Maria Giovanna Marrosu

Università degli studi di Cagliari, Cagliari, Sardinia, Italy

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Publications (264)1221.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson's disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20-30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.
    Journal of Neurology 08/2015; DOI:10.1007/s00415-015-7873-6 · 3.84 Impact Factor
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    ABSTRACT: Recently, nabiximols was approved as a treatment in MS spasticity. Data leading to approval and clinical use of nabiximols, although widely recognised, are based on subjective scales. Movement analysis procedures would obtain more detailed data about the impact on mobility. The aim of the study was to quantitatively assess the functional modification of gait patterns induced by nabiximols in MS. We evaluated three-dimensional gait analysis (spatial–temporal and kinematic) variation by means of one-way ANOVA. Twenty patients were enrolled— 9 male and 11 female—with mean EDSS of 5.3 (SD ± 0.81) and mean reduction of numerical rating scale during nabiximols treatment of 1.88. The spatial–temporal parameters of gait revealed an increased speed (+15 %, p<0.001), cadence (+6 %, p<0.001) and stride length (+10 %, p\0.001) after treatment. Regarding the kinematics data, the Gait Profile Score after treatment was reduced by 10 % (p<0.001): Significant changes involved the pelvic area, hip rotation and knee flexion–extension. We found that nabiximols is able to improve the speed, cadence and stride length. Furthermore, the dynamics of the proximal segment of the legs and the knee movement results after treatment are closer to the physiologic values.
    Journal of Neurology 08/2015; DOI:10.1007/s00415-015-7866-5 · 3.84 Impact Factor
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    ABSTRACT: A 39-year-old woman was admitted to hospital because of a sensory hemisyndrome caused by a contrast-enhancing demyelinating lesion of the cervical cord. MRI, CSF examination and subsequent clinical and neuroradiological follow-up led to the diagnosis of multiple sclerosis. The patient had noticed an involuntary contraction of a small muscle fascicle on the right side of the chin for a year. Electromyographic and video recordings confirmed the synkinesis between the orbicularis oculi and lower facial muscles, a finding distinct from the myokymic discharges reported in multiple sclerosis and more similar to the synkinesis associated with hemifacial spasm. © The Author(s), 2015.
    Multiple Sclerosis 08/2015; DOI:10.1177/1352458515584415 · 4.86 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by inflammation and accompanied and followed by neurodegeneration. Missense mutations of the TAR DNA Binding Protein gene (TARDBP) located in the chromosome 1p36.22 region, and the hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) are pathogenic in other neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Assuming that TARDBP Ala382Thr mutation and C9orf72 expansion may underlie MS, we evaluated their frequency in a large cohort of MS patients and controls from Sardinia, an island characterized by a very high frequency of MS and an unusual genetic background. Genomic DNA was extracted from peripheral blood and analyzed for the presence of a TARDBP Ala382Thr mutation and C9orf72 expansion. Difference in the frequency of these mutations between MS patients and controls was calculated using the χ 2 test with a standard 2 × 2 table. The Ala382Thr mutation in its heterozygous state was found in 27/1833 patients (1.4%) and 20/1475 controls (1.3%), whereas C9orf72 pathogenic repeat expansion was found in 6/1014 MS patients (0.6%) and 2/333 controls (0.6%). Individuals carrying the mutations did not present with other neurodegenerative conditions and any differences were reported between groups. TARDBP Ala382Thr mutation and C9orf72 expansion do not play a major role in MS pathogenesis in the Sardinian population. Further analyses on larger samples of MS patients from other populations are needed to better define the possible role of these genes in the complex interplay between neuroinflammation and neurodegeneration in MS.
    The Italian Journal of Neurological Sciences 08/2015; DOI:10.1016/j.jns.2015.07.036
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    ABSTRACT: Multiple sclerosis (MS) is a complex autoimmune disease originated from the interplay between genetic and environmental factors. An overlap of clinical and neuroradiological parameters has been described between MS and an adult-onset neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome (FXTAS). This syndrome is caused by a trinucleotide premutation expansion of a CGG sequence in the 55-200 repeat range, which is located in the fragile-X mental retardation 1 (FMR1) gene. Female premutation carriers have an increased propensity for immune-mediated disorders. Recently, a case of co-occurrence of MS and FXTAS was reported. Assuming that the premutation expansion may play a role in the MS susceptibility, we evaluated its frequency in a cohort of MS patients from Sardinia, an island characterized by a very high frequency of MS. Nuclear DNA was extracted by standard methods, purified with bisulfite treatment and then amplified twice by PCR with specific primers. Microsatellite analysis was performed and emizogotic subjects were sequenced. Clinical data of patients were also collected. Only 1/755 MS patients exhibited the premutation expansion with a heterozygosis pattern (30/58). No pathogenic repeat expansions (>200 repeats) were found in the entire cohort. Repeats labeled as the gray zone (45-60 repeats) were observed in 15/755 patients. No specific clinical features concerning disease course, disease activity, and disability were reported for these patients. Our results do not support a possible role for premutation or gray zone alleles in MS Sardinian patients. Further studies are needed to better understand the relationship between FXTAS and MS.
    Neurological Sciences 07/2015; DOI:10.1007/s10072-015-2339-2 · 1.50 Impact Factor
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    ABSTRACT: Balance training represents a critical part of the rehabilitation process of individuals living with multiple sclerosis (MS) since impaired postural control is a distinctive symptom of the disease. In recent years, the use of the Nintendo Wii system has become widespread among rehabilitation specialists for this purpose, but few studies have verified the effectiveness of such an approach using quantitative measures of balance. In this study, we analyzed the postural sway features of a cohort of twenty-seven individuals with MS before and after 5 weeks of unsupervised home-based balance training with the Wii system. Center of pressure (COP) time-series were recorded using a pressure platform and processed to calculate sway area, COP path length, displacements, and velocities in mediolateral (ML) and anteroposterior (AP) directions. Although the results show a significant reduction in sway area, COP displacements, and velocity, such improvements are essentially restricted to the ML direction, as the Wii platform appears to properly stimulate the postural control system in the frontal plane but not in the sagittal one. Available Wii games, although somewhat beneficial, appear not fully suitable for rehabilitation in MS owing to scarce flexibility and adaptability to MS needs and thus specific software should be developed.
    BioMed Research International 06/2015; · 2.71 Impact Factor
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    ABSTRACT: Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 06/2015; DOI:10.1016/j.neurobiolaging.2015.06.013 · 4.85 Impact Factor
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    ABSTRACT: Levodopa-carbidopa intestinal gel infusion (LCIG) is indicated in patients with advanced levodopa-responsive Parkinson's disease (PD) for the treatment of motor fluctuations and dyskinesias unsatisfactorily managed with conventional medication. The outcome of non-motor symptoms - particularly affective and behavioral ones - following LCIG initiation remains scarcely explored, especially with respect to the changes undergone by oral dopaminergic drugs. Here we describe 4 PD patients who developed dopamine agonist withdrawal syndrome (DAWS) symptoms correlated with rapid taper of these drugs after LCIG initiation. We identified 4 cases developing apathy and depression after the rapid withdrawal of Dopamine agonists (DAs) consequent to LCIG introduction. The clinical data were obtained through detailed review of medical records. Within few days after DAs withdrawal, all 4 patients developed apathy, anhedonia and depression, despite the marked reduction of dyskinesias and the improvement of motor fluctuations after LCIG introduction. We unsuccessfully tried to manage these and other DAWS symptoms by increasing LCIG flow. Within 6 months, all patients spontaneously presented a slow but gradual improvement of DAWS symptoms, not requiring any further treatment strategy or LCIG discontinuation. To our knowledge, this is the first report describing the occurrence of DAWS symptoms in advanced PD patients after DAs withdrawal in LCIG and highlighting the difficulty of distinguishing postoperative effects from drug withdrawal symptoms. Therefore we wish to draw attention of clinicians to the risk of developing DAWS in advanced PD patients switched to LCIG monotherapy. In such cases, a rapid taper of DAs should be avoided. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 06/2015; DOI:10.1016/j.parkreldis.2015.05.018 · 4.13 Impact Factor
  • G Fenu · L Lorefice · J Frau · G C Coghe · M G Marrosu · E Cocco
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    ABSTRACT: Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system. Pharmacological therapy of MS includes symptomatic drugs, treatment for relapses (corticosteroid and intravenous immunoglobulin) and disease modifying drugs (DMDs) defined as pharmacological agents that have an impact on relapse rate, disability accumulation and radiological outcomes. Two different therapeutic approaches are widely used in MS: escalation and induction therapy. Escalation therapy consists of an early start with first line DMDs (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate) and if DMDs are ineffective or partially effective, switching to second line drugs (mitoxantrone, natalizumab, fingolimod). Induction therapy consists of the early use of immunosuppressant drugs followed by long-term maintenance treatment, generally with immunomodulatory agents. While the use of natalizumab and fingolimod as first line drugs is indicated for aggressive forms of MS, the indication for mitoxantrone as an induction treatment arises from randomized studies demonstrating that induction therapy with mitoxantrone followed by DMD maintenance is more effective than monotherapy with beta interferon. However, the safety profile of induction drugs indicates this is not an acceptable therapeutic strategy for all MS patients in all phases of the disease. The coming challenge is to identify patients at high risk of disability development from their clinical characteristics, radiological findings or biomarkers. Furthermore, future studies to establish an individual safety profile stratification are needed.
    Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Cu rrent Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 05/2015; 14(1). DOI:10.2174/1871523014666150504122220
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    Eleonora Cocco · Maria Giovanna Marrosu
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    ABSTRACT: Several treatments are currently available for relapsing-remitting multiple sclerosis. Among them, interferon (IFN) beta remains a valid treatment approach because of its good benefit/risk profile. Due to the need for frequent administration (weekly, at a minimum), the use of IFN beta is limited by uncomfortable side effects that could reduce adherence to and persistence with the treatment. The use of subcutaneous polyethylene glycol (PEG)ylated interferon beta-1a (PEG-IFN) has been proposed to offer a better combination of pharmacokinetic and pharmacodynamic profiles and therapy-related side effects. A 125 μg dose of PEG-IFN given every 2 or 4 weeks was tested in two Phase I studies and shown to be as safe and efficient as IFN beta-1a but with a longer half-life. A Phase III trial (ADVANCE) comparing 125 μg of PEG-IFN given every 2 or 4 weeks with placebo in 1,512 patients with relapsing-remitting multiple sclerosis showed significant reductions in both the annualized relapse rate (ARR) and the occurrence of new or newly enlarged T2 brain lesions in both experimental groups versus placebo after the first year. Moreover, 38% fewer patients showed progression of disability (P=0.04) in the PEG-IFN groups. During the second year, the ARR was further reduced in the PEG-IFN 2-week treatment group (0.230 at 1 year versus 0.178 at 2 years) and was maintained in the 4-week treatment group. Patients who received immediate PEG-IFN treatment showed improved clinical efficacy (ARR, risk of relapse, 12-week disability progression) and magnetic resonance imaging parameters (new T2 and newly enlarging lesions, gadolinium-positive lesions) compared with those with delayed treatment. The effects were more evident with the 2-week dose for all endpoints considered. Furthermore, PEG-IFN was well tolerated, and no new safety concerns arose. In conclusion, PEG-IFN has good efficacy and a good safety profile. The available data support the use of PEG-IFN as a suitable therapeutic option in patients with relapsing-remitting multiple sclerosis.
    Therapeutics and Clinical Risk Management 05/2015; 11:759. DOI:10.2147/TCRM.S69123 · 1.47 Impact Factor
  • L Lorefice · G Fenu · J Frau · G C Coghe · M G Marrosu · E Cocco
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    ABSTRACT: Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS.
    Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Cu rrent Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 04/2015; 14(1). DOI:10.2174/1871523014999150415130224
  • Lorena Lorefice · Fenu G · Trincas G · Moro MF · Frau J · Coghe GC · Cocco E · Marrosu MG · Carta MG
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    ABSTRACT: Mood disorders are very common among multiple sclerosis (MS) patients, but their frequency in patients with progressive course (PMS) has not been adequately researched. Our study aimed to determine the frequency of mood disorders among patients with PMS compared with those with relapsing-remitting MS (RMS) and to explore the associations with disability and disease duration. The study included consecutive outpatients affected by MS according the 2010 revised Mc Donald diagnostic criteria. Psychiatric diagnoses were determined according to DSM-IV by psychiatrists using structured interview tools (ANTAS-SCID). Demographic and clinical data of patients were also collected. Disease courses were defined according to the re-examined phenotype descriptions by the Committee and MS Phenotype Group. Intergroup comparisons were performed by Chi-square test, while logistic regression analysis was performed to assess possible factors associated with mood disorders. In total, 240 MS patients (167 women) were enrolled; of these, 18 % (45/240) had PMS. The lifetime DSM-IV major depression diagnosis (MDD) was established in 40 and 23 % of the PMS and RMS patients, respectively. Using logistic regression analysis, the presence of MDD was independent from disease duration and disability and dependent on PMS course (P = 0.02; OR 2.2). Patients with PMS presented with MDD more frequently than those with RMS, independently from disease duration and physical disability. These findings highlight the importance of considering mood disorders, especially MDD, in the management of PMS patients.
    Neurological Sciences 04/2015; DOI:10.1007/s10072-015-2220-3 · 1.50 Impact Factor
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    ABSTRACT: To verify the serological response mounted against antigenic peptides from HERV-Wenv protein, we analyzed 80 multiple sclerosis (MS) serum samples, 27 of which were re-analyzed after a 6-month follow-up IFN-β therapy, and 73 healthy controls. Indirect ELISAs were carried out to detect antibodies specific for all the synthetic peptides derived from HERV-Wenv. Two antigenic peptides, HERV-Wenv93-108 (31.25%, p<0.0001) and HERV-Wenv248-262 (15%, p=0.02), were highly recognized by MS patients' antibodies when compared to healthy subjects. Moreover, antibody titer against these two peptides slightly decreased after six months of IFN-β-based therapy. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of neuroimmunology 03/2015; 280. DOI:10.1016/j.jneuroim.2015.03.003 · 2.79 Impact Factor
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    ABSTRACT: Background Mycobacterium avium subspecies paratuberculosis (MAP) is associated with MS in Sardinia. Because anti-MAP antibodies (Abs) were more frequent in interferon-beta treated patients, we hypothesize that interferon-beta could interact with the immune system. Methods Anti-MAP Abs were searched in the blood of 89 patients before commencing interferon-beta and after at least six months. Results Anti-MAP Abs were detected before and during treatment in 18.7% and 34.7% of patients, respectively. Twenty-three (20.5%) patients became positive during therapy, and 5 (4.4%) patients became negative (p = 0.001). Conclusions The study supports the hypothesis that interferon-beta could interact with the immune system, enhancing the immunological response against MAP.
    Journal of the Neurological Sciences 02/2015; 61(1-2). DOI:10.1016/j.jns.2015.01.004 · 2.26 Impact Factor
  • Jessica Frau · G. Coghe · L. Lorefice · G. Fenu · B. Cadeddu · M. G. Marrosu · E. Cocco
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    ABSTRACT: Multiple sclerosis (MS) is a long-lasting neurological disease with onset in young adult age. Patients with MS are less active than healthy people, and their sedentary lifestyle might lead to secondary diseases or worsening of symptoms, disability and quality of life. In the study, we evaluated the attitude of physical activity (PA) of a group of MS patients and the differences in practice PA before and after the diagnosis. A randomly recruited group of patients with MS fulfilled a questionnaire about their attitudes towards PA before the onset and after the diagnosis of the disease. Clinical and demographic data were recorded. Out of 118 patients, 37 % practiced PA only before the diagnosis, 9 % only after and 52 % during both periods. After the diagnosis, 64 % of participants noted some negative differences in PA, in particular less physical resistance and worsening of symptoms, and 38 % stopped PA. However, patients referred benefits from PA after diagnosis. Individual exercises rather than group activities were preferred after diagnosis. Only 26 % of patients knew that adapted PA existed and the differences between adapted PA and classic physiotherapy. We observed a reduction in the practice of PA in patients after the diagnosis of MS, in particular for disease-related reasons. Nevertheless, active patients referred benefits from PA. It is important to know the point of view of patients towards developing individualized training programs. In this way, it could be possible to achieve more benefits from PA and reduce the negative effects.
    Neurological Sciences 02/2015; 36(6). DOI:10.1007/s10072-015-2100-x · 1.50 Impact Factor
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    ABSTRACT: Mycobacterium avium subsp. paratuberculosis (MAP) infections have been recently linked to multiple sclerosis in Sardinian population, with amino acid sequence 301-309 of MAP2694 protein possessing a high antigenic potential. Peptide presentation by HLA protein is an important step in adaptive immune response to pathogens, which is linked to stable peptide-HLA complex. In this study we focus on two predisposing (*15:01, *03:01) and two protective (*16:01, *15:02) HLA-DRB1 proteins in Sardinian population. We investigate in detail their binding characteristics to the MAP2694-derived peptide, with the aim to link disease susceptibility to protein structural-dynamical features and ultimately to molecular mechanisms contributing to the disease. Using dihedral angle principal components analysis, we observe distinct chemical configurations and dynamics of the HLA peptide binding, between the predisposing and protective proteins upon binding. The difference persists in the collective motion of residues near the amino-terminal region of the peptide-binding groove involving polymorphic HLA-DRB1 residue 86. Buried surface area and binding energy estimations also support the protein distinction, suggesting a preferential peptide binding towards the predisposing proteins. Finally, water dynamics analysis in the binding groove highlighted the role of slow water molecules in bridging H-bond interactions between the protein and peptide residues. Our work demonstrates the ability of molecular simulations to characterize MAP peptide binding to the proteins associated with multiple sclerosis in Sardinia. Overall, this distinction between the predisposing and protective proteins can be associated to a biological mechanism that functionally contributes to disease onset in predisposed individuals.
    New Journal of Chemistry 12/2014; 39(2). DOI:10.1039/C4NJ01903B · 3.16 Impact Factor
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    ABSTRACT: Background Familial lipodystrophies are rare inherited disorders associated with redistribution of body fat and development of dyslipidemia, insulin resistance and diabetes. We previously reported two siblings with unusual late-onset familial partial lipodystrophy in whom heretofore known causative genes had been excluded. We hypothesized they had a mutation in a novel lipodystrophy gene. Methods Our approach centred on whole exome sequencing of the patients' DNA, together with genetic linkage analysis and a bioinformatic prioritization analysis. All candidate variants were assessed in silico and available family members were genotyped to assess segregation of mutations. Results Our prioritization algorithm led us to a novel homozygous nonsense variant, namely p.Ala507fsTer563 in the LIPE gene encoding hormone sensitive lipase, an enzyme that is differentially expressed in adipocytes and steroidogenic tissues. Pathogenicity of the mutation was supported by bioinformatic analyses and variant cosegregation within the family. Conclusions We have identified a novel nonsense mutation in LIPE, which likely explains the lipodystrophy phenotype observed in these patients.
    The Canadian journal of cardiology 12/2014; 30(12). DOI:10.1016/j.cjca.2014.09.007 · 3.94 Impact Factor
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    ABSTRACT: It has been shown that different genes could be associated with distinctive clinical and radiological phenotypes of FTD. TARDBP gene has been described worldwide in few cases of FTD so its phenotype is still unclear. The objective is to study the clinical and radiological characteristics of TARDBP-related FTD. In the present study, we report clinical, neuropsychological and radiological features of five new Sardinian non-related cases of FTD carriers of the p.A382T TARDBP mutation. Furthermore, we reviewed non-related FTD cases with TARDBP mutations previously described in literature. The p.A382T missense mutation of TARDBP was present in the 21.7 % of familial cases of our FTD cohort (5/23) and in no one of the sporadic patients. 3 of 5 patients showed a temporal variant FTD and 4/5 a predominant temporal involvement at MRI. The review of the literature of FTD cases with TARDBP mutations showed that in 5 of 16 cases, the clinical phenotype was consistent with temporal variant of FTD or semantic dementia (31 %) and in 7 of 16 cases neuroimaging showed predominant temporal lobe involvement (43.7 %). Our study further supports the pathogenetic role of TARDBP mutations in pure FTD and in the full spectrum of FTD/ALS. The presence of a predominant temporal lobe involvement in a high percentage of FTD mutated patients with a peculiar clinical pattern could be useful in the differential diagnosis with other forms of dementia/FTD both sporadic and familial.
    Journal of Neurology 11/2014; 262(2). DOI:10.1007/s00415-014-7575-5 · 3.84 Impact Factor
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    ABSTRACT: A large number of reports indicate the association of Epstein-Barr virus (EBV), and Mycobacterium avium subsp. paratuberculosis (MAP) with multiple sclerosis (MS). OBJECTIVE: To gain a better understanding of the role of these two pathogens, we investigated the host response induced by selected antigenic peptides. METHODS: We examined both humoral and cell-mediated responses against peptides deriving from EBV tegument protein BOLF1, the MAP_4027 and the human interferon regulatory factor 5 (IRF5424-434) homolog in several MS patients and healthy controls (HCs). RESULTS: Antibodies against these peptides were highly prevalent in MS patients compared to HCs. Concerning MS patients, BOLF1305-320, MAP_402718-32 and IRF5424-434 peptides were able to induce mainly Th1-related cytokines secretion, whereas Th2-related cytokines were down-regulated. Flow cytometry analyses performed on a subset of MS patients highlighted that these peptides were capable of inducing the release of pro-inflammatory cytokines: IFN-γ and TNF-α by CD4+ and CD8+ T lymphocytes, and IL-6 and TNF-α by CD14+ monocyte cells. CONCLUSION: Our data demonstrated that both EBV and MAP epitopes elicit a consistent humoral response in MS patients compared to HCs, and that the aforementioned peptides are able to induce a T-cell-mediated response that is MS correlated.
    Multiple Sclerosis 11/2014; 12(8). DOI:10.1177/1352458514557304 · 4.86 Impact Factor

Publication Stats

4k Citations
1,221.62 Total Impact Points


  • 1979–2015
    • Università degli studi di Cagliari
      • • Department of Public Health, Clinical and Molecular Medicine
      • • Department of Biomedical Science
      Cagliari, Sardinia, Italy
  • 2014
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florens, Tuscany, Italy
  • 1998–2013
    • Università degli Studi di Sassari
      • Dipartimento di Scienze Biomediche
      Sassari, Sardinia, Italy
  • 2012
    • Second University of Naples
      Caserta, Campania, Italy
  • 2011
    • Azienda Ospedaliera Universitaria Cagliari
      Cagliari, Sardinia, Italy
  • 2010
    • National Research Council
      • Institute of Neurogenetics and Neuropharmacology IRGB
      Roma, Latium, Italy
  • 2000
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
    • KU Leuven
      • Rega Institute for Medical Research
      Leuven, VLG, Belgium