[Show abstract][Hide abstract] ABSTRACT: Previous studies reported that Multiple Sclerosis (MS) patients treated with natalizumab for one or two years exhibit a significant reduction in relapse rate and in cognitive impairment, but the long term effects on cognitive performance are unknown. This study aimed to evaluate the effects of natalizumab on cognitive impairment in a cohort of 24 consecutive patients with relapsing remitting MS treated for 3 years. The neuropsychological tests, as well as relapse number and EDSS, were assessed at baseline and yearly for three years. The impact on cortical atrophy was also considered in a subgroup of them, and are thus to be considered as preliminary. Results showed a significant reduction in the number of impaired neuropsychological tests after three years, a significant decrease in annualized relapse rate at each time points compared to baseline and a stable EDSS. In the neuropsychological assessment, a significant improvement in memory, attention and executive function test scores was detected. Preliminary MRI data show that, while GM volume did not change at 3 years, a significantly greater parahippocampal and prefrontal gray matter density was noticed, the former correlating with neuropsychological improvement in a memory test. This study showed that therapy with Natalizumab is helpful in improving cognitive performance, and is likely to have a protective role on grey matter, over a three years follow-up.
PLoS ONE 07/2015; 10(7). DOI:10.1371/journal.pone.0131803 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Specific cognitive rehabilitation in multiple sclerosis (MS) resulted to be effective compared to no treatment. So far the possible role of an aspecific psychological intervention on cognition has not been investigated.
Objective: The aim of the SMICT RCT was to compare the efficacy of a specific cognitive training with an aspecific psychological intervention in relapsing-remitting MS patients.
Methods: From a sample of 150 patients, with the same disability and immunomodulatory therapy, submitted to neuropsychological examination, 45 impaired in at least one test were included and 41 randomized to have either a specific cognitive training for the impaired function (22) or to an aspecific psychological intervention (19) for 4 months, starting after baseline examination. Neuropsychological tests and functional scales were administered at baseline and 1 year later.
Results: After 1 year, the mean number of pathological tests was significantly lower in the specific treatment group, compared to the aspecific group. Memory and attention/speeded information processing functions were mostly improved. Depression and quality of life were not different between groups at follow up.
Conclusion: Our study demonstrates that an intensive and domain specific cognitive approach results to be more effective than aspecific psychological intervention in patients with MS.
Frontiers in Neurology 01/2015; 5(278). DOI:10.3389/fneur.2014.00278
[Show abstract][Hide abstract] ABSTRACT: One of the major problems in clinical neuropsychology is to apply ecological, easily administrable and sensitive tests that can help in the diagnosis of executive functions. In the present paper we present normative values for the D-KEFS sorting test (ST), exploring the ability of reasoning, categorization abilities, problem solving, flexibility of thinking and abstraction. We collected normative data in a group of 181 normal Italian subjects aged between 20 and 69 years old, matched for educational level. Multiple regression analysis was performed to evaluate the potential effects of age, sex and education. Age and education had a significant effect on ST performance. Our study provided normative data for the D-KEFS ST for the adult Italian population, corrections of raw scores for relevant demographic factors, and percentile grids for both baseline data and on re-testing after 9 months of follow-up. These normative Italian values support the use of the D-KEFS ST as a valid instrument for initial neuropsychological evaluation and longitudinal analysis of executive functions in clinical practice and for research purposes.
[Show abstract][Hide abstract] ABSTRACT: We investigated the patterns of regional distribution of focal lesions, white matter (WM) and gray matter (GM) atrophy in patients with cortical (cort) MS in comparison to classical (c) MS patients. Nine cort-MS, nine c-MS and nine age-matched healthy controls (HC) underwent a brain MRI exam, including FLAIR and high-resolution T1-weighted scans. MS patients underwent neurological and neuropsychological assessment. Between-group differences of GM and WM volumes and their correlations with neuropsychological performances were assessed with voxel-based morphometry. FLAIR and T1 lesion probability maps (LPMs) were also obtained. Performance at neuropsychological tests was worse in cort-MS than in c-MS patients. Compared to HC, MS patients had a distributed pattern of GM and WM atrophy. No GM/WM area was more atrophic in c-MS vs cort-MS patients. Compared to c-MS, cort-MS patients experienced GM atrophy of frontal-temporal-parietal areas and cingulate cortex and WM atrophy of the cingulum bundle, bilateral cerebral peduncles, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. FLAIR and T1 LPMs did not differ between c-MS vs cort-MS patients. A higher susceptibility to neurodegenerative processes in key brain regions known to be related to cognitive functions is likely to underlie the clinical manifestations of cort-MS.
Journal of Neurology 06/2014; 261(9). DOI:10.1007/s00415-014-7409-5 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Brief Repeatable Battery (BRB) of Neuropsychological Tests is one of the most widely used instruments to assess cognitive functioning in multiple sclerosis patients. However, to date, normative data for the Italian population are available only for the version A, which limits the use of the battery in longitudinal evaluations. We administered the BRB version B to 132 healthy subjects to obtain normative values taking into account the influences of demographic factors on the test scores and calculating corrections for these relevant factors (age, gender and education). Higher age and educational level were associated with better performance on all the tests. The World List Generation was also influenced by gender, since women performed better than men. Moreover, some tests of the version B seem to be easier than those of version A. Our data can improve the applicability of the BRB for both clinical and research purposes in longitudinal assessments.
[Show abstract][Hide abstract] ABSTRACT: We investigated whether the efficacy of 12-week cognitive rehabilitation in MS patients persists six months after treatment termination and, together with resting state (RS) functional connectivity (FC), changes on neuropsychological performance at follow-up.
Eighteen MS patients with cognitive deficits, assigned randomly either to undergo treatment (n=9) or not (n=9), underwent neuropsychological evaluation at baseline (t0), after 12 weeks of rehabilitation (t1) and at six-month follow-up (t2). RS fMRI was obtained at t0 and t1. Changes in neuropsychological performance and their correlations with RS FC modifications were assessed using longitudinal linear models.
At t2 vs. t0, compared with the control group, treated group patients improved in tests of attention, executive function, depression and quality of life (QoL). Neuropsychological scores in these tests at t2 were significantly correlated with RS FC changes in cognitive-related networks and RS FC of the anterior cingulum. RS FC changes in the default mode network predicted cognitive performance and less severe depression, whereas RS FC changes of the executive network predicted better QoL.
Changes in RS FC of cognitive-related networks helps to explain the persistence of the effects of cognitive rehabilitation after several months in relapsing-remitting multiple sclerosis patients and their improvement on depression and QoL scales.
[Show abstract][Hide abstract] ABSTRACT: We describe behavioral and neuropsychological outcome of a patient (N.S.), who showed a bilateral paramedian thalamic ischemic lesion, with particular reference to the longitudinal evolution of topographical disorientation (TD) and confabulations. We report clinical neuropsychological/behavioral data over a 43-month follow-up. The results show early after the stroke a severe amnesic-confabulatory syndrome with dysexecutive deficits, associated with memory disorders both for visuo-spatial and verbal materials and TD both for known and new places. Behavioral disinhibition and anosognosia for cognitive deficits were also observed. All cognitive impairments have been recovered during the long-term follow-up. Bilateral paramedian thalamic infarcts often lead to severe and long-lasting neurological and cognitive impairments. Only a few cases showed good recovery. Our patient represents an interesting and uncommon case of bilateral paramedian thalamic syndrome with a significant neuropsychological recovery.
[Show abstract][Hide abstract] ABSTRACT: Background
Neuropsychological rehabilitation efficacy in multiple sclerosis (MS) is a currently investigated issue. We reported, in a single blind controlled study, that an intensive short duration cognitive training of attention and executive functions significantly improves the treated functions and reduces depression in MS. The persistence of these effects over time are unknown.Objective
To evaluate the persistence over time of neuropsychological improvement due to cognitive training nine months after rehabilitation onset.Methods
This is a single blind randomized controlled study. 24 MS patients were randomly assigned to experimental group (n=13) and received PC assisted neuropsychological treatment for three months, or to control group (n=11), receiving no treatment. Patients were submitted to neuropsychological evaluation, depression and quality of life questionnaires at baseline, three months and nine months later.ResultsNine months follow up compared to baseline evaluation shows a statistically significant improvement (p<0.05) in attention, information processing and executive functions tests (PASAT 3″, COWA/S, WCSTpe), in depression and quality of life questionnaires in rehabilitated patients only. reliable change index (RCI) and modified RCI confirmed the clinical significance of this improvement in rehabilitated patients.Conclusions
Three months intensive neuropsychological rehabilitation of attention, information processing and executive functions induces a long lasting and clinically relevant neuropsychological improvement over time and a persistent depression and quality of life amelioration in patients with RR MS.
Multiple Sclerosis and Related Disorders 10/2012; 1(4):168–173. DOI:10.1016/j.msard.2012.06.004 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate brain changes after cognitive rehabilitation in patients with clinically stable relapsing-remitting (RR) multiple sclerosis (MS) by using neuropsychologic assessment and structural and functional magnetic resonance (MR) imaging techniques.
The study was conducted with approval of the involved institutional review boards. Written informed consent was obtained from each participant. Twenty patients with RR MS and cognitive deficits at baseline were randomly assigned to undergo treatment (n = 10), which entailed computer-assisted cognitive rehabilitation of attention and information processing and executive functions, or to serve as a control subjects (n = 10) without cognitive rehabilitation. All patients underwent a standardized neuropsychologic assessment and MR imaging at baseline and after 12 weeks. Changes in gray matter (GM) volumes on three-dimensional T1-weighted images and changes in normal-appearing white matter (NAWM) architecture on diffusion-weighted images were assessed. Changes in functional activity at functional MR imaging during the Stroop task and at rest were also investigated by using linear models.
As compared with their performance at baseline, the patients in the treatment group improved at tests of attention and information processing and executive functions. Neither structural modifications to GM volume nor modifications to NAWM architecture were detected at follow-up in both groups. Functional MR imaging demonstrated modifications of the activity of the posterior cingulate cortex (PCC)/precuneus and dorsolateral prefrontal cortex (PFC) during the Stroop task, as well as modifications of the activity of the anterior cingulum, PCC and/or precuneus, left dorsolateral PFC, and right inferior parietal lobule at rest in the treatment group compared with the control group. In the treatment group, functional MR imaging changes were correlated with cognitive improvement (P < .0001 to .01).
Rehabilitation of attention and information processing and executive functions in RR MS may be effected through enhanced recruitment of brain networks subserving the trained functions.
[Show abstract][Hide abstract] ABSTRACT: The study evaluates the possible relations between cognitive impairment, persisting anosognosia for hemiplegia and peripersonal neglect. Thirty eight chronic right hemisphere stroke patients were divided in three age- and education-matched groups: A (n = 13) patients with left hemiparesis, peripersonal neglect, and anosognosia for hemiplegia; B (n = 12) patients with left hemiparesis and peripersonal neglect, and C (n = 13) patients with left hemiparesis only. We used MMSE and WAIS Verbal IQ and verbal subtests to assess cognitive impairment in patients, in order to avoid a bias due to visuospatial deficit, which is common in patients with neglect. VIQ, Information, Digit Span and Vocabulary WAIS subtests as well as MMSE were found to be significantly lower in group A versus group B. No difference was found in any test between groups B and C, indicating a general worse cognition in patients compared to those without anosognosia for hemiplegia. Patients with anosognosia for hemiplegia also showed larger brain lesions and, more frequently, frontal, parietal, temporal and basal ganglia involvement, particularly if they had low verbal IQ, indicating a relationship between cognitive impairment, persisting anosognosia for hemiplegia and large right hemisphere lesions.
[Show abstract][Hide abstract] ABSTRACT: The disability, cognitive impairment, fatigue and depression are interacting features in multiple sclerosis (MS), whose relation is still unclear. The objective of this study was to evaluate in a sample of MS patients, the frequency of depressive symptoms, its predicting factors and relation with cognitive impairment, fatigue and disability. 255 consecutive MS patients and 166 healthy subjects were assessed for the presence of depressive symptoms with the Beck Depression Inventory-Fast Screen (BDI-FS). Patients with BDI-FS ≥ 4 were further investigated for the presence of neuropsychological impairment. Depressive symptoms were significantly more frequent and severe in patients than in controls. EDSS score was the only predicting factor of depression (3.5 = threshold EDSS score for depressive symptoms) in patients, whereas neuropsychological impairment was not correlated with BDI-FS and fatigue was found to be significantly correlated with attention, executive function and memory test scores, as well as with BDI-FS score in patients.
[Show abstract][Hide abstract] ABSTRACT: The objective of the study was to assess the natalizumab effect on the course of cognitive impairment in patients with relapsing-remitting multiple sclerosis (MS). Patients with active relapsing-remitting MS (n = 17) were treated with natalizumab for 1 year. The quasi control group included patients (n = 7) with clinically stable MS. Assessment of disease course [expanded disability status scale (EDSS); number of relapses] and neuropsychological impairment [Wisconsin card sorting test (WCST); controlled oral word associations; verbal/non-verbal memory tests; paced auditory serial addition test] was conducted at baseline and after 1 year. Natalizumab-treated patients experienced significantly fewer relapses compared with the previous year (P < 0.05). At 1-year follow-up, EDSS score was unchanged and neuropsychological assessments of memory/executive functions showed a significant improvement in natalizumab-treated patients (all P < 0.05). No changes were observed in the quasi control group. This preliminary study suggests that natalizumab could be effective in ameliorating cognitive functions in patients with active relapsing-remitting MS, over 1-year follow-up.
[Show abstract][Hide abstract] ABSTRACT: To go from one place to another, we routinely generate internal representations of surrounding spaces, which can include egocentric (body-centred) and allocentric (world-centred) coordinates, combined into route and survey representations.Recent studies have shown how both egocentric and allocentric representations exist in parallel and are joined to support behaviour according to the task.Our study investigated the transfer from survey (map-like) to route representations in healthy and brain-damaged subjects. The aim was two-fold: first, to understand how this ability could change with age in a sample of healthy participants, aged from 40 to 71 years old; second, to investigate how it is affected after a brain lesion in a 8 patients' sample, with reference to specific neuropsychological frames.
Participants were first required to perform the paper and pencil version of eight mazes, then to translate the map-like paths into egocentric routes, in order to find the right way into equivalent Virtual Reality (VR) mazes.Patients also underwent a comprehensive neuropsychological evaluation, including a specific investigation of some topographical orientation components.
As regards the healthy sample, we found age-related deterioration in VR task performance. While education level and gender were not found to be related to performance, global cognitive level (Mini Mental State Examination), previous experience with computer and fluidity of navigation into the VR appeared to influence VR task results.Considering the clinical sample, there was a difficulty in performing the VR Maze task; executive functions and visuo-spatial abilities deficits appeared to be more relevant for predicting patients' results.
Our study suggests the importance of developing tools aimed at investigating the survey to route transfer ability in both healthy elderly and clinical samples, since this skill seems high cognitive demanding and sensitive to cognitive decline.Human-computer interaction issues should be considered in employing new technologies, such as VR environments, with elderly subjects and neurological patients.
Journal of NeuroEngineering and Rehabilitation 01/2011; 8(1):6. DOI:10.1186/1743-0003-8-6 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report follow-up data on the efficacy of natalizumab therapy on neuropsychological impairment on an italian MS group of 39 patients at 1 year and of 11 patients at 2 years. Results show a significant reduction in relapse rate, in the number of impaired neuropsychological tests as well as in several single executive function and reasoning tests scores at 1 year. Improvement persisted at 2 years, including also memory and speed processing tasks. These data support the efficacy of natalizumab therapy in all the clinical domains, including cognitive deterioration, in multiple sclerosis patients.