Flavia Mattioli

Multiple Sclerosis: Effects of Cognitive Rehabilitation on Structural and Functional MR Imaging Measures—An Explorative Study

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSION 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.

Neuropsychological assessment in multiple sclerosis: a follow-up study with magnetic resonance imaging

SummaryNineteen moderately impaired patients with clinically definite multiple sclerosis and an initially relapsing-remitting course were included in a neuropsychological and magnetic resonance imaging (MRI) follow-up study. The average test/re-test interval was about 2 years. The neuropsychological findings were indicative of a very mild overall impairment; the patients, as a group, showed no evidence of cognitive deterioration in the follow-up period. A numerical estimation of the severity of cerebral demyelination shown by MRI did not indicate a significant change. No correlation between cognitive performance variations and MRI changes was found.

Persistent post-traumatic retrograde amnesia: a neuropsychological and (18F)FDG PET study.

We report the case of a 48-year old woman who, after a severe closed head injury, developed a severe and persistent disruption of retrograde memory, associated with a mild impairment of learning abilities. The patients dense amnesia spared only the childhood period and included both explicit memory (autobiographical and semantic) and procedural skills. Because of her partially spared learning ability and intact language, intensive training by family members resulted in the reacquisition and retention of many autobiographical events and of some skills she had lost after the accident. Brain CT scan and MRI were normal; a PET study with (18F)FDG revealed a significant bilateral reduction of metabolism in the hippocampus and anterior cingulate cortex, suggesting a role for these structures in memory for past events.

Changes of brain resting state functional connectivity predict the persistence of cognitive rehabilitation effects in patients with multiple sclerosis.

Objective: 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. Methods: 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. Results: 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. Discussion: 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.

Neuropsychological rehabilitation in adult multiple sclerosis

Neuropsychological impairment affects 40–65% of multiple sclerosis patients, mainly involving speed in information processing, attention, executive functions and memory. Deterioration occurs over time independently from disability and seems to correlate particularly with magnetic resonance imaging (MRI) atrophy measures. Studies on therapies effective in controlling cognitive impairment are scanty. We found that intensive and specific training of attention, information processing and executive functions is significantly effective in ameliorating both neuropsychological treated functions and in reducing depression. Preliminary functional MRI data suggest that possible neural correlates of this neuropsychological training could be an exercise-induced activation of prefrontal and cingulate cortices.

Prevalence of TAU mutations in an Italian clinical series of familial frontotemporal patients

Frontotemporal dementia (FTD) is a clinical entity grouping different diagnostic conditions. FTD can occur in a sporadic form; however in 30-50% of cases a familial form of FTD has been observed. Mutations in the TAU gene were associated to familial FTD linked to chromosome 17. Our aim was to investigated the proportion of FTD cases attributable to TAU gene mutations in an Italian clinical series. We analyzed 38 patients with FTD; of these, 13 had a positive family history of FTD. All TAU gene exons and flanking intronic regions were sequenced. In our familial FTD sample the estimation of TAU gene mutations accounted for a relative low prevalence (7.6%); based on our results we could argue the existence of other mutations in regulatory regions in the TAU gene or, on the other hand, other genes might be responsible for the most cases of familial FTD.

Confabulation and delusional misidentification: a four year follow-up study.

We describe a patient, AZ, who showed, in addition to an amnesic syndrome which eventually improved, longstanding confabulation and delusional misidentification following bilateral frontal and right temporal post-traumatic lesions. Confabulation appeared in personal recollections and on long-term verbal memory testing. Misidentification concerned mainly his wife and house. During the four year follow-up AZs confabulation progressively shrinked so as to become restricted to verbal memory tasks. By contrast, misidentification persisted. General semantic memory was unimpaired throughout, while performance on frontal tests was initially poor and partly improved in time. We argue that confabulation and misidentification, though often intermingled and occurring after similar lesion pattern, should be considered as different neuropsychological entities.

Early Aphasia Rehabilitation Is Associated With Functional Reactivation of the Left Inferior Frontal Gyrus: A Pilot Study

Background and Purpose— Early poststroke aphasia rehabilitation effects and their functional MRI (fMRI) correlates were investigated in a pilot, controlled longitudinal study. Methods— Twelve patients with mild/moderate aphasia (8 Broca, 3 anomic, and 1 Wernicke) were randomly assigned to daily language rehabilitation for 2 weeks (starting 2.2 [mean] days poststroke) or no rehabilitation. The Aachen Aphasia Test and fMRI recorded during an auditory comprehension task were performed at 3 time intervals: mean 2.2 (T1), 16.2 (T2), and 190 (T3) days poststroke. Results— Groups did not differ in terms of age, education, aphasia severity, lesions volume, baseline fMRI activations, and in task performance during fMRI across examinations. Rehabilitated patients significantly improved in naming and written language tasks (P<0.05) compared with no rehabilitation group both at T2 and T3. Functional activity at T1 was reduced in language-related cortical areas (right and left inferior frontal gyrus and middle temporal gyrus, right inferior parietal lobule and superior temporal gyrus) in patients compared with controls. T2 and T3 follow-ups revealed a cortical activation increase, with significantly greater activation in the left hemisphere areas in rehabilitated patients at T2 and T3, and a time×treatment effect at T2 in the left inferior Broca area after rehabilitation. Left inferior frontal gyrus activation at T2 significantly correlated with naming improvement. Conclusions— Early poststroke aphasia treatment is useful, has durable effects, and may lead to early enhanced recruitment of brain areas, particularly the left inferior frontal gyrus, which persists in the chronic phase.

Frequency and patterns of subclinical cognitive impairment in patients with ANCA-associated small vessel vasculitides.

We investigated the prevalence of disease-related cognitive impairment in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated small vessel vasculitides (SVV). We studied 43 patients with ANCA-associated SVV (Wegeners granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MP)), with no evidence of focal neurological deficits and dementia and in whom other potential causes of cognitive decline were carefully excluded. All patients underwent a detailed neuropsychological evaluation and their performances were compared with those of matched healthy controls. Patients were considered to be affected by subclinical cognitive impairment when they had abnormal results in at least two neuropsychological tests. Magnetic resonance imaging (MRI) scans of the brain were also obtained in 11 patients.The average neuropsychological test scores were not significantly different between the SVV patients and the control subjects. Thirteen patients had abnormal results in two tests (seven patients) or three or more tests (six patients). Most frequently, abnormal tests were the Rey Figure Recall (six cases), the Wisconsin Card Sorting Test (six cases), and the reaction times (eight cases). The frequency and extent of brain MRI abnormalities were higher in impaired than in unimpaired patients. This study demonstrates that 30% of clinically nondemented SVV patients can have a subclinical neuropsychological impairment, characterized by mild abstract reasoning loss, mental speed reduction and nonverbal memory impairment. MRI findings in impaired patients are consistent with the presence of an SVV-mediated subcortical damage of the brain.

Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes

Background: There is limited and inconsistent information on the clinical determinants of cognitive impairment (CI) in multiple sclerosis (MS). Objective: The aim of this study was to compare the prevalence and profile of CI across MS disease subtypes and assess its clinical determinants. Methods: Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop test in consecutive patients with MS referred to six Italian centers. CI was defined as impairment in ⩾ 2 cognitive domains. Results: A total of 1040 patients were included, 167 with clinically isolated syndrome (CIS), 759 with relapsing remitting (RR), 74 with secondary progressive (SP), and 40 with primary progressive (PP) disease course. The overall prevalence of CI was 46.3%; 34.5% in CIS, 44.5% in RR, 79.4% in SP, and 91.3% in PP. The severity of impairment and the number of involved domains were significantly higher in SP and primary progressive multiple sclerosis (PPMS) than in CIS and RR. In multivariable logistic regression analysis, the presence of CI was significantly associated with higher Expanded Disability Status Scale (EDSS) and older age. Conclusion: CI is present in all MS subtypes since the clinical onset and its frequency is increased in the progressive forms, but these differences seem to be more associated with patient age and physical disability than to disease subtype per se.