Alterations of Microstructure and Sodium Homeostasis in Fast Amyotrophic Lateral Sclerosis Progressors: A Brain DTI and Sodium MRI Study.

BACKGROUND AND PURPOSE: While conventional MR imaging has limited value in amyotrophic lateral sclerosis, nonconventional MR imaging has shown alterations of microstructure using diffusion MR imaging and recently sodium homeostasis with sodium MR imaging. We aimed to investigate the topography of brain regions showing combined microstructural and sodium homeostasis alterations in amyotrophic lateral sclerosis subgroups according to their disease-progression rates. MATERIALS AND METHODS: Twenty-nine patients with amyotrophic lateral sclerosis and 24 age-matched healthy controls were recruited. Clinical assessments included disease duration and the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Patients were clinically differentiated into fast (n = 13) and slow (n = 16) progressors according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale progression rate. 3T MR imaging brain protocol included 1H T1-weighted and diffusion sequences and a 23Na density-adapted radial sequence. Quantitative maps of diffusion with fractional anisotropy, mean diffusivity, and total sodium concentration were measured. The topography of diffusion and sodium abnormalities was assessed by voxelwise analyses. RESULTS: Patients with amyotrophic lateral sclerosis showed significantly higher sodium concentrations and lower fractional anisotropy, along with higher sodium concentrations and higher mean diffusivity compared with healthy controls, primarily within the corticospinal tracts, corona radiata, and body and genu of the corpus callosum. Fast progressors showed wider-spread abnormalities mainly in the frontal areas. In slow progressors, only fractional anisotropy measures showed abnormalities compared with healthy controls, localized in focal regions of the corticospinal tracts, the body of corpus callosum, corona radiata, and thalamic radiation. CONCLUSIONS: The present study evidenced widespread combined microstructural and sodium homeostasis brain alterations in fast amyotrophic lateral sclerosis progressors.

Functional connectivity and cognitive changes after donepezil treatment in healthy participants.

RATIONALE: Donepezil is a potent, noncompetitive, reversible, clinically effective acetylcholinesterase inhibitor. The effects of this drug on healthy brains have seldom been investigated. OBJECTIVES: The primary objective of the present study was to identify possible functional connectivity markers of the effect of donepezil in healthy young adult volunteers. METHODS: The study had a double-blind, randomized, crossover design. 30 healthy adult volunteers underwent resting-state MRI scans during 15 days of donepezil or placebo treatment, in accordance with the design. RESULTS: Results showed significant differences in intrinsic functional connectivity between donepezil and placebo, mainly in the right executive control network (RECN). More specifically, we found a decrease in the connectivity of the right inferior parietal node with other RECN nodes. Analysis using the cingulate cortex and parahippocampal regions as seeds also revealed complex modulation of functional connectivity in the donepezil condition. CONCLUSIONS: In conclusion, donepezil treatment for 15 days may result in reorganization of resting-state networks, compared with placebo.

Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The inhomogeneous magnetization transfer technique has demonstrated high specificity for myelin, and has shown sensitivity to multiple sclerosis-related impairment in brain tissue. Our aim was to investigate its sensitivity to spinal cord impairment in MS relative to more established MR imaging techniques (volumetry, magnetization transfer, DTI). MATERIALS AND METHODS: Anatomic images covering the cervical spinal cord from the C1 to C6 levels and DTI, magnetization transfer/inhomogeneous magnetization transfer images at the C2/C5 levels were acquired in 19 patients with MS and 19 paired healthy controls. Anatomic images were segmented in spinal cord GM and WM, both manually and using the AMU40 atlases. MS lesions were manually delineated. MR metrics were analyzed within normal-appearing and lesion regions in anterolateral and posterolateral WM and compared using Wilcoxon rank tests and z scores. Correlations between MR metrics and clinical scores in patients with MS were evaluated using the Spearman rank correlation. RESULTS: AMU40-based C1-to-C6 GM/WM automatic segmentations in patients with MS were evaluated relative to manual delineation. Mean Dice coefficients were 0.75/0.89, respectively. All MR metrics (WM/GM cross-sectional areas, normal-appearing and lesion diffusivities, and magnetization transfer/inhomogeneous magnetization transfer ratios) were observed altered in patients compared with controls (P < .05). Additionally, the absolute inhomogeneous magnetization transfer ratio z scores were significantly higher than those of the other MR metrics (P < .0001), suggesting a higher inhomogeneous magnetization transfer sensitivity toward spinal cord impairment in MS. Significant correlations with the Expanded Disability Status Scale (ρ = -0.73/P = .02, ρ = -0.81/P = .004) and the total Medical Research Council scale (ρ = 0.80/P = .009, ρ = -0.74/P = .02) were observed for inhomogeneous magnetization transfer and magnetization transfer ratio z scores, respectively, in normal-appearing WM regions, while weaker and nonsignificant correlations were obtained for DTI metrics. CONCLUSIONS: With inhomogeneous magnetization transfer being highly sensitive to spinal cord damage in MS compared with conventional magnetization transfer and DTI, it could generate great clinical interest for longitudinal follow-up and potential remyelinating clinical trials. In line with other advanced myelin techniques with which it could be compared, it opens perspectives for multicentric investigations.

Malformations of cortical development: The role of 7-Tesla magnetic resonance imaging in diagnosis.

Comparison studies between 7T and 1.5 or 3T magnetic resonance imaging (MRI) have demonstrated the added value of ultra-high field (UHF) MRI to better identify, delineate and characterize malformations of cortical development (MCD), and to disambiguate doubtful findings observed at lower field strengths. High resolution structural sequences such as magnetization prepared two rapid acquisition gradient echoes (MP2RAGE), fluid and white matter suppression MP2RAGE (FLAWS), and susceptibility-weighted imaging (SWI) appear to be key to the improvement of MCD diagnosis in clinical practice. 7T MRI offers not only images of high resolution and contrast but also provides many quantitative approaches capable of acting as more efficient probes of microstructure and ameliorating the categorization of MCDs. Post-processing of multiparametric ultra-high resolution and quantitative data may also be used to improve automated detection of MCD via machine learning. Therefore, 7T MRI can be considered as a useful tool in the presurgical evaluation of drug-resistant partial epilepsies, particularly, but not exclusively, in cases of normal appearing conventional MRI. It also opens many perspectives in the fields of in vivo histology and computational anatomy.

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated. RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.

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.

Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a 'European ADNI study'.

BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid ß peptide 1-42 (Aß42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aß42 in the cerebrospinal fluid (Aß positive). Compared to the aMCI group with high Aß42 levels (Aß negative), Aß positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.

Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study.

INTRODUCTION: Progressive atrophy occurs in brain regions involved in the working memory network along the schizophrenia's course, but without parallel evolution of working memory impairment. We investigated the functional organization inside this network at different stages of the disease. METHODS: Twenty-eight patients with schizophrenia (16 with long disease duration (>60 months) and 12 with short disease duration (<60 months)) and eleven healthy controls underwent structural and functional MRI during an n-back task to determine atrophy and activation patterns. RESULTS: At similar n-back performances and relative to short disease duration patients, long disease duration patients activated more frontal temporal parietal and frontal network during 0-back and 1-back tasks respectively. n-back scores were correlated to atrophy in the frontal-temporal areas. DISCUSSION: Functional reorganization in the working memory network may play a compensatory role during the first ten years of schizophrenia.

Sodium imaging as a marker of tissue injury in patients with multiple sclerosis.

Recent studies have suggested that intra-axonal sodium accumulation contribute to axonal degeneration in patients with MS. Advances in MRI hardware and software allow acquisition of brain sodium signal in vivo. This review begins with a summary of the experimental evidence for impairment of sodium homeostasis in MS. Then, MRI methods for sodium acquisition are reviewed and the application of the techniques in patients with MS is discussed. Sodium imaging and ultra-high field MRI have the potential to provide tissue-specific markers of neurodegeneration in MS.

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, Spearman's rank test), but this relationship was not significant in the hippocampus itself (P>0.18, Spearman's 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.

Combined diffusion imaging and MR spectroscopy in the diagnosis of human prion diseases.

BACKGROUND AND PURPOSE: The physiopathologic bases underlying the signal intensity changes and reduced diffusibility observed in prion diseases (TSEs) are still poorly understood. We evaluated the interest of MRS combined with DWI both as a diagnostic tool and a way to understand the mechanism underlying signal intensity and ADC changes in this setting. MATERIALS AND METHODS: We designed a prospective study of multimodal MR imaging in patients with suspected TSEs. Forty-five patients with a suspicion of TSE and 11 age-matched healthy volunteers were included. The MR imaging protocol included T1, FLAIR, and DWI sequences. MRS was performed on the cerebellum, pulvinar, right lenticular nucleus, and frontal cortex. MR images were assessed visually, and ADC values were calculated. RESULTS: Among the 45 suspected cases, 31 fulfilled the criteria for probable or definite TSEs (19 sCJDs, 3 iCJDs, 2 vCJDs, and 7 genetic TSEs); and 14 were classified as AltDs. High signals in the cortex and/or basal ganglia were observed in 26/31 patients with TSEs on FLAIR and 29/31 patients on DWI. In the basal ganglia, high DWI signals corresponded to a decreased ADC. Metabolic alterations, increased mIns, and decreased NAA were observed in all patients with TSEs. ADC values and metabolic changes were not correlated; this finding suggests that neuronal stress (vacuolization), neuronal loss, and astrogliosis do not alone explain the decrease of ADC. CONCLUSIONS: MRS combined with other MR imaging is of interest in the diagnosis of TSE and provides useful information for understanding physiopathologic processes underlying prion diseases.

[Cognitive impairment]. / 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 brain's 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.

Efficiency of cognitive control recruitment in the very early stage of multiple sclerosis: a one-year fMRI follow-up study.

Functional magnetic resonance imaging (FMRI) studies have established that patients with multiple sclerosis show stronger activation in the lateral prefrontal cortices (LPFC) than healthy control subjects during effortful cognitive tasks. The aim of the present study was to assess the impact of these activation changes on cognitive performances. In addition to 19 controls, who were tested at a single time-point to define a standard pattern of fMRI activation during the performance of the Paced Auditory Serial Addition Task (PASAT), 13 patients with clinically isolated syndrome underwent a longitudinal fMRI examination while performing the PASAT at the beginning of the study (M0) and one year later (M12). Relative to the M0 scores, PASAT performances improved in eight patients (group A) and either decreased (n = 4) or remained unchanged (n = 1) (group B) in five patients at M12. Random effect analyses (SPM2; Wellcome Institute, London, England) were performed to compare intra-group time-related effects on brain activation (paired t-test between M0 and M12), and inter-group differences were also compared between the two groups of patients (analysis of covariance with PASAT performances as the covariate). Relative to group B, group A showed larger increase in activation between M0 and M12 in the right LPFC. In the whole group of patients, interaction analyses showed that the differences in the PASAT scores between M0 and M12 were correlated with the differences in activation observed in the right LPFC. This longitudinal study shows that in patients with early multiple sclerosis, the increased levels of activation in the right LPFC was associated with improved individual working memory and processing speed performances.

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.

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.

[Future of non conventional MR techniques in MS]. / Qu'attendre des nouvelles techniques IRM dans l'étude de la sclérose en plaques.

Although conventional magnetic resonance imaging (MRI) is used for diagnosing multiple sclerosis (MS) and monitoring disease activity and course, the correlation between conventional MRI data and clinical findings remains weak. This "clinical-MRI paradox" could be partly due to the lack of MRI specificity related to the heterogeneous pathological substrates of MS and to its inability to quantify the extent of damage in the normal-appearing tissue. Recently, non-conventional MRI techniques, including magnetization transfer MRI, diffusion tensor MRI, and proton MR spectroscopy have been applied to improve our understanding of the pathophysiology of MS. These techniques may provide information about structural and biochemical changes occurring within and outside macroscopic MS lesions (inflammation, demyelination, axonal loss), in particular in the normal-appearing white and grey matter. These techniques could also significantly improve our ability to monitor inflammatory demyelination and axonal injury. In the same way, functional MRI gives us the potential substrate to assess the mechanisms of adaptive cortical reorganization, which may limit the irreversible consequences of MS tissue injury.

[Indications for cerebral MR proton spectroscopy in 2007]. / Spectroscopie par résonance magnétique du proton. Quelles indications neurologiques en 2007?

Magnetic resonance spectroscopy (MRS) is being increasingly performed alongside the more conventional MRI sequences in the exploration of neurological disorders. It is however important to clearly differentiate its clinical applications aiming at improving the differential diagnosis or the prognostic evaluation of the patient, from the research protocols, when MRS can contribute to a better understanding of the pathophysiology of the disease or to the evaluation of new treatments. The most important applications in clinical practice are intracranial space occupying lesions (especially the positive diagnosis of intracranial abscesses and gliomatosis cerebri and the differential diagnosis between edema and tumor infiltration), alcoholic, hepatic, and HIV-related encephalopathies and the exploration of metabolic diseases. Among the research applications, MRS is widely used in multiple sclerosis, ischemia and brain injury, epilepsy and neuro degenerative diseases.

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.

BACKGROUND: 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.