Antibiotic Use and Risk of Multiple Sclerosis: A Nested Case-Control Study in Emilia-Romagna Region, Italy.

INTRODUCTION: Known risk factors for multiple sclerosis (MS) include smoking, a low vitamin D status, obesity, and EBV, while the inflammatory feature of the disease strongly suggests the presence of additional infectious agents. The association between use of antibiotics and MS risk that could shed light on these factors is still undetermined. We aimed to evaluate the association between antibiotics and MS risk, in the Emilia-Romagna region (RER), Italy. METHODS: All adult patients with MS seen at any RER MS center (2015-2017) were eligible. For each of the 877 patients included, clinical information was collected and matched to 5 controls (RER residents) (n = 4,205) based on age, sex, place of residence, and index year. Information on antibiotic prescription was obtained through the linkage with the RER drug prescription database. RESULTS: Exposure to any antibiotic 3 years prior to the index year was associated with an increased MS risk (OR = 1.52; 95% CI = 1.29-1.79). Similar results were found for different classes. No dose-response effect was found. DISCUSSION/CONCLUSIONS: Our results suggest an association between the use of antibiotics and MS risk in RER population. However, further epidemiological studies should be done with information on early life and lifestyle factors.

Health-related quality of life in clinically isolated syndrome and risk of conversion to multiple sclerosis.

BACKGROUND AND OBJECTIVES: A few studies have found that low scores on self-rated health and quality of life measures are associated with following worsening disability in multiple sclerosis (MS). We wanted to estimate the association between self-rated quality of life scores among patients with clinically isolated syndrome (CIS) and the risk of subsequent conversion to definite MS. METHODS: One hundred sixty-two patients from the GERONIMUS cohort with a symptom or sign suggestive of MS and without a definite diagnosis of MS at the time of inclusion were asked to evaluate their health-related quality of life according to MSQoL-54 scale. They were clinically assessed and mood and depression scales were applied. The association between the scores of these scales and the risk of converting to definite MS during a 5-year follow-up was estimated using the Cox- proportional hazard regression model. RESULTS: Quality of life at examination was significantly lower compared to those of an age- and sex-adjusted general Italian population. During the follow-up, 116 patients (72%) converted to definite MS. No significant predictive effects were found for the summary scales of MSQol-54 or other scales. The estimates did not change after adjusting for age, sex, BMI, education, MRI findings, Expanded Disability Status Scale (EDSS) score, and treatment at time of examination. CONCLUSION: Persons with CIS in this cohort reported reduced self-rated quality of life compared to the general population, but variation in these scores was not associated with subsequent conversion from CIS to clinical definite MS.

First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. METHODS: In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued. RESULTS: Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. CONCLUSION: The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study.

The aim of the study was to estimate the rate of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to investigate variables predicting conversion in a cohort of patients presenting with symptoms suggestive of MS. Patients with a first symptom suggestive of MS in the preceding 6 months and exclusion of other diseases were enrolled in an observational prospective study from December 2004 through June 2007. Conversion from CIS to MS according to both McDonald and Clinically Defined Multiple Sclerosis (CDMS) criteria was prospectively recorded until March 2010. The multivariate Cox proportional hazard model was used to assess the best predictive factors of conversion from CIS to MS. Among 168 patients included in the analysis, 122 converted to MS according to McDonald criteria whereas 81 converted to MS according to CDMS criteria. The 2-year probability of conversion was 57% for McDonald Criteria and 36% for CDMS criteria. Variables at enrolment significantly associated with conversion according to McDonald criteria were age and positivity for Barkhof criteria, and according to Poser's CDMS criteria, age, positivity for Barkhof criteria and no disease modifying therapy. In this large prospective cohort study the conversion rate from CIS to MS in patients presenting with recent symptoms suggestive of MS was within the range of previous observational studies and lower than that reported in the placebo arm of randomized trials. We confirm the prognostic value of MRI in addition to the previous experimental data on the protective role of disease-modifying therapies.

A pilot study for rehabilitation of central executive deficits after traumatic brain injury.

PRIMARY OBJECTIVE: An impairment of the central executive system (CES) of working memory (WM) is a common consequence of traumatic brain injury (TBI), and may also explain deficits in divided attention, long-term memory and executive functions. Here we investigated the efficacy of a rehabilitative program (working memory training: WMT) targeting the CES in improving WM and other cognitive functions dependent on this system. METHODS AND PROCEDURES: Nine TBI patients with severe WM deficits underwent the WMT (experimental training). The WMT was preceded by a general stimulation training (GST; control training). Patients' cognitive performance was evaluated at the admission, after the GST and at the end of the WMT. MAIN OUTCOMES AND RESULTS: Whereas the GST had no effect on patients' performance, after the WMT patients improved in all the cognitive functions dependent on the CES, but not in those functions not thought to tap this system. Importantly, a beneficial WMT effect was found on patients' everyday life functioning. CONCLUSIONS: The results support the efficacy of the WMT in recovering CES impairments.

Central executive system impairment in traumatic brain injury.

PRIMARY OBJECTIVE: This study investigated whether cognitive impairment after traumatic brain injury (TBI) can be considered a consequence of (1) a speed processing deficit or (2) an impairment of the Central Executive System (CES) of working memory. METHODS AND PROCEDURES: Thirty-seven TBI patients underwent a standardized battery of neuropsychological tests evaluating speed processing, sustained attention, short-term memory, working memory, divided attention, executive functions and long-term memory. MAIN OUTCOMES AND RESULTS: Patients showed severe deficits in working memory, divided attention, executive functions and long-term memory. Divided attention, long-term memory and executive functions deficits significantly correlated with working memory, but not with speed processing deficits. Moreover, multiple regression analyses showed that a CES impairment and not a speed processing deficit predicted divided attention, executive functions and long-term memory deficits. The severity and the site of brain lesions did not predict the level of CES or speed processing impairment. CONCLUSIONS: The cognitive impairment following TBI seem to be caused by an impairment of the Central Executive System, rather than a speed processing deficit.

Risk factors for cryptogenic and idiopathic partial epilepsy: a community-based case-control study in Copparo, Italy.

OBJECTIVES: The etiology of epilepsy remains unknown in most cases. We sought to investigate the role of some pre-, peri- and postnatal factors in the etiology of idiopathic and cryptogenetic partial epilepsy. METHODS: We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The study was performed in 55 cases and 165 controls. A standardized questionnaire was used to collect information in face-to-face interviews. RESULTS: Multivariate logistic regression analysis found that a personal history of febrile convulsions [odds ratio (OR) = 4.01, 95% confidence interval (CI) = 1.3-19.1] and a family history of seizures in first-degree relatives (OR = 4.5, 95% CI = 1.8-18.6) were independent risk factors for the condition under study. We failed to demonstrate an association between partial epilepsy and previously suggested perinatal risk factors. CONCLUSION: The findings of this study further support the hypothesis of a genetic propensity for seizures, which may be expressed early by the occurrence of febrile convulsions.

Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case-control study.

We analyzed the association between the environmental exposure to trace elements and the risk of sporadic amyotrophic lateral sclerosis (ALS) in a population-based case-control study in the Emilia-Romagna region in northern Italy. We evaluated exposure to selected trace elements by measuring toenail concentrations of the same by means of inductively coupled plasma optical spectrometry and instrumental neutron activation analysis. The final number enrolled in the study was 22 patients and 40 controls. Disease progression, assessed through a clinical score, was generally unassociated with toenail trace element levels, with the exception of an inverse relation with zinc and selenium content and a direct correlation with copper concentration. In logistic regression analysis, we found no evidence of an association between ALS risk and toenail content of cadmium, lead, copper, zinc, manganese, selenium, chromium, cobalt, iron, and aluminum. This investigation does not suggest a major role in sporadic ALS etiology of environmental exposure to these trace elements, though results for zinc, selenium, and copper should be evaluated with caution due to the potential limitations of toenails as biomarkers of chronic exposure in patients.