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Jean-Claude Baron

Publications and source records attributed to Jean-Claude Baron.

At least 19 recordsLinked to original sources
PubMed2006

Intrinsic activated microglia map to the peri-infarct zone in the subacute phase of ischemic stroke.

BACKGROUND AND PURPOSE: Microglial activation is an important component of the neuroinflammatory response to ischemic stroke. Experimental studies have outlined such patterns temporally and spatially. In vivo studies in stroke patients have relied on positron emission tomography and (R)-PK11195, a ligand that binds peripheral benzodiazepine binding sites. In this study we sought to establish temporal and spatial patterns of microglial activation in ischemic stroke with particular emphasis on a defined peri-infarct zone. METHODS: Using this technique, we studied carotid territory ischemic stroke patients in 3 time windows up to 30 days after ictus. Controls were studied in a single session. [11C](R)-PK11195 injection was followed by 3-dimensional acquisition over 60 minutes. Cerebral blood volume (CBV) was measured afterward with the use of standard C15O paradigms. Analysis employed the reference tissue model in which ipsilateral cerebellum was used to generate parametric binding potential maps corrected for CBV. Data were coregistered to T1-based MRI. Using control data to identify 99% confidence limits, a region of interest analysis was applied to identify significant binding in core infarction, contralateral hemisphere, and within a defined peri-infarct zone. RESULTS: Four patients (mean age, 66 years) were imaged across 9 sessions. Four age-matched controls were studied. Within this model, ipsilateral cerebellum was validated as a reference tissue. With the use of control-derived confidence limits and correction for CBV, significant binding potential rises were identified beyond 72 hours and extending to 30 days in core infarction, contralateral hemisphere, and peri-infarct zone. CONCLUSIONS: In ischemic stroke patients, minimal activation of microglia is seen before 72 hours. Beyond this, binding potential rises in core infarction, peri-infarct zone, and contralateral hemisphere to 30 days. This may represent a therapeutic opportunity that extends beyond time windows traditionally reserved for neuroprotection.

Acute Disease↗
PubMed2006

Local relationships between restricted water diffusion and oxygen consumption in the ischemic human brain.

BACKGROUND AND PURPOSE: MR is widely used to depict still ischemic but viable tissue in acute stroke. However, the relationship between the apparent diffusion coefficient (ADC) and energy failure from reduced oxygen supply are unknown in man. METHODS: Acute carotid-territory stroke patients were studied prospectively with both diffusion tensor-imaging and back-to-back steady-state 15O-PET. Substantial numbers of voxels with oxygen extraction fraction >0.70 (ie, significant ongoing hypoxia) were identified in 3 patients (imaged at 7, 16 and 21 hours after stroke onset). In this voxel population, the quantitative relationships between the ADC and cerebral metabolic rate of oxygen (CMRO2), and ADC and cerebral blood flow (CBF), were assessed. RESULTS: The ADC remained essentially unchanged until CBF reached values approximately 20 mls/100g per min, beyond which it declined linearly. In contrast, except when severely reduced, the ADC was a poorer predictor of CMRO2. For both CBF and CMRO2, however, the relationship with ADC became steeper with longer times since onset, ie, the same ADC reflected lower perfusion and CMRO2 with elapsed time. CONCLUSIONS: Despite the small sample and late times from stroke onset, the findings indicate that the degree of restricted water diffusion reliably reflects the severity of oxygen deprivation below the penumbral threshold but is less strongly related to metabolic disruption, which may explain why the ADC does not reliably predict tissue outcome. However, the same degree of diffusion restriction may correspond to greater severity of tissue disruption with elapsing time, which has relevance for stroke therapy. Time elapsed since stroke onset should be taken into account when interpreting ADC declines and in voxel-based infarct prediction models.

Aged, 80 and over↗
PubMed2006

Motor imagery: a backdoor to the motor system after stroke?

BACKGROUND AND PURPOSE: Understanding brain plasticity after stroke is important in developing rehabilitation strategies. Active movement therapies show considerable promise but depend on motor performance, excluding many otherwise eligible patients. Motor imagery is widely used in sport to improve performance, which raises the possibility of applying it both as a rehabilitation method and to access the motor network independently of recovery. Specifically, whether the primary motor cortex (M1), considered a prime target of poststroke rehabilitation, is involved in motor imagery is unresolved. SUMMARY OF REVIEW: We review methodological considerations when applying motor imagery to healthy subjects and in patients with stroke, which may disrupt the motor imagery network. We then review firstly the motor imagery training literature focusing on upper-limb recovery, and secondly the functional imaging literature in healthy subjects and in patients with stroke. CONCLUSIONS: The review highlights the difficulty in addressing cognitive screening and compliance in motor imagery studies, particularly with regards to patients with stroke. Despite this, the literature suggests the encouraging effect of motor imagery training on motor recovery after stroke. Based on the available literature in healthy volunteers, robust activation of the nonprimary motor structures, but only weak and inconsistent activation of M1, occurs during motor imagery. In patients with stroke, the cortical activation patterns are essentially unexplored as is the underlying mechanism of motor imagery training. Provided appropriate methodology is implemented, motor imagery may provide a valuable tool to access the motor network and improve outcome after stroke.

Adult↗
PubMed2006

18FDG PET in vascular dementia: differentiation from Alzheimer's disease using voxel-based multivariate analysis.

The brain metabolic pattern of vascular dementia (VaD) remains poorly characterized. Univariate voxel-based analysis ignores the functional correlations among structures and may lack sensitivity and specificity. Here, we applied a novel voxel-based multivariate technique to a large ((18)F)2-fluoro-2-deoxy-D-glucose positron emission tomography data set. The sample consisted of 153 subjects, one-third each being probable subcortical VaD, probable Alzheimer disease (AD) (matched for Mini-Mental-State examination (MMSE) and age), and normal controls (NCs). We first applied principal component (PC) analysis and removed PCs significantly correlated to age. The remainders were used as feature vectors in a canonical variate analysis to generate canonical variates (CVs), that is, linear combinations of PC-scores. The first two CVs efficiently separated the groups. CV(1) separated VaD from AD with 100% accuracy, whereas CV(2) separated NC from demented subjects with 72% sensitivity and 96% specificity. Images depicting CV(1) and CV(2) showed that lower metabolism differentiating VaD from AD mainly concerned the deep gray nuclei, cerebellum, primary cortices, middle temporal gyrus, and anterior cingulate gyrus, whereas lower metabolism in AD versus VaD concerned mainly the hippocampal region and orbitofrontal, posterior cingulate, and posterior parietal cortices. The hypometabolic pattern common to VaD and AD mainly concerned the posterior parietal, precuneus, posterior cingulate, prefrontal, and anterior hippocampal regions, and linearly correlated with the MMSE. This study shows the potential of voxel-based multivariate methods to highlight independent functional networks in dementing diseases. By maximizing the separation between groups, this method extracted a metabolic pattern that efficiently differentiated VaD and AD.

Aged↗
PubMed2006

Imaging visual recognition memory network by PET in the baboon: perirhinal cortex heterogeneity and plasticity after perirhinal lesion.

We recently mapped the visual recognition memory network in the behaving baboon using a positron emission tomography (PET) activation paradigm with 18F-fluoro-deoxyglucose during a visual delayed matching-to-sample task. This study confirmed the key role of the perirhinal cortex and documented an unexpected left-sided advantage. Specific contribution of each subdivision of the perirhinal cortex has, however, never been investigated. Furthermore, although alteration to the perirhinal cortex has been implicated in several brain disorders, putative plasticity within the entire brain network after perirhinal damage remains largely unknown. To confirm our previous data and to investigate these latter issues, we used our PET activation paradigm on a second healthy baboon before and after 16 months after bilateral excitotoxic lesions of the perirhinal cortex. Activation common to our two healthy baboons occurred only in the left rostroventral perirhinal cortex (i.e., areas 36pm and rostral 36r) and insular cortex. Although histologic analysis disclosed that the perirhinal lesions achieved in the present baboon were essentially caudal to this preoperatively activated area, memory performance was severely impaired. Concomitant with this long-lasting cognitive deficit, changes in the neural network implicated in the task were observed, involving disappearance of the preoperative activations and appearance of a significant activation of the frontal and occipital cortices. However, different activation patterns were found in the first and last eight postoperative months. These findings highlight the functional heterogeneity of the perirhinal cortex and evidence progressive plasticity after perirhinal cortex damage.

Animals↗
PubMed2005

Decomposition of metabolic brain clusters in the frontal variant of frontotemporal dementia.

Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research program the principal brain clusters characterized by a common variability in cerebral metabolism in FTD. Seventy patients with frontal variant (fv) FTD were selected according to international clinical recommendations; principal component analysis (PCA) was performed on FDG-PET metabolic images, looking for covariance clusters in this large population. A first metabolic cluster included most of the lateral and medial prefrontal cortex, bilaterally; PC1 scores correlated with performances on memory and executive neuropsychological tasks. Moreover, FDG-PET images in fv-FTD were further characterized by a metabolic covariance in two clusters comprising the subcallosal medial frontal region, the temporal pole, medial temporal structures and the striatum, separately in the left and in the right hemisphere. The study provides original data-driven arguments for metabolic involvement of separate brain clusters in the rostral limbic system, corresponding to pathological poles differentially affected in each FTD patient.

Adult↗
PubMed2005

Quantification of index tapping regularity after stroke with tri-axial accelerometry.

OBJECTIVE: Quantifying intrinsic components of movement may help to better understand the nature of motor deficits after stroke. Here we quantify the ability of stroke patients to finger tap in rhythm with auditory cues given at physiological rate. METHODS: Using tri-axial accelerometry, we measured tapping regularity (Regularity Index) during auditory-cued index-to-thumb tapping at 1.25 Hz in 20 prospectively selected right-handed chronic stroke patients (mean age 61 yrs) and 20 right-handed healthy subjects (7 young and 13 age matched; mean age 24 and 58 yrs, respectively). With the aim to validate our method, two measures of clinical deficit, the European Stroke Scale (ESS) and the maximum number of index-thumb taps in 15s (IT-Max) were recorded on the same day. RESULTS: There was no effect of age or hand used on the Regularity Index in the control subjects. In patients, the Regularity Index of their affected hand was significantly worse compared to their unaffected hand and to age-matched controls (p<0.05 and p<0.01, respectively). The Regularity Index significantly correlated with the ESS and IT-Max in the clinically expected direction (p=0.025 and 0.001, respectively). CONCLUSION: These data indicate that our method has validity to quantify finger-tapping regularity. After stroke, there is a deficit in the ability to keep pace with auditory cues that correlates, but does not equate, with other indices of motor function. Quantifying tapping regularity may provide novel insights into the mechanisms underlying recovery of finger dexterity after stroke.

Acoustic Stimulation↗
PubMed2005

Stroke attributable to a calcific embolus from the brachiocephalic trunk.

BACKGROUND AND PURPOSE: Calcific brain embolization is a rare event that is usually secondary to cardiac valve calcification. We present a case of stroke caused by embolization of calcific material from the brachiocephalic trunk, probably induced by radiotherapy. SUMMARY OF CASE: A 56-year-old right-handed female developed left-sided hemiparesis, hemihypesthesia, and sensory inattention. She had a history of right breast carcinoma that was excised 8 years previously followed by radiotherapy. She had no other history of note. Computed tomography of the head and magnetic resonance imaging confirmed a calcific embolus in right middle cerebral artery and an acute infarction in the corresponding territory. Plain chest radiography, carotid ultrasonography, transthoracic and transoesophageal echocardiography failed to demonstrate the source of calcific embolism. Computed tomography of the thorax revealed heavy calcification of the brachiocephalic trunk and the origin of the right common carotid artery. CONCLUSIONS: Undertaking a vigilant systematic search for the source in cases of calcific embolization is necessary. The aorta and its main branches are possible, yet unusual, sources of calcific emboli that merit investigation.

Atherosclerosis↗
PubMed2005

Histopathological effects of delayed reperfusion after middle cerebral artery occlusion in the anesthetized baboon.

In patients with middle cerebral artery (MCA) territory stroke, attempts to recanalize the brain are currently being extended beyond the classic 3-h time window. Mechanical thrombectomy is particularly attractive as it may carry lesser risks of severe hemorrhagic transformation than thrombolysis. However, whether late reperfusion per se promotes hemorrhagic transformation and increases infarct volume as compared to permanent occlusion is unclear. There is no study of the histopathologic sequelae of late reperfusion following MCA occlusion (MCAo) in the non-human primate. Five young adult baboons completed a specially designed protocol of 20-h MCAo (under etomidate anaesthesia), followed by 4-week survival and finally perfusion-fixation. Infarct volume was measured histologically using validated stereological methods. The results were compared to our previously published series of 6 h and permanent MCAo performed with identical experimental and post mortem procedures. An infarct was present in each baboon, consistently involving the caudate head, internal capsule and putamen; the adjacent inferior frontal cortex was involved in one subject. Infarct volume was significantly larger than with 6 h MCAo, as expected, but did not differ from permanent MCAo. There was no evidence of hemorrhage around the infarcted area in any animal. We found that following a 20 h ischemic episode, the infarct volume was similar to that found with permanent occlusion, with no evidence of hemorrhagic transformation. Cautiously extrapolating to the human situation, our findings suggest that even late mechanical recanalization may not promote brain damage and could be considered in selected cases.

Anesthesia↗
PubMed2005

Stroke research in the modern era: images versus dogmas.

Recovery of function following ischaemic stroke is a fascinating clinical observation. It comprises several modes, e.g. spectacular recovery in a matter of hours or days and gradual recovery over months or even years. That a non-functioning neural system can regain its function, even partially so, is challenging because of the obvious therapeutic implications. Until the mid-70s, however, dogmas largely prevailed which underpinned the then nihilistic approach to stroke patients. Proving these dogmas wrong has been a major achievement of modern stroke research. Thanks particularly to physiological imaging, key observations from the basic neurosciences have translated into the clinical realm in ways immediately understandable to the clinician, allowing the emergence of pathophysiology-based management.

Cerebral Cortex↗
PubMed2005

The diffusion-weighted lesion in acute stroke: heterogeneous patterns of flow/metabolism uncoupling as assessed by quantitative positron emission tomography.

BACKGROUND: To investigate what the hyperintense lesion in diffusion-weighted imaging (DWI) of acute ischaemic stroke represents metabolically, we prospectively imaged acute carotid-territory stroke patients with DWI along with fully quantitative positron emission tomography (PET), which gives physiological maps of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2) and the oxygen extraction fraction (OEF). METHOD: Of 10 patients who consented, 5 (3 males, 2 females, 53-84 years, NIHSS 6-16) completed the imaging protocol of back-to-back DWI and PET within 21 (mean 15.7, range 7-21) h of stroke onset. All images were co-registered with the DWI lesion forming a region of interest (ROI) that was transferred to the PET parametric maps (OEF, CBF, CMRO2). Patterns of blood flow and metabolism were assessed within the DWI ROI. RESULTS: Within the DWI lesions, the following patterns were observed: very low CBF and CMRO2/variable OEF; low CBF/high OEF, and high CBF/low OEF. There was a heterogeneity of patterns between and within DWI lesions. In addition, areas of hyperperfusion (with low OEF) and areas of hypoperfusion (with high OEF) were seen outside the DWI lesions. CONCLUSION: The DWI lesion does not have a single flow/metabolism counterpart, suggesting that it reflects various stages of the ischaemic process.

Acute Disease↗
PubMed2005

The pathophysiology of watershed infarction in internal carotid artery disease: review of cerebral perfusion studies.

BACKGROUND AND PURPOSE: In carotid disease, infarcts can occur in the cortical as well as internal watershed (WS), or both. Better understanding the pathophysiology of WS infarcts would guide treatment. Two distinct hypotheses, namely low-flow and micro-embolism, are equally supported by neuropathological and physiological studies. Here we review the evidence regarding the mechanisms for WS stroke in carotid disease and whether they differ between cortical and internal WS infarcts. SUMMARY OF REVIEW: After a brief account of the anatomy of the WS and the cerebrovascular physiology in circumstances of low perfusion pressure, the literature concerning the mechanisms of WS infarction in carotid disease is reviewed and discussed with emphasis on imaging and ultrasound studies of the cerebral hemodynamics. CONCLUSIONS: The evidence strongly favors a hemodynamic mechanism for internal WS infarction, especially regarding the so-called rosary-like pattern in the centrum semiovale. However, the relationships between cortical WS infarction and hemodynamic compromise appear more complicated. Thus, although severe hemodynamic compromise appears to underlie combined cortical and internal WS infarction, artery-to-artery embolism may play an important role in isolated cortical WS infarcts. Based on the high prevalence of microembolic signals documented by ultrasound in symptomatic carotid disease, a recent hypothesis postulates that embolism and hypoperfusion play a synergetic role, according to which small embolic material prone to lodge in distal field arterioles would be more likely to result in cortical micro-infarcts when chronic hypoperfusion prevails. Future studies combining imaging of brain perfusion, diffusion-weighted imaging, and ultrasound detection of microembolic signals should help resolve these issues.

Carotid Artery Diseases↗
PubMed2005

Imaging.

Explore the source record for details and available documents.

Animals↗
PubMed2005

Cerebrovascular effects of sodium nitroprusside in the anaesthetized baboon: a positron emission tomographic study.

The effects of sodium nitroprusside (SNP), a potent hypotensive agent, on cerebral blood flow (CBF) have been extensively studied in clinical and experimental situations but the results remain controversial. Whereas its properties would predict a dilatation of cerebral blood vessels, most studies report either no change or a decrease in CBF. The aim of this study was to investigate the effects of SNP on CBF, cerebral blood volume (CBV), and cerebral oxygen metabolism (CMRO2), by means of positron emission tomography in the anaesthetized baboon. Measurements were performed during normotension (mean arterial pressure (MABP): 97+/-16 mm Hg) and repeated following SNP-induced hypotension (MABP: 44+/-9 mm Hg). Sodium nitroprusside led to an increase in CBF and CBV (+30% and +37%, respectively, P<0.05), whereas no change in CMRO2 was noted. Linear regression analysis of CBF values as a function of MABP confirmed that CBF increases when MABP is reduced by SNP. The comparison between these cerebrovascular changes and those found during trimetaphan-induced hypotension in our previously published studies further argues for a direct dilatatory effect of SNP on cerebral blood vessels.

Adjuvants, Anesthesia↗
PubMed2005

FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment.

The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.

Aged↗
PubMed2005

The potential for utilizing the "mirror neurone system" to enhance recovery of the severely affected upper limb early after stroke: a review and hypothesis.

Recovery of upper limb movement control after stroke might be enhanced by repetitive goal-directed functional activities. Providing such activity is challenging in the presence of severe paresis. A possible new approach is based on the discovery of mirror neurons in the monkey cortical area F5, which are active both in observing and executing a movement. Indirect evidence for a comparable human "mirror neurone system" is provided by functional imaging. The primary motor cortex, the premotor cortex, other brain areas, and muscles appropriate for the action being observed are probably activated in healthy volunteers observing another's movement. These findings raise the hypothesis that observation of another's movement might train the movement execution system of stroke patients who have severe paresis to bring them to the point at which they could actively participate in rehabilitation consisting of goal-directed activities. The point of providing an observation therapy would be to facilitate the voluntary production of movement; therefore, the condition of interest would be observation with intent to imitate. However, there is as yet insufficient evidence to enable the testing of this hypothesis in stroke patients. Studies in normal subjects are needed to determine which brain sites are activated in response to observation with intent to imitate. Studies in stroke subjects are needed to determine how activation is affected after damage to different brain areas. The information from such studies should aid identification of those stroke patients who might be most likely to benefit from observation to imitate and therefore guide phase I clinical studies.

Arm↗
PubMed2004

'In the course of time': a PET study of the cerebral substrates of autobiographical amnesia in Alzheimer's disease.

Neuroimaging studies in healthy subjects have yielded controversial results about the neural substrates of autobiographical memory. Moreover, the neural networks responsible for autobiographical amnesia remain poorly understood. Since autobiographical memory is frequently altered in Alzheimer's disease (AD), we used this degenerative disorder as a model and applied a correlative approach between resting cerebral glucose utilization (CMRGlc) and temporally graded memory scores to identify the cerebral structures whose synaptic dysfunction subserves the impairment in autobiographical memory. To this end, we studied a group of 17 AD patients with mild to moderate dementia in whom autobiographical memory was assessed using a specially designed task from three broad time periods [the previous 5 years (period A); middle age (period B); and teenage and childhood (period C)], and measures of resting CMRGlc were obtained with PET. The patients performed less well than a control group for all three time periods and showed the expected temporal gradient, with the most remote period being best preserved (Ribot's gradient). Qualitative analysis showed that remote memories concerned generic (i.e. semantic) rather than specific (i.e. episodic) events. We found a significant positive correlation between autobiographical scores and the metabolism of the right hippocampus (extending to the lingual gyrus), restricted to period A. In addition, period A scores were significantly correlated with the right middle and inferior frontal gyri and the right middle temporal gyrus. Period B scores correlated chiefly with the prefrontal cortex bilaterally (bilateral superior, bilateral middle and right inferior gyri). Metabolic correlations with period C scores were restricted to the left middle frontal gyrus. These findings show striking differences in metabolic correlations with the autobiographical time period, in agreement with prevalent theories of normal functioning of human memory. Thus, in accordance with theories of long-term memory consolidation, we find the expected implication of the hippocampal region in the recall of recent memories, and a disengagement of this structure when the retention interval is beyond 5 years. Moreover, according to the hemispheric encoding/retrieval asymmetry model based on activation studies in healthy subjects, the fact that recent memories preferentially involved the right prefrontal cortex whereas remote memories involved the left prefrontal cortex supports the notion of semanticization of memories with time interval, such that preserved remote memories in AD have a predominantly semantic character.

Aged↗