Publications by authors named "Alberto Gajofatto"

62 Publications

"If You Can't Control the Wind, Adjust Your Sail": Tips for Post-Pandemic Benefit Finding from Young Adults Living with Multiple Sclerosis. A Qualitative Study.

Int J Environ Res Public Health 2021 04 14;18(8). Epub 2021 Apr 14.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.

The COVID-19 outbreak has impacted the wellbeing of people worldwide, potentially increasing maladaptive psychological responses of vulnerable populations. Although young adults with multiple sclerosis (yawMS) might be at greater risk of developing psychological distress linked to the pandemic, they might also be able to adapt to stress and find meaning in adverse life events. The aim of the present study was to explore benefit finding in response to the pandemic in a sample of yawMS. As part of a larger project, data were collected using a cross-sectional, web-based survey. Benefit finding was analysed using a qualitative thematic approach; descriptive and inferential statistics were performed to describe the sample and compare sub-groups. Out of 247 respondents with mostly relapsing-remitting MS, 199 (31.9 ± 6.97 years) reported at least one benefit. Qualitative analysis showed that during the pandemic yawMS found benefits related to three themes: personal growth, relational growth, and existential growth. No differences in benefit finding were found between age sub-groups (18-30 vs. 31-45). Participants reported a wide range of benefits, some of which seem to be specific to MS or the pandemic. Results have been transformed into tips to be introduced in clinical practice to promote resilience in yawMS through meaning making.
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http://dx.doi.org/10.3390/ijerph18084156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070973PMC
April 2021

A Bio-Psycho-Social Co-created Intervention for Young Adults With Multiple Sclerosis (ESPRIMO): Rationale and Study Protocol for a Feasibility Study.

Front Psychol 2021 23;12:598726. Epub 2021 Feb 23.

Section of Clinical Psychology, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Background: Multiple sclerosis (MS), the most common neurological disease that causes disability in youth, does not only affect physical functions but is also associated with cognitive impairment, fatigue, depression, and anxiety and can significantly impact health-related quality of life (HRQoL). Since MS is generally diagnosed at a young age-a period of great significance for personal, relational, and professional development-adaptation can become highly challenging. Therefore, enhancing the competence of young people to adaptively cope with these potential challenges is of utmost importance in order to promote their potentialities and talents. It has been shown that psychological interventions targeting MS patients can enhance resilience and HRQoL and that regular physical activity (PA) and social engagement can improve psychological well-being. However, literature on the development of global interventions based on the bio-psycho-social model of the disease is missing. Even less attention has been paid to interventions dedicated to young adults with MS (YawMS) and to the involvement of patients in the development of such programs.

Aims: In collaboration with MS patients, this study aims to develop a bio-psycho-social intervention (ESPRIMO) for YawMS, aiming to improve their HRQoL and to explore its feasibility, acceptability, and effects.

Methods: To tailor the intervention to the specific needs of YawMS, "patient engagement principles" will be adopted in the co-creation phase, performing a web survey and focus groups with patients and healthcare professionals. In the intervention phase, a pilot sample of 60 young adults with MS will be enrolled. The co-created intervention, composed of group sessions over a 12-week period, will cover psycho-social strategies and include physical activities. Adopting a longitudinal, pre-post evaluation design, self-report questionnaires measuring HRQoL and other bio-psycho-social features (e.g., resilience, well-being, mindfulness traits, self-efficacy, perceived social support, psychological symptoms, illness perception, committed action, fatigue, attitudes, subjective norms, perceived behavioral control, motivation, perception of autonomy support for PA, barriers and intentions to PA) will be administered, the quantity and quality of PA will be measured, and a questionnaire developed by the authors will be used to evaluate the feasibility and acceptability of the ESPRIMO intervention.
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http://dx.doi.org/10.3389/fpsyg.2021.598726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940381PMC
February 2021

Insights for Fostering Resilience in Young Adults With Multiple Sclerosis in the Aftermath of the COVID-19 Emergency: An Italian Survey.

Front Psychiatry 2020 22;11:588275. Epub 2021 Feb 22.

Section of Clinical Psychology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Recent evidence has demonstrated that the COVID-19 pandemic is taking a toll on the mental health of the general population. The psychological consequences might be even more severe for patients with special healthcare needs and psychological vulnerabilities due to chronic diseases, such as multiple sclerosis (MS). Thus, we aimed to explore the psychological impact of this pandemic and of the subsequent healthcare service changes on young adults with MS living in Italy and to examine their coping strategies and preferences regarding psychological support in the aftermath of the pandemic. Data were collected using a cross-sectional, web-based survey advertised on social networks. We report both quantitative (descriptive statistics, -tests, and one-way ANOVA) and qualitative data (inductive content analysis). Two hundred and forty-seven respondents (mean age 32 ± 7 years), mainly with relapsing-remitting MS, from all Italian regions participated. Participants felt more worried, confused, sad, and vulnerable because of the disease "during" the pandemic in comparison to their self-evaluation of the period "before" the COVID-19 outbreak. Similarly, their perception of control over MS decreased "during" the pandemic in comparison to the retrospective evaluation of the period "before" the COVID-19 outbreak ( < 0.01). Canceled/postponed visits/exams were listed as the most frequent MS management changes, with modified/postponed pharmacological treatment representing the most stressful change. Psychological support in dealing with pandemic-related fears and improving MS acceptance and well-being was considered extremely important by almost 40% of the respondents. Different coping strategies were mentioned in the qualitative section of the survey, with social support, hobbies, and keeping busy being the most frequent ones. Considering the enormous impact of the pandemic on young adults with MS, we urge MS clinical centers to implement psychological support programs that address the potentially long-lasting psychological negative impact, thus fostering the therapeutic alliance that is being threatened by the infection prevention measures imposed during the pandemic, and promoting psychological resources for adaptively managing future waves of COVID-19.
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http://dx.doi.org/10.3389/fpsyt.2020.588275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938709PMC
February 2021

NfL levels predominantly increase at disease onset in MOG-Abs-associated disorders.

Mult Scler Relat Disord 2021 May 11;50:102833. Epub 2021 Feb 11.

Section of Neurology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

The unpredictable course and uncertain impact of relapses make treatment strategies of anti-myelin oligodendrocyte glycoprotein antibodies associated disorders (MOGAD) challenging. We analysed neurofilament light chain levels (NfL) in onset and follow-up sera of 18 patients with MOGAD to clarify the timing of axonal damage. In comparison with disease onset values (median 8.9 pg/mL, range 1.8-97), NfL levels remained stable or decreased in most follow-up measurements (n=52, median 6.7 pg/mL, range 0.2-207), including those measured on relapses. The predominant axonal damage occurs during onset, which could be the main driving factor of final disability, with subsequent relevant clinical and therapeutic implications.
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http://dx.doi.org/10.1016/j.msard.2021.102833DOI Listing
May 2021

Defining the course of tumefactive multiple sclerosis: A large retrospective multicentre study.

Eur J Neurol 2021 Apr 12;28(4):1299-1307. Epub 2021 Jan 12.

Department of Clinical and Experimental Epilepsy, Queen Square, UCL Queen Square Institute of Neurology, London, UK.

Background And Purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS.

Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected.

Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5 years, range: 11-68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3 years (range: 0.1-10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0-7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03-1.14, p < 0.01), a higher number of TDLs (OR: 1.67, 95% CI: 1.02-2.74, p < 0.05) and the presence of infiltrative TDLs (OR: 3.34, 95% CI: 1.18-9.5, p < 0.001) at baseline.

Conclusions: The management of TuMS might be challenging because of its peculiar characteristics. Large prospective studies could help to define the clinical characteristics and the best treatment algorithms for people with TuMS.
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http://dx.doi.org/10.1111/ene.14672DOI Listing
April 2021

Harmonization of real-world studies in multiple sclerosis: Retrospective analysis from the rirems group.

Mult Scler Relat Disord 2020 Oct 12;45:102394. Epub 2020 Jul 12.

Rehabilitation Department, Mons. L. Novarese, Moncrivello, Vercelli, Italy.

Background: Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies. In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group.

Methods: RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ).

Results: Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p = 0.02; τ=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p = 0.02; τ=1.00).

Discussion: We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.
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http://dx.doi.org/10.1016/j.msard.2020.102394DOI Listing
October 2020

Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study.

J Neurol Neurosurg Psychiatry 2020 09 13;91(9):914-920. Epub 2020 Jul 13.

Department of Medical Sciences, Università degli Studi di Cagliari, Cagliari, Sardegna, Italy.

Introduction: Delta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation.

Materials And Methods: This prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline.

Results: A total of 1845 patients were recruited from 32 MS Italian centres. At T1, 1502 (81.4%) of patients reached a Numerical Rating Scale (NRS) improvement of ≥20%, with an NRS reduction of 26.9% at T1 and of 34.4% at T5. At T5, 725 patients (48.3% of 1502) discontinued treatment with highest discontinuation rate at T2 and T3. Daily number of puffs was generally stable through the observation period. The multivariate analysis showed that higher NRS scores at baseline (OR 2.28, 95% CI 1.15 to 6.36, p<0.01) and higher differences of NRS between T0 and T1 (OR 2.11, 95% CI 1.08 to 8.26, p<0.05) were associated with an increased probability to continue therapy after 18 months.

Discussion: THC:CBD effects were sustained for 18 months with a relatively stable number of puffs per day. About 50% of patients abandoned THC:CBD therapy for loss of efficacy or adverse events.
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http://dx.doi.org/10.1136/jnnp-2019-322480DOI Listing
September 2020

Dimethyl fumarate vs Teriflunomide: an Italian time-to-event data analysis.

J Neurol 2020 Oct 6;267(10):3008-3020. Epub 2020 Jun 6.

Department "G.F. Ingrassia", MS Center University of Catania, Policlinico G. Rodolico, V. Santa Sofia 78, 95123, Catania, Italy.

Background: The introduction of oral disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment.

Objectives: To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients.

Materials And Methods: Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified. The events investigated were "time-to-first-relapse", "time-to-Magnetic-Resonance-Imaging (MRI)-activity" and "time-to-disability-progression".

Results: 1445 patients were enrolled (1039 on DMF, 406 on TRF) and followed for a median of 34 months. Patients on TRF were older (43.5 ± 8.6 vs 38.8 ± 9.2 years), with a predominance of men and higher level of disability (p < 0.001 for all). Patients on DMF had a higher number of relapses and radiological activity (p < .05) at baseline. Time-varying Cox-model for the event "time-to-first relapse" revealed that no differences were found between the two groups in the first 38 months of treatment (HR = 0.73, CI = 0.52 to 1.03, p = 0.079). When the time-on-therapy exceeds 38 months patients on DMF had an approximately 0.3 times lower relapse hazard risk than those who took TRF (HR = 3.83, CI = 1.11 to 13.23, p = 0.033). Both DMTs controlled similarly MRI activity and disability progression.

Conclusions: Patients on DMF had higher relapse-free survival time than TRF group after the first 38 months on therapy.
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http://dx.doi.org/10.1007/s00415-020-09959-1DOI Listing
October 2020

Diagnostic features of initial demyelinating events associated with serum MOG-IgG.

J Neuroimmunol 2020 07 7;344:577260. Epub 2020 May 7.

Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona and Neurology Unit B, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Background: Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated.

Materials And Methods: Between October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months. We assessed the sensitivity and specificity of a live-cell MOG-IgG assay for each final diagnosis at last follow-up, for the 2018 international recommendations for MOG-IgG testing, and for other combinations of clinical and laboratory characteristics.

Results: Clinical presentations included acute myelitis (n = 48), optic neuritis (n = 36), multifocal encephalomyelitis (n = 4), and brainstem syndrome (n = 3). Twenty-four patients were MOG-IgG positive. Sensitivity and specificity of MOG-IgG test applied to the 2018 international recommendations were 28.4% and 86.7%, while they were 42.1% and 88.6% when applied to DE of unclear aetiology as defined above with two or more among: 1_no periventricular and juxtacortical MS-like lesions on brain MRI; 2_longitudinally extensive MRI optic nerve lesion; 3_no CSF-restricted oligoclonal bands; 4_CSF protein > 50 mg/dl.

Conclusions: Simplified requirements compared to those currently proposed for MOG-IgG testing could facilitate the applicability of the assay in the diagnosis of adults with DEs of unclear aetiology.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577260DOI Listing
July 2020

Upregulated serum miR-128-3p in progressive and relapse-free multiple sclerosis patients.

Acta Neurol Scand 2020 Nov 5;142(5):511-516. Epub 2020 Jun 5.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section, Verona, Italy.

Background: Circulating microRNAs have emerged as novel multiple sclerosis (MS) biomarkers.

Aims: To assess the association between candidate miR expression in serum samples of patients with MS and the disease course.

Methods: Serum levels of ten microRNAs (ie, miR-199, miR-128-3p, miR-20a-5p, miR-27a-3p, miR-15b-5p, miR-325, miR-92a1-5p, miR-223-5p, miR-22-5p, and miR-23a-5p) were measured in 74 MS cases and 17 non-MS controls consecutively enrolled at Verona University Hospital. The association of microRNA expression with patients' clinical and MRI features was analyzed. Candidate microRNAs were detected by real-time PCR and expressed as ratio of each microRNA level to a normalizer.

Results: Serum miR-128-3p levels were higher in progressive than relapsing MS (median ratio 2.86 vs 0.73, P = .036). In addition, miR-128-3p was upregulated in patients without relapses after sample collection compared to cases who relapsed (1.64 vs 0.82; P = .014). miR-128-3p levels and relapse rate were inversely correlated (r = -.44, P = .008).

Conclusions: Serum levels of mir-128-3p could be related to biological mechanisms underlying MS activity and progression.
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http://dx.doi.org/10.1111/ane.13288DOI Listing
November 2020

Amyloid myopathy: an intriguing diagnosis.

Clin Neurol Neurosurg 2020 08 18;195:105848. Epub 2020 Apr 18.

Department of Biomedical and Neuromotor Sciences, Alma Mater University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1016/j.clineuro.2020.105848DOI Listing
August 2020

Characterization of Upper Limb Impairments at Body Function, Activity, and Participation in Persons With Multiple Sclerosis by Behavioral and EMG Assessment: A Cross-Sectional Study.

Front Neurol 2019 14;10:1395. Epub 2020 Feb 14.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and disabling disease which primarily affects individuals in their early life between 20 and 40 years of age. MS is a complex condition, which may lead to a variety of upper limb (UL) dysfunctions and functional deficits. To explore upper limb impairments at body function, activity, and participation in persons with MS (PwMS) and severe hand dexterity impairment by behavioral and surface electromyography (sEMG) assessments. This observational cross-sectional study involved 41 PwMS with severe hand dexterity impairment stratified according to the Expanded Disability Status Scale (EDSS) into mild-moderate ( = 17; EDSS, 1-5.5), severe ambulant ( = 15; EDSS, 6-6.5), and severe nonambulant ( = 9; EDSS, 7-9.5). Behavioral outcome measures exploring body function, activity, and participation were administered. The sEMG activity of six upper limb muscles of the most affected side was measured during a reaching task. The most severe group was significantly older and more affected by secondary progressive MS than the other two groups. Positive significant associations between UL deterioration and impairments at different International Classification of Functioning, Disability, and Health domains were noted in the most severe group. The progressive decline in manual dexterity was moderately to strongly associated with the deterioration of the overall UL activity (ρ = 0.72; < 0.001) and disuse (amount of use ρ = 0.71; < 0.001; quality of movement ρ = 0.77; < 0.001). There was a low correlation between manual dexterity and UL function (ρ = 0.33; = 0.03). The muscle activation pattern investigated by sEMG was characterized by a decrease in modularity and timing delay in the wrist extensor muscles activation in the severe ambulant patients (EDSS, 6-6.5). Similar impairments were observed in the proximal muscles (anterior deltoid) in the more advanced stages (EDSS ≥ 7). Behavioral assessment, together with measures of muscle activation patterns, allows investigating the pathophysiology of UL impairments in PwMS across progressive neurological disability severity to implement task-specific rehabilitation interventions.
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http://dx.doi.org/10.3389/fneur.2019.01395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034433PMC
February 2020

Changing therapeutic strategies and persistence to disease-modifying treatments in a population of multiple sclerosis patients from Veneto region, Italy.

Mult Scler Relat Disord 2020 Jun 10;41:102004. Epub 2020 Feb 10.

Section of Neurology B, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Background: The availability of new disease-modifying treatments (DMTs) in the last years has changed the therapeutic strategies used in Multiple Sclerosis (MS). We aimed to describe trend in DMTs utilization and persistence to treatment in a large sample of patients attending 10 MS centres from four provinces of Veneto, Italy.

Methods: Demographic, clinical and DMTs information of patients regularly followed from January 2011 to August 2018 were recorded and analysed. Persistence at 12, 24 months and at last follow-up was assessed by Kaplan Meier survival analysis. Multivariable Cox- proportional hazard model was used to identify predictors of persistence.

Results: Of 3025 MS patients 65.7% were in treatment al last follow-up. Dimethylfumarate (DMF) was the most prescribed single drug among first-line and fingolimod among second-line DMTs. In the cohort of 1391 cases starting any DMT since 2011 12.9% stopped within 6 months, 24% within 12 and 40.3% within 24 months. Disease duration > 5 years at therapy start was predictive of greater risk of discontinuation, while age and sex were not. DMF use was predictive of higher persistence at 12 and 24 months, but not at last follow-up when azathioprine and glatiramer acetate showed the highest persistence compared to other DMTs. Side effects represented the main reason of discontinuation.

Conclusion: The use of the new oral DMTs greatly increased since their approval but persistence in the long-term is not better than with old drugs. The treatment choice is still a challenge both for patients and their doctors.
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http://dx.doi.org/10.1016/j.msard.2020.102004DOI Listing
June 2020

Antibody response against HERV-W in patients with MOG-IgG associated disorders, multiple sclerosis and NMOSD.

J Neuroimmunol 2020 01 6;338:577110. Epub 2019 Nov 6.

Section of Neurology, Department of Clinical, Surgery and Experimental Sciences, University of Sassari, Italy. Electronic address:

Increased expression of the retroviruses of HERV-W family has been linked to multiple sclerosis (MS) pathophysiology; nothing is known at the moment about MOG-IgG associated disorders. We compared antibody response against HERV-W peptides among patients with MOG-IgG associated disorders, multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD). A total of 102 serum samples were retrospectively analyzed. Antibody reactivity against HERV-W env peptides was similar in MOG-IgG associated disorders and MS, but different from AQP4-IgG positive NMOSD. Our findings expand the diagnostic role of HERV-W antibodies to the spectrum of demyelinating disorders associated with MOG-IgG.
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http://dx.doi.org/10.1016/j.jneuroim.2019.577110DOI Listing
January 2020

Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study.

Mult Scler Relat Disord 2020 Jan 19;37:101461. Epub 2019 Oct 19.

Rehabilitation Department, Mons. L. Novarese, Moncrivello, Vercelli, Italy.

Background: The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study.

Methods: Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data.

Results: Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier.

Conclusion: MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.
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http://dx.doi.org/10.1016/j.msard.2019.101461DOI Listing
January 2020

Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases.

Neurology 2019 11 23;93(20):e1867-e1872. Epub 2019 Oct 23.

From the Section of Neurology (S.M., A.G., M.Z., D.A., S.M., S.F.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona; Neurology Unit (L.B., R.D., G.S., S.L., M.I.P.), Department of Medical, Surgical, and Experimental Sciences, University of Sassari; Neurology Unit (B.B.), AOUI Verona, Italy; and Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria.

Objective: To determine the diagnostic relevance of myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) in CSF of seronegative cases by retrospectively analyzing consecutive time-matched CSF of 80 MOG-Ab-seronegative patients with demyelinating disease.

Methods: The cohort included 44 patients with NMOSD and related disorders and 36 patients with multiple sclerosis (MS). Two independent neurologists blinded to diagnosis analyzed MOG-Abs by live cell-based immunofluorescence assay with goat anti-human immunoglobulin (Ig) G (whole molecule) antibody. Sera were tested at dilutions of 1:20 and 1:40, and a cutoff of 1:160 was considered for serum positivity. CSF specimens were tested undiluted and at 1:2 dilution with further titrations in case of positivity. Anti-IgG-Fc and anti-IgM-µ secondary antibodies were used to confirm the exclusive presence of MOG-IgG in positive cases. CSF of 13 MOG-Abs seropositive cases and 36 patients with neurodegenerative conditions was analyzed as controls.

Results: Three seronegative cases had CSF MOG-Abs (4% of the whole cohort or 7% of cases excluding patients with MS, in which MOG-Abs seem to lack diagnostic relevance). In particular, 2 patients with neuromyelitis optica spectrum disorder (NMOSD) and 1 with acute disseminated encephalomyelitis had MOG-Abs in CSF. Analysis with anti-IgG-Fc and anti-IgM confirmed the exclusive presence of MOG-IgG in the CSF of these patients. Among the control group, MOG-Abs were detectable in the CSF of 8 of 13 MOG-Ab-seropositive cases and in none of the patients with neurodegenerative disorders.

Conclusion: Although serum is the optimal specimen for MOG-Ab testing, analyzing CSF could improve diagnostic sensitivity in seronegative patients. This observation has relevant diagnostic impact and might provide novel insight into the biological mechanisms of MOG-Ab synthesis.
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http://dx.doi.org/10.1212/WNL.0000000000008479DOI Listing
November 2019

Conversion to Secondary Progressive Multiple Sclerosis: Patient Awareness and Needs. Results From an Online Survey in Italy and Germany.

Front Neurol 2019 22;10:916. Epub 2019 Aug 22.

IRCCS Neuromed, Pozzilli, Italy.

Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders. The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified. Participants were consenting adults with SPMS since ≤5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs. Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany ( = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28-35% obtained second opinions, and 48-56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy ( < 0.001). Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13-0.78 for Central Italy; OR 0.21, 95% CI 0.08-0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47-41.37 for dependent vs. autonomous patients). All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: "physiotherapy" and "active patient care involvement." The other two differed across countries: "an individualized health care plan" and "information on social rights and policies" in Italy, and "psychological support" and "cognitive rehabilitation" in Germany. Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries.
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http://dx.doi.org/10.3389/fneur.2019.00916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713887PMC
August 2019

Biopsychosocial model of resilience in young adults with multiple sclerosis (BPS-ARMS): an observational study protocol exploring psychological reactions early after diagnosis.

BMJ Open 2019 08 2;9(8):e030469. Epub 2019 Aug 2.

Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

Introduction: Multiple sclerosis (MS), the most common neurological disease causing disability in young adults, is widely recognised as a major stress factor. Studies have shown that the first years after the diagnosis are distressing in terms of adjustment to the disease and that MS negatively affects patients' psychological well-being, quality of life (QoL) and social functioning. However, the links between disease-specific variables at diagnosis, resilience and psychological adjustment of patients with MS remain largely unexplored, especially in adolescents and young adults. This observational study aims to fill the gap of knowledge on iosychoocial characteristics and esilience of young dults with MS to evaluate the relationship among these variables and to develop a biopsychosocial model of resilience.

Methods And Analysis: Biological and clinical characteristics of young adults newly diagnosed with MS will be investigated by collecting clinical information, performing neurological examinations, MRI and analysing cerebrospinal fluid and blood biomarkers (eg, measures of inflammation), body composition, gut microbiota and movement/perceptual markers. Psychosocial characteristics (eg, psychological distress, coping strategies), QoL, psychological well-being and resilience will be assessed by self-report questionnaires. Comparative statistics (ie, analysis of variance or unpaired samples t-test, correlation and regression analyses) will be applied to evaluate the relationship among biological, psychological and social factors. The results are expected to allow a comprehensive understanding of the determinants of resilience in young patients with MS and to inform resilience interventions, tailored to young patients' specific needs, aiming to reduce the risk of maladaptive reactions to the disease and to improve psychological well-being and QoL.

Ethics And Dissemination: The study has been approved by the Verona University Hospital Ethics Committee (approval number: 2029CESC). The findings will be disseminated through scientific publications in peer-reviewed journals, conference presentations, social media and specific websites.

Trial Registration Number: ClinicalTrials.gov (NCT03825055).
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http://dx.doi.org/10.1136/bmjopen-2019-030469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687017PMC
August 2019

Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases.

Mult Scler J Exp Transl Clin 2019 Apr-Jun;5(2):2055217319848463. Epub 2019 May 15.

Clinical Department of Neurology, Medical University of Innsbruck, Austria.

Background: Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological mechanisms compared to multiple sclerosis.

Objective: The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis.

Methods: Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays. First, we analysed a panel of 32 cytokines/chemokines in a discovery group (nine aquaporin-4-antibody seropositive, nine myelin oligodendrocyte glycoprotein-antibody seropositive, eight encephalitis, 10 multiple sclerosis). Significantly dysregulated cytokines/chemokines were validated in a second cohort (11 aquaporin-4-antibody seropositive, 18 myelin oligodendrocyte glycoprotein-antibody seropositive, 18 encephalitis, 33 multiple sclerosis).

Results: We found 11 significantly altered cytokines/chemokines in cerebrospinal fluid and serum samples in the discovery group (a proliferation-inducing ligand, fractalkine=CX3CL1, growth-regulated oncogene-α, interleukin-1 receptor antagonist, interleukin-6, interleukin-8=CXCL8, interleukin-10, interleukin-21, interferon-ɣ-induced protein-10=CXCL10, monokine induced by interferon-ɣ=CXCL9, macrophage inflammatory protein-1ß=CCL4). Most of these cytokines/chemokines were up-regulated in autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein positive patients compared to multiple sclerosis. We confirmed these results for cerebrospinal fluid interleukin-6 and serum interleukin-8, growth-regulated oncogene-α, a proliferation-inducing ligand and macrophage inflammatory protein-1β in the validation set. Receiver-operating characteristic analysis revealed increased levels of cerebrospinal fluid interleukin-6, serum interleukin-8 and growth-regulated oncogene-α in most patients with autoantibody-associated neurological diseases.

Conclusion: This study suggests that distinctive cerebrospinal fluid and serum cytokine/chemokine profiles are associated with autoantibody-mediated demyelination, but not with multiple sclerosis.
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http://dx.doi.org/10.1177/2055217319848463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537078PMC
May 2019

"Better explanations" in multiple sclerosis diagnostic workup: A 3-year longitudinal study.

Neurology 2019 05 1;92(22):e2527-e2537. Epub 2019 May 1.

From the Departments of Neuroscience, Biomedicine and Movement (M.C., A. Gajofatto) and Neurological and Movement Sciences (G.S.), University of Verona; Department of Neurosciences (C.G., C.T.), Azienda Ospedaliera San Camillo Forlanini, Roma; Department of Basic Medical Sciences, Neurosciences and Sense Organs (C.T., D.P.), University of Bari; Policlinico Gemelli (G.F.), Rome; Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BIONEC) (P.R.), Università di Palermo; Istituto Neurologico Mediterraneo (R.F.), Pozzilli; Department of Neurology and Psychiatry (L.P.), Sapienza University of Rome; Multiple Sclerosis Center (P.A.), ASST Valle Olona, PO di Gallarate; Multiple Sclerosis Center (C.C.), Ospedale di Montichiari, Spedali Civili di Brescia; Clinica Neurologica (M.D.), Dipartimento di Medicina, Università di Perugia; Department of Biomedical, Metabolic and Neurosciences (D.F.), University of Modena and Reggio Emilia, Modena; Neurologia 2-CRESM (S.M.), AOU San Luigi Gonzaga, Orbassano; Multiple Sclerosis Centre (S.L.), A.O.U. Policlinico-Vittorio Emanuele, Catania; Neurology Clinic (G.D.), Multiple Sclerosis Center, SS. Annunziata Hospital, Chieti; Department of Medicine, Surgery and Neuroscience (M.L.S.), University of Siena; Department of Medical Science and Public Health (E.C.), University of Cagliari; Department of Medical, Surgical, Neurological, Metabolic and Aging Science (A. Gallo), University of Campania; Department of Neuroscience, Reproductive Sciences (R.L.), University Federico II, Naples, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine, UK; Ospedale di Vaio (I.P.), Centro SM, Fidenza, Parma; Ospedale San Raffaele (M.E.R.), Milan; and Department of Rehabilitation (C.S.), Mons L Novarese Hospital, Moncrivello, Italy.

Background: The exclusion of other diseases that can mimic multiple sclerosis (MS) is the cornerstone of current diagnostic criteria. However, data on the frequency of MS mimics in real life are incomplete.

Methods: A total of 695 patients presenting with symptoms suggestive of MS in any of the 22 RIREMS centers underwent a detailed diagnostic workup, including a brain and spinal cord MRI scan, CSF and blood examinations, and a 3-year clinical and radiologic follow-up.

Findings: A total of 667 patients completed the study. Alternative diagnoses were formulated in 163 (24.4%) cases, the most frequent being nonspecific neurologic symptoms in association with atypical MRI lesions of suspected vascular origin (40 patients), migraine with atypical lesions (24 patients), and neuromyelitis optica (14 patients). MS was diagnosed in 401 (60.1%) patients according to the 2017 diagnostic criteria. The multivariate analysis revealed that the absence of CSF oligoclonal immunoglobulin G bands (IgG-OB) (odds ratio [OR] 18.113), the presence of atypical MRI lesions (OR 10.977), the absence of dissemination in space (DIS) of the lesions (OR 5.164), and normal visual evoked potentials (OR 3.550) were all independent predictors of an alternative diagnosis.

Interpretation: This observational, unsponsored, real-life study, based on clinical practice, showed that diseases that mimicked MS were many, but more than 45% were represented by nonspecific neurologic symptoms with atypical MRI lesions of suspected vascular origin, migraine, and neuromyelitis optica. The absence of IgG-OB and DIS, the presence of atypical MRI lesions, and normal visual evoked potentials should be considered suggestive of an alternative disease and red flags for the misdiagnosis of MS.
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http://dx.doi.org/10.1212/WNL.0000000000007573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659006PMC
May 2019

Serum and CSF neurofilament light chain levels in antibody-mediated encephalitis.

J Neurol 2019 Jul 3;266(7):1643-1648. Epub 2019 Apr 3.

Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Policlinico GB Rossi, P.le LA Scuro 10, 37135, Verona, Italy.

Circulating and cerebrospinal fluid (CSF) neurofilament light chain (NfL) levels represent a reliable indicator of disease activity and axonal damage in different neuroinflammatory conditions. Recently, high CSF NfL levels have been detected in active autoimmune encephalitis, as opposed to significant lower levels after clinical improvement. The aim of the present study was to evaluate serum and CSF NfL concentration in patients with autoimmune encephalitis and to analyse the association between NfL levels and clinical, MRI, and CSF data. We retrospectively included 25 patients with neurological syndromes associated with autoantibodies to neuronal cell surface antigens and we collected clinical, MRI, CSF, and follow-up data. Using an ultrasensitive method (Simoa, Quanterix), we measured NfL levels in serum and CSF samples of all patients and in 25 sera of healthy controls. Serum NfL levels were higher in all cases, including 20 patients with inflammatory MRI/CSF features and 5 non-inflammatory cases (median 16.9 pg/ml, range 4.5-90) than in controls (median 6.9 pg/ml, range 2.7-12.8; p < 0.001). A correlation between serum and CSF NfL levels was found (r = 0.461, p = 0.023), whereas no significant association was observed between NfL levels and clinical, MRI/CSF inflammatory burden, and antibody type. In the 13 available follow-up samples, correlation between disease activity and NfL values was also observed. In conclusion, NfL levels are significantly increased in the serum of patients with antibody-mediated encephalitis, independently of the MRI/CSF inflammatory profile. These findings support the presence of ongoing axonal damage and suggest the co-occurrence of different mechanisms for neuronal/axonal involvement in antibody-associated CNS syndromes.
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http://dx.doi.org/10.1007/s00415-019-09306-zDOI Listing
July 2019

2017 McDonald criteria for multiple sclerosis: Earlier diagnosis with reduced specificity?

Mult Scler Relat Disord 2019 Apr 3;29:23-25. Epub 2019 Jan 3.

Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona and Neurology Unit B, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale L.A. Scuro, 10 37134 Verona, Italy.

Background: McDonald criteria for multiple sclerosis (MS) diagnosis were revised in 2017.

Objective: Aim of our study was to evaluate and compare the sensitivity and specificity of 2017 and 2010 McDonald criteria in patients presenting with an initial demyelinating event (IDE).

Methods: We retrospectively identified patients with an IDE and collected clinical, MRI and CSF data in order to demonstrate fulfilment of 2010 and 2017 McDonald criteria.

Results: 2017 McDonald criteria showed 100% (86.8-100%) sensitivity and 13.8% (3.9-31.7%) specificity.

Conclusion: 2017 McDonald criteria appear to have higher sensitivity but reduced specificity compared to 2010 McDonald criteria.
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http://dx.doi.org/10.1016/j.msard.2019.01.008DOI Listing
April 2019

Effects of High-intensity Robot-assisted Hand Training on Upper Limb Recovery and Muscle Activity in Individuals With Multiple Sclerosis: A Randomized, Controlled, Single-Blinded Trial.

Front Neurol 2018 24;9:905. Epub 2018 Oct 24.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Integration of robotics and upper limb rehabilitation in people with multiple sclerosis (PwMS) has rarely been investigated. To compare the effects of robot-assisted hand training against non-robotic hand training on upper limb activity in PwMS. To compare the training effects on hand dexterity, muscle activity, and upper limb dysfunction as measured with the International Classification of Functioning. This single-blind, randomized, controlled trial involved 44 PwMS (Expanded Disability Status Scale:1.5-8) and hand dexterity deficits. The experimental group ( = 23) received robot-assisted hand training; the control group ( = 21) received non-robotic hand training. Training protocols lasted for 5 weeks (50 min/session, 2 sessions/week). Before (T0), after (T1), and at 1 month follow-up (T2), a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Action Research Arm Test. Secondary outcomes: Nine Holes Peg Test; Fugl-Meyer Assessment Scale-upper extremity section; Motricity Index; Motor Activity Log; Multiple Sclerosis (MS) Quality of Life-54; Life Habits assessment-general short form and surface electromyography. There were no significant between-group differences in primary and secondary outcomes. Electromyography showed relevant changes providing evidence increased activity in the extensor carpi at T1 and T2. The training effects on upper limb activity and function were comparable between the two groups. However, robot-assisted training demonstrated remarkable effects on upper limb use and muscle activity. https://clinicaltrials.gov NCT03561155.
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http://dx.doi.org/10.3389/fneur.2018.00905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207593PMC
October 2018

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

Neurol Sci 2019 Jan 25;40(1):75-80. Epub 2018 Sep 25.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1007/s10072-018-3582-0DOI Listing
January 2019

HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod.

Mult Scler Relat Disord 2018 Jul 2;23:24-26. Epub 2018 May 2.

Department of Otorhinolaryngology, Bussolengo Hospital, Verona, Italy. Electronic address:

Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected. Fingolimod was stopped as a precautionary measure in May 2017, and the patient currently continues his follow up at our Department. Immunocompromised patients are at risk for developing HPV-related malignancies probably in light of the suppression of T-cell immunity, therefore an increased risk for HPV activation in MS patients treated with disease modifying therapies (DMTs) characterized by a more pronounced immunosuppressant activity cannot be excluded. Given the absence of studies on larger cohorts of MS patients exposed to DMTs, additional monitoring for HPV infection during fingolimod treatment is not currently recommended. However, vigilance for this possible association is warranted.
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http://dx.doi.org/10.1016/j.msard.2018.04.018DOI Listing
July 2018

A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study.

J Neurol 2018 May 16;265(5):1174-1183. Epub 2018 Mar 16.

Neurology Unit, Centro di Recupero e Rieducazione Funzionale, Moncrivello, VC, Italy.

In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.
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http://dx.doi.org/10.1007/s00415-018-8831-xDOI Listing
May 2018

Mycobacterium avium subspecies paratuberculosis and myelin basic protein specific epitopes are highly recognized by sera from patients with Neuromyelitis optica spectrum disorder.

J Neuroimmunol 2018 05 28;318:97-102. Epub 2018 Feb 28.

Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43b, 07100 Sassari, Italy. Electronic address:

Epstein-Barr virus (EBV) is the main environmental agent associated to neuromyelitis optica spectrum disorder (NMOSD). Following to studies reporting an increased prevalence of antibodies against peptides derived from Mycobacterium avium subsp. paratuberculosis (MAP) homologous to EBV and human epitopes (MBP, IRF5) in multiple sclerosis (MS), we investigated whether seroreactivity to these antigens display a NMOSD-specific pattern. The sera of 34 NMOSD patients showed elevated levels of antibodies against MAP and MBP compared to healthy controls (44% vs. 5%, p < 0.0002 and 50% vs. 2%, p < 0.0001, respectively), while, unlike in MS, responsiveness to EBV was similar.
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http://dx.doi.org/10.1016/j.jneuroim.2018.02.013DOI Listing
May 2018

Inflammatory intrathecal profiles and cortical damage in multiple sclerosis.

Ann Neurol 2018 04;83(4):739-755

Neurology B, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.

Objective: Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course?

Methods: To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases. Combined cytokine/chemokine CSF profiling and 3T magnetic resonance imaging (MRI) were performed at diagnosis in 2 independent cohorts of MS patients (35 and 38 subjects) and in 26 non-MS patients.

Results: Increased expression of proinflammatory cytokines (IFNγ, TNF, IL2, and IL22) and molecules related to sustained B-cell activity and lymphoid-neogenesis (CXCL13, CXCL10, LTα, IL6, and IL10) was detected in the meninges and CSF of postmortem MS cases with high levels of meningeal inflammation and GM demyelination. Similar proinflammatory patterns, including increased levels of CXCL13, TNF, IFNγ, CXCL12, IL6, IL8, and IL10, together with high levels of BAFF, APRIL, LIGHT, TWEAK, sTNFR1, sCD163, MMP2, and pentraxin III, were detected in the CSF of MS patients with higher levels of GM damage at diagnosis.

Interpretation: A common pattern of intrathecal (meninges and CSF) inflammatory profile strongly correlates with increased cortical pathology, both at the time of diagnosis and at death. These results suggest a role for detailed CSF analysis combined with MRI as a prognostic marker for more aggressive MS. Ann Neurol 2018 Ann Neurol 2018;83:739-755.
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http://dx.doi.org/10.1002/ana.25197DOI Listing
April 2018

Levofloxacin-induced hemichorea-hemiballism in a patient with previous thalamic infarction.

Neurol Sci 2018 08 6;39(8):1483-1485. Epub 2018 Mar 6.

Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, P.le L.A. Scuro 10, 37134, Verona, Italy.

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http://dx.doi.org/10.1007/s10072-018-3298-1DOI Listing
August 2018