that this gyrus is the principal site of ischaemic penumbra in the model; in 41% of experiments similar conditions were also present on the suprasylvian gyrus.

Animals↗