Giancarlo Coghe

Università degli studi di Cagliari, Cagliari, Sardinia, Italy

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Publications (14)48.41 Total impact

  • [Show abstract] [Hide abstract]
    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 01/2015; · 2.26 Impact Factor
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    ABSTRACT: A critical aspect of multiple sclerosis (MS) treatments is understanding the effect of disease-modifying drugs (DMDs) on the long-term risk of disability and whether the effect is related to disability at start of treatment.
    Multiple Sclerosis 09/2014; · 4.86 Impact Factor
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    ABSTRACT: The assessment of gait abnormalities in individuals with Multiple Sclerosis (MS) represents a key factor in evaluating the effectiveness of rehabilitation treatments. Despite the availability of sophisticated equipment to objectively evaluate the kinematic aspects of gait, there are still some difficulties in processing the large and complex amount of data they produce in the daily clinical routine. On the basis of the above-mentioned considerations we propose a novel characterization of gait kinematics in individuals with MS, based on a single measure (Gait Profile Score, GPS) obtained from a quantitative three-dimensional analysis of gait performed using an opto-electronic system. We also investigated the correlation between GPS and the Expanded Disability Status Scale (EDSS) values. Thirty-four patients suffering from relapsing-remitting MS (13 female, 21 male, mean age 46.7 years) with an EDSS score of ≤ 6 underwent a gait analysis from which the GPS index was calculated. Their results were compared with those of a control group of healthy age- and gender-matched subjects. The GPS of individuals with MS was found significantly higher with respect to controls (9.12° vs. 5.67°, p < 0.001) as the result of kinematic differences in gait patterns referring to pelvic tilt and rotation, hip flexion-extension and rotation, knee flexion-extension and ankle dorsi- and plantar-flexion. A moderate correlation was also found between the EDSS score of the participants and their GPS values (r = 0.63, p < 0.001). The GPS index thus appears suitable to represent gait deviations from physiological patterns in individuals affected by MS and potentially useful in assessing the outcomes related both to rehabilitation programs and pharmacologic/physical therapies.
    Journal of the Neurological Sciences 07/2014; · 2.26 Impact Factor
  • Neurological Sciences 05/2014; 35(11). · 1.50 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) has a major impact on the physical, psychological and social life of patients and their families. The aim of this study was to evaluate the different perceptions of patients and caregivers about management of MS, particularly about the same items, to gather information to ameliorate the care of patients. We evaluated what MS patients and caregivers perceive as unmet needs and compared patients' opinions with caregivers' opinions using a multidimensional questionnaire. The questionnaire was specifically designed for the study, taking into account different aspects of the global care perceived by patients and care givers, such as information about MS, medical treatment and rehabilitation, patients' relationships with medical staff and their psychological and social life. We administered the questionnaire to 497 patients and 206 caregivers. Results showed that the majority of participants were satisfied with medical staff but expressed a desire that staff be more forthcoming with information about MS. As for medical treatment concerns, more patients found there to be useful a multidisciplinary approach than caregivers did. Both required psychological support for patients but patients felt a greater need for it at the time of diagnosis, whereas caregivers felt it was required post-diagnosis. Both reported significant strains on patient relationships at work but no effect on other social interactions. A better understanding of MS patient needs, starting from the point of view of patients and caregivers, could have a great impact on quality of life and on management of the disease.
    BMC Neurology 11/2013; 13(1):177. · 2.49 Impact Factor
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    ABSTRACT: There is an urgent need to identify the best strategies to prevent the loss of natalizumab (N) beneficial effects after its suspension. The objective is to evaluate the clinical and radiological disease activity and to test the efficacy of immunomodulatory/immunosuppressive drugs (IT) after N suspension. Clinical and radiological data from 54 patients 2 years before treatment (pre-N), during treatment (on-N) and after interruption, during 1-year follow-up (post-N) were retrospectively collected. Annualized relapse rate (ARR), expanded disability status scale (EDSS), presence of new T2 lesions and Gd+ (gadolinium enhancing) T1 lesions were evaluated. Pre-N ARR at 1 year was 1.74 while post-N ARR was 0.94 (p = 0.0053). We observed that post-N disease activity never raised over pre-N levels, neither post-N ARR nor post-N EDSS. In patients retreated with N after suspension, post-N ARR was significantly lower than pre-N ARR (p = 0.017), but not in patients treated with other IT or in patients not treated with any disease modifying drugs (DMD). The mean time of freedom from new T2 lesions and new Gd+ lesions was lower in post-N period compared to on-N (T2 lesions p = 0.0000, Gd+ lesions p = 0.0000). In conclusion, a "rebound" pattern was not identified in our cohort, though the disease activity rapidly returned after N, regardless of the treatment used.
    Neurological Sciences 08/2013; 35(3). · 1.50 Impact Factor
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    ABSTRACT: Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao's brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms.
    PLoS ONE 06/2013; 8(6):e67357. · 3.53 Impact Factor
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    ABSTRACT: We performed a case-control study in 2,555 multiple sclerosis (MS) Sardinian patients and 1,365 healthy ethnically matched controls, analyzing the interactions between HLA-DRB1-DQB1 haplotypes and defining a rank of genotypes conferring a variable degree of risk to the disease. Four haplotypes were found to confer susceptibility (*13∶03-*03∶01 OR = 3.3, Pc 5.1×10(-5), *04∶05-*03∶01 OR = 2.1, Pc 9.7×10(-8), *15∶01-*06∶02 OR = 2.0, Pc = 9.1×10(-3), *03∶01-*02∶01 OR = 1.7 Pc = 7.9×10(-22)) and protection (*11, OR = 0.8, Pc = 2.7×10(-2), *16∶01-*05∶02 OR = 0.6, Pc = 4.8×10(-16), *14∶01-4-*05∶031 = OR = 0.5, Pc = 9.8×10(-4) and *15∶02-*06∶01 OR = 0.4, Pc = 5.1×10(-4)). The relative predispositional effect method confirms all the positively associated haplotypes and showed that also *08 and *04 haplotypes confers susceptibility, while the *11 was excluded as protective haplotype. Genotypic ORs highlighted two typologies of interaction between haplotypes: i) a neutral interaction, in which the global risk is coherent with the sum of the single haplotype risks; ii) a negative interaction, in which the genotypic OR observed is lower than the sum of the OR of the two haplotypes. The phylogenic tree of the MS-associated DRB1 alleles found in Sardinian patients revealed a cluster represented by *14∶01, *04∶05, *13∶03, *08∶01 and *03∶01 alleles. Sequence alignment analysis showed that amino acids near pocket P4 and pocket P9 differentiated protective from predisposing alleles under investigation. Furthermore, molecular dynamics simulation performed on alleles revealed that position 70 is crucial in binding of MBP 85-99 peptide. All together, these data suggest that propensity to MS observed in Sardinian population carried by the various HLA-DRB1-DQB1 molecules can be due to functional peculiarity in the antigen presentation mechanisms.
    PLoS ONE 04/2013; 8(4):e59790. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. OBJECTIVES: The objectives of this study were to confirm this association and evaluate its role in clinical features. METHODS: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). RESULTS: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10-11), and 123 MS and 10 HCs (p = 2.59 × 10-23), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). CONCLUSION: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.
    Multiple Sclerosis 02/2013; · 4.86 Impact Factor
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    ABSTRACT: Background: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. Objectives: The objectives of this study were to confirm this association and evaluate its role in clinical features. Methods: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). Results: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10−11), and 123 MS and 10 HCs (p = 2.59 × 10−23), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). Conclusion: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.
    Multiple Sclerosis 02/2013; · 4.86 Impact Factor
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    ABSTRACT: LMNA gene mutations are associated with cardiac and skeletal muscle alterations. A cohort of 21 mutated individuals was assessed with clinical and instrumental investigations over the years. The median observation period was 6 years. Cardiac compromise was detected in 16 patients. Bradyarrhythmias were the most frequent manifestations, followed by supraventricular arrhythmias. Two individuals suffered from nonsustained and 1 from sustained ventricular tachyarrhythmias. Dilated cardiomyopathy was detected in 3 patients. Evaluation of the frequencies of the clinical expressions showed a high probability of suffering from analogue heart compromise in study subjects bearing the same LMNA gene mutation. Cardiac involvement represents a very common phenotypic expression of LMNA gene mutation. Subjects sharing common genetic background seem to suffer from analogue pattern of cardiac manifestation.
    Muscle & Nerve 08/2012; 46(2):187-92. · 2.31 Impact Factor
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    ABSTRACT: Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients' genotypic risk of developing MS. A transmission disequilibrium test (TDT) of the DRB1*-DQB1* haplotypes in 943 trio families, confirmed a higher than expected transmission rate (over-transmission) of the *13:03-*03:01 (OR = 2.9, P = 7.6×10(-3)), *04:05-*03:01 (OR = 2.4, P = 4.4×10(-6)) and *03:01-*02:01 (OR = 2.1, P = 1.0×10(-15)) haplotype. In contrast, the *16:01-*05:02 (OR = 0.5, P = 5.4×10(-11)) and the *15:02-*06:01 (OR = 0.3, P = 1.5×10(-3)) haplotypes exhibited a lower than expected transmission rate (under-transmission). The independence of the transmission of each positively and negatively associated haplotype was confirmed relative to all positively associated haplotypes, and to the negatively associated *16:01-*05:02 haplotype. In patients, carriage of two predisposing haplotypes, or of protective haplotypes, respectively increased or decreased the patient's risk of developing MS. The risk of MS followed a multiplicative model of genotypes, which was, in order of decreasing ORs: *04:05-*0301/*03:01-*02:01 (OR = 4.5); *03:01-*02:01/*03:01-*02:01 (OR = 4.1); and the *16:01-*05:02/*16:01-*0502 (OR = 0.2) genotypes. Analysis of DRB1 and DQB1 protein chain residues showed that the Val/Gly residue at position 86 of the DRB1 chain was the only difference between the protective *16:01- *15:02 alleles and the predisposing *15:01 one. Similarly, the Ala/Val residue at position 38 of the DQB1 chain differentiated the positively associated *06:02 allele and the negatively associated *05:02, *06:01 alleles. These findings show that the association of specific, independent DRB1*-DQB1* haplotypes confers susceptibility or resistance to MS in the MS-prone Sardinian population. The data also supports a functional role for specific residues of the DRB1 and DQB1 proteins in predisposing patients to MS.
    PLoS ONE 04/2012; 7(4):e33972. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate the incidence and dose-dependency of mitoxantrone (MTX)-associated acute myelocytic leukemia (AML) in the network of Italian multiple sclerosis (MS) clinics. METHODS: We performed a multicenter retrospective cohort study of patients treated with MTX in MS centers under the Italian national health care system between 1998 and 2008. Demographic, disease, treatment, and follow-up information were collected using hospital records. RESULTS: Data were available for 3,220 patients (63% women) from 40 Italian centers. Follow-up (mean ± SD) was 49 ± 29 months (range 12-140 months). We observed 30 cases of AML (incidence 0.93% [95% confidence interval 0.60%-1.26%]). The mean cumulative dose was higher in patients with AML (78 vs 65 mg/m(2), p = 0.028). The median interval from the start of therapy to AML diagnosis was longer than expected at 33 months (range 13-84 months); 8 patients (27%) developed AML 4 years or more after the first MTX infusion. The rate of mortality associated with AML was 37%. CONCLUSIONS: This higher than expected risk of AML and related mortality requires that treatment decisions must be made jointly between clinicians and patients who understand their prognosis, treatment options, and treatment-related risks. The now large exposed MS population must be monitored for hematologic abnormalities for at least 6 years from the end of therapy, to ensure the rapid actions needed for early diagnosis and treatment of AML
    Neurology 11/2011; 77(21-77):1887-95.. · 8.30 Impact Factor
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    ABSTRACT: Sardinia is a known high-risk area for multiple sclerosis (MS), but no data for south-western Sardinia (SWS) are available. SWS has a genetically homogeneous population, apart from St Peter Island, and represents a peculiar environment related to the industrial, mineralogical and military economy. To estimate prevalence and incidence and to evaluate temporal trends and geographical distribution of MS in SWS. Methods: MS prevalence was evaluated on 31 December 2007 and crude mean annual incidence rate was defined between 2003 and 2007. Temporal trend in MS incidence was assessed using the Armitage test. To identify MS clusters, Standard Morbidity Ratio (SMR) was calculated for each village and geographical distribution prevalence by means of a Bayesian hierarchical model. Total crude prevalence rate was 210.4 (95% CI 186.3-234.5): 280.3 (95% CI 241.4-319.3) for females, 138 (95% CI 110.1-165.8) for males. The crude mean annual incidence rate was 9.7/100,000 (95% CI 3.4-13.2): 4.7/100,000 (95% CI 2.4-17.0) and 14.6/100,000 (95% CI 11.8-34.8) for males and females respectively. MS incidence has increased over the last 50 years. Cluster analysis showed an SMR of 0.2 (95% CI 0.05-0.68, p = 0.002) on the island of San Pietro, and 2.0 (95% CI 1.35-2.95, p = 0.001) in Domusnovas. Spatial distribution of MS was confirmed by Bayesian geographical analysis. Our data confirm Sardinia as a high-risk area for MS and support the relevance of genetic factors in MS, as evidenced in St Peter Island. However, we found an unexpectedly high MS prevalence in one village, in particular in males, suggesting an environmental influence on MS occurrence.
    Multiple Sclerosis 06/2011; 17(11):1282-9. · 4.86 Impact Factor
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    ABSTRACT: We report our experience in long-term treatment of relapsing remitting multiple sclerosis patients with natalizumab (N). In November 2009 we evaluated 141 patients (126 AIFA criterion A, 15 AIFA criterion B). We paid particular attention to the treatment period and the patients follow-up; during the whole therapeutic program, they undergone to clinical and radiological evaluation for every 3 months. The compliance was optimal and we found no significant side effects. 26 patients completed the 24 monthly doses. After 24 months 51% of patients were free from disease activity. We found a reduction in relapses and EDSS, moreover the clinical improvement was also confirmed by radiological examinations. Our results show that the best therapeutic results are achieved by early initiation of treatment.
    Neurological Sciences 01/2011; 31 Suppl 3(S3):309-12. · 1.50 Impact Factor