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Jean Pelletier

Publications and source records attributed to Jean Pelletier.

16 recordsLinked to original sources
PubMed2006

A branched-chain organic acid linked to multiple sclerosis: first identification by NMR spectroscopy of CSF.

(1)H NMR spectroscopy of cerebrospinal fluid (CSF) is currently being used to study metabolic profiles characteristic of distinct multiple sclerosis (MS) manifestations. For select MS patient groups, we have previously detected significantly increased concentrations of several identified metabolites and one unidentified compound. We now present, for the first time, the identification of the latter molecule, beta-hydroxyisobutyrate (BHIB). A combination of dedicated 1D and 2D (1)H NMR experiments was employed for signal assignment. To our knowledge, BHIB has not previously been identified in (1)H NMR spectra of biofluids or biological tissues. Our assignment suggests new biochemical pathways involved in specific MS pathologies.

Acids↗
PubMed2006

[Contribution of nuclear magnetic resonance imaging in multiple sclerosis].

Conventional MRI has become essential in the field of multiple sclerosis (MS). It reveals brain injury in visualising focal lesions of demyelination of the white matter, damage of the blood-brain barrier, and tissue loss within the lesions. These parameters are now used for an early diagnosis and for assessing the efficacy of new therapies. For years, neuroimaging research groups have been developing MRI techniques to get more sensitive and specific parameters of brain injury. Such techniques provide information on the extent of atrophy (volume, brain thickness), the metabolism (MR spectroscopy), the tissue structure (magnetization transfer and diffusion) and the compensation processes (functional MRI) of the brain. They lead to new approaches for analysing the pathophysiological processes at work in MS and their course in time.

Brain↗
PubMed2006

Functional magnetic resonance imaging and cognition at the very early stage of MS.

Dysfunction of high controlled information processing is present in patients with multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is that disruption of communication inside large-scale cortical networks, occurring as a consequence of white matter damage, may constitute the anatomical substrate of cognitive impairment at the very early stage of MS. Disturbance of interregional synchronization might be the main pathogenic factor in controlled information processing deficiency in early MS. Preliminary functional MRI studies (fMRI) have provided important clues to corroborate the connectivity hypotheses. First, brain connectivity assessed by fMRI has brought new data about the influence of diffuse white matter damage on connectivity efficiency inside large-scale networks. These studies have suggested that connectivity disturbances occur inside the working memory network in patients at the very early stage of MS and appear related to the extent of structural white matter damage. Also, fMRI studies have suggested that patients may partially compensate for connectivity impairment by a greater cognitive control. Such a compensatory mechanism could limit the determinant functional impact of diffuse white matter damage on high controlled information processing.

Age of Onset↗
PubMed2006

Structural and functional surrogates of cognitive impairment at the very early stage of multiple sclerosis.

Following our previous reports based on parametric MRI methods (T(2)-weighted MRI, statistical mapping analysis of magnetization transfer ratio images and functional MRI) applied to a population of 18 patients with clinically isolated syndrome suggestive of multiple sclerosis, we have reviewed the possible structural and functional surrogates of MS that could explain the subtle cognitive impairment related to attention and working memory deficits evaluated with paced auditory serial addition test (PASAT). We propose that the brain substrates underlying cognitive impairment observed at the very early stage of MS are multifactorial. Several components could influence PASAT performances in patients: i) the extent of diffuse white matter damage, ii) the location of visible and non visible lesions, iii) the connectivity efficiency between distant brain functional areas involved in working memory processes and iv) the cortical reorganization. Nevertheless, individually, each of these parameters may have few influences on PASAT performance in patients. Using a multiregression model built with independent MR parameters, a very good evaluation of PASAT scores has been obtained in this limited number of patients explaining 90% of the variance. In conclusion, the different aspects of tissue and functional pathological brain underpinnings must be accounted to monitor accurately new therapeutic strategies for the treatment of early cognitive deficits related to MS.

Adult↗
PubMed2006

Assessment of clinical reasoning in the context of uncertainty: the effect of variability within the reference panel.

The Script Concordance Test (SCT) assesses reasoning in the context of uncertainty. Because there is no single correct answer, scoring is based on the comparison of answers provided by examinees with those provided by members of a reference panel made up of experienced practitioners. The study aimed to assess the discriminatory power of the SCT based on the variability of the reference panel's answers. Items from a bank covering different family medicine domains were classified into 3 groups according to the degree of variability of answers provided by a pool of experienced doctors. A variability index (mean squared error) was used to select items in the low, moderate and high variability categories. A 102-item test (Cronbach's alpha 0.70), made up of 3 subtests of each category, was administered to 3 contrasting groups in family medicine: 157 clerkship students, 30 residents and 30 practising doctors. anova and effect size (ES) were used to quantify and test the discrimination power of the 3 subtests. The high variability subtest showed high effect size for discrimination between extreme groups (ES = 1.5; F = 16.3, P < 0.001), whereas the moderate variability subtest showed less effect size (ES = 0.56; F = 57, P = 0.041). The low variability subtest did not discriminate significantly (ES = 0.31; F = 2.9, P = 0.06). Variability of answers within the reference panel is a key component of the discriminatory power of the SCT. In accordance with theory, the presence of variability ensures discrimination between levels of clinical experience. These results imply important considerations for the construction of efficient SCTs.

Analysis of Variance↗
PubMed2005

Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis.

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.

Adult↗
PubMed2005

Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry.

Oligoclonal free light chains (FLC) banding has been described in multiple sclerosis (MS) and should be correlated with disease activity. However, discrepancies between studies have been reported because of differences in methods. A new quantitative, rapid, and automated method using nephelometry is now available. Our objective was to investigate the interest of this method for the diagnosis and prognosis of MS. For this purpose, FLC index was determined in paired samples of CSF and serum from consecutive and unselected patients from the same department of neurology. We enrolled 89 patients (33 MS, 15 "possible MS", and 41 controls) and correlated with IgG index, IgG oligoclonal banding, and clinical MS progression criteria. The main results were (1) FLC kappa index was more sensitive but less specific than IgG index for the diagnosis of MS, (2) two MS patients were negative for oligoclonal banding but exhibited a positive kappa index, (3) no relation between FLC kappa indices, MS clinical criteria, and disease progression was found. In conclusion, FLC kappa index should be considered as a useful complementary test for MS diagnosis. Its pronostic interest remains to be determined on a larger cohort of possible MS patients.

Adolescent↗
PubMed2005

Altered functional connectivity related to white matter changes inside the working memory network at the very early stage of MS.

Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T(2) lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.

Acoustic Stimulation↗
PubMed2005

First isolation of Bacteroides thetaiotaomicron from a patient with a cholesteatoma and experiencing meningitis.

A 45-year-old man with a cholesteatoma experienced purulent meningitis. Microbial analysis of cerebrospinal fluid yielded in pure culture a gram-negative bacillus. Phenotypic methods were suggestive of a Bacteroides distasonis or either a Bacteroides thetaiotaomicron or Bacteroides ovatus infection. The isolate was identified by 16S rRNA gene sequence analysis as B. thetaiotaomicron. This is the first case of B. thetaiotaomicron meningitis in pure culture.

Bacteroides↗
PubMed2005

Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis.

BACKGROUND AND PURPOSE: In the early stage of Multiple Sclerosis (MS), conventional MR imaging parameters such as T2 lesion load fail to explain the clinical status of patients. In the present work, we aimed to determine the ability of magnification transfer imaging to better reflect the relationship between local tissue damage and functional status of MS patients. METHODS: We performed a comparative statistical mapping analysis on brain tissue magnetization transfer ratio (MTR) data measured in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) and 18 matched control subjects. RESULTS: In the patients with CISSMS, a pattern of significant low MTR values was observed in the white matter, corpus callosum, bilateral occipitofrontal fascicles, right fornix, right parietal white matter, external capsule, right superior longitudinal fasciculus (SLF), right inferior longitudinal fasciculus, optica radiata, parietal white matter, right cingulum, gray matter, bilateral thalamus, bilateral caudate, right insula, and left Brodmann area (BA) 8. No correlation was found between local MTR decrease and Expanded Disability Status Scale score. Significant correlations between MTR and MS Functional Composite scores (Spearman rank test, P <.05) were observed in the left BA40, right SLF, right frontal white matter, splenium, and anterior corpus callosum. Local MTR values correlated with Paced Auditory Serial Addition Test scores in the left BA40, right BA4, right SLF, and splenium. CONCLUSION: Statistical mapping analysis of brain MTR data provides valuable information on the relationship between the location of brain tissue damage and its functional impact in patients with MS, even in the earliest stage of the disease.

Activities of Daily Living↗
PubMed2004

Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis.

PURPOSE: To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). MATERIALS AND METHODS: We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. RESULTS: A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. CONCLUSION: These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.

Adult↗
PubMed2003

Changes in the 5-HT2A receptor system in the pre-mammillary hypothalamus of the ewe are related to regulation of LH pulsatile secretion by an endogenous circannual rhythm.

BACKGROUND: We wanted to determine if changes in the expression of serotonin 2A receptor (5HT2A receptor) gene in the premammillary hypothalamus are associated with changes in reproductive neuroendocrine status. Thus, we compared 2 groups of ovariectomized-estradiol-treated ewes that expressed high vs low LH pulsatility in two different paradigms (2 groups per paradigm): (a) refractoriness (low LH secretion) or not (high LH secretion) to short days in pineal-intact Ile-de-France ewes (RSD) and (b) endogenous circannual rhythm (ECR) in free-running pinealectomized Suffolk ewes in the active or inactive stage of their reproductive rhythm. RESULTS: In RSD ewes, density of 5HT2A receptor mRNA (by in situ hybridization) was significantly higher in the high LH group (25.3 +/- 1.4 vs 21.4 +/- 1.5 grains/neuron, P < 0.05) and 3H-Ketanserin binding (a specific radioligand) of the median part of the premammillary hypothalamus tended to be higher in the high group (29.1 +/- 4.0 vs 24.6 +/- 4.2 fmol/mg tissu-equivalent; P < 0.10). In ECR ewes, density of 5HT2A receptor mRNA and 3H-Ketanserin binding were both significantly higher in the high LH group (20.8 +/- 1.6 vs 17.0 +/- 1.5 grains/neuron, P < 0.01, and 19.7 +/- 5.0 vs 7.4 +/- 3.4 fmol/mg tissu-equivalent; P < 0.05, respectively). CONCLUSIONS: We conclude that these higher 5HT2A receptor gene expression and binding activity of 5HT2A receptor in the premammillary hypothalamus are associated with stimulation of LH pulsatility expressed before the development of refractoriness to short days and prior to the decline of reproductive neuroendocrine activity during expression of the endogenous circannual rhythm.

Animals↗
PubMed2003

Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS.

Recent functional magnetic resonance imaging (fMRI) studies have suggested that functional cortical changes seen in patients with early relapsing-remitting multiple sclerosis (MS) can have an adaptive role to limit the clinical impact of tissue injury. To determine whether cortical reorganization occurs during high cognitive processes at the earliest stage of multiple sclerosis (MS), we performed an fMRI experiment using the conventional Paced Auditory Serial Addition Test (PASAT) as paradigm in a population of ten patients with clinically isolated syndrome suggestive of multiple sclerosis (CISSMS). At the time of the fMRI exploration, mean disease duration was 6.8 +/- 3.3 months. We compared these results to those obtained in a group of ten education-, age-, and sex-matched healthy controls. Subjects were explored on a 1.5 T MRI system using single-shot gradient-echo EPI sequence. Performances of the two groups during PASAT recorded inside the MR scanner were not different. Statistical assessment of brain activation was based on the random effect analysis (between-group analysis two-sample t-test P < 0.005 confirmed by individual analyses performed in the surviving regions P < 0.05 Mann Whitney U-test). Compared to controls, patients showed significantly greater activation in the right frontopolar cortex, the bilateral lateral prefrontal cortices, and the right cerebellum. Healthy controls did not show greater activation compared to CISSMS patients. The present study argues in favor of the existence of compensatory cortical activations at the earliest stage of MS mainly located in regions involved in executive processing in patients performing PASAT. It also suggests that fMRI can evidence the active processes of neuroplasticity contributing to mask the clinical cognitive expression of brain pathology at the earliest stage of MS.

Adult↗