Ganser-like syndrome after loss of psychic self-activation syndrome: psychogenic or organic?

Very few data are available on the long-term changes in the cognitive abilities of patients with loss of psychic self-activation syndrome (LPSAS). Here, we present a 25-year follow-up study on a case of LPSAS resulting from bilateral pallidal lesions caused by carbon monoxide intoxication. Typical signs of LPSAS were observed, showing no changes in severity, but Ganser syndrome (GS) gradually developed and worsened during the follow-up period. GS is generally assumed to be a psychogenic syndrome, but an organic etiology has been suspected by the authors of several case reports. Here, atypical features of GS plead against the independence of GS and LPSAS. DaTSCAN and brain 18FDG-PET were performed. Since left hippocampal hypometabolism has been previously described in patients with functional amnesia, it is possible that long periods of mental inactivity may have psychological consequences, but the atypical features of GS also suggest that an organic mechanism may be involved.

Intact subliminal processing and delayed conscious access in multiple sclerosis.

Periventricular white matter damage affecting large bundles connecting distant cortical areas may constitute the main neuronal mechanism for the deficit of controlled information processing observed in patients with early multiple sclerosis (MS). Visual backward masking has been demonstrated to affect late stages of conscious perception involving long-range interactions between visual perceptual areas and higher level integrative cortices while leaving intact early feed-forward visual processing and even complex processing such as object recognition or semantic processing. We therefore hypothesized that patients with early MS would have an elevated masking threshold, because of an impairment of conscious perception whereas subliminal processing of masked stimuli would be preserved. Twenty-two patients with early MS and 22 normal controls performed two backward-masking experiments. We used Arabic digits as stimuli and varied quasi-continuously the temporal interval with a subsequent mask, thus allowing us to progressively "unmask" the stimuli. We finely quantified the visibility of the masked stimuli using both objective and subjective measures, thus obtaining accurate estimates of the threshold duration for access to consciousness. We also studied the priming effect caused by the variably masked numbers on a comparison task performed on a subsequently presented and highly visible target number. The threshold for access to consciousness of masked stimuli was elevated in MS patients compared to controls, whereas non-conscious processing of these stimuli, as measured by priming, was preserved. These findings suggest that conscious access to masked stimuli depends on the integrity of large-scale cortical integrative processes, which involve long-distance white matter projections, and are impaired due to diffuse demyelinating injury in patients with early MS.

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

Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T(1) 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 T(1)-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 T(1) Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T(2) 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 T(1) 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.

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.

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.

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.

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.

Haplotype study of West European and North African Unverricht-Lundborg chromosomes: evidence for a few founder mutations.

Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy common in Finland and North Africa, and less common in Western Europe. ULD is mostly caused by expansion of a dodecamer repeat in the cystatin B gene ( CSTB) promoter. We performed a haplotype study of ULD chromosomes (ULDc) with the repeat expansion. We included 48 West European Caucasian (WEC) and 47 North African (NA) ULDc. We analysed eight markers flanking CSTB(GT10-D21S1890-D21S1885-D21S2040-D21S1259- CSTB-D21S1912-PFKL-D21S171) and one intragenic variant in the CSTB 3' UTR (A2575G). We observed a founder effect in most of the NA ULD patients, as 61.7% of the NA ULDc (29/47) shared the same haplotype, A1 (1-1-A-1-6-7), for markers D21S1885-D21S2040-A2575G-D21S1259-D21S1912-PFKL. Moreover, if we considered only the markers D21S1885, D21S2040, A2575G and D21S1259, 43 of the 47 NA ULDc shared the same alleles 1-1-A-1, haplotype A. As previously shown, the WEC ULDc were heterogeneous. However, the Baltic haplotype, A3 (5-1-1-A-1-1), was observed in ten WEC ULDc (20.8%) and the CSTB 3'UTR variant, which we called the Alps variant, was observed in 17 ULDc (35.4%). Finally, as almost all NA patients, like Scandinavian patients, were of the haplotype A, we assumed that there was an ancient common founder effect in NA and Baltic ULD patients. We estimated that the putative most recent common ancestral ULD carrier with this haplotype A must have existed about 2,500 years ago (100-150 generations). Finally, this work provides evidence for the existence of only a small number of founder mutations in ULD.