Mauro Catalan

I nterferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy

Background Brain atrophy, as assessed by magnetic resonance imaging (MRI), has been correlated with disability in patients with multiple sclerosis (MS). Recent evidence indicates that both white matter (WM) and gray matter (GM) are subject to atrophy in patients with MS. Although neurological deficiencies in MS are primarily due to loss of WM, the clinical significance of GM atrophy has not been fully explored in MS. Methods We have undertaken a three-year, open-label study, comparing 26 patients who elected to receive intramuscular interferon beta-1a (IFN β-1a) therapy, with 28 patients who elected not to receive therapy. Both groups had quantitative cranial MRI scans at study entry and after three years, and standardized clinical assessments every six months. Brain parenchymal fraction (BPF), GM fraction (GMF), and WM fraction (WMF) percent changes were calculated, and T2- and T1-lesion volumes (LVs) assessed. Results After three years, mean percent (%) change in BPF favored the IFN β-1a treatment group (IFN β-1a —1.3% versus the control group —2.5%, P=0.009), as did the mean percent change in GMF (+0.2 versus —1.4%, P=0.014), and the mean percent change in T1-LV (—9.3 versus +91.6%, P=0.011). At the end of the study, there was a significant within-patient decrease in BPF for both groups (P=0.02 for the IFN β-1a treatment group, and P<0.001 for the control group), a significant within-patient decrease in WMF for the IFN β-1a treatment group (P=0.01), and a significant decrease in GMF for the control group (P=0.013) when compared with baseline. Conclusion Over a three-year period, treatment with IFN β-1a significantly slowed the progression of whole-brain and GM atrophy, and of T1-hypointense LV accumulation, when compared with the control group. Multiple Sclerosis 2007; 13: 490-501. http://msj.sagepub.com

Short-term brain atrophy changes in relapsing–remitting multiple sclerosis

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.

Treatment of Fatigue in Multiple Sclerosis Patients: A Neurocognitive Approach

The objective of the study was to treat fatigue in patients with multiple sclerosis (MS) by a neurocognitive rehabilitation program aimed at improving motor planning by using motor imagery (MI). Twenty patients with clinically definite MS complaining of fatigue were treated for five weeks with exercises of neurocognitive rehabilitation twice a week. Patients were evaluated by Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MSQoL54, Expanded Disability Status Scale (EDSS), and MS Functional Composite (MSFC). After treatment, a decrease in fatigue was detected with both FSS (P = 0.0001) and MFIS (P = 0.0001). MSFC (P = 0.035) and MSQoL54 (P = 0.002) scores improved compared to baseline. At six-month followup, the improvement was confirmed for fatigue (FSS, P = 0.0001; MFIS P = 0.01) and for the physical subscale of MSQoL54 (P = 0.049). No differences in disability scales were found. These results show that neurocognitive rehabilitation, based on MI, could be a strategy to treat fatigue in MS patients.

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue

PurposeThis study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue.Materials and methodsWe enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05).ResultsCompared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex.ConclusionsPatients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.RiassuntoObiettivoScopo del nostro lavoro è stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.Materiali e metodiSono stati arruolati 24 pazienti destrimani con SM recidivante-remittente (12 senza e 12 con fatica) e 15 volontari sani. L’indagine in risonanza magnetica (RM) (1,5 T) è stata eseguita in tutti i soggetti mediante sequenze convenzionali ed echo-planar imaging (EPI) per lo studio funzionale. Il compito motorio consisteva nel finger tapping sequenziale con la mano dominante. Sono state ottenute mappe statistiche di attivazione motoria. Il confronto fra i gruppi è stato condotto mediante analisi della varianza (ANOVA) (p<0,05).RisultatiRispetto ai controlli, nel gruppo di pazienti senza fatica è stato osservato un incremento dell’attivazione a livello delle aree sensitivo-motorie primarie, motoria supplementare di destra e premotoria di sinistra. è stata inoltre rilevata una maggiore attivazione a livello del cervelletto, controlateralmente al movimento, e a livello del lobulo parietale superiore bilateralmente. Dal confronto tra i due gruppi di pazienti, nei pazienti con fatica è emersa, a destra, una maggior attivazione a livello dell’area premotoria, del putamen e della corteccia prefrontale dorsolaterale.ConclusioniIn pazienti affetti da SM, l’insorgenza del sintomo fatica è accompagnato da una maggior attivazione del circuito motorio-attentivo omolaterale al movimento.Obiettivo Scopo del nostro lavoro e stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.

RM-f durante un compito motorio in pazienti con sclerosi multipla e fatica

PurposeThis study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue.Materials and methodsWe enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05).ResultsCompared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex.ConclusionsPatients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.RiassuntoObiettivoScopo del nostro lavoro è stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.Materiali e metodiSono stati arruolati 24 pazienti destrimani con SM recidivante-remittente (12 senza e 12 con fatica) e 15 volontari sani. L’indagine in risonanza magnetica (RM) (1,5 T) è stata eseguita in tutti i soggetti mediante sequenze convenzionali ed echo-planar imaging (EPI) per lo studio funzionale. Il compito motorio consisteva nel finger tapping sequenziale con la mano dominante. Sono state ottenute mappe statistiche di attivazione motoria. Il confronto fra i gruppi è stato condotto mediante analisi della varianza (ANOVA) (p<0,05).RisultatiRispetto ai controlli, nel gruppo di pazienti senza fatica è stato osservato un incremento dell’attivazione a livello delle aree sensitivo-motorie primarie, motoria supplementare di destra e premotoria di sinistra. è stata inoltre rilevata una maggiore attivazione a livello del cervelletto, controlateralmente al movimento, e a livello del lobulo parietale superiore bilateralmente. Dal confronto tra i due gruppi di pazienti, nei pazienti con fatica è emersa, a destra, una maggior attivazione a livello dell’area premotoria, del putamen e della corteccia prefrontale dorsolaterale.ConclusioniIn pazienti affetti da SM, l’insorgenza del sintomo fatica è accompagnato da una maggior attivazione del circuito motorio-attentivo omolaterale al movimento.Obiettivo Scopo del nostro lavoro e stato valutare l’attivazione corticale durante un compito motorio in pazienti con sclerosi multipla (SM) e fatica.

Action Observation Plus Sonification. A Novel Therapeutic Protocol for Parkinson’s Patient with Freezing of Gait

Freezing of gait (FoG) is a disabling symptom associated with falls, with little or no responsiveness to pharmacological treatment. Current protocols used for rehabilitation are based on the use of external sensory cues. However, cued strategies might generate an important dependence on the environment. Teaching motor strategies without cues [i.e., action observation (AO) plus Sonification] could represent an alternative/innovative approach to rehabilitation that matters most on appropriate allocation of attention and lightening cognitive load. We aimed to test the effects of a novel experimental protocol to treat patients with Parkinson’s disease (PD) and FoG, using functional, and clinical scales. The experimental protocol was based on AO plus Sonification. 12 patients were treated with 8 motor gestures. They watched eight videos showing an actor performing the same eight gestures, and then tried to repeat each gesture. Each video was composed by images and sounds of the gestures. By means of the Sonification technique, the sounds of gestures were obtained by transforming kinematic data (velocity) recorded during gesture execution, into pitch variations. The same 8 motor gestures were also used in a second group of 10 patients; which were treated with a standard protocol based on a common sensory stimulation method. All patients were tested with functional and clinical scales before, after, at 1 month, and 3 months after the treatment. Data showed that the experimental protocol have positive effects on functional and clinical tests. In comparison with the baseline evaluations, significant performance improvements were seen in the NFOG questionnaire, and the UPDRS (parts II and III). Importantly, all these improvements were consistently observed at the end, 1 month, and 3 months after treatment. No improvement effects were found in the group of patients treated with the standard protocol. These data suggest that a multisensory approach based on AO plus Sonification, with the two stimuli semantically related, could help PD patients with FoG to relearn gait movements, to reduce freezing episodes, and that these effects could be prolonged over time.