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 Ϯ 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 Ͻ 0.005 confirmed by individual analyses performed in the surviving regions P Ͻ 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. Hum. Brain

The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

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.