Sant'Antonio Abate, Italy
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Marziniak M.,Kbo Isar Amper Klinikum Munich Ost | Ghorab K.,Limoges University Hospital Center | Kozubski W.,Poznan University of Medical Sciences | Pfleger C.,University of Aalborg | And 3 more authors.
Multiple Sclerosis and Related Disorders | Year: 2016

In the past 5 years, the combination of developments in diagnostic strategy and approval of new disease-modifying therapies has provided an opportunity to achieve dramatic improvements in patient outcomes in multiple sclerosis (MS). However, across Europe there are several factors that may prevent patients from receiving the best therapy at the appropriate time, and there is variation among countries in terms of which of these factors are most relevant. Here, we review current MS clinical practices in a number of countries in the European Union to identify differences regarding initiation of treatment in patients with clinically isolated syndrome or relapsing-remitting MS, and differences in the timing of treatment switch or escalation. While recognizing that policy is not static in any country, we believe that patients' interests would be better served if a European treatment guideline was developed. Such a guideline could both inform and be informed by national policies, facilitating the dissemination of best clinical practice internationally. © 2016 Elsevier B.V. All rights reserved.


Ghezzi A.,Centro Studi Sclerosi Multipla | Comi G.,Vita-Salute San Raffaele University
Neurological Sciences | Year: 2011

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS. © 2010 Springer-Verlag.


PubMed | kbo Isar Amper Klinikum Munich Ost, University of Coimbra, Centro Studi Sclerosi Multipla, Limoges University Hospital Center and 3 more.
Type: | Journal: Multiple sclerosis and related disorders | Year: 2016

In the past 5 years, the combination of developments in diagnostic strategy and approval of new disease-modifying therapies has provided an opportunity to achieve dramatic improvements in patient outcomes in multiple sclerosis (MS). However, across Europe there are several factors that may prevent patients from receiving the best therapy at the appropriate time, and there is variation among countries in terms of which of these factors are most relevant. Here, we review current MS clinical practices in a number of countries in the European Union to identify differences regarding initiation of treatment in patients with clinically isolated syndrome or relapsing-remitting MS, and differences in the timing of treatment switch or escalation. While recognizing that policy is not static in any country, we believe that patients interests would be better served if a European treatment guideline was developed. Such a guideline could both inform and be informed by national policies, facilitating the dissemination of best clinical practice internationally.


Gonzalez-Rosa J.J.,San Raffaele Scientific Institute | Inuggi A.,San Raffaele Scientific Institute | Blasi V.,San Raffaele Scientific Institute | Cursi M.,San Raffaele Scientific Institute | And 5 more authors.
International Journal of Psychophysiology | Year: 2013

We investigated the neural correlates underlying response inhibition and conflict detection processes using ERPs and source localization analyses simultaneously acquired during fMRI scanning. ERPs were elicited by a simple reaction time task (SRT), a Go/NoGo task, and a Stroop-like task (CST). The cognitive conflict was thus manipulated in order to probe the degree to which information processing is shared across cognitive systems. We proposed to dissociate inhibition and interference conflict effects on brain activity by using identical Stroop-like congruent/incongruent stimuli in all three task contexts and while varying the response required. NoGo-incongruent trials showed a larger N2 and enhanced activations of rostral anterior cingulate cortex (ACC) and pre-supplementary motor area, whereas Go-congruent trials showed a larger P3 and increased parietal activations. Congruent and incongruent conditions of the CST task also elicited similar N2, P3 and late negativity (LN) ERPs, though CST-incongruent trials revealed a larger LN and enhanced prefrontal and ACC activations. Considering the stimulus probability and experimental manipulation of our study, current findings suggest that NoGo N2 and frontal NoGo P3 appear to be more associated to response inhibition rather than a specific conflict monitoring, whereas occipito-parietal P3 of Go and CST conditions may be more linked to a planned response competition between the prepared and required response. LN, however, appears to be related to higher level conflict monitoring associated with response choice-discrimination but not when the presence of cognitive conflict is associated with response inhibition. © 2013.


Ghezzi A.,Centro Studi Sclerosi Multipla | Goretti B.,University of Florence | Portaccio E.,University of Florence | Roscio M.,Centro Studi Sclerosi Multipla | Amato M.P.,University of Florence
Neurological Sciences | Year: 2010

Cognitive impairment has been recently recognized in patients with pediatric multiple sclerosis in more than 30% of cases. Altered functions with variable frequency are: attention, language (receptive, verbal fluency, naming), visual-spatial and motor functions, spatial memory, executive functions and abstract reasoning. Fatigue and affective disorders are associated, but not correlated with cognitive impairment. The frequency and severity of cognitive impairment increase with time. Cognitive impairment has a negative impact on patient's life limiting social, academic and recreational activities. © 2010 Springer-Verlag.


PubMed | Russian National Research Medical University, Hospital Of Pediatria Samic Prof Dr Juan P Garrahan, University of Ottawa, New York University and 3 more.
Type: | Journal: Journal of the neurological sciences | Year: 2016

To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries (rest of World; ROW).Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon -1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [<12 years] and adolescents [12-17 years]).US adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5 kg/m(2)), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon -1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon -1a to another DMT before the end of the observation period.This retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon -1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance.


Waldman A.,Children's Hospital of Philadelphia | Ghezzi A.,Centro Studi Sclerosi Multipla | Bar-Or A.,Montreal Neurological Institute | Mikaeloff Y.,Unite de Reeducation Neurologique Infantile | And 2 more authors.
The Lancet Neurology | Year: 2014

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood-and adolescent-onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. © 2014 Elsevier Ltd.


PubMed | Centro Studi Sclerosi Multipla, Unite de Reeducation Neurologique Infantile, Children's Hospital of Philadelphia, Montreal Neurological Institute and Service de Neurologie Pediatrique
Type: Journal Article | Journal: The Lancet. Neurology | Year: 2014

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood-and adolescent-onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed.


Ghezzi A.,Centro Studi Sclerosi Multipla
Therapeutic Advances in Neurological Disorders | Year: 2010

Multiple sclerosis (MS) in children and adolescents accounts for 3-10% of the whole MS population, and is characterized by a relapsing course in almost all cases. The frequency of relapses is higher than in adult onset MS, at least in the first years of evolution. The objective of treatment is to speed the recovery after a relapse, to prevent the occurrence of relapses, and to prevent disease progression and neurodegeneration. The use of drugs for MS in children and adolescents has not been studied in clinical trials, so their use is mainly based on results from trials in adults and from observational studies. There is a consensus to treat acute relapses with intravenous high-dose corticosteroids. The possibility of preventing relapses and disease progression is based on the use of immunomodulatory agents. Interferon-beta (IFNB) and glatiramer acetate (GA) have been demonstrated to be safe and well tolerated in pediatric MS patients, and also to reduce relapse rate and disease progression. Cyclophosphamide and natalizumab could be offered as second-line treatment in patients with a poor response to IFNB or GA. New oral and injectable drugs will be available in the near future: if safe and well tolerated in the long-term follow up of adults with MS, they could be tested in the pediatric MS population. © The Author(s), 2010.


PubMed | Centro Studi Sclerosi Multipla
Type: Journal Article | Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology | Year: 2013

Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI. The objective of the study is to evaluate the outcome and safety of ET in Italian MS patients. Italian MS centers that are part of the Italian MS Study Group were all invited to participate to this retrospective study. A structured questionnaire was used to collect detailed clinical data before and after the ET. Data from 462 patients were collected in 33 centers. ET consisted of balloon dilatation (93 % of cases) or stent application. The mean follow-up duration after ET was 31 weeks. Mean EDSS remained unchanged after ET (5.2 vs. 4.9), 144 relapses occurred in 98/462 cases (21 %), mainly in RR-MS patients. Fifteen severe adverse events were recorded in 3.2 % of cases. Given the risk of severe adverse events and the lack of objective beneficial effects, our findings confirm that at present ET should not be recommended to patients with MS.

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