Biomedical subjects

Francine Chassoux

Publications and source records attributed to Francine Chassoux.

5 recordsLinked to original sources

PubMed2005

Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier.

The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculture-based model of human BBB and in vivo with positron emission tomography (PET). The 11 compounds were fluoropyridinyl derivatives labeled with the positron-emitter fluorine-18, [(18)F]F-A-85380 [2-[(18)F]fluoro-3-[2(S)-2 azetidinylmethoxy]pyridine], and 10 selected N-substituted-azetidinyl and pyrrolidinyl closely related [(18)F]fluoropyridinyl derivatives (including [N'-aromatic/aliphatic]-thioureas, -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound. Dynamic PET studies were performed in rats with the same compounds, and a two-compartment model analysis was used to calculate their in vivo permeability coefficients. The 11 derivatives differed in their degree of BBB passage and transport mechanism. The analysis of PET data showed a significant cerebral uptake for six derivatives, for which the in vitro evaluation indicated active influx or free diffusion. Five derivatives displayed low in vivo cerebral uptake, in agreement with the observation of an in vitro active efflux. Overall, there was a remarkable correlation between the in vitro and in vivo permeability coefficients (r = 0.99). This double study proves a close correlationship between the assessment of the BBB passage in vitro and in vivo. The in vitro model of human BBB offers the possibility of subtle discrimination of various BBB permeability degrees and transport mechanisms. Conversely, small animal PET imaging appears suitable to screen directly in vivo brain targeting of drugs or radiopharmaceutical candidates.

Algorithms↗

PubMed2005

Involvement of the basal ganglia in refractory epilepsy: an 18F-fluoro-L-DOPA PET study using 2 methods of analysis.

UNLABELLED: Studies in animal models and epileptic patients have led to the suggestion that the basal ganglia (BG) are involved in seizures. PET with 6-18F-L-3,4-fluorodihydroxyphenylalanine (18F-fluoro-L-DOPA) has recently demonstrated a reduction of striatal dopamine uptake in drug-resistant epileptic patients with ring chromosome 20 (r20) using a multiple-time graphical analysis. The aim of the present study was to evaluate the involvement of dopamine in other epileptic syndromes using a multiple-time graphical analysis and the all-brain statistical parametric mapping (SPM) analysis. METHODS: Patients with drug-resistant epilepsy were divided into 3 groups: group 1, with r20 epilepsy (n = 16; mean age +/- SD, 21.5 +/- 5.4 y); group 2, with resistant generalized "absence-like" epilepsy (n = 10; mean age, 32.3 +/- 11.4 y); and group 3, with drug-resistant temporal lobe epilepsy with hippocampal sclerosis (n = 9; mean age, 35.2 +/- 10.3 y). We compared 2 strategies of analysis of the 18F-fluoro-L-DOPA uptake constant (K(i), min(-1)) in BG using a multiple-time graphical analysis using regions of interest (the gold-standard method) and an SPM analysis using a voxel-by-voxel statistical t test to avoid a priori hypotheses in the analysis. Each epileptic group was compared with a group of healthy volunteers (n = 10; mean age, 45.1 +/- 16.5 y). RESULTS: A decrease of the mean K(i) value was observed in the striatum in all groups of patients with both types of analysis. With multiple-time graphical analysis, the reduction was evident using the averaged K(i) values over both hemispheres in each BG. Unilateral decreases in each BG were detected in SPM analysis. A ratio of decrease of 18F-fluoro-L-DOPA uptake was observed in the 3 groups of patients. Only the SPM analysis showed a decrease of 18F-fluoro-L-DOPA uptake ipsilateral to the seizure side in patients with temporal lobe epilepsy. Moreover, the all-brain SPM analysis showed a decrease of 18F-fluoro-L-DOPA uptake in the substantia nigra bilaterally (P < 0.001). CONCLUSION: This result confirms the involvement of dopamine neurotransmission in seizure control related to the type of epileptic syndrome. The difference in epileptic types may depend in part on the seizure frequency.

Adult↗

PubMed2004

Diffusion tensor imaging of partial intractable epilepsy.

Our aim was to assess the value of diffusion tensor imaging (DTI) in patients with partial intractable epilepsy. We used DTI (25 non-collinear directions) in 15 patients with a cortical lesion on conventional MRI. Fractional anisotropy (FA) was measured in the internal capsule, and in the normal-appearing white matter (WM), adjacent to the lesion, and away from the lesion, at a set distance of 2-3 cm. In each patient, increased or decreased FA measurements were those that varied from mirror values using an arbitrary 10% threshold. Over the whole population, ipsi- and contralateral FA measurements were also compared using a Wilcoxon test (p<0.05). Over the whole population, FA was significantly reduced in the WM adjacent to and away from the lesion, whilst being normal in the internal capsule. FA was reduced by more than 10% in the WM adjacent to and distant from the lesion in 13 and 12 patients respectively. For nine of the ten patients for whom the surgical resection encompassed the limits of the lesion on conventional MRI, histological data showed WM alterations (gliosis, axonal loss, abnormal cells). DTI often reveals WM abnormalities that are undetected on conventional MRI in patients with partial intractable epilepsy.

Adolescent↗

PubMed2003

Metabolic changes and electro-clinical patterns in mesio-temporal lobe epilepsy: a correlative study.

Interictal hypometabolism is commonly found in mesio-temporal lobe epilepsy (MTLE), but its pathophysiology remains incompletely understood. We hypothesized that metabolic changes reflect the preferential networks involved by ictal discharges. We analysed the topography of interictal hypometabolism according to electro-clinical patterns in 50 patients with unilateral hippocampal sclerosis (HS) and consistent features of MTLE. Based on electro-clinical correlations, we identified four groups: (i) mesial group (13 cases) characterized by mesial seizure onset without evidence of early spread beyond the temporal lobe; (ii) anterior mesio-lateral group (AML; 18 cases) with early anterior spread involving the anterior lateral temporal cortex and insulo-fronto-opercular areas; (iii) widespread mesio-lateral group (WML; 15 cases) with wide spread (involving both anterior and posterior lateral temporal and perisylvian areas); and (iv) bitemporal (BT) group (four cases) with early contralateral temporal spread. Results of [18F]fluorodeoxyglucose-PET imaging in each group were compared with those of 10 control subjects using statistical parametric mapping software (SPM99). MRI data and surgical outcome in each group were compared with metabolic findings. Hypometabolism was limited to hippocampal gyrus, temporal pole and insula in the mesial group. Gradual involvement of lateral temporal cortex, insula and perisylvian areas was observed in the AML and WML groups. The BT group differed from the others with mild bitemporal involvement, bilateral insular hypometabolism and longer epilepsy duration. MRI structural abnormalities outside of the mesial formations were detected in 65% of the cases. Neither the severity of HS nor temporal atrophy appeared related to the topography of hypometabolism. However, temporal hypometabolism was more extended when temporo-polar signal changes were detected. Among operated patients (n = 43), seizure-free outcome was obtained in 82%. Surgical outcome appeared more favourable in the mesial group. However, the difference between the four groups was not significant. Our results suggest that hypometabolism in MTLE may be related to ictal discharge generation and spread pathways, even if structural changes and epilepsy duration may also play a role.

Adolescent↗

PubMed2003

Stereo-EEG: the Sainte-Anne experience in focal cortical dysplasias.

Focal cortical dysplasias represent a cause of intractable epilepsy that can be cured by surgery if complete lesional resection can be performed. However, the lesional limits are difficult to assess by imaging, and some focal cortical dysplasias can be missed by magnetic resonance imaging. The combination of high-resolution magnetic resonance imaging and neurophysiological findings provided by direct intra-lesional recordings has greatly improved diagnosis and surgical outcome in focal cortical dysplasias. Stereo-EEG has demonstrated that dysplastic areas show continuous spiking activity persisting after diazepam injection and are the site of ictal discharge onset. Surgery guided by stereo-EEG made seizure-free outcome possible for all patients recently investigated and who had undergone surgery in our centre for extra-temporal partial epilepsy associated with focal cortical dysplasias (10 patients, mean follow-up: 15 months). Moreover, we demonstrated that limited resections can be performed safely in eloquent cortex without permanent disability. These results demonstrate the usefulness of stereo-EEG in surgical treatment for focal cortical dysplasias, despite the invasive nature of this procedure.

Adolescent↗