Articoli e pubblicazioni


Brain Imaging Behav. 2012 May 15.

Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis.

Nocentini U, Bozzali M, Spanò B, Cercignani M, Serra L, Basile B, Mannu R, Caltagirone C, De Luca J.


Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, Rome, Italy.


Cognitive impairment may result in significant disability in patients with Multiple Sclerosis (MS). Previous Magnetic Resonance Imaging (MRI) studies on cognition in MS were mainly based on measures of gross brain involvement. This study, using voxel-based morphometry (VBM), aims to investigate associations between the regional distribution of grey matter (GM) damage and cognitive performance in patients with MS. Eighteen MS patients underwent an extensive neuropsychological battery and MRI, including T2-weighted scans and T1-weighted volumes. A group of 18 healthy individuals were also investigated by MRI and served as controls for the VBM. A cross-sectional analysis was first performed, to assess the pattern of regional GM atrophy in MS patients. Then, the impact of regional GM damage on patients’ neuropsychological performance was investigated by multiple regression analyses in the patient group. Correlations between global indexes of brain damage and neuropsychological measures were also assessed for comparison with previous literature. The comparison between MS patients and healthy controls revealed a widespread pattern of regional GM atrophy. Consistent with previous studies, associations were found between neuropsychological scores, and global brain atrophy and T2-lesion volumes. Critically, significant associations were found between scores on the Symbol Digit Modalities test and Long Delay Cued Recall on the California Verbal Learning Test, and regional GM volumes in well localized areas of the prefrontal, parietal, temporal, and insular cortex. This study confirms that global assessments of brain damage correlate with measures of cognitive impairment in MS. Interestingly, VBM contributes to clarify those brain regions that more likely determine the cognitive deficits observed in patients. These findings clarify the pathophysiology of cognitive impairment in MS, and propose measures which could be considered for longitudinal monitoring of patients.



Mult Scler. 2010 Feb;16(2):178-88. Epub 2009 Dec 9.

Multiparametric MR investigation of the motor pyramidal system in patients with ‘truly benign’ multiple sclerosis.

Spanò B, Cercignani M, Basile B, Romano S, Mannu R, Centonze D, Caltagirone C, Bramanti P, Nocentini U, Bozzali M.



Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.


One possible explanation for the mismatch between tissue damage and preservation of neurological functions in patients with benign multiple sclerosis (BMS) is that the pathophysiology differs from that occurring in other multiple sclerosis (MS) phenotypes. The objective of this study was to identify pathologically specific patterns of tissue integrity/damage characteristics of patients with BMS, and markers of potential prognostic value. The pyramidal system was investigated in 10 BMS patients and 20 controls using voxel-based morphometry to assess grey matter (GM) atrophy, and diffusion tractography and quantitative magnetization transfer to quantify the microstructural damage in the corticospinal tracts (CSTs). Widespread reductions in GM volume were found in patients compared with controls, including the primary motor cortex. A significant decrease was observed in the mean macromolecular pool ratio (F) of both CSTs, with no fractional anisotropy (FA) change. GM volume of the primary motor areas was associated with clinical scores but not with the CST parameters. The mismatch between F and FA suggests the presence of extensive demyelination in the CSTs of patients with BMS, in the absence of axonal damage. The lack of correlation with GM volume indicates a complex interaction between disruptive and reparative mechanisms in BMS.



Abstract SIN 2010:


Regional grey matter atrophy explains processing speed and verbal memory impairment in Multiple Sclerosis.


Barbara Spanò1,2,Mara Cercignani1, Ugo Nocentini3,4, Barbara Basile1, Laura Serra1, Rosalba Mannu3, John De Luca5,6, Placido Bramanti7, Carlo Caltagirone3,4, Marco Bozzali1.

1Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.

2Laboratorio di Neurobioimmagini, IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy.

3Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, Rome, Italy.

4Depatment of Neuroscience, University of Rome “Tor Vergata”, Rome, Italy.

5Kessler Foundation Research Center, West Orange, NJ, United States.

6Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey, United States.

7Direzione Scientifica, IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy.



To investigate, in a group of patients with multiple sclerosis (MS) [1], associations between regional grey matter (GM) damage and cognitive performances in those domains which are typically impaired in MS, using voxel-based morphometry (VBM).



We recruited 18 patients with definite MS. Full neurological examination and neuropsychological assessment were performed 24 hours before MRI acquisition. An extensive neuropsychological battery was used for the assessment of frequent cognitive dysfunctions in MS. Each subject underwent MRI at 3T, by collecting dual-echo scans and T1-weighted volumes.

T1-wighted volumes were processed according to the unified VBM protocol (ref), using SPM8. We investigated the association between regional GM volumes (GMvol) and each score obtained at cognitive tests, using multiple regression analyses. In each analysis, age, gender and total intracranial volume (ICV) were entered as covariates of no interest. All p values were corrected for multiple comparisons. Potential  associations between global brain measures, neuropsychological scores, T2 lesion volumes (T2LL) and clinical/neuropsychological variables were also assessed, using SPSS13.0.



Global GMvol were significantly correlated with scores obtained at the Rey Complex Figure Test (RCFT) Immediate (R=0.5; p=0.05), and Benton Judgment of Line Orientation Test (BJLOT) (R=0.5; p=0.03), which assess visuo-spatial and memory functions respectively. No correlation was found between global WMvol and any clinical/cognitive measure. T2LL was correlated with RCFT-Delayed (R=-0.5; p=0.05) and BJLOT scores (R=-0.05; p=0.06).


VBM analysis showed the regional GMvol of several areas to be associated (FWE-corrected, p<0.05) with scores obtained at specific neuropsychological tests. Symbol Digit Modalities Test (SDMT) scores (assessing processing speed) correlated with  GMvol in the frontal pole bilaterally, and in the right pre- and post-central gyrus, middle and inferior frontal gyrus, central opercular cortex, planum polare and temporal pole. California Verbal Learning Test Second Edition-Long Delay Cued Recall (CVLT-LDCR) scores (assessing associative long-term verbal memory) correlated with  GMvol in the left frontal pole, and in the right pre- and post-central gyrus, supramarginal gyrus, central opercular cortex, planum polare and insular cortex.



Consistently with previous studies, the global brain damage correlates with cognitive impairment in MS. VBM analysis contributes to clarify with higher anatomical localization which brain regions are most implicated in determining cognitive disabilities specific of patients with MS. The direct associations between regional GMvol in fronto-temporal areas and SDMT and CVLT-LDCR scores provide additional evidence that these brain regions are part of a common network subserving processing speed and long-term verbal memory.


1.McDonald WI et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 2001; 50:121-127.

2.Ashburner J, Friston KJ. Voxel-based morphometry-the methods. NeuroImage 2000; 11: 805-821.


Eur J Neurol. 2009 Dec;16(12):1312-7. Epub 2009 Jun 29.


An exploration of anger phenomenology in multiple sclerosis.

Nocentini U, Tedeschi G, Migliaccio R, Dinacci D, Lavorgna L, Bonavita S, Bresciamorra V, Comanducci G, Coniglio G, Livrea P, Mannu R, Orefice G,Paciello M, Patti F, Quattrone A, Salemi G, Savettieri G, Simone IL, Valentino P, Zappia M, Bonavita V, Musicco M, Caltagirone C.


Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy.



Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics.


About 195 cognitively unimpaired MS patients (150 relapsing-remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients’ angerscore distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance.


Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients.


The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex.


An exploration into anger phenomenology in MS patients and its relationships with clinical, cognitive and psychological variables


  1. Comanducci 1, S. Bonavita2, V. Bonavita3,4, C. Caltagirone1,5, G. Coniglio6, D. Dinacci2, L. Lavorgna2, P. Livrea7, R. Mannu1, R. Migliaccio2, M. Musicco1,8, A. Nicoletti9, U. Nocentini1,5, G. Orefice3, M. Paciello6, F. Patti9, A. Quattrone10, G. Salemi11, G. Savettieri11, I.L. Simone7, P. Valentino10 and G. Tedeschi2


1 Neurology Unit, I.R.C.C.S. Fondazione “S. Lucia”, Roma; 2 Department of Neurological Sciences, Second University of Naples, Naples; 3 Department of Neurology, University of Naples “Federico II”, Naples; 4 Istituto Diagnosi e Cura “Hermitage”, Capodimonte, Naples; 5 Neurology Department, “Tor Vergata” University, Roma; 6 Department of Neurology, “San Carlo” Hospital, Potenza; 7 Department of Neurological and Psychiatric Sciences, University of Bari, Bari; 8 ITB-CNR Segrate, Milan; 9 Department of Neurology, University of Catania, Catania; 10 Institute of Neurology, University of Catanzaro, Catanzaro; 11 Department of Neurology, Ophthalmology, Otorhinolaryngology and Psychiatry, University of Palermo, Palermo.


The aim of the actual research was to explore, in a consistent group of MS patients, the phenomenology of anger and its correlation with anxiety, depression, cognitive status and the main clinical variables.


300 subjects with an MS diagnosis. Standardized self – administered questionnaires for evaluation of Anger (STAXI), Anxiety (STAIY1-2), and Depression (CMDI); a neuropsychological battery exploring attention, verbal and visual memory, language, visuo-spatial and executive functions; main demographic and clinical variables collection protocol.


In the framework of a multi-center survey, all MS patients were evaluated by means of the three questionnaires and tested with the neuropsychological battery; main demographic and clinical variables data were collected.


Six aspects of anger (Trait, State, Withheld, Expressed, Control, Total) and the respective percentile distributions were considered in comparison with norms for the Italian population. Taking into account the entire sample of MS patients, the higher percentages of subjects were represented in the I-II percentiles for Trait-, State-, Expressed-, Control-Anger, whereas the higher percentages were in the IV percentile for Withheld- and Total-Anger. Since cognitive impairment can bias the reliability of self-administered questionnaires, the percentile distributions for MS patients with no or only a mild cognitive impairment (n = 194) were calculated: the same pattern of percentile distribution as for the entire sample was found. In these 194 MS patients sample, the clinical variables do not show significant relationships with the various anger parameters and cognitive performance seems to influence anger phenomenology only marginally; instead, the various aspects of anger appear significantly related both with anxiety and depression.


In a 194 MS patients sample, without significant cognitive dysfunction, in which Trait and State Anger do not seem to reach particularly high levels, anger feelings appear mainly unexpressed, related to other emotional aspects such as anxiety and depression and are slightly influenced by cognition. The explorative nature of the actual study did not permit a deeper understanding of the registered phenomena, but withheld anger seems to be another element of the stressful experience of MS patients.


The need to understand the meaning, causes, consequences and correlations of the anger phenomenology and, particularly, of the significant amount of withheld anger that resulted in the MS patients sample of the actual survey, require further studies, since anger can exert important direct and indirect influences on the health and the functioning, the life and the relationships of these persons.




Multiparametric MR investigation of the motor pyramidal system in relapsing-remitting multiple sclerosis. 

AUTORI: B. Spanò, M. Cercignani, B. Basile, U. Nocentini, R. Mannu, S, Marino, P. Bramanti, C. Caltagirone, M. Bozzali. The Multiple Sclerosis Journal

Regional grey matter atrophy explains processing speed and verbal memory impairment in Multiple Sclerosis. M. Cercignani, U. Nocentini, B.Basile , L.Serra, R. Mannu, J.DeLuca, P Bramanti, C.Caltagirone, M. Bozzali

Comitato Scientifico del XLI Congresso SIN. Catania 27 ottobre 2010


Abstract: Impairment of emotional processing in Multiple Sclerosis: an event-related fMRI study

  1. Basile, U. Nocentini, G. Comanducci, R. Mannu, C. Caltagirone and M. Bozzali

Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy, 2Department of Clinical and Behavioural Neurology, Santa Lucia Foundation,

Rome, Italy, Department of Neuroscience, University Tor Vergata, Rome, Italy. the Multiple Sclerosis


Journal 2009

Multiparametric MR investigation of the motor pyramidal system in patients with truly benign MS

AUTORI: Barbara SpanòM, Mara Cercignani, Barbara Basile, Silvia Romano, Rosalba Mannu, Diego Centonze, Carlo Caltagirone, Placido Bramanti, Ugo Nocentini, Marco Bozzali.

the Multiple Sclerosis Journal

An exploration of anger phenomenology in multiple sclerosis

  1. Nocentini, G. Tedeschi, R. Migliaccio, D. Dinacci, L. Lavorgna, S. Bonavita,
  2. Bresciamorra, G. Comanducci, G. Coniglio, P. Livrea, R. Mannu, G. Orefice, M. Paciello,
  3. Patti, A. Quattrone, G. Salemi, G. Savettieri, I.L. Simone, P. Valentino, M. Zappia,
  4. Bonavita, M. Musiccol and C. Caltagirone,

European Journal of Neurology 2009, 16: 1312–1317



Anger in Multiple Sclerosis patients: phenomenology and relationship to other psychological variables.the Multiple Sclerosis Journal 2008.

Comunicative function and executive defictis cause againg right-hemisphere lasions to have different effects on the cognitive processing of prosody. AUTORI: Elisa Cravello, Rosalba Mannu, Ugo Nocentini, Antonio Schindler, Helene Còté, Yves Joanette, Paolo Di Benedetto, Federica Mondolo, Emanuele Biasutti, Alessandro Tavano. (submitted).2008

Le abilità prosodiche linguistiche ed emotive: l’influenza dell’età cronologica, del genere e del livello d’istruzione .AUTORI: Elisa Cravello, Rosalba Mannu, Antonio Schindler, Federica Mondolo, Daniela Marchione, Paolo Di Benedetto, Hélène Côté, Yves Joanette, Ugo Nocentini, Emanuele Biasutti

( submitted)


Congresso Società Latinioamericana di Neuropsicologia: Studio: prosodia linguistica y emocional en pacientes con lesiones del hemisferio derecho y en sujetos de un grupo de control. Autori : Tavano a, cravello e, schindler a, mannu r, nocentini u, biasutti e.”.

Clinical case solving : paresi periferica del facciale come sintomatologia di esordio in un caso SM. Autori: Nocentini u, Mannu r. Sanofi aventis 2007

Clinical case solving :disturbo del gusto come sintomatologia di esordio in un caso di SM.

autori: Nocentini U, mannu R. Sanofi aventis 2007