Publications by authors named "Antonio Carotenuto"

62 Publications

Cognitive trajectories in multiple sclerosis: a long-term follow-up study.

Neurol Sci 2021 Jun 8. Epub 2021 Jun 8.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Background: Cognitive impairment occurs in multiple sclerosis (MS) and undergoes a progressive worsening over disease course. However, clinicians still struggle to predict the course of cognitive function. To evaluate baseline clinical and imaging predictors of cognitive abilities worsening over time, we performed a latent trajectory analysis for cognitive performances in MS patients, up to 15 years from disease onset.

Methods: We collected age, sex, education, dominant and non-dominant 9-hole peg test (9HP) and timed 25-foot walk (T25-FW) as well as MRI measures (grey matter volume and lesion load) within 6 months from disease diagnosis for relapsing-remitting MS (RR-MS) patients. At diagnosis and over the follow-up, we also assessed cognitive status through the symbol digit modalities test (SDMT). Cognitive impairment was defined by applying age-, gender- and education-adjusted normative values. Group-based trajectory analysis was performed to determine trajectories, and the predictive value of clinical and imaging variables at baseline was assessed through multinomial logistic regression.

Results: We included 148 RR-MS (98 females and 50 males). Over 11 ± 4 year follow-up, 51.4% remained cognitively stable whereas 48.6% cognitively worsened. Cognitively worsening patients had a higher T25FW time (p = 0.004) and a reduced hippocampal volume at baseline (p = 0.04).

Conclusion: Physical disability as well as hippocampal atrophy might depict patients at risk of cognitive worsening over the disease course. Therefore, using such predictors, clinicians may select patients to carefully evaluate for cognitive impairment as to eventually introduce cognitive rehabilitation treatments.
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http://dx.doi.org/10.1007/s10072-021-05356-2DOI Listing
June 2021

Digital Technology in Clinical Trials for Multiple Sclerosis: Systematic Review.

J Clin Med 2021 May 26;10(11). Epub 2021 May 26.

Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, 80138 Naples, Italy.

Clinical trials in multiple sclerosis (MS) have been including digital technology tools to overcome limitations in treatment delivery and disease monitoring. In March 2020, we conducted a systematic search on pubmed.gov and clinicaltrials.gov databases (with no restrictions) to identify all relevant published and unpublished clinical trials, in English language, including MS patients, in which digital technology was applied. We used "multiple sclerosis" and "clinical trial" as the main search words, and "app", "digital", "electronic", "internet" and "mobile" as additional search words, separately. Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Digital technology has been used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms (e.g., electronic recording of motor performance). Other clinical trials have been using digital technology for monitoring symptoms that would be otherwise difficult to detect (e.g., fatigue, balance), for measuring treatment adherence and side effects, and for self-assessment purposes. Collection of outcome measures is progressively shifting from paper-based on site, to internet-based on site, and, in the future, to internet-based at home, with the detection of clinical and treatment features that would have remained otherwise invisible. Similarly, remote interventions provide new possibilities of motor and cognitive rehabilitation.
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http://dx.doi.org/10.3390/jcm10112328DOI Listing
May 2021

Needs and Experiences of Children and Adolescents with Pediatric Multiple Sclerosis and Their Caregivers: A Systematic Review.

Children (Basel) 2021 May 25;8(6). Epub 2021 May 25.

Department of Psychology, Maynooth University, Maynooth W23 F2K8, Ireland.

In the present study we conduct a systematic review to evaluate the needs and experience of people with pediatric multiple sclerosis (MS) and their caregivers. The literature search was conducted across 10 academic databases, adhering to PRISMA-P guidelines. Quality appraisal was conducted using the mixed method appraisal test for individual studies, and GRADE-CERQual to establish overall confidence of findings. Results were analyzed using a process of narrative synthesis. We identified 26 studies which included 2253 children/adolescents with MS (CAMS) and 1608 caregivers. MS was reported to negatively impact experiences for CAMS in domains such as of school performance, social relationships, mental health, and overall physical functioning. Specifically, fatigue and social support were reported as the most important barriers and facilitators for CAMS, respectively. In terms of caregiver experience, negative impacts were reported on social functioning, mental health, and quality of life. Additionally, lack of awareness concerning MS was one of the biggest challenges reported. Caregivers expressed needs for psychological and social support. This study provides the first evidence regarding the needs and experiences of CAMS and their caregivers. Findings can be used to address policy gaps for supporting families affected by pediatric MS.
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http://dx.doi.org/10.3390/children8060445DOI Listing
May 2021

Interplay Between Cognitive and Bowel/Bladder Function in Multiple Sclerosis.

Int Neurourol J 2021 May 6. Epub 2021 May 6.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, 'Federico II' University, Via Pansini 5, 80131, Naples, Italy.

Purpose: to evaluate the prevalence of bowel/bladder dysfunction in multiple sclerosis (MS) and the association with cognitive impairment.

Methods: We prospectively enrolled 150 MS patients. Patients were administered the Symbol Digit Modality Test (SDMT), and filled the Neurogenic Bowel Dysfunction Score (NBDS) and the Actionable Bladder Symptom Screening Tool (ABSST). Association between bowel/bladder dysfunction and cognitive function was assessed through hierarchical regression models using SDMT and clinic-demographic features as independent variables and NBDS or ABSST score as dependent variables.

Results: Prevalence for bowel/bladder deficit was 44.7%, with 26 patients (17.3%) suffering from bowel deficits and 60 patients (40%) from bladder deficits. Total NBDS and ABSST correlated with SDMT (coeff. = -0.10, p<0.001 and coeff. = -0.03, p=0.04, respectively) after correction for demographic features and physical disability.

Conclusions: Bowel/bladder disorders are common in MS and are associated with both physical and cognitive disability burden. As SDMT is embedded into routine clinical assessment, a lower score may warrant investigating bowel/bladder dysfunction due their strong interplay.
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http://dx.doi.org/10.5213/inj.2040346.173DOI Listing
May 2021

A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis.

Brain Sci 2021 Apr 16;11(4). Epub 2021 Apr 16.

Department of Neurosciences, Reproductive Science and Odontostomatology, Federico II University, 80131 Naples, Italy.

Background: Cardiovascular comorbidities have been associated with cognitive decline in the general population.

Objectives: To evaluate the associations between cardiovascular risk and neuropsychological performances in MS.

Methods: This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R).

Results: Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = -8.54; 95%CI = -15.51, -1.57; and Coeff = -0.11; 95%CI = -0.20, -0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R.

Conclusions: In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function.
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http://dx.doi.org/10.3390/brainsci11040502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071566PMC
April 2021

Pregnancy outcomes in alemtuzumab treated women with multiple sclerosis: a case series.

Neurol Sci 2021 Apr 15. Epub 2021 Apr 15.

Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy.

Data on pregnancy outcome in alemtuzumab-treated women are scarce and derived from safety reports of clinical trials. We report on seven women with overall eight pregnancies during treatment with alemtuzumab in a real-world setting. All pregnancies occurred within 9 months after alemtuzumab treatment, and two of them within 4 months despite patients being informed on pregnancy prevention. We found one congenital cytomegalovirus infection, one spontaneous abortion, one elective abortion due to extrauterine pregnancy, and five live births without congenital abnormalities or birth defects.
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http://dx.doi.org/10.1007/s10072-020-04975-5DOI Listing
April 2021

Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy.

Mult Scler 2021 Apr 15:13524585211005657. Epub 2021 Apr 15.

Department of Health Sciences, University of Genova, Genova, Italy.

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity.

Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models.

Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse.

Discussion And Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.
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http://dx.doi.org/10.1177/13524585211005657DOI Listing
April 2021

Possible progressive multifocal leukoencephalopathy and active multiple sclerosis under dimethyl fumarate: the central role of MRI in informing therapeutic decisions.

BMC Neurol 2021 Apr 5;21(1):146. Epub 2021 Apr 5.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, "Federico II" University, Naples, Italy.

Background: Progressive multifocal leukoencephalopathy (PML) can rarely occur in Multiple Sclerosis (MS) patients undergoing dimethyl fumarate (DMF) treatment. Our case stresses the limits of current diagnostic and stratification risk criteria, highlighting the potential role of Magnetic Resonance Imaging (MRI) in advising clinical choices.

Case Presentation: A 54 years old MS male patient treated with DMF, after 3 years of clinical stability developed a subacute clinical worsening. He had no severe lymphopenia but MRI signs suggestive of a coexistence of PML and MS activity. Although his viral title was negative, DMF was discontinued, with clinical and radiological improvement.

Conclusions: This case highlights the challenges behind PML diagnosis, especially in patients not fulfilling the risk stratification criteria and that might present with concurrent disease activity, stressing the potential role of MRI in informing therapeutic decisions.
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http://dx.doi.org/10.1186/s12883-021-02165-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020541PMC
April 2021

Physical Exercise Moderates the Effects of Disability on Depression in People with Multiple Sclerosis during the COVID-19 Outbreak.

J Clin Med 2021 Mar 16;10(6). Epub 2021 Mar 16.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy.

Physical disability impacts psychosocial wellbeing in people with multiple sclerosis. However, the role of physical activity in this context is still debated. By taking advantage of a previous survey, conducted online from 22 April to 7 May 2020, we performed a post-hoc analysis with the aim to assess the associations between disability, physical exercise, and mental health in multiple sclerosis. We retrieved the following data: (i) sociodemographic information, (ii) changes in lifestyle (including exercise), (iii) physical disability, as measured with the Patient-Determined Disease Steps scale, and (iv) anxiety feelings and depressive symptoms assessed via the items included in the Quality of Life in Neurological Disorders measurement system. Examination of the interaction plot showed that the effect of disability on depression, but not on anxious symptoms, was significant for all levels of physical exercise (low: b = 1.22, 95% C.I. 0.85, 1.58, < 0.001; moderate: b = 0.95, 95% C.I. 0.66, 1.24, < 0.001; and high: b = 0.68, 95% C.I. 0.24, 1.13, = 0.003). Based on these data, we can conclude that disability significantly impacted depression during the COVID-19 pandemic, with physical activity playing a moderating role. Our results suggest that favoring exercise in multiple sclerosis (MS) would ameliorate psychological wellbeing regardless of the level of physical disability.
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http://dx.doi.org/10.3390/jcm10061234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002261PMC
March 2021

Neuroimaging Correlates of Cognitive Dysfunction in Adults with Multiple Sclerosis.

Brain Sci 2021 Mar 9;11(3). Epub 2021 Mar 9.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", 80131 Naples, Italy.

Cognitive impairment is a frequent and meaningful symptom in multiple sclerosis (MS), caused by the accrual of brain structural damage only partially counteracted by effective functional reorganization. As both these aspects can be successfully investigated through the application of advanced neuroimaging, here, we offer an up-to-date overview of the latest findings on structural, functional and metabolic correlates of cognitive impairment in adults with MS, focusing on the mechanisms sustaining damage accrual and on the identification of useful imaging markers of cognitive decline.
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http://dx.doi.org/10.3390/brainsci11030346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000635PMC
March 2021

Ocrelizumab depletes T-lymphocytes more than rituximab in multiple sclerosis.

Mult Scler Relat Disord 2021 Apr 28;49:102802. Epub 2021 Jan 28.

Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy. Electronic address:

Background: We aim to directly compare changes in lymphocyte subpopulations between chimeric (rituximab) and humanised (ocrelizumab) anti-CD20 antibodies in multiple sclerosis (MS).

Methods: In this retrospective analysis of prospectively collected data, we included 88 patients with MS, treated with rituximab (n=50) or ocrelizumab (n=38). We used flow cytometry in the peripheral blood to count total lymphocytes and lymphocytes expressing different phenotypic markers (CD4, CD8, CD19, CD20, CD4/CD8 ratio), before treatment and after 1, 3 and 6 months.

Results: On linear mixed effect regression models, after 1, 3 and 6 months, patients treated with rituximab and with ocrelizumab were similar in total lymphocyte count, CD19 lymphocytes, CD20 lymphocytes and CD4/CD8 ratio. However, patients treated with ocrelizumab presented with lower CD4 T lymphocytes and CD8 T lymphocytes after 1, 3 and 6 months (all p<0.05). No between-treatment difference in EDSS progression was found.

Discussion: B-cell levels in the peripheral blood were equally decreased by rituximab and ocrelizumab. On the contrary, CD4 and CD8 T lymphocyte reduction was more pronounced in ocrelizumab, when compared with rituximab, suggesting a broader immunomodulatory effect for the humanised antibody to be confirmed and correlated with clinical efficacy in the long term.
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http://dx.doi.org/10.1016/j.msard.2021.102802DOI Listing
April 2021

Prevalence of SARS-CoV-2 Antibodies in Multiple Sclerosis: The Hidden Part of the Iceberg.

J Clin Med 2020 Dec 16;9(12). Epub 2020 Dec 16.

Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", 80138 Naples, Italy.

Background: We compared the prevalence of SARS-CoV-2 IgG/IgM in multiple sclerosis (MS), low-risk, and high-risk populations and explored possible clinical correlates.

Methods: In this cross-sectional study, we recruited MS patients, low-risk (university staff from non-clinical departments), and high-risk individuals (healthcare staff from COVID-19 wards) from 11 May to 15 June 2020. We used lateral flow immunoassay to detect SARS-CoV-2 IgG and IgM. We used t-test, Fisher's exact test, chi square test, or McNemar's test, as appropriate, to evaluate between-group differences.

Results: We recruited 310 MS patients (42.3 ± 12.4 years; females 67.1%), 862 low-risk individuals (42.9 ± 13.3 years; females 47.8%), and 235 high-risk individuals (39.4 ± 10.9 years; females 54.5%). The prevalence of SARS-CoV-2 IgG/IgM in MS patients (n = 9, 2.9%) was significantly lower than in the high-risk population (n = 25, 10.6%) ( < 0.001), and similar to the low-risk population (n = 11, 1.3%) ( = 0.057); these results were also confirmed after random matching by age and sex (1:1:1). No significant differences were found in demographic, clinical, treatment, and laboratory features. Among MS patients positive to SARS-CoV-2 IgG/IgM (n = 9), only two patients retrospectively reported mild and short-lasting COVID-19 symptoms.

Conclusions: MS patients have similar risk of SARS-CoV-2 infection to the general population, and can be asymptomatic from COVID-19, also if using treatments with systemic immunosuppression.
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http://dx.doi.org/10.3390/jcm9124066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766741PMC
December 2020

Validation of the Italian version of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19.

Neurol Sci 2020 Nov 21. Epub 2020 Nov 21.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, 'Federico II' University, Naples, Italy.

Background: People with multiple sclerosis (MS) may experience sexual dysfunction throughout the disease course. Validated scales to assess sexual dysfunction in MS for Italian patients are lacking. Hence, we aimed at validating Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-19) for Italian MS patients.

Methods: We included both male and female MS patients. Each patient completed the Italian translation of the MSISQ-19. Construct validity was explored by the exploratory factor analysis and the Cronbach's alpha coefficient. Test-retest stability and concurrent internal and external validity were examined by Pearson' correlation coefficients.

Results: We enrolled 369 MS patients (323 female and 46 male). Italian MSISQ-19 showed a Cronbach's alpha of 0.92. MSISQ-19 test and retest total scores correlated between each other (r = 0.48, p = 0.01). MSISQ-19 total score also correlated with primary, secondary and tertiary subscales (p < 0.001).

Conclusion: The Italian Version of the MSISQ-19 showed satisfactory internal consistency and reliability with moderately adequate test-retest reproducibility, suggesting that it may be used as a valuable measure of sexual dysfunction in the Italian population.
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http://dx.doi.org/10.1007/s10072-020-04873-wDOI Listing
November 2020

The Framingham cardiovascular risk score and 5-year progression of multiple sclerosis.

Eur J Neurol 2021 Mar 21;28(3):893-900. Epub 2020 Nov 21.

Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Centre, Federico II University, Naples, Italy.

Background And Purpose: Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10-year risk of developing macrovascular disease. Our objectives were to evaluate the possible association between the Framingham risk score at baseline and MS relapses, disability, and disease-modifying therapy (DMT) choices over a 5-year follow-up.

Methods: This is a retrospective cohort study including 251 MS subjects. At baseline, we calculated the Framingham risk score considering the following variables: age, sex, diabetes, smoking, systolic blood pressure, and body mass index. MS outcomes including relapses, disability, and treatments were collected over 5 years. Cox proportional regression models were employed to estimate hazard ratios (HRs).

Results: A one-point increase in the Framingham risk score was associated with 31% higher risk of relapse (HR = 1.31; 95% confidence interval [CI] = 1.03, 1.68), 19% higher risk of reaching of EDSS 6.0 (HR = 1.19; 95% CI = 1.05, 3.01), and 62% higher risk of DMT escalation (HR = 1.62; 95% CI = 1.22, 3.01).

Conclusions: Higher cardiovascular risk was associated with higher risk of relapses, disability, and DMT escalation in MS. Early identification, correction, and treatment of cardiovascular comorbidities should be carefully considered within MS management.
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http://dx.doi.org/10.1111/ene.14608DOI Listing
March 2021

Persistence, adherence, healthcare resource utilisation and costs for interferon Beta in multiple sclerosis: a population-based study in the Campania region (southern Italy).

BMC Health Serv Res 2020 Aug 26;20(1):797. Epub 2020 Aug 26.

Department of Public Health, Federico II University, Naples, Italy.

Background: To differentiate five formulations of Interferon Beta for the treatment of multiple sclerosis (MS) in clinical practice, by analysing persistence, adherence, healthcare resource utilisation and costs at population level.

Methods: In this population-based study, we included individuals with MS living in the Campania Region of Italy from 2015 to 2017, on treatment with intramuscular Interferon Beta-1a (Avonex® = 618), subcutaneous pegylated Interferon Beta-1a (Plegridy® = 259), subcutaneous Interferon Beta-1a (Rebif® = 1220), and subcutaneous Interferon Beta-1b (Betaferon® = 348; and Extavia® = 69). We recorded healthcare resource utilisation from administrative databases (hospital discharges, drug prescriptions, MS-related outpatients), and derived costs from the Regional formulary. We classified hospital admissions into MS-related and non-MS-related. Persistence (time to switch to other disease modifying treatments (DMTs)), and adherence (medication possession ratio (MPR) = medication supply obtained/medication supply expected during follow-up period) were calculated.

Results: Patients treated with Rebif® were younger, when compared with other Interferon Beta formulations (p < 0.01). The probability of switching to other DMTs was 60% higher for Betaferon®, 90% higher for Extavia®, and 110% higher for Plegridy®, when compared with Rebif® (p < 0.01). Plegridy® presented with 7% higher adherence (p < 0.01), and Betaferon® with 3% lower adherence (p = 0.03), when compared with Rebif®. The probability of MS-related hospital admissions was 40% higher in Avonex® (p = 0.03), 400% higher in Betaferon® (p < 0.01), and 60% higher in Plegridy® (p = 0.04), resulting into higher non-DMT-related costs, when compared with Rebif®.

Discussion: Interferon Beta formulations presented with different prescription patterns, persistence, adherence, healthcare resource utilisation and costs, with Rebif® being used in younger patients and with less MS-related hospital admissions.
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http://dx.doi.org/10.1186/s12913-020-05664-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448448PMC
August 2020

Peripapillary Vessel Density as Early Biomarker in Multiple Sclerosis.

Front Neurol 2020 17;11:542. Epub 2020 Jun 17.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

To evaluate retinal vessel density (VD) in macular and in peripapillary regions in patients with recent onset of multiple sclerosis, at initial demyelinating event (IDE) and in matched relapsing-remitting multiple sclerosis (RRMS) patients. We evaluated VD in superficial capillary plexus, deep capillary plexus, choriocapillaris and radial peripapillary capillary plexus in IDE, RRMS patients and in matched healthy controls (HCs) through Optical Coherence Tomography Angiography (OCT-A). Clinical history, including history of optic neuritis, Expanded Disability Status scale and disease duration of patients were collected. Thirty patients (20 with IDE and 10 with RRMS) and 15 HCs were enrolled. IDE patients showed a lower VD in radial peripapillary capillary plexus compared with controls (coeff. β = -3.578; = 0.002). RRMS patients displayed a lower VD in both superficial capillary plexus and radial peripapillary capillary plexus compared with HCs (coeff. β = -4.955; = 0.002, and coeff. β = -7.446; < 0.001, respectively). Furthermore, RRMS patients showed a decreased VD in radial peripapillary capillary plexus compared with IDE patients (coeff. β = -3.868; = 0.003). Peripapillary region vessel density reduction, revealed through OCT-A, might be considered as an early event in MS, and might be relevant as a biomarker of disease pathology.
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http://dx.doi.org/10.3389/fneur.2020.00542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311750PMC
June 2020

Single-Center 8-Years Clinical Follow-Up of Cladribine-Treated Patients From Phase 2 and 3 Trials.

Front Neurol 2020 17;11:489. Epub 2020 Jun 17.

Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy.

Cladribine is approved for the treatment of highly-active relapsing multiple sclerosis (MS), where it is also effective on disability progression. In the present single-center study, we aim to report on the 8-years clinical follow-up of 27 patients included in phase 2 and 3 clinical trials for cladribine. We included patients exposed to cladribine ( = 13) or placebo ( = 14) in ONWARD, CLARITY, and ORACLE-MS trials, and followed-up at the same center after trial termination. Outcomes of long-term disease progression were recorded. During 8-year follow-up, patients treated with cladribine presented with reduced risk of EDSS progression (HR = 0.148; 95%CI = 0.031, 0.709; = 0.017), of reaching EDSS 6.0 (HR = 0.115; 95%CI = 0.015, 0.872; = 0.036), and of SP conversion (HR = 0.010; 95%CI = 0.001, 0.329; = 0.010), when compared with placebo. Our exploratory study provides additional evidence that cladribine may be useful to prevent or, at least, mitigate the risk of disability progression after 8 years.
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http://dx.doi.org/10.3389/fneur.2020.00489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311570PMC
June 2020

Assessment of retinal vascular network in amnestic mild cognitive impairment by optical coherence tomography angiography.

PLoS One 2020 3;15(6):e0233975. Epub 2020 Jun 3.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, "Federico II" University Naples, Naples, Italy.

Objective: To assess the presence of retinal vascular network abnormalities in amnestic mild cognitive impairment (aMCI) patients and healthy subjects (HS) through optical coherence tomography angiography (OCTA).

Methods: OCTA and SD-OCT were performed in aMCI patients and cognitive normal HS. A complete neuropsychological evaluation was performed. Differences in vessel density (VD) in each retinal vascular plexus and in foveal avascular zone (FAZ) were evaluated with linear mixed model after correction for age, sex and disease duration.

Results: Twenty-seven aMCI patients (10 Single domain aMCI, 17 Multidomain aMCI) and 29 HS were enrolled. aMCI patients showed a statistically significant reduced VD in superficial capillary plexus (SCP), deep capillary plexus (DCP) and an increased FAZ compared to controls. When aMCI patients were divided in single domain (SD) and multiple domains (MD) aMCI, SD aMCI showed no VD differences in SCP, DCP and Radial Peripapillary Capillary, while the FAZ area was significantly larger compared to controls. In MD aMCI, VD values were lower and FAZ was increased compared to controls. Comparing both aMCI groups, MD aMCI showed a significant reduction in VD values of SCP. No correlation was found between mini mental state examination (MMSE) scores and OCTA parameters.

Conclusions: OCTA is able to detect changes in retinal microvascular network in early cognitive deficits and, the most sensitive alteration seems to be the enlargement of the FAZ. This non-invasive tool provides useful information on retinal involvement patterns in MCI diagnosis and follow up. Vascular network impairment seems to be related to the number of domains affected and not to MMSE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269252PMC
August 2020

Unraveling diagnostic uncertainty in transition phase from relapsing-remitting to secondary progressive multiple sclerosis.

Mult Scler Relat Disord 2020 Aug 24;43:102211. Epub 2020 May 24.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Background: Clinicians struggle to timely diagnose secondary-progressive multiple sclerosis (SP-MS), with a 'transition phase' period of diagnostic uncertainty. We aimed at defining clinical markers predicting evolution to SP-MS.

Methods: We reviewed 210 newly diagnosed MS patients experiencing at least one confirmed disability worsening (CDW). CDWs were classified as disability worsening either due to incomplete recovery following relapse (r-CDW), or independent of relapse activity (nr-CDW). Logistic regression and Cox regression models were used to evaluate variables at CDW associated with SP-MS diagnosis.

Results: On CDW, higher EDSS (OR: 2.73, p=0.002) and nr-CDW (OR: 2.63, p=0.03) were associated with conversion to SP-MS over the follow-up. In addition, the risk of SP-MS was higher in patients with EDSS>3.0 at CDW (HR: 2.26, p<0.001), and with time to second CDW <24 months (HR: 0.98, p<0.001), compared with patients that experienced a CDW but did not receive SP-MS diagnosis (AUC: 0.95, Sensitivity: 0.83, Specificity: 0.96).

Conclusion: At their first CDW, patients with higher EDSS, experiencing CDW without relapse and developing a further CDW within 2 years are at higher risk of SP-MS conversion. This provides proxies for conversion to SP-MS since first episode of CDW.
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http://dx.doi.org/10.1016/j.msard.2020.102211DOI Listing
August 2020

Effectiveness of fingolimod in real-world relapsing-remitting multiple sclerosis Italian patients: the GENIUS study.

Neurol Sci 2020 Oct 21;41(10):2843-2851. Epub 2020 Apr 21.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

Background: Fingolimod is the first oral agent approved for treatment of relapsing-remitting multiple sclerosis (RRMS). We aimed to evaluate fingolimod effectiveness in a real-world sample of RRMS patients.

Methods: A retrospective, multicentre study in patients treated with fingolimod, whom clinical and radiological data were collected in the 2 years preceding and following the initiation of fingolimod.

Results: Out of 414 patients, 56.8% received prior first-line injectable disease-modifying therapies, 25.4% were previously treated with natalizumab, 1.2% with immunosuppressant agents, and 16.7% were treatment naive. The annualized relapse rate decreased by 65% in the first year and by 70% after two years of treatment. Age ≤ 40 years, ≥ 1 relapse in the 24 months before fingolimod initiation and previous treatment with natalizumab were risk factors for relapses. Overall, 67.9% patients had no evidence of disease activity (NEDA-3) after 1 year and 54.6% after 2 years of treatment. A higher proportion of naïve (81.2% in 1 year and 66.7% after 2 years) or first-line injected patients (70.2% and 56.6%) achieved NEDA-3 than those previously treated with natalizumab (54.3% and 42.9%).

Conclusions: Fingolimod appeared to be effective in naive patients and after first-line treatment failure in reducing risk of relapse and disease activity throughout the 2-year follow-up.
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http://dx.doi.org/10.1007/s10072-020-04380-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479005PMC
October 2020

Botulinum toxin for the management of spasticity in multiple sclerosis: the Italian botulinum toxin network study.

Neurol Sci 2020 Oct 12;41(10):2781-2792. Epub 2020 Apr 12.

Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Sciences and Odontostomatology, "Federico II" University of Naples, Via Sergio Pansini 5, edificio 17 piano terra, 80131, Naples, Italy.

Background: Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates.

Methods: This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0-9.0)).

Results: BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p < 0.001), higher modified Ashworth scale (Coeff = 0.796; p < 0.001) and non-ambulatory patients (Coeff = 209.382; p = 0.006). Lower BT dose was used in younger patients (Coeff = - 1.746; p = 0.009), with relapsing-remitting MS (Coeff = - 60.371; p = 0.012). BT dose was higher in patients with previous BT injections (Coeff = 5.167; p = 0.001), and with concomitant treatments (Coeff = 43.576; p = 0.022). Three patients (0.7%) reported on post-injection temporary asthenia/weakness (n = 2) and hypophonia (n = 1).

Conclusion: BT was used for spasticity and its consequences from the early stages of MS, without significant adverse effects. MS-specific goals and injection characteristics can be used to refer MS patients to BT treatment, to decide for the strategy of BT injections and to guide the design of future clinical trials and observational studies.
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http://dx.doi.org/10.1007/s10072-020-04392-8DOI Listing
October 2020

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications.

J Neurol 2020 Jul 26;267(7):2042-2053. Epub 2020 Mar 26.

Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

There is mounting evidence regarding the role of impairment in neuromodulatory networks for neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. However, the role of neuromodulatory networks in multiple sclerosis (MS) has not been assessed. We applied resting-state functional connectivity and graph theory to investigate the changes in the functional connectivity within neuromodulatory networks including the serotonergic, noradrenergic, cholinergic, and dopaminergic systems in MS. Twenty-nine MS patients and twenty-four age- and gender-matched healthy controls performed clinical and cognitive assessments including the expanded disability status score, symbol digit modalities test, and Hamilton Depression rating scale. We demonstrated a diffuse reorganization of network topography (P < 0.01) in serotonergic, cholinergic, noradrenergic, and dopaminergic networks in patients with MS. Serotonergic, noradrenergic, and cholinergic network functional connectivity derangement was associated with disease duration, EDSS, and depressive symptoms (P < 0.01). Derangements in serotonergic, noradrenergic, cholinergic, and dopaminergic network impairment were associated with cognitive abilities (P < 0.01). Our results indicate that functional connectivity changes within neuromodulatory networks might be a useful tool in predicting disability burden over time, and could serve as a surrogate endpoint to assess efficacy for symptomatic treatments.
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http://dx.doi.org/10.1007/s00415-020-09806-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320961PMC
July 2020

Predictors of Nabiximols (Sativex) discontinuation over long-term follow-up: a real-life study.

J Neurol 2020 Jun 2;267(6):1737-1743. Epub 2020 Mar 2.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Nabiximols is an effective treatment for spasticity in MS. However, treatment discontinuation over-time might occur and predictors of sustained treatment persistence over long-term follow-up in real-world settings are highly needed. We aim at evaluating baseline predictors of treatment persistence on Nabiximols. This is a retrospective real-world study including MS patients treated with Nabiximols. At baseline (Nabiximols prescription), we evaluated disability using the EDSS, and cognitive function using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Nabiximols discontinuation was evaluated after 4 weeks of treatment ("titration phase''), and over the follow-up ("treatment phase"). We included 396 MS patients (228 females and 168 males). After 4 weeks (titration phase), 266 MS patients (67.2%) were considered persistent on treatment, while 130 patients dropped out. After 19 ± 21 months (treatment phase), 136 out of 266 MS patients (51.1%) were still on treatment, whereas 130 patients dropped at follow-up. Higher EDSS and cognitive impairment predicted treatment discontinuation at follow-up (p = 0.04 and p = 0.005, respectively). In conclusion, higher physical and cognitive disability predicted Nabiximols treatment discontinuation over 2 years in MS patients suffering from spasticity. Nabiximols should be started earlier to decrease the likelihood of treatment discontinuation over time.
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http://dx.doi.org/10.1007/s00415-020-09739-xDOI Listing
June 2020

2D linear measures of ventricular enlargement may be relevant markers of brain atrophy and long-term disability progression in multiple sclerosis.

Eur Radiol 2020 Jul 25;30(7):3813-3822. Epub 2020 Feb 25.

Department of Neurosciences and Reproductive and Odontostomatological Sciences, University "Federico II", Naples, Italy.

Objectives: Aim of this study was to investigate the reliability and validity of 2D linear measures of ventricular enlargement as indirect markers of brain atrophy and possible predictors of clinical disability.

Methods: In this retrospective longitudinal analysis of relapsing-remitting MS patients, brain volumes were computed at baseline and after 2 years. Frontal horn width (FHW), intercaudate distance (ICD), third ventricle width (TVW), and 4th ventricle width were obtained. Two-dimensional measures associated with brain volume at correlation analyses were entered in linear and logistic regression models testing the relationship with baseline clinical disability and 10-year confirmed disability progression (CDP), respectively. Possible cutoff values for clinically relevant atrophy were estimated via receiver operating characteristic (ROC) analyses and probed as 10-year CDP predictors using hierarchical logistic regression.

Results: Eighty-seven patients were available (61/26 = F/M; 34.1 ± 8.5 years). Moderate negative correlations emerged between ICD and TVW and normalized brain volume (NBV; p < 0.001) and percentage brain volume change per year (PBVC/y) and FHW, ICD, and TVW annual changes (p ≤ 0.005). Baseline disability was moderately associated with NBV, ICD, and TVW (p < 0.001), while PBVC/y predicted 10-year CDP (p = 0.01). A cutoff percentage ICD change per year (PICDC/y) value of 4.38%, corresponding to - 0.91% PBVC/y, correlated with 10-year CDP (p = 0.04). These estimated cutoff values provided extra value for predicting 10-year CDP (PBVC/y: p = 0.001; PICDC/y: p = 0.03).

Conclusions: Two-dimensional measures of ventricular enlargement are reproducible and clinically relevant markers of brain atrophy, with ICD and its increase over time showing the best association with clinical disability. Specifically, a cutoff PICDC/y value of 4.38% could serve as a potential surrogate marker of long-term disability progression.

Key Points: • Assessment of ventricular enlargement as a rapidly accessible indirect marker of brain atrophy may prove useful in cases in which brain volume quantification is not practicable. • Two-dimensional linear measures of ventricular enlargement represent reliable, valid, and clinically relevant markers of brain atrophy. • A cutoff annualized percentage brain volume change of - 0.91% and the corresponding annualized percentage increase of 4.38% for intercaudate distance are able to discriminate patients who will develop long-term disability progression.
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http://dx.doi.org/10.1007/s00330-020-06738-4DOI Listing
July 2020

Associations between cognitive impairment at onset and disability accrual in young people with multiple sclerosis.

Sci Rep 2019 12 2;9(1):18074. Epub 2019 Dec 2.

Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Differently from the adult multiple sclerosis (MS) population, the predictive value of cognitive impairment in early-onset MS is still unknown. We aim to evaluate whether cognitive performances at disease onset predict disease progression in young people with MS. This is a retrospective study on early onset (<25 years) MS patients, who had a baseline cognitive evaluation at disease onset. Demographic and longitudinal clinical data were collected up to 7 years follow up. Cognitive abilities were assessed at baseline through the Brief Repeatable Battery. Associations between cognitive abilities and clinical outcomes (occurrence of a relapse, and 1-point EDSS progression) were evaluated with stepwise logistic and Cox regression models. We included 51 patients (26 females), with a mean age at MS onset of 17.2 ± 3.9 years, and an EDSS of 2.5 (1.0-6.0). Over the follow-up, twenty-five patients had at least one relapse, and 7 patients had 1-point EDSS progression. Relapse occurrence was associated with lower 10/36 SPART scores (HR = 0.92; p = 0.002) and higher WLG scores (HR = 1.05; p = 0.01). EDSS progression was associated with lower SDMT score (OR: 0.70; p = 0.04). Worse visual memory and attention/information processing were associated with relapses and with increased motor disability after up to 7-years follow-up. Therefor, specific cognitive subdomains might better predict clinical outcomes than the overall cognitive impairment in early-onset MS.
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http://dx.doi.org/10.1038/s41598-019-54153-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889418PMC
December 2019

[F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis.

Eur J Nucl Med Mol Imaging 2020 02 21;47(2):366-378. Epub 2019 Oct 21.

Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, IoPPN, King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK.

Purpose: We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [F]florbetapir PET-MR imaging.

Methods: We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [F]florbetapir PET-MR and both a clinical and cognitive assessment. [F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70-90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling.

Results: [F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = -0.15, P < 0.001, coeff. = -0.12, P < 0.001 and coeff. = -0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (-10.9%, P = 0.005). SUV and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26).

Conclusion: Our findings demonstrate that [F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.
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http://dx.doi.org/10.1007/s00259-019-04533-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974490PMC
February 2020

Very late-onset recurrent myelitis in a patient diagnosed with antiphospholipid syndrome: A puzzle of autoimmunity.

J Neuroimmunol 2019 12 4;337:577051. Epub 2019 Sep 4.

NSRO Department Federico II University, Naples, Italy.

We describe the case of a man with a very-late onset neuromyelitis optica spectrum disorder syndrome (NMOSD) who was initially diagnosed as recurrent antiphospholipid syndrome-associated myelitis. This case illustrates that a puzzle of autoreactive antibodies can be detected in patients having neurological syndromes belonging to the NMOSD. Prompt identification and timely immunosuppression prevent relapses and the accumulation of irreversible disability.
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http://dx.doi.org/10.1016/j.jneuroim.2019.577051DOI Listing
December 2019

Outcomes after fingolimod to alemtuzumab treatment shift in relapsing-remitting MS patients: a multicentre cohort study.

J Neurol 2019 Oct 17;266(10):2440-2446. Epub 2019 Jun 17.

Department of Medical Sciences and Public Health, Multiple Sclerosis Centre, University of Cagliari-ATS Sardegna, Via Is Guadazzonis 2, 09126, Cagliari, Italy.

Background: A high reactivation of multiple sclerosis (MS) was reported in patients treated with alemtuzumab after fingolimod. We aimed to understand whether this shift enhanced the risk for reactivation in a real-life cohort.

Methods: Subjects with relapsing MS, shifting from fingolimod to alemtuzumab were enrolled. We collected the following data: age, sex, disease duration, relapses after fingolimod withdrawal, new T2/gadolinium (Gd)-enhancing lesions in the last magnetic resonance imaging (MRI) during fingolimod and in the first, while on alemtuzumab, lymphocyte counts at alemtuzumab start, and Expanded Disability Status Scale (EDSS) before and after alemtuzumab.

Results: We enrolled 77 patients (women 61 (79%); mean age 36.2 years (SD 9.6), and disease duration 12.3 years (SD 6.8) at fingolimod discontinuation; median washout 1.8 months). The annualised relapse rate was 0.89 during fingolimod, 1.32 during washout, and 0.15 after alemtuzumab (p = 0.001). The EDSS changed from a median of 3 (IQR 2-4) at the end of fingolimod to 2.5 after alemtuzumab (IQR 1.5-4) (p = 0.013). The washout length and the lymphocyte count before alemtuzumab were not associated with EDSS change after alemtuzumab (p = 0.59 and p = 0.33, respectively). MRI activity decreased after alemtuzumab compared to that during fingolimod (p = 0.001). At alemtuzumab start, lymphocyte counts were < 0.8 × 10/mL in 21 patients.

Conclusions: In our cohort, alemtuzumab reduced relapse, new T2/Gd-enhancing lesions, and EDSS score, as compared to the previous periods (fingolimod/washout). These results were not related to washout length or lymphocyte counts. Therefore, a rapid initiation of alemtuzumab after fingolimod does not seem to be a risk factor for MS reactivation.
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http://dx.doi.org/10.1007/s00415-019-09424-8DOI Listing
October 2019

Correction to: Normative values of the Rao's Brief Repeatable Battery in an Italian young adolescent population: the influence of age, gender, and education.

Neurol Sci 2019 May;40(5):1099-1100

Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy.

The published version of this article unfortunately contained a mistake in Table 2.
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http://dx.doi.org/10.1007/s10072-019-03880-wDOI Listing
May 2019

Coenzyme Q10 supplementation reduces peripheral oxidative stress and inflammation in interferon-β1a-treated multiple sclerosis.

Ther Adv Neurol Disord 2019 18;12:1756286418819074. Epub 2019 Feb 18.

Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy.

Background: Oxidative stress is a driver of multiple sclerosis (MS) pathology. We evaluated the effect of coenzyme Q10 (CoQ10) on laboratory markers of oxidative stress and inflammation, and on MS clinical severity.

Methods: We included 60 relapsing-remitting patients with MS treated with interferon beta1a 44μg (IFN-β1a) with CoQ10 for 3 months, and with IFN-β1a 44μg alone for 3 more months (in an open-label crossover design). At baseline and at the 3 and 6-month visits, we measured markers of scavenging activity, oxidative damage and inflammation in the peripheral blood, and collected data on disease severity.

Results: After 3 months, CoQ10 supplementation was associated with improved scavenging activity (as mediated by uric acid), reduced intracellular reactive oxygen species production, reduced oxidative DNA damage, and a shift towards a more anti-inflammatory milieu in the peripheral blood [with higher interleukin (IL)-4 and IL-13, and lower eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), interferon (IFN)-γ, IL-1α, IL-2R, IL-9, IL-17F, macrophage inflammatory proteins (MIP)-1α, regulated on activation-normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF). Also, CoQ10 supplementation was associated with lower Expanded Disability Status Scale, fatigue severity scale, Beck's depression inventory, and the visual analogue scale for pain.

Conclusions: CoQ10 supplementation improved scavenging activity, reduced oxidative damage, and induced a shift towards a more anti-inflammatory milieu, in the peripheral blood of relapsing-remitting MS patients treated with 44μg IFN-β1a 44μg. A possible clinical effect was noted but deserves to be confirmed over longer follow ups.
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http://dx.doi.org/10.1177/1756286418819074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381428PMC
February 2019