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Biomedical subjects

D Leys

Publications and source records attributed to D Leys.

At least 37 records · Page 2Linked to original sources

Crystal structure of DMGO provides a prototype for a new tetrahydrofolate-binding fold.

The crystal structure of DMGO (dimethylglycine oxidase) from Arthrobacter globiformis in complex with folate compounds has revealed a novel THF (tetrahydrofolate)-binding fold [Leys, Basran and Scrutton (2003) EMBO J. 22, 4038-4048]. This fold is widespread among folate-binding proteins. The crystal structures of aminomethyltransferase (T-protein), YgfZ and TrmE all reveal similar THF-binding folds despite little similarity in sequence or function. The THF-binding site is highly specific for reduced folate compounds and most members of this fold family enhance the nucleophilic character of the THF N10 position.

Binding Sites↗

Indications for revascularization in patients with internal carotid artery stenosis.

Three different strategies should be associated for ischaemic stroke prevention in patients with internal carotid artery stenosis: vascular risk factors control, anti-thrombotic agents, and carotid revascularization. Patients are selected for carotid revascularization on the basis of the presence of clinical symptoms and degree of stenosis. The optimal indication for carotid surgery is a severe recently symptomatic stenosis, since the benefits are marginal in high-grade asymptomatic stenosis, and in moderate symptomatic stenosis. Angioplasty with endoprothesis is an alternative to surgery, but it must be restricted to symptomatic stenosis either in randomized trials, or in severe stenosis in patients in whom surgery is contra-indicated.

Angioplasty, Balloon↗

Influence of pre-existing dementia on the risk of post-stroke epileptic seizures.

BACKGROUND: Seizures occur in 10% of stroke patients, but their predictors have not been clearly identified. Pre-existing dementia is present in 12-16% of stroke patients and, at the community level, patients with dementia have increased risk of seizures. However, the question of whether pre-existing dementia is associated with a higher risk of seizures after stroke has never been studied. AIM: To evaluate whether pre-existing dementia is associated with an increased risk of seizures after stroke. METHODS: The study was conducted on 202 consecutive stroke patients recruited to the Lille stroke/dementia study (97 men; median age, 75 years; range, 42-100). Pre-stroke cognitive functions were evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly, with a cutoff value of 104 for the diagnosis of dementia. Seizures were defined as early seizures when occurring within seven days of stroke onset, and as late seizures when occurring more than seven days after stroke. RESULTS: Of 202 patients, 33 (16.3%) met the criteria for pre-existing dementia, and 11 (5.4%) developed early seizures. During 289 person-years of follow up, 14 patients developed late seizures, resulting in an incidence rate of 4.8 new cases/100 person-years. Pre-existing dementia was not associated with the occurrence of early seizures, but was independently associated with the occurrence of late seizures (adjusted odds ratio, 4.66; 95% confidence interval, 1.34 to 16.21). CONCLUSION: Stroke patients with pre-existing dementia have an increased risk of late seizures. Any factor increasing the risk of seizures (drugs, metabolic changes) should be avoided in these patients.

Adult↗

[Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events in patients with documented coronary artery disease].

Coronary arteries are the most frequent location of atherosclerosis. Coronary artery disease is the first cause of death related to atherothrombosis. In addition, patients with a prior history of acute coronary syndromes exhibit a 10% annual risk of recurrence. Although there seems to be a close correlation between the extension of CAD and the severity of atherosclerotic lesions in extra coronary arterial beds, the prevalence of these extracoronary asymptomatic lesions depends on their location. Hence, the prevalence of renal artery disease defined as stenosis > or = 50% or of peripheral artery disease defined as an ABI < 0.9 is estimated to be 20% up to 30%, whereas the prevalence of both carotid artery disease defined as stenosis > or = 70% or aortic aneurysm is estimated to be 5%. Conversely, the annual absolute risk of stroke among CAD patients is estimated at 1% while it remains unknown for vascular events related to PAD or aortic lesions. These data suggest that a systematic screening for asymptomatic extracoronary atherosclerotic lesions among CAD patients cannot be justified without a better knowledge of the prevalence of these lesions. In addition, the identification of the predicting factors for the presence and the development of these asymptomatic lesions is warranted. Finally, the potential benefit in terms of therapeutic intervention of such screening needs to be evaluated. These important issues warrant further clinical studies with appropriate design.

Coronary Artery Disease↗

Depressive symptoms after stroke and relationship with dementia: A three-year follow-up study.

OBJECTIVE: To determine frequency, determinants, and time course of poststroke depressive symptoms (DS) and their relationship with dementia. METHODS: Two hundred two consecutive stroke patients were prospectively evaluated for DS, followed up over a 3-year period. Patients with Montgomery and Asberg Depression Rating Scale (MADRS) scores of >/==" BORDER="0">7 were considered as having DS. The severity of the neurologic deficit, functional outcome, and dementia were quantified with the Orgogozo Scale, modified Rankin Scale, Informant Questionnaire on Cognitive Decline in the Elderly, and an extensive battery of neuropsychological tests. RESULTS: DS were present in 43% of survivors after 6 months, 36% after 12 months, 24% after 24 months, and 18% after 36 months. The severity of the neurologic deficit at admission was the only independent predictor of DS at month 6. DS at month 6 were more frequent in patients with previous depression, dementia, and right superficial lesions. Younger age and right superficial lesions were the two variables independently associated with the presence of DS at month 36. The time course of the various DS differed, sadness remaining frequent 3 years after stroke (50%), whereas slowness, psychic slowness, lack of energy, and concentration difficulties remained frequent at month 36 in patients with dementia. CONCLUSION: DS are frequent after stroke. Their time course varies and depends on the cognitive status; this variation contributes to differences among previous studies on poststroke depression.

Adult↗

[Spinal cord ischemia].

Traditional data and recent advances in the field of spinal cord ischemia are reviewed, with special attention to clinical and radiological features, as well as underlying etiology, outcome, and pathophysiology. Acute spinal cord ischemia includes arterial and venous infarction and global ischemia resulting from cardiac arrest or severe hypotension. MRI has become the technique of choice for the imaging diagnosis of spinal cord infarction. Correlation of clinical and MRI data has allowed diagnosis of clinical syndromes due to small infarcts in the central or peripheral arterial territory of the spinal cord. Diffusion-weighted MR imaging may increase the sensitivity and specificity for diagnosis of acute spinal cord infarction. Diagnosis of venous spinal cord infarction remains difficult. As for global ischemia, neuropathological studies demonstrated a great sensitivity of spinal cord to ischemia, with selective vulnerability of lumbosacral neurons. Chronic spinal cord ischemia results in a syndrome of progressive myelopathy. The cause is usually an arteriovenous malformation. Most often, diagnosis may be suspected on MRI, leading to diagnostic, and eventually therapeutic, spinal angiography.

Arteries↗

[Neurologic emergencies].

Neurological symptoms are a very frequent cause of consultation in emergency units and require consultation with neurologists and neuroradiologists. The most frequent diagnoses are stroke syndrome, seizure, headache, confusion, meningitis and meningo-encephalitis, and facial palsy. The morbidity and mortality of neurological emergencies are strongly related to prompt medical management of the patients which often requires neuroimaging studies. The most common neurological emergencies will be reviewed.

Coma↗

Spinal cord infarction: clinical and magnetic resonance imaging findings and short term outcome.

BACKGROUND: Most studies on spinal cord infarction have been conducted in single centres; they usually consisted of case reports, or of larger series of patients recruited over a large period of time, with heterogeneous diagnostic procedures. Therefore, the clinical and radiological presentation of spinal cord infarcts and their short term outcome remain poorly understood. OBJECTIVE: To define clinical and magnetic resonance imaging (MRI) findings, and short term outcome in patients with spinal cord infarcts. METHODS: The authors prospectively included patients within 10 days of onset. An MRI scan was required and repeated when initially normal. RESULTS: Twenty eight consecutive patients were included over a 24 month period in 16 neurological centres. The infarct was cervical in seven patients, thoracic in three, thoracolumbar in 15, and restricted to the conus in three. On axial MRI scans the infarct was located in the central territory of the anterior spinal artery in 21 patients, and in the peripheral arterial territory in three. At month two, 15 patients had a good outcome and 13 had a poor outcome, including three deaths. Patients who, at onset, could not walk, had bladder dysfunction, or proprioceptive deficits were more likely to have a poor outcome. At month two, pain had occurred in 10 of the 25 survivors and was associated neither with the initial severity, nor the extent of the infarct on MRI. CONCLUSION: The two month outcome mainly depends on the initial severity of the neurological deficit; however, a few patients with a severe impairment at onset had a good outcome, especially when proprioception remained normal at onset. The study does not support the hypothesis that pain occurs more frequently in small spinal infarcts.

Adult↗

Impairment of endothelial function in patients with spontaneous cervical artery dissection: evidence for a general arterial wall disease.

BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) accounts for 10-20% of ischemic strokes in young adults. Although trauma and preexisting disorders of the arterial wall are the main predisposing factors, most CADs are considered 'spontaneous'. We hypothesized that CAD could originate in systemic vascular disease bound to the intima-media interface without clinical signs. If this hypothesis is true, endothelium-dependent vasodilation would be impaired in response to a physiological stimulus such as an increase in blood flow. METHODS: Flow-mediated arterial dilation was studied in 65 consecutive patients with spontaneous CAD: 26 with carotid artery dissection (ICAD), and 39 with vertebral artery dissection (VAD). CAD patients with vascular risk factors, trivial or obvious cervical trauma, or connective tissue disease were excluded. Twenty-three patients with ischemic stroke of unknown cause were included as controls. Using high-resolution ultrasonography, brachial artery diameter was measured at rest, during post-ischemic hyperemia (flow-mediated endothelium-dependent dilation), and after sublingual glyceryl trinitrate spray (endothelium-independent dilation). RESULTS: The mean +/- SD values of the flow-mediated vasodilation index were 5.7 +/- 6.2% in ICAD, 5.0 +/- 9.3% in VAD and 13.2 +/- 6.5% in controls (p < 0.0005), without any difference between ICAD and VAD. Endothelium-independent dilation mean values were 21.5 +/- 9.5% in ICAD, 25.1 +/- 12.5% in VAD, and 20.8 +/- 8.4% in controls, without a significant difference between groups (p = 0.49). CONCLUSIONS: These results give evidence of impaired endothelium-dependent vasodilation in CAD patients that is not the result of stroke, and suggest that an underlying abnormality of the arterial wall layers may predispose to CAD.

Adult↗

Angioplasty and stenting for high-grade internal carotid artery stenosis: safety study in 39 selected patients.

BACKGROUND: Carotid angioplasty and stenting (CAS) is sometimes used as an alternative to surgery, despite the lack of evidence for its safety and efficacy. METHOD: Over a 33-month period, 39 consecutive patients with a stenosis >/=70% underwent CAS (4 in a randomized trial and 35 because of contra-indications for surgery). RESULTS: In 5 patients (13%; 95% CI: 3-23), a major complication occurred (3 disabling ischaemic strokes, 1 myocardial infarction, 1 acute interstitial nephropathy). In 7 patients (18%; 95% CI: 6-30), a minor complication occurred (5 transient ischaemic attacks, 1 transient confusional state, 1 non-disabling ischaemic stroke). CONCLUSION: CAS cannot be considered as a routine procedure and should be restricted to high-risk patients unfit for surgery.

Adult↗

Percutaneous transluminal angioplasty of proximal vertebral artery stenosis: long-term clinical follow-up of 16 consecutive patients.

We report long-term (average 30 months) clinical and radiological follow-up of 16 consecutive patients with uni- or bilateral proximal vertebral artery stenosis who underwent percutaneous transluminal angioplasty (PTA), without stenting, between 1995 and 1998. Assessment was performed by an independent neurologist. All patients but one remained asymptomatic during follow-up; moderate restenosis was observed in four. PTA of the proximal vertebral artery is safe but in the absence of knowledge of the natural history of atherosclerotic vertebral artery stenosis, whether it is beneficial or not remains unproven. The decision as to whether to perform this procedure is individual.

Adult↗

Leukoaraiosis more than dementia is a predictor of stroke recurrence.

BACKGROUND AND PURPOSE: It has been suggested that poststroke dementia is associated with a higher risk of stroke recurrence. Leukoaraiosis, however, might be a confounding factor because it is a risk factor for stroke recurrence and cognitive decline. Our aim was to determine the influence of prestroke and poststroke dementia on the 3-year risk of stroke recurrence. METHODS: We evaluated prestroke cognitive functions in 202 stroke patients >or=40 years of age using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), with a cutoff of 104 for the diagnosis of dementia. Patients were followed up for 3 years. Dementia was diagnosed on the basis of International Classification of Diseases, 10th revision, criteria in survivors who underwent a neurologist visit or from the IQCODE score in survivors who did not. The severity of leukoaraiosis was assessed with a visual rating scale on CT scans without contrast performed at the acute stage of stroke. At each follow-up contact, stroke recurrences were recorded. RESULTS: During 385 person-years of follow-up, a total of 29 patients developed 33 stroke recurrences, resulting in an incidence rate of 8.6 per 100 person-years. We did not find any influence of dementia on the risk of stroke recurrence. Leukoaraiosis, however, was a strong predictor of stroke recurrence within 3 years after stroke. CONCLUSIONS: Dementia was not a predictor of stroke recurrence, but leukoaraiosis was strongly associated with stroke recurrence. Special attention in the secondary prevention of stroke must be given to patients with leukoaraiosis with or without dementia.

Adult↗

Cerebral venous thrombosis 3-year clinical outcome in 55 consecutive patients.

An early diagnosis and heparin therapy have contributed to a decreased mortality in cerebral venous thrombosis (CVT). However, predictors of outcome are difficult to identify, because most studies suffered heterogeneity in diagnostic findings and treatments, retrospective design, and recruitment bias. The aim of this study was to evaluate the clinical outcome in 55 consecutive patients with CVT admitted over a 4-year period. The study population consisted of 42 women and 13 men, with a median age of 39 years (range 16-68). The diagnosis was performed with MRI in 53 patients, and angiography in 2. The outcome was assessed with the modified Rankin scale (mRs). After a median follow-up of 36 months (range: 12-60), 45 patients were independent (mRS 0-2), and 10 were dependent or dead (mRS 3-6). Of 48 survivors, 7 had seizures, 6 motor deficits, 5 visual field defects, 29 headache (migraine in 14, tension headache in 13, other in 2). The logistic regression analysis found focal deficits and cancer at time of diagnosis, as independent predictors of dependence or death at year 3, and isolated intra-cranial hypertension as an independent predictor of survival and independence. Mortality rates are low in the absence of cancer and focal deficits, and more than 80 % of survivors are independent after 3 years. However, 3/4 of survivors have residual symptoms. Therefore, despite a low mortality rate, CVT remains a serious disorder.

Adult↗

[Ischemic strokes in young adults].

PURPOSE: The incidence of cerebral ischemia occurring between 15 and 45 years of age is of 60 to 200 new cases per year per million inhabitants. The causes of cerebral ischemia consist of complications of atherosclerosis, cardio embolism, small-vessel occlusion, other determined causes and unknown causes. The breakdown of the causes differ from that of elderly subjects with a prominence of "unknown causes" and "other determined causes". KEY MESSAGE: The association of a patent foramen ovale and an interatrioseptal aneurysm is a marker of an increased risk of recurrence. Cervical-artery dissections are the leading cause of cerebral ischemia in young adults and are usually associated with a good outcome in patients who survive the acute stage. Depending on the exhaustivity of the diagnostic work-up, 30 to 50% of cases have no clear cause. Mortality rate and recurrence rates in cerebral ischemia occurring in young adults are low. A negative diagnostic work-up is associated with a low risk of recurrence. Epilepsy is frequent. The incidence of cerebral ischemia occurring during pregnancies is 4,3 for 100,000 deliveries. Specific causes are led by eclampsia, and reversible angiopathies of the post partum period. FUTURE: If the outcome is good, the causes are multiple and research should focus on the identification of new causes and the natural history in many of them.

Adolescent↗