1,720,986 research outputs found
Fatigue in multiple sclerosis: a clinical and MRI studi
Full text linkLa fatica è un sintomo molto commune nella sclerosis multipla (SM), identificato come una sensazione insormontabile di stanchezza, mancanza di energia e sensazione di esaurimento. Molti studi di neurofisiologia e neuroimmagini hanno mostrato una reclutamento anomalo dei circuiti corticali e sottocorticali nei pazienti con SM e fatica, supportando l’ipotesi che questo sintomo abbia un’origine central. Sebbene le specifiche aree corticali coinvolte non siano ancora state identificate, ci sono alcune evidenze del coinvolgimento del giro precentrale, del giro cingolato, dell’insula e del cervelletto.
Lo scopo principale di questo studio è definire l’attivazione di specifiche aree cerebrali in risonanza magnetica funzionale (RM-f) in pazienti affetti da SM con fatica, in condizioni di riposo e durante un compito motorio.
I pazienti con SM sano stati selezionati dall’Ambulatorio sclerosis multipla del Policlinico GB Rossi di Verona, con età compresa tra 18 e 55 anni, con decorso recidivante-remittente (RR), punteggio inferior a 4,5 alla scala di disabilità (EDSS), che lamentano il sintomo fatica per più del 50% della giornata per almeno 6 settimane, e un punteggio medio alla Fatigue severity scale (FSS) maggiore o uguale a 5.0. Un gruppo di pazienti con SM RR senza fatica (FSS medio inferiore a 5.0), omogenei per sesso, età e disabilità ai pazienti con fatica, è stato incluso. I due gruppi includono pazienti destrimani. I pazienti selezionati non devono presentare sintomi neurologici all’arto superior di destra che possano interferire con il compito motorio richiesto per lo studio in RM-f. Un punteggio alla scala Montgomery and Asberg Depression Rating rappresenta un criterio di esclusione. Pazienti in terapia con farmaci contrastanti la fatica (amantadine e 4-aminopiridina) durante il mese precedente saranno esclusi dallo studio. Un gruppo di soggetti sani omogenei per sesso ed età ai pazienti è stato selezionato come controllo per lo studio radiologico. Pazienti e controlli sani sono stati sottoposti a RM convenzionale e funzionale.
Sono stati inclusi 6 pazienti con fatica, 6 pazienti senza fatica e 3 controlli sani, tutti sottoposti a RM. Pazienti affetti da SM hanno mostrato un’attivazione correlate al compito motorio nell’area sensorimotoria primaria, area supplementare motoria, giro frontale inferior e cervelletto bilateralmente. Inoltre, I pazienti affetti da fatica hanno mostrato una maggiore attivazione cerebrale dell’area motoria rispetto ai pazienti senza la fatica e ai controlli.Fatigue is a very common symptom in multiple sclerosis (MS), described as an overwhelming sense of tiredness, lack of energy and feeling of exhaustion. Several electrophysiological and imaging studies have shown an abnormal recruitment of cortical and subcortical networks in MS patients with fatigue, supporting the hypothesis of a central genesis of this symptom. Although the specific central nervous system regions involved have not been clearly identified, there is some evidence that the precentral gyrus, cingulate gyrus, insula and cerebellum are involved.
The main purpose of this study is to define the functional MRI (f-MRI) activation pattern of brain areas in MS patients with fatigue during resting state and during a motor task.
MS patients will be selected from the MS Outpatients Clinic at G. Rossi Hospital, Verona, aged 18-55 years, with a relapsing-remitting (RR) course, Expanded Disability Status Scale (EDSS) score ≤4.5, complaint of fatigue for ≥50% of days for >6 weeks, and mean Fatigue Severity Scale (FSS) score ≥5.0. Patients will be selected for right-hand dominance. A group of RRMS patients without fatigue and with mean FSS score =17 at the Montgomery and Asberg Depression Rating Scale will be an exclusion criteria. Patients on therapy with anti-fatigue drugs (amantadine and 4-aminopyridine) within the previous month will be excluded. A group of healthy subjects, age- and gender-matched to MS patients, will be enrolled as controls for MRI evaluation. Patients and controls will undergo conventional and f-MRI scans. T1 lesion load, T2 lesion load will be calculated on conventional MRI scans. Functional MRI will be performed in resting state and during a simple motor task.
To date, twelve MS patients, six with and six without fatigue, and three healthy controls have undergone MRI.
MS patients showed activation related to motor-task in primary somatosensory area bilaterally, supplementary motor area, inferior frontal gyrus and cerebellum bilaterally. Moreover, patients complaining fatigue appeared to activate more motor brain areas compared to both MS patients without fatigue and controls
Investigational immunosuppressants in early stage clinical trials for the treatment of multiple sclerosis
No full textMultiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS. The websites clinicaltrials.gov, clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and phase 3 trials starting from 2012. Twelve drugs were identified, including 7 monoclonal antibodies and 5 small molecules. Expert opinion. Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with relapsing disease and using efficacy endpoints based on magnetic resonance imaging measures of inflammatory activity. Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs, suggesting that mechanisms of action that have already shown promise for MS treatment are being exploited to find new therapies with improved safety, tolerability, and convenience of dosing. Clinical trials of immunosuppressants for progressive MS are largely lacking
Primary progressive multiple sclerosis: current therapeutic strategies and future perspectives
No full textMultiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents. Expert Commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. Other emerging treatment strategies include cell metabolism modulation and inflammatory pathways inhibition, which are being investigated in several ongoing phase II and III placebo-controlled trials. Future PP MS trials will need to systematically include efficacy endpoints other than physical disability alone, such as cognition, quality of life, advanced MRI measures and molecular biomarkers
Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis
Full text linkFingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS), a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-β1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management
Correlation between cerebrospinal fluid markers of neurodegeneration and MRI measures of gray matter pathology in multiple sclerosis
No full textObjective
Pathological studies established that irreversible neurological disability in multiple sclerosis (MS) is associated with axonal and neuronal injury which can be detected by advanced cerebrospinal fluid (CSF) analysis and MRI techniques. However, the link between the two approaches and the advantage of combining them have not been explored in detail. This cross-sectional study is aimed at examining the correlation between CSF-detected neurodegeneration and MRI gray matter involvement in MS.
Materials and Methods
Starting from December 2011, consecutive patients with clinically isolated syndrome (CIS) or MS, diagnosed according to 2010 McDonald's criteria and with a CSF sample stored at Verona University Hospital Laboratory of Neuropathology have been considered eligible for the study. Enrolled subjects underwent CSF analysis, including ELISA to determine neurofilament light chain (NFL) concentration, and brain MRI, including volumetric T1-weighted, Fast Fluid Attenuated Inversion Recovery (FLAIR), and Double Inversion Recovery (DIR) sequences. All patients had a baseline neurological examination to estimate expanded disability status scale (EDSS) score. The correlation between CSF NFL concentration and MRI markers of gray matter pathology was analyzed as well as the association between these variables and neurological disability.
Results
As of May 2014, 40 eligible patients have been identified of which 25 have completed CSF analysis and MRI protocol. The study group is made of 17 females and 8 males with median age at inclusion of 31.5 (16.7-59.5) years. Three subjects have a CIS, 20 relapsing-remitting and 2 primary progressive MS with a median interval between clinical onset and study entry of 4.9 (0.1-379.5) months. Median EDSS score at CSF collection was 2.0 (0-4.0). Median CSF NFL concentration was 3304 (808-15000) ng/l and it did not change significantly according to sex, age, clinical course, disease duration and EDSS score. All patients had dissemination of lesions in space on MRI, while 8 subjects (32%) had one or more cortical lesions on DIR images. Median NFL concentration was 2854 (808-9973) ng/l in CSF of patients with evidence of cortical involvement and 3718 (1120-15000) ng/l in CSF of cases with no cortical lesions (p=0.6).
Discussion and Conclusions
In the present series, patients with MS and CIS had CSF NFL concentration well above the normal upper limit reported by previous studies. Based on preliminary results, NFL levels appear to be similar in the CSF of MS cases with and without cortical lesions detected on MRI. Further research on a larger sample and with additional measures is warranted
Prognostic value of multimodal evoked potentials in multiple sclerosis: the EP score.
No full textEvoked potentials (EPs) have long been used as diagnostic tools in multiple sclerosis (MS), although their importance decreased as magnetic resonance imaging (MRI) became available. However, the prognostic value of EPs in MS has not been completely established. The aim of the study was to analyze the prognostic significance of EPs in a cohort of MS cases. From the Verona University Hospital MS Clinic database we retrospectively identified 80 MS patients who underwent a complete neurophysiological evaluation, including visual, brain stem, somatosensory and motor EPs and who were followed for at least 5 years after the study. EPs abnormalities were quantified through an index of global EPs alteration (EP score). The relationship between EP score and disability in terms of Expanded Disability Status Scale (EDSS) was analyzed by the Kaplan-Meier survival method and Spearman ρ correlation coefficient. ROC curves were used to determine the best EP score cut off to predict different EDSS endpoints. For each endpoint, sensitivity, specificity, positive and negative predictive value of EP score were calculated. We found a significant correlation (p < 0.001) between EP score and EDSS score at the time of neurophysiological study and at 1, 3 and 5 years of follow-up, particularly for motor and somatosensory EPs. Kaplan-Meier curves confirmed an increased risk of disability in those patients with EP score higher than the median value. EP score of 8 or 9 showed the highest sensitivity and specificity in predicting EDSS 4.0 and 6.0. EPs are reliable procedures to predict disability in MS patients. The correlation between EPs abnormalities and EDSS is higher than between conventional MRI and EDSS
Smoking-related cue reactivity in a virtual reality setting: association between craving and EEG measures
Full text linkBACKGROUND: Cue-reactivity is the array of responses that smokers exhibit when exposed to conditioned and contextual stimuli previously associated to substance use. The difficulty to experimentally recreate the complexity of smokers' spatial experience and context requires more ecological models. Virtual reality (VR) creates a state of immersion close to reality allowing controlled assessments of behavioral responses. To date, no studies investigated brain activation associated to smoking cue-reactivity in VR using electroencephalography (EEG).AIMS: To investigate whether a VR cue-reactivity paradigm (a) may increase smoking craving, (b) is feasible with EEG recording, and (c) induces craving levels associated to EEG desynchronization.METHODS: Smokers (N=20) and non-smokers (N=20) were exposed to neutral and smoking-related VR scenarios, without and with smoking conditioned stimuli, respectively. EEG was recorded from occipital and parietal leads throughout the sessions to assess alpha band desynchronization. Smoking and food craving and presence visual analogue scales (VAS) were assessed during the session.RESULTS: To be smoker, but not non-smoker, significantly influenced smoking craving VAS induced by smoking cue VR but not by neutral VR. No significant food craving changes was observed during the VR sessions. The new finding was that EEG alpha band power in posterior leads was significantly increased by the smoking context scenario only in smokers, and that the degree of smoking (i.e., heavy vs. light) was significantly associated to this neurophysiological measure.CONCLUSIONS: This study demonstrated, for the first time, the feasibility of EEG recording in a VR setting, suggesting that EEG desynchronization may be a neurophysiological marker of smoking cue-reactivity
Long survival and clinical stability in Marburg's variant multiple sclerosis.
No full textMarburg’s variant multiple sclerosis (MS) is an acute and aggressive atypical form of MS, leading frequently to death in few months. A 32-year-old man with motor and sensory symptoms suggestive of acute myelopathy, rapidly followed by cerebellar dysfunction and consciousness impairment. Clinical, laboratory and radiological evaluations suggested a central nervous system demyelinating disease. The diagnosis was Marburg’s variant MS, usually leading to death in short time. He underwent different treatments, including steroids, cyclophosphamide, plasma exchange and lastly interferon-beta. The patient reached clinical stability with severe residual disability, persistent after 3 years from onset. This observation suggests that subjects with Marburg’s MS might reach long clinical stability
Physical disability and cognitive impairment evolution in benign multiple sclerosis: a five years prospective study
No full textBackground. Benign multiple sclerosis (BMS) definition is generally based on a minimum disease duration (DD) during which a maximum expanded disability status scale (EDSS) score is reached. However, EDSS does not account sufficiently for cognitive deficits, which may be as disabling as motor impairment
Objectives. To study prospectively the evolution of physical disability and cognitive performance of BMS patients
Methods. Among 300 patients seen at Verona MS Center between January and June 2008, 36 patients with relapsing-remitting (RR) course, DD ≥10 years, and EDSS score ≤2.0 were defined BMS cases. Of these, 24 gave consent for inclusion in the study along with 13 sex- and age-matched non-benign MS (n-BMS) patients with RR course, DD≥10 years and EDSS score from 2.5 to 4.5. The two groups were followed for 5 years with neurological examination at least every year and neuropsychological assessment at baseline and at study conclusion. Conventional MRI analysis was done for patients who had a brain scan with the same protocol in 2008 and 2013.
Results. At inclusion BMS subjects were 41±8 years old (mean±standard deviation) with median DD of 15 years (range 11-29) and median EDSS score 1.5 (range 0-2), while n-BMS patients were 46±8 years old, had median DD of 16 years (range 10-27) and median EDSS score 3.0 (range 2.5-4.5). At baseline 16% of patients in both groups failed two or more neuropsychological tests. After 5 years, 23 BMS and 12 n-BMS patients had completed the study. The EDSS score worsened in 8% and 46% of cases, respectively (p=0.008), while the proportion of patients with ≥2 failed neuropsychological tests at 5 years increased at 25% in both groups. BMS and n-BMS patients who failed ≥2 tests had a significantly worse work and financial status both at baseline and at 5 years follow-up even after excluding subjects with EDSS score >3.5. Brain MRI T2 lesion location and number increase over time were not significantly associated with neurological and cognitive outcomes.
Conclusions. Patients classified as having BMS according to widely used criteria had better physical disability outcome at 5 years compared to n-BMS cases. However, rates of initial cognitive impairment and neuropsychological decline over time did not differ between the two groups, including the possible impact on work and social functioning. Neuropsychological testing is essential even in MS patients with minimal or no physical disability given the distinct trajectories followed by disease progression in cognitive and motor domains
- …
