J.P. Ranjeva

Profile of memory impairment and gray matter loss in amnestic mild cognitive impairment

The present study assessed the patterns of cortical gray matter (GM) loss in patients with amnestic mild cognitive impairment (aMCI) with distinct profiles of memory impairment, i.e. aMCI patients failing on both recall and recognition memory vs. aMCI patients showing impaired recall but preserved recognition memory. This distinction is usually not taken into account in studies on aMCI and the aim of the present study was to assess whether this distinction is useful. Twenty-eight aMCI patients and 28 matched controls subjects were included. All aMCI patients failed a recall memory task (inclusion criteria). All underwent a visual recognition memory task (DMS48). However, 12 succeeded on this task while 16 failed. Relative gray matter (GM) loss was measured using voxel-based morphometry. When comparing aMCI patients to controls regardless of the profile of memory impairment, GM loss was found in temporal, parietal and frontal areas. However, in aMCI patients with preserved recognition (but impaired recall), GM loss was confined to frontal areas. This contrasted with GM loss in the right medial temporal lobe and bilateral temporo-parietal regions in aMCI patients with impaired recall and recognition memory, a pattern of GM loss usually described in early AD. We conclude that different profiles of memory impairment in aMCI patients are associated with distinct patterns of GM loss.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis. A two-year longitudinal MRI/MRSI study of corpus callosum.

Backgrounds Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. Goal and methods To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. Results Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. Conclusion These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MS : A MRSI study

AbstractProton magnetic resonance spectroscopic imaging (1H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T1 gadolinium-enhancing lesions in patients at the very early stage of multiple sclerosis (MS). The spectroscopic examination was performed in the axial plane using a home-designed acquisition-weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms). Bilateral thalami and the medial occipital cortex were explored in 35 patients (15 with and 20 without T1-Gd enhancing lesions) with clinically isolated syndrome suggestive of MS and in 30 controls. The mean duration since the first presenting symptom was 9.1 (±6.7) months. The two groups of patients (with or without T1 Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T2 lesion load. The spatial contamination of surrounding WM tissues was obtained in each GM region by determining the tissue component in the ROI from GM and WM probability maps smoothed with the point spread function of the MRSI acquisition. Contribution of WM signal was important (60%) inside thalami while the region centered on the medial occipital cortex was well representative of GM metabolism (>70%). Comparisons of relative metabolite levels (ratios of each metabolite over the sum of all metabolites) between all patients and controls showed significant decrease in relative N-acetyl aspartate (NAA) levels, increase in relative choline-containing compounds (Cho) levels and no change in relative creatine/phosphocreatine levels inside the three ROIs. Decrease in relative NAA levels and increase in relative Cho levels were found in patients with inflammatory activity, while no metabolic alterations were present in patients without T1 Gd-enhancing lesions. These results suggest that abnormalities in GM metabolism observed in patients at the very early stage of MS are mainly related to neuronal dysfunction occurring during acute inflammatory processes.

Performance in recognition memory is correlated with entorhinal/perirhinal interictal metabolism in temporal lobe epilepsy

In addition to the hippocampus, the entorhinal/perirhinal cortices are often involved in temporal lobe epilepsy (TLE). It has been proposed that these anterior parahippocampal structures play a key role in recognition memory. We studied the voxel-based PET correlation between number of correctly recognized targets in a new recognition memory paradigm and interictal cerebral metabolic rate for glucose, in 15 patients with TLE with hippocampal sclerosis. In comparison to healthy subjects, patients had decreased recognition of targets (P<0.001) and ipsilateral hypometabolism (relative to side of hippocampal sclerosis) of the hippocampus, entorhinal/perirhinal cortices, medial temporal pole, and middle temporal gyrus (P<0.05, corrected by false discovery rate method). Performance correlated with interictal metabolism of ipsilateral entorhinal/perirhinal cortices (P<0.005, Spearmans rank test), but this relationship was not significant in the hippocampus itself (P>0.18, Spearmans rank test). These findings highlight the preferential involvement of entorhinal/perirhinal cortices in recognition memory in patients with TLE, and suggest that recognition memory paradigms may be useful in assessing anterior parahippocampal functional status in TLE.

A MRS-MRI-fMRI exploration of the brain. Impact of long-lasting persistent vegetative state

Background: The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. However, very little is known about the actual degree of perception in these patients and the extent of progressive brain injury induced by very prolonged unawareness. Methods: The authors have conducted a 2-year longitudinal study using a multimodal MRI-MRSI-fMRI protocol in four patients in long-lasting PVS (over 3 years at inclusion) characterized by various brain injuries. Results: Although one subject showed initially preserved local brain metabolism and brain activity related to primary perception suggesting the presence of potential residual brain plasticity even in this critical stage, none of the four patients recovered to consciousness during the 2 years of the protocol. Moreover, significant deterioration of parameters related to brain atrophy, metabolism and functional excitability of primary cortices was observed in all patients during the follow-up. Conclusions: Heterogeneity of brain injury, consequences of long term minimal brain activity and potential factors that prevent recovery to consciousness are discussed.

Spectroscopie par résonance magnétique cérébrale

Resume Les sequences de spectroscopie par resonance magnetique (SRM) permettent une exploration non invasive du metabolisme cerebral au cours d’un examen IRM. Les ameliorations recentes, en termes de programmation des sequences et de quantification des metabolites, les rendent maintenant facilement utilisables dans un cadre clinique. Pour obtenir un examen informatif et de qualite, certaines regles simples doivent etre respectees dans le choix des sequences et le positionnement des voxels. Il faut distinguer les applications de recherche de la SRM, ou cet examen a principalement pour but de mieux comprendre la physiopathologie d’une maladie et ses indications cliniques, ou cette exploration peut fournir des elements directement utiles a la prise en charge du malade. Ces dernieres sont principalement les tumeurs cerebrales (diagnostic etiologique et differentiel, bilan d’extension et suivi therapeutique), la souffrance cerebrale diffuse, les encephalopathies (hepatique et liee au VIH en particulier) et le diagnostic des maladies metaboliques.

Spectroscopie par résonance magnétique du proton. Quelles indications neurologiques en 2007

Resume La spectroscopie par resonance magnetique (SRM) est un examen neuroradiologique de plus en plus frequemment pratique dans l’exploration des pathologies neurologiques en complement des sequences plus classiques d’IRM. Il importe toutefois de bien differencier ses applications cliniques, pouvant contribuer a la demarche diagnostique ou a l’evaluation pronostique du malade, des indications du domaine de la recherche visant a mieux comprendre la physiopathologie de la maladie ou a evaluer l’efficacite de nouveaux traitements. Les principales indications cliniques de la SRM sont actuellement les processus occupants intracrâniens (en particulier le diagnostic positif d’abces et de gliomatose cerebrale et le diagnostic differentiel œdeme/infiltration tumorale), les encephalopathies alcooliques, hepatiques, et liees au VIH et la caracterisation des maladies metaboliques. Parmi les applications du domaine de la recherche, on peut particulierement retenir la sclerose en plaques, l’ischemie et la souffrance cerebrale, l’epilepsie et les maladies neurodegeneratives.

Applications de la spectrométrie de résonance magnétique (SRM) à l'étude des perturbations métaboliques affectant le cerveau au cours de l'alcoolisme

The purpose of this article is to provide an overview of the current applications of magnetic resonance spectroscopy (MRS) to the investigation of cerebral metabolism in alcoholic patients. The specific metabolic changes associated with the intoxication process (tolerance, dependance), abstinence and alcohol-related diseases (alcoholic encephalopathy, cirrhosis, Gayet-Wernickes encephalopathy, Marchiafava-Bignami syndrome) are described.

Les troubles cognitifs

Cognitive impairment is common in multiple sclerosis (MS), occurring at all stages of the disease, even at the earliest, and can be a major source of disability, social impairment, and impoverished quality of life. Cognitive dysfunction is mainly focused on working memory, conceptual reasoning, verbal fluency, speed of information processing, attention and executive function. Measures of information-processing speed appear to be the most robust and sensitive markers of cognitive impairment in MS patients. Cognitive testing in MS patients is complex and cognitive screening tests are time- and cost-saving test instruments. A comprehensive and sensitive cognitive test procedure should be administered to detect cognitive dysfunction, and recent studies demonstrate that single, predominantly speed-related cognitive tests may be superior to extensive and time-consuming test batteries in screening cognitive decline. Additional clinical factors, including disease course, fatigue, and affective disturbance, can impact the degree of MS-related cognitive impairment. Despite weak correlation with disease duration and physical disability status, the degree of cognitive impairment in MS has been related to the extent of topographically specific neuronal tissue damage and loss. Numerous studies have applied conventional and quantitative magnetic resonance imaging (MRI) techniques to correlate the profile and degree of cognitive impairment with various MRI-detectable abnormalities. The burden of MRI-visible lesions does not fully account for the degree of MS-related cognitive impairment. Nonconventional MRI findings suggest the extent of subtle tissue damage in normal-appearing white and grey matter to correlate best with the severity of cognitive impairment in MS patients. Structural MRI approaches have recently been extended by functional MRI studies scrutinizing the brains ability for adaptive functional reorganization in the presence of widespread tissue damage. Cognitive impairment in MS seems to be not simply the result of tissue destruction, but also a balance between tissue destruction, tissue repair, and adaptive functional reorganization. These findings highlight the need to screen for cognitive deficits in MS patients to conduct potential cognitive rehabilitation intervention.Resume Le dysfonctionnement cognitif est frequent et precoce chez les patients atteints de sclerose en plaques (SEP). L’importance des troubles rencontres est variable selon le domaine cognitif considere mais les perturbations predominent sur la memoire de travail, les capacites attentionnelles, les fonctions executives, le raisonnement abstrait, la perception visuospatiale et la vitesse de traitement de l’information. Le recours a des tests psychometriques standardises, reproductibles et permettant d’obtenir des indicateurs sensibles a l’existence et a l’evolutivite de ces troubles a ete propose, mais ceux-ci apparaissent peu specifiques et particulierement sensibles a l’apprentissage ou effet test re-test. Les supports morphologiques rendant compte de la presence et de la gravite des perturbations cognitives rencontrees dans la SEP restent discutes. Plus que l’importance et la distribution topographique des lesions, il semble que le facteur determinant a l’apparition des troubles cognitifs soit represente par l’atteinte diffuse et precoce de la substance blanche qui pourrait avoir un impact fonctionnel majeur sur la realisation de tâches cognitives complexes sollicitant les grandes voies d’association intra et inter hemispheriques. Une meilleure approche des perturbations cognitives au stade precoce de la maladie pourrait permettre, d’une part d’integrer celles-ci dans l’evaluation du degre de handicap, d’autre part d’envisager des procedures de prise en charge specifiques.

New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study

Objective In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions. Methods EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected). Results At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0–3] at Year 1 to 2.5 [range: 0–6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression. Conclusion The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.