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Biomedical subjects

Julien Bogousslavsky

Publications and source records attributed to Julien Bogousslavsky.

At least 19 recordsLinked to original sources
PubMed2005

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Activities of Daily Living↗
PubMed2004

Anteromedian, central, and posterolateral infarcts of the thalamus: three variant types.

BACKGROUND AND PURPOSE: Thalamic infarcts have traditionally been classified into 4 territories: anterior, paramedian, inferolateral, and posterior. The purpose of this study was to review this classical versus variant distribution in patients with thalamic stroke. METHODS: We reviewed all patients with a first clinical stroke included in the Lausanne Stroke Registry between 1990 and 2002. Among 71 patients with an acute stroke isolated to the thalamus confirmed by MRI, we selected all patients with lesions outside the classical territories and studied their clinical, etiological, and radiological features. RESULTS: A total of 21 patients (30% of all thalamic stroke patients) showed infarction outside the classical territories, allowing us to delineate 3 variant distributions: (1) Anteromedian territory (9 patients [13%]) involving anterior and paramedian territories, with predominantly cognitive impairment, including executive dysfunction, anterograde amnesia, and aphasia in left-sided or bilateral lesions. The most frequent stroke mechanism was cardiac embolism. (2) Central territory (4 patients [6%]), with lesions on the central part of the thalamus, resulting in a variety of neurological and neuropsychological signs, reflecting the involvement of several adjacent structures. Microangiopathy was the most frequent etiology. (3) Posterolateral territory (8 patients [11%]), involving inferolateral and posterior territories, with hemihypesthesia as the most frequent manifestation, followed by hemiataxia, executive dysfunction, and aphasia in left-sided lesions. Artery-to-artery embolism and microangiopathy were the main stroke mechanisms. CONCLUSIONS: We describe 3 variant topographic patterns of thalamic infarction with distinct manifestations and etiologies. We postulate that these infarcts are the result of a variation in thalamic arterial supply or reflect borderzone ischemia.

Adult↗
PubMed2004

Stroke incidence and 30-day case-fatality in a suburb of Tbilisi: results of the first prospective population-based study in Georgia.

BACKGROUND AND PURPOSE: Although stroke is one of the main public health problems worldwide, no study of stroke incidence has been performed in Georgia, and therefore, a population-based registry was established to determine the incidence and case-fatality rates of first-ever stroke. METHODS: We identified all first-ever strokes between November 2000 and July 2003 in a defined population of 51,246 residents in the Sanzona suburb of Tbilisi, the capital of Georgia, using overlapping sources of information and standard diagnostic criteria. RESULTS: A total of 233 first-ever strokes occurred during the study period. The crude annual incidence rate was 165 (95% CI, 145 to 188) per 100,000 residents. The corresponding rate adjusted to the standard "world" population was 103 (95% CI, 89 to 117). In terms of stroke subtype, the crude annual incidence rate per 100,000 inhabitants was 89 (95% CI, 74 to 106) for ischemic stroke, 44 (95% CI, 34 to 57) for intracerebral hemorrhage, 16 (95% CI, 10 to 25) for subarachnoidal hemorrhage, and 16 (95% CI, 10 to 25) for unspecified stroke, and the corresponding case-fatality rates at 1 month were 19.2%, 48.4%, 47.8%, and 69.6%. CONCLUSIONS: The overall stroke incidence rate in an urban population of Georgia is comparable to those reported in developed countries. As for the stroke subtypes, there is an excess of hemorrhagic strokes compared with other registries. Geographical and lifestyle variations may explain these findings, whereas inadequacy of the stroke care system in Georgia might contribute to the high case-fatality.

Adult↗
PubMed2004

Underfunding of stroke research: a Europe-wide problem.

BACKGROUND AND PURPOSE: Previous studies in the United States and the United Kingdom have shown that stroke research is underfunded compared with coronary heart disease (CHD) and cancer research despite the high clinical and financial burden of stroke. We aimed to determine whether underfunding of stroke research is a Europe-wide problem. METHODS: Data for the financial year 2000 to 2001 were collected from 9 different European countries. Information on stroke, CHD, and cancer research funding awarded by disease-specific charities and nondisease-specific charity or government- funded organizations was obtained from annual reports, web sites, and by direct communication with organizations. RESULTS: There was marked and consistent underfunding of stroke research in all the countries studied. Stroke funding as a percentage of the total funding for stroke, CHD, and cancer was uniformly low, ranging from 2% to 11%. Funding for stroke was less than funding for cancer, usually by a factor of > or =10. In every country except Turkey, funding for stroke research was less than that for CHD. CONCLUSIONS: This study confirms that stroke research is grossly underfunded, compared with CHD and cancer, throughout Europe. Similar data have been obtained from the United States suggesting that relative underfunding of stroke research is likely to be a worldwide phenomenon.

Biomedical Research↗
PubMed2004

D-JNKI1, a cell-penetrating c-Jun-N-terminal kinase inhibitor, protects against cell death in severe cerebral ischemia.

BACKGROUND AND PURPOSE: In 2 models of severe ischemic injury, we have evaluated the neuroprotective action of D-JNKI1, a cell-penetrating and protease-resistant peptide selectively inhibiting the c-Jun-N-terminal kinase (JNK). METHODS: Hippocampal slices from newborn rats were subjected to oxygen (5%) and glucose (1 mmol/L) deprivation for 30 minutes. Cell death was evaluated with propidium iodide, and the evoked potential responses were recorded in the CA1 region after stimulation in CA3. Male ICR-CD1 mice were subjected to permanent endoluminal "suture" middle cerebral artery occlusion (MCAo). The lesion size was determined after 24 hours by triphenyl-tetrazolium chloride staining, and neurological scores and rotarod treadmill performance were used to evaluate the neurological outcome. RESULTS: In vitro, D-JNKI administration 6 hours after oxygen glucose deprivation reduced cell death at 24 hours from 21%+/-8% (n=10) to 5%+/-3% (n=7, P<0.01). This protective effect was still seen at 48 hours, paralleled by an improved amplitude of the evoked potential response. In vivo in the mouse, D-JNKI1 administration 3 hours after ischemia significantly reduced the infarct volume from 162+/-27 mm(3) (n=14) to 85+/-27 mm(3) (n=9, P<0.001). The functional outcome was also improved. CONCLUSIONS: JNK inhibition prevents cell death induced by oxygen and glucose deprivation in hippocampal slice cultures in vitro and by permanent suture MCAo in vivo. D-JNKI1 is a powerful neuroprotectant in models of both mild and severe cerebral ischemia, with an extended therapeutic window. Further investigations are needed to identify the relevant JNK target(s) mediating ischemic neuronal death.

Animals↗
PubMed2004

Controlled contrast transcranial Doppler and arterial blood gas analysis to quantify shunt through patent foramen ovale.

BACKGROUND AND PURPOSE: A right-to-left shunt can be identified by contrast transcranial Doppler ultrasonography (c-TCD) at rest and/or after a Valsalva maneuver (VM) or by arterial blood gas (ABG) measurement. We assessed the influence of controlled strain pressures and durations during VM on the right-to-left passage of microbubbles, on which depends the shunt classification by c-TCD, and correlated it with the right-to-left shunt evaluation by ABG measurements in stroke patients with patent foramen ovale (PFO). METHODS: We evaluated 40 stroke patients with transesophageal echocardiography-documented PFO. The microbubbles were recorded with TCD at rest and after 4 different VM conditions with controlled duration and target strain pressures (duration in seconds and pressure in cm H2O, respectively): V5-20, V10-20, V5-40, and V10-40. The ABG analysis was performed after pure oxygen breathing in 34 patients, and the shunt was calculated as percentage of cardiac output. RESULTS: Among all VM conditions, V5-40 and V10-40 yielded the greatest median number of microbubbles (84 and 95, respectively; P<0.01). A significantly larger number of microbubbles were detected in V5-40 than in V5-20 (P<0.001) and in V10-40 than in V10-20 (P<0.01). ABG was not sensitive enough to detect a shunt in 31 patients. CONCLUSIONS: The increase of VM expiratory pressure magnifies the number of microbubbles irrespective of the strain duration. Because the right-to-left shunt classification in PFO is based on the number of microbubbles, a controlled VM pressure is advised for a reproducible shunt assessment. The ABG measurement is not sensitive enough for shunt assessment in stroke patients with PFO.

Adult↗
PubMed2004

Management of atherothrombosis with clopidogrel in high-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH): study design and baseline data.

BACKGROUND: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. METHODS: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. RESULTS: Enrollment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. CONCLUSION: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.

Arteriosclerosis↗
PubMed2004

Charcot and art: from a hobby to science.

Jean-Martin Charcot not only was one of the founders of modern neurology, but he displayed an exceptionally developed visual perception and memory, with special artistic gifts, which he used first as a hobby and subsequently as a tool in his profession. Previously unpublished drawings emphasize Charcot's talents in caricature, including autoderision. One of the best achievements of Charcot in correlating the clinic with art includes his thorough study of artistic representations of "possessed states", which allowed him to refine his work on hysteria. The artist and the scientist are two unique facets of Charcot, whose permanent coexistence help to understand his legacy.

Art↗
PubMed2004

Altered decision-making in multiple sclerosis: a sign of impaired emotional reactivity?

We assessed decision-making capacity and emotional reactivity in 20 patients with multiple sclerosis (MS) and in 16 healthy subjects using the Gambling Task (GT), a model of real-life decision making, and the skin conductance response (SCR). Demographic, neurological, affective, and cognitive parameters were analyzed in MS patients for their effect on decision-making performance. MS patients persisted longer (slope, -3.6%) than the comparison group (slope, -6.4%) in making disadvantageous choices as the GT progressed (p < 0.001), suggesting significant slower learning in MS. Patients with higher Expanded Disability Status Scale scores (EDSS >2.0) showed a different pattern of impairment in the learning process compared with patients with lower functional impairment (EDSS </=2.0). This slower learning was associated with impaired emotional reactivity (anticipatory SCR 3.9 vs 6.1 microSiemens [microS] for patients vs the comparison group, p < 0.0001; post-choice SCR 3.9 vs 6.2 microS, p < 0.0001), but not with executive dysfunction. Impaired emotional dimensions of behavior (assessed using the Dysexecutive Questionnaire, p < 0.002) also correlated with slower learning. Given the considerable consequences that impaired decision making can have on daily life, we suggest that this factor may contribute to handicap and altered quality of life secondary to MS and is dependent on emotional experience. Ann Neurol 2004.

Adult↗