Maria Giovanna Marrosu

Università degli studi di Cagliari, Cagliari, Sardinia, Italy

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Publications (276)1218.93 Total impact

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    ABSTRACT: Background Recently, a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been developed as an international and standardized brief cognitive test, which is easily performed in everyday clinical practice for neuropsychological assessment in multiple sclerosis (MS). However, we need to gather more information about this tool compared to other neuropsychological batteries. The aim of our study is to compare the performance of BICAMS and Brief Repeatable Battery (BRB) in MS subjects. Methods Tests of the BRB and BICAMS were administered to MS patients recruited from 11 Italian MS centres. Cognitive impairment (CI) was defined as the failure on at least two tests (scores below the fifth percentile) on the BRB and as the failure on at least one test of the BICAMS. The agreement between the performances on the two batteries was assessed through Cohen’s K statistic. Finally we calculated the effects sizes for each test of the two batteries using Cohen’s d. Results The two batteries were administered to 192 MS patients (142 women, 50 men; mean age 41.4 ± 10.8 years, mean education 12.3 ± 3.5 years). Mean scores of patients were lower compared to those of healthy subjects in all the cognitive measures examined. Forty-six MS patients were identified as impaired and 48 as unimpaired on both of the batteries, when the Symbol Digit Modalities Test (SDMT) was included in the analysis. Cohen’s K statistic was 0.46 which corresponds to a moderate accord. If the SDMT was excluded from the BRB, 37 MS patients were identified as impaired and 57 as unimpaired on both of the batteries. Cohen’s K statistic was 0.3 which corresponds to a poor accord. The SDMT, the Paced Auditory Serial Addition Test (PASAT) 3 and 2 yielded higher d values (SDMT 0.83, PASAT 3 0.65, PASAT 2 0.84). Conclusions This study confirms the feasibility of BICAMS in everyday clinical practice for the identification of CI and highlights the good psychometric properties of the SDMT.
    BMC Neurology 12/2015; 15(1). DOI:10.1186/s12883-015-0460-8 · 2.04 Impact Factor
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    ABSTRACT: We investigated intrafamilial phenotypic variability in carriers of the C9orf72 mutation, analysing clinical, neuropsychological and imaging characteristics of various members from a large Sardinian kindred with FTD or ALS. We compared these with those of C9 + patients in our ALS and FTD cohorts. Results showed that three patients carried the C9orf72 mutation: two with ALS and one with FTD and Parkinsonism. C9 + patients in our bvFTD Sardinian cohort had a higher frequency of Parkinsonism than non-mutated patients (75% vs. 36.3%, p <0.02). Parkinsonism was present in 2.7% of our ALS cohort and 3.3% of the C9 + patients. The prevalence of Parkinsonism in C9 + patients in the bvFTD and ALS cohorts showed a statistically significant difference (p <0.006). In conclusion, Parkinsonism was frequently associated with FTD but not ALS in a large Sardinian family, a finding reflected in the wider C9orf72 associated Sardinian ALS and FTD populations.
    11/2015; DOI:10.3109/21678421.2015.1111904
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    ABSTRACT: Background: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. Objectives: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. Methods: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. Results: A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Conclusions: Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis.
    Multiple Sclerosis 10/2015; DOI:10.1177/1352458515611222 · 4.82 Impact Factor
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    31h Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Barcelona; 10/2015
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    ABSTRACT: Background: Recent studies identified > 100 non-HLA (human leukocyte antigen) multiple sclerosis (MS) susceptibility variants in Northern European populations, but their role in Southern Europeans is largely unexplored. Objective: We aimed to investigate the cumulative impact of those variants in two Mediterranean populations: Continental Italians and Sardinians. Methods: We calculated four weighted Genetic Risk Scores (wGRS), using up to 102 non-HLA MS risk variants and 5 HLA MS susceptibility markers in 1691 patients and 2194 controls from continental Italy; and 2861 patients and 3034 controls from Sardinia. We then assessed the differences between populations using Nagelkerkes R2 and the area under the Receiver Operating Characteristic (ROC) curves. Results: As expected, the genetic burden (mean wGRS value) was significantly higher in MS patients than in controls, in both populations. Of note, the burden was significantly higher in Sardinians. Conversely, the proportion of variability explained and the predictive power were significantly higher in continental Italians. Notably, within the Sardinian patients, we also observed a significantly higher burden of non-HLA variants in individuals who do not carry HLA risk alleles. Conclusions: The observed differences in MS genetic burden between the two Mediterranean populations highlight the need for more genetic studies in South Europeans, to further expand the knowledge of MS genetics.
    Multiple Sclerosis 10/2015; 21(11):1385-1395. DOI:10.1177/1352458515596599 · 4.82 Impact Factor
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    Manuela Galli · Giancarlo Coghe · Paola Sanna · Eleonora Cocco · Maria Giovanna Marrosu · Massimiliano Pau ·
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    ABSTRACT: This study analyzes how multiple sclerosis (MS) does affect one of the most common voluntary activities in life: the gait initiation (GI). The main aim of the work is to characterize the execution of this task by measuring and comparing relevant parameters based on center of pressure (COP) patterns and to study the relationship between these and the level of expanded disability status scale (EDSS). To this aim, 95 MS subjects with an average EDSS score of 2.4 and 35 healthy subjects were tested using a force platform during the transition from standing posture to gait. COP time-series were acquired and processed to extract a number of parameters related to the trajectory followed by the COP. The statistical analysis revealed that only a few measurements were statistically different between the two groups and only these were subsequently correlated with EDSS score. The correlation analysis underlined that a progressive alteration of the task execution can be directly related with the increase of EDSS score. These finding suggest that most of the impairment found in people with MS comes from the first part of the COP pattern, the anticipatory postural adjustments (APAs). The central nervous system performs APAs before every voluntary movement to minimize balance perturbation due to the movement itself. Gait Initiation's APAs consist in some ankle muscles contractions that induce a backward COP shift to the swing limb. The analysis here performed highlighted that MS affected patients have a reduced posterior COP shift that reveals that the anticipatory mechanism is impaired.
    Multiple Sclerosis and Related Disorders 09/2015; 4(6):594-597. DOI:10.1016/j.msard.2015.09.005 · 0.88 Impact Factor
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    ABSTRACT: Cerebral microbleeds (CMB) might reflect specific underlying vascular pathologies like cerebral amyloid angiopathy (CAA). In the present study we report the gradient-echo MRI pattern of two siblings with P284S PSEN1 mutation. T2* gradient-echo images of the two subjects demonstrated multiple microbleeds in lobar regions. The role and causes of CMB in sporadic Alzheimer's disease (AD) patients have not been clearly established and useful contributions could derive from familial AD studies. Furthermore, since CAA is a potential risk factor for developing adverse events in AD immunization trials, the identification in vivo of CAA through non-invasive MRI methods could be useful to monitoring side effects.
    Journal of Alzheimer's disease: JAD 09/2015; 47(3):535-538. DOI:10.3233/JAD-150165 · 4.15 Impact Factor
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    Massimiliano Pau · Giancarlo Coghe · Federica Corona · Maria Giovanna Marrosu · Eleonora Cocco ·
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    ABSTRACT: Purpose This study proposes to characterize the gait patterns of individuals with Multiple Sclerosis (MS) affected by spasticity using quantitative gait analysis. Method Cross-sectional study on 38 individuals with MS, 19 affected by lower limb spasticity and 19 not affected, the latter forming the control group. Both groups were evaluated while walking using three-dimensional gait analysis. Spatio-temporal parameters of gait, kinematic data expressed by means of Gait Profile Score (GPS) and Range of Motion (ROM), as well as muscular activation, were evaluated. Results The results show that spasticity originates a peculiar gait pattern characterized by reduced speed, cadence, stride length, swing phase and increased double support time, but they also reveal specific alterations in kinematics and muscular activation. In particular, significantly higher values of GPS, reduced hip and knee flexion-extension ROM and abnormal activation of the rectus femoris were observed in individuals with spasticity. Conclusions In people with MS presenting spastic gait, the availability of quantitative data appears crucial in verifying the effectiveness of pharmacologic and rehabilitative treatments, also considering that spasticity scales may not be satisfactory in relating the assessed spasticity with both perception of the patients and the actual body functionalities.
    Journal of the Neurological Sciences 09/2015; DOI:10.1016/j.jns.2015.09.352 · 2.47 Impact Factor
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    ABSTRACT: The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.
    Brain 09/2015; DOI:10.1093/brain/awv260 · 9.20 Impact Factor
  • Paolo Solla · Antonino Cannas · Maria Giovanna Marrosu · Francesco Marrosu ·

    Parkinsonism & Related Disorders 09/2015; DOI:10.1016/j.parkreldis.2015.09.039 · 3.97 Impact Factor
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    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 · 3.38 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 · 3.38 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 · 4.82 Impact Factor
  • L Lorefice · Mrmurru · G Fenu · D Corongiu · J Frau · S Cuccu · G.C. Coghe · S Tranquilli · E Cocco · M.G. Marrosu ·
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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
  • L Lorefice · S Tranquilli · G Fenu · M R Murru · J Frau · M Rolesu · G C Coghe · F Marrosu · M G Marrosu · E Cocco ·
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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 · 1.45 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; 2015(2). DOI:10.1155/2015/916478 · 1.58 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; 36(10). DOI:10.1016/j.neurobiolaging.2015.06.013 · 5.01 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; 21(8). DOI:10.1016/j.parkreldis.2015.05.018 · 3.97 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

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5k Citations
1,218.93 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
  • 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
  • 1998-2009
    • Università degli Studi di Sassari
      • Dipartimento di Scienze Biomediche
      Sassari, Sardinia, Italy
  • 1995
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom