Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study.

BACKGROUND AND PURPOSE: The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction. MATERIALS AND METHODS: Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability. RESULTS: Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability. CONCLUSIONS: Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.

A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis.

BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS) and lacks effective treatment. Cognitive rehabilitation is widely applied in neurorehabilitation settings. Functional magnetic resonance imaging (fMRI) may help in investigating changes in brain activity and provide a tool to assess the efficacy of rehabilitation. AIM: To investigate the effect on brain activity as measured by fMRI of a cognitive rehabilitation programme in patients with MS and cognitive impairment. METHOD: Fifteen patients with MS and cognitive impairment and five healthy subjects were recruited. Neuropsychological assessments were performed in patients with MS at study entry and after rehabilitation to assess cognitive changes. fMRI scans were performed at week -5 (baseline), week 0 (immediately before rehabilitation) and week 5 (immediately after rehabilitation). The fMRI paradigm was the Paced Auditory Serial Addition Test (PASAT). The cognitive rehabilitation programme was composed of 15 computer-aided drill and practice sessions and five non-computer-aided cognitive stimulation group sessions (over 5 weeks). Strict guidelines ensured comparability of all rehabilitation interventions. RESULTS: Patients had increased brain fMRI activity after rehabilitation in several cerebellar areas when compared with healthy subjects. After rehabilitation, patients had significantly improved their performance on the backward version of the Digit Span Test (p = 0.007) and on a composite score of neuropsychological outcomes (p = 0.009). CONCLUSION: The results of the present study indicate that this cognitive rehabilitation programme increases brain activity in the cerebellum of cognitively impaired patients with MS. The role of fMRI in the assessment of neurorehabilitation schemes warrants further investigation.

Brain volumetry counterparts of cognitive impairment in patients with multiple sclerosis.

BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS). Tissue-specific atrophy measures have been shown to correlate with cognitive performance in several studies. Voxel-based morphometry (VBM) aims to identify regional differences in the local composition of brain tissue and makes possible to correlate these findings with cognitive impairment patterns. AIM: To investigate the associations between cognitive impairment in MS and tissue-specific atrophy and regional distribution of grey matter. METHOD: 15 patients with MS and cognitive impairment were included. Demographic (age and years of schooling) and clinical (Multiple Sclerosis Functional Composite-MSFC and subtests, Expanded Disability Status Scale-EDSS, disease duration) variables were recorded and neuropsychological assessments performed (Trail Making Test A and B-TMTA and B, Symbol Digit Modalities Test-SDMT, Digit Span Test-DST and Rey's Auditory Verbal Learning Test Delayed Recall-RAVLT-DR). Magnetic resonance (MR) 3D sequences (MPRAGE) were performed on all subjects and tissue-specific volumes (SIENAx and SPM2 software) and VBM grey matter probability maps (SPM2) were obtained. RESULTS: Moderate correlations were obtained between tissue volumes obtained with SPM2 and SIENAx. Using SIENAx moderate correlations were obtained between normalised brain volume (NBV) and disease duration (rho=-0.575, p=0.025) and RAVLT-DR (rho=0.518, p=0.048). Using SPM2 moderate correlations were obtained between white matter and brain parenchymal fractions (WMF and BPF) and RAVLT-DR (rho=0.572 and 0.539, p=0.026 and 0.038), between grey matter fraction (GMF) and Z scores on the Paced Auditory Serial Addition Test (PASAT) (rho=0.570, p=0.026), and between BPF and disease duration (rho=-0.6, p=0.018). Significant correlations were observed only between regional grey matter probability maps and grey matter (and to a much lesser extent white matter) volumes from SPM2. CONCLUSION: Quantitative tissue-specific atrophy measures may display better correlations with patients' variables than regional grey matter atrophy distribution obtained using VBM methodology. These results should be confirmed in larger samples.

Long-term emotional state of multiple sclerosis patients treated with interferon beta.

OBJECTIVE: To assess the long-term emotional state of multiple sclerosis (MS) patients treated with interferon beta (IFNbeta) for at least four years. METHODS: Patients who had started IFNbeta therapy prior to 2000 with a baseline psychological assessment were identified and scheduled for long-term emotional assessment with the following questionnaires--the Hamilton Depression Rating Scale, the Beck Depression Inventory and the State-Trait Anxiety Inventory. RESULTS: A total of 262 patients started IFNbeta therapy in our MS clinic within the period 1995-1999. Baseline emotional assessment was available from 246 MS patients. Long-term assessment was conducted on 234 patients. After a mean follow-up of 65 months (43-98), 52 patients (22.3%) had withdrawn from IFNbeta therapy. The comparisons, obtained from baseline and follow-up scores, showed an improvement in the depressive and anxiety symptoms of patients who adhered to IFNbeta treatment. Logistic regression analysis indicated that an increase in physical disability and the presence of depressive symptoms at baseline were best predictors for long-term depressive symptoms. CONCLUSIONS: The present results support the absence of emotional worsening in MS patients treated with IFNbeta for a long period of time. Increased disability and the presence of baseline depressive symptoms predicted the presence of depressive symptoms at follow-up.

[Cannabis and alcohol use as prognosis factors in the short-term progress of schizophrenia]. / Consumo de cannabis y alcohol como factores pronósticos en la evolución a corto plazo de la esquizofrenia.

Data from 62 schizophrenic patients (DSM III), aged 18 to 30, who were treated in the public medical system, and showed a relapse in 1987, after an one-year-follow up, were analyzed. It was observed that cannabis and alcohol use increased the probability of a relapse of schizophrenia in the follow-up period, whilst moderate alcohol use (less than 70 cc of pure alcohol/day) had no influence in the probability of relapse.

Cannabis consumption as a prognostic factor in schizophrenia.

Data were analysed from 62 schizophrenic patients between 18 and 30 years of age, treated at the community mental health centres in Navarra, who had relapsed and then completed a one-year follow-up study. Factors influencing the course of illness during follow-up were: continuing cannabis consumption; previous cannabis intake; non-compliance with treatment; and stress.