Publications by authors named "Luca Prosperini"

121 Publications

Scoring the 10-year risk of ambulatory disability in multiple sclerosis: the RoAD score.

Eur J Neurol 2021 Mar 31. Epub 2021 Mar 31.

Centre d'Esclerosi Multiple de Catalunya (Cemcat), Dept. of Neurology/ Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.

Background: Both baseline prognostic factors and short-term predictors of treatment response can influence the long-term risk of disability accumulation in patients with relapsing-remitting multiple sclerosis (RRMS).

Objective: To develop and validate scoring system combining baseline prognostic factors and one-year variables of treatment response into a single numeric score predicting the long-term risk of disability.

Methods: We analyzed two independent datasets of patients with RRMS who started Interferon Beta or Glatiramer Acetate, had an Expanded Disability Status Scale (EDSS) score <4.0 at treatment start and were followed for at least 10 years. The first dataset ("training set") included patients attending three MS Centers in Italy and served as framework to create the so-called RoAD score (Risk of Ambulatory Disability). The second ("validation set") included a cohort of patients followed in Barcelona, Spain, to explore the performance of RoAD score in predicting the risk of reaching an EDSS score≥6.0.

Results: The RoAD score, derived from the training set (n = 1,225), was based on demographic (age) and clinical baseline prognostic factors (disease duration, EDSS) and one-year predictors of treatment response (number of relapses, presence of gadolinium-enhancement and new T2 lesions). The best cut-off score for discriminating patients at higher risk of reaching the disability milestone was ≥4. When applied to the validation set (n = 296), patients with a RoAD score ≥4 had an approximately 4-fold increased risk for reaching the disability milestone (p<0.001).

Discussion: We propose the RoAD score as an useful tool to predict individual prognosis of patients with RRMS to optimize treatment strategy.
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http://dx.doi.org/10.1111/ene.14845DOI Listing
March 2021

Ozone-induced encephalopathy: A novel iatrogenic entity.

Eur J Neurol 2021 Mar 3. Epub 2021 Mar 3.

Neurology Department, San Camillo Forlanini Hospital, Rome, Italy.

Background And Purpose: Ozone-based treatments can be associated with central nervous system toxicity, which we have termed ozone-induced encephalopathy (OIE). A detailed description of its phenotype is lacking.

Methods: Three cases with findings suggestive of OIE are presented, and the literature is reviewed.

Results: Case 1 is a healthy 59-year-old man presenting with loss of consciousness, cortical blindness, restlessness, and anterograde amnesia immediately following a cervical ozone-therapy (OT) session for chronic neck pain. Brain magnetic resonance imaging (MRI) on admission was normal. A follow-up scan demonstrated a subtle increased T2 fluid-attenuated inversion recovery signal within the left cerebellum; an echocardiography showed a patent foramen ovale (PFO). Case 2 is a 56-year-old woman with history of migraine, PFO, and lumbar pain who presented with headache, bilateral visual impairment, motor dysphasia, and agitation. All her symptoms began immediately after lumbar OT. Her brain MRI was negative. Case 3 is a healthy 27-year-old man who complained of vertigo and mild blurred vision 5 min following a cervical ozone injection. His neurological examination and brain MRI were normal. All three patients had full recovery within 48 h. We found eight additional cases of OIE in the literature.

Conclusions: OIE should be considered in patients presenting with neurological symptoms in close relation to OT. OIE is likely a novel iatrogenic entity with a complex pathogenesis; it is probably underreported because it mimics other neurological conditions.
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http://dx.doi.org/10.1111/ene.14793DOI Listing
March 2021

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study.

J Neurol 2021 Feb 22. Epub 2021 Feb 22.

Multiple Sclerosis Centre, Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.

Objective: To identify baseline factors associated with disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) under teriflunomide treatment.

Methods: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment.

Results: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0-4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007).

Conclusions: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.
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http://dx.doi.org/10.1007/s00415-021-10455-3DOI Listing
February 2021

Clinical course of central nervous system demyelinating neurological adverse events associated with anti-TNF therapy.

J Neurol 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy.

Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight patients presenting with demyelinating CNS events while on treatment with anti-TNFα for autoimmune diseases and followed up for a medium period of 4 years. Four patients presented with isolated demyelinating events, three patients fulfilled the criteria for multiple sclerosis (MS), and one patient showed worsening of pre-existing MS after anti-TNF therapy initiation. All patients except one, showed a good medium-term prognosis. Our observation supports an association between anti-TNFα treatment and demyelinating events and suggests that a prompt discontinuation of the drug may lead to a favorable demyelinating disease outcome.
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http://dx.doi.org/10.1007/s00415-021-10460-6DOI Listing
February 2021

Adjuvant chemotherapy after severe myelotoxicity during chemoradiation phase in malignant gliomas. Is it feasibile? Results from AINO study (Italian Association for Neuro-Oncology).

J Neurol 2021 Feb 20. Epub 2021 Feb 20.

Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.

Background: Malignant gliomas (MG) are aggressive brain tumours in adults. The standard of care is concurrent radiation plus temozolomide (TMZ) [chemo-radiotherapy (CRT)] followed by TMZ maintenance up to 6 months. TMZ is considered to have a low toxicity profile, but several studies reported occurrence of severe myelosuppression, especially during the concomitant phase. Toxicity may be prolonged, thus treatment should be discontinued.

Purpose: To evaluate the risk of recurrente myelotoxicity during adjuvant chemotherapy (CT) in patients who recovered from severe myelotoxicity during CRT.

Methods: We retrospectively collected data on patients with MG who developed and recovered from severe myelotoxicity during CRT from eight Italian neuro-oncology centers.

Results: We included 87 patients. Histology was Glioblastoma (GBM) in 78 patients (89.7%); 60% of patients were female. After myelotoxicity recovery, 54 (62%) received treatment. The majority of them (82%, n = 44) received adjuvant TMZ and 18% (n = 10) others treatments. Out of 44 patients who received adjuvant TMZ, 34% experienced the re-occurrence of grade 3-4 myelotoxicity which required permanent CT discontinuation in 6 (13%) cases. Patients who received TMZ or other treatments had longer overall (OS) (adjusted HR 0.46, p = 0.008) and progression free survival (PFS) (adjusted HR 0.57, p = 0.034) than those who remained untreated.

Conclusion: Our study suggests that after severe myelotoxicity the majority of patients received treatment, particularly with TMZ. Only a fraction of patients experienced toxicity recurrence, suggesting that TMZ is well tolerated and had an impact on PFS and OS.
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http://dx.doi.org/10.1007/s00415-021-10438-4DOI Listing
February 2021

Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis.

J Neurol 2021 Jan 26. Epub 2021 Jan 26.

Multiple Sclerosis Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.

Background: Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5-10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce.

Objectives: To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption.

Methods: Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II-III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm.

Results: Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II-III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery.

Conclusion: ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.
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http://dx.doi.org/10.1007/s00415-021-10412-0DOI Listing
January 2021

Prevalence and patterns of subclinical motor and cognitive impairments in non-disabled individuals with early multiple sclerosis: a multicenter cross-sectional study.

Ann Phys Rehabil Med 2021 Jan 14:101491. Epub 2021 Jan 14.

Rehabilitation Department, CRRF Mons L Novarese, 13040 Loc. Trompone, Moncrivello VC, Italy.

Background: Motor and cognitive disorders appear early in the course of multiple sclerosis (MS) and develop gradually over time.

Objective: To study the frequency and pattern of subtle functional disorders in people with MS (PwMS) with no overt signs of disability in an early phase of the disease and their association with walking impairments in daily activities.

Methods: In this cross-sectional study, we recruited PwMS with an Expanded Disability Status Scale (EDSS) score ≤ 2.5 and disease duration ≤ 5 years. Participants were assessed with functional scales rating walking endurance (6-Min Walk Test), perceived walking ability (Twelve-item Multiple Sclerosis Walking Scale), balance (Fullerton Advanced Balance scale_short), manual dexterity (Nine Hole Peg Test), fatigue (Fatigue Severity Scale), and cognitive impairments (Brief International Cognitive Assessment).

Results: About 90% of the 82 PwMS (mean [SD] EDSS score 1.5 [0.7] and disease duration 2.2 [1.7] years) showed endurance values below the expected score; almost 30% showed impairment, and for 57%, perceived walking ability score was abnormal. Balance was impaired in 48% of participants, as was manual dexterity (29%) and fatigue (24%), but only a few showed cognitive impairments. Only 11% of PwMS had no abnormal score on the scales used in the assessment. As compared with EDSS score 0 to 1.5, with EDSS score 2 to 2.5, performance was worse for endurance (difference ±61.0 m, p=0.016), perceived walking ability (-11 points, p=0.002), balance (+1.9 points, p=0.005), manual dexterity (-2.8 sec, p=0.004), and fatigue (-1.3 points, p=0.013). Factors that predicted perceived walking ability were balance (B = -1.37, p<0.001) and fatigue (B = 5.11, p<0.001) rather than endurance (B = -0.01, p=048).

Conclusion: Even PwMS with no clinical disability and classified as having "no problem walking" present walking and other functional deficits when assessed with specific functional tests. The addition of specific tools could better identify subtle motor and cognitive deficits. Finally, the assessment of balance disorders and fatigue is important to understand individuals' perceived walking impairments in daily activities.
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http://dx.doi.org/10.1016/j.rehab.2021.101491DOI Listing
January 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.

Clinica Neurologica, Dipartimento di Medicina e Chirurgia, Università degli Studi di Perugia, Perugia, Italy.

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

Unilateral meningitis: unusual central nervous system involvement in rheumatoid arthritis.

Pract Neurol 2020 Nov 28. Epub 2020 Nov 28.

Department of Neurosciences, San Camillo Forlanini Hospital, Roma, Italy.

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http://dx.doi.org/10.1136/practneurol-2020-002685DOI Listing
November 2020

Age-related adverse events of disease-modifying treatments for multiple sclerosis: A meta-regression.

Mult Scler 2020 Oct 26:1352458520964778. Epub 2020 Oct 26.

Department of Neurosciences, San Camillo-Forlanini Hospital, Rome, Italy.

Objective: To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action.

Methods: We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms.

Results: A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25,  < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51,  < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52,  = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms ( = 0.017), especially above 45 years of age.

Discussion: Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
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http://dx.doi.org/10.1177/1352458520964778DOI Listing
October 2020

'Posture second' strategy predicts disability progression in multiple sclerosis.

Mult Scler 2020 Oct 13:1352458520963926. Epub 2020 Oct 13.

Department of Neurosciences, San Camillo- Forlanini Hospital, Rome, Italy.

We assessed 168 patients with multiple sclerosis (MS) by force platform to obtain the dual-task cost (DTC) of balance, that is, the change in postural sway from quiet standing to dual-task condition (Stroop test). After a median follow-up time of 3.5 years from this assessment, disability progression occurred in 45 (27%) patients. Disability progression was predicted by the adoption of a 'posture second' strategy, that is, values of DTC of balance exceeding those obtained from 62 healthy controls, even after controlling by demographic and clinical characteristics. The DTC of balance may potentially represent a novel and easy tool to predict MS progression.
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http://dx.doi.org/10.1177/1352458520963926DOI Listing
October 2020

Vaccinations in patients with multiple sclerosis: A Delphi consensus statement.

Mult Scler 2021 03 17;27(3):347-359. Epub 2020 Sep 17.

Multiple Sclerosis Center, IRCCS San Raffaele Hospital, Milan, Italy/Neurology Department, IRCCS San Raffaele Hospital, Milan, Italy.

Background: Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking disease-modifying drugs.

Methods: A modified Delphi consensus process (October 2017-June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.

Results: Recommendations include the need for an 'infectious diseases card' of each patient's infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.

Conclusion: Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
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http://dx.doi.org/10.1177/1352458520952310DOI Listing
March 2021

The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement.

Mult Scler 2021 03 17;27(3):331-346. Epub 2020 Sep 17.

III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, University of Milan, Milan, Italy.

The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.
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http://dx.doi.org/10.1177/1352458520952311DOI Listing
March 2021

A Comprehensive Approach to Disentangle the Effect of Cerebellar Damage on Physical Disability in Multiple Sclerosis.

Front Neurol 2020 30;11:529. Epub 2020 Jun 30.

Department of Human Neurosciences, "Sapienza" Rome University, Rome, Italy.

Cerebellar damage occurs frequently in multiple sclerosis (MS) patients, with a wide exhibition of symptoms particularly as impairments of balance and gait. Recent studies implementing new postprocessing magnetic resonance imaging (MRI) techniques showed how cerebellar subregional atrophy provides an explanation of disability in MS. The aim of this work was to evaluate the relationship between quantitative measures of physical disability, cerebellar subregional atrophy, and cerebellar peduncle disruption. Forty-nine MS patients and 32 healthy subjects as controls (HS) underwent a 3-Tesla MRI including 3D T1-weighted and diffusion tensor imaging. Patients underwent static posturography to calculate the body's center of pressure (COP) displacement, Expanded Disability Status Scale (EDSS), and 25-ft walking test (25-FWT). Cerebellar lobular volumes were automatically calculated using the Spatially Unbiased Infratentorial Toolbox. Tract-based spatial statistics (TBSS) in FSL was used to process diffusion tensor imaging (DTI) Fit-generated fractional anisotropy (FA) maps to assess structural connectivity of cerebellar peduncles. Stepwise multivariate linear regression analyses were used to explore relationships between variables. Cerebellar volumes (anterior and posterior, as well as lobular volumes from I to X) were significantly lower in patients with MS than HS ( < 0.05). FA in all cerebellar peduncles was lower in MS patients than in HS ( < 0.05). EDSS and 25-FWT showed an association with atrophy of lobule VIIIb (β = -0.37, < 0.01, and β = -0.45, < 0.001, respectively) COP measures inversely correlated with volume of lobules I-IV (β = -0.37, < 0.01, and β = -0.36, < 0.01). Lower FA in the three cerebellar peduncles of MS patients positively correlated with cerebellar lobular volumes. Our findings show how sensorimotor cerebellum atrophy and disruption of both afferent and efferent cerebellar connections contribute to physical disability in MS patients.
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http://dx.doi.org/10.3389/fneur.2020.00529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338682PMC
June 2020

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

The Use of Social Media and Digital Devices Among Italian Neurologists.

Front Neurol 2020 16;11:583. Epub 2020 Jun 16.

Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, MRI Research Center SUN-FISM, AOU - University of Campania "Luigi Vanvitelli", Naples, Italy.

Digital devices and online social networks are changing clinical practice. In this study, we explored attitudes, awareness, opinions, and experiences of neurologists toward social media and digital devices. Each member of the Italian Society of Neurology (SIN) participated in an online survey (January to May 2018) to collect information on their attitude toward digital health. Four hundred and five neurologists participated in the study. At work, 95% of responders use the personal computer, 87% the smartphone, and 43.5% the tablet. These devices are used to obtain health information (91%), maintain contact with colleagues (71%), provide clinical information (59%), and receive updates (67%). Most participants (56%) use social media to communicate with patients, although 65% are against a friendship with them on social media. Most participants interact with patients on social media outside working hours (65.2%) and think that social media have improved (38.0%) or greatly improved (25.4%) the relationship with patients. Most responders (66.7%) have no wearable devices available in clinical practice. Italian neurologists have different practices and views regarding the doctor-patient relationship in social media. The availability of digital devices in daily practice is limited. The use of social networks and digital devices will increasingly permeate into everyday life, bringing a new dimension to health care. The danger is that advancement will not go hand in hand with a legal and cultural adaptation, thus creating ambiguity and risks for clinicians and patients. Neurologists will need to be able to face the opportunities and challenges of this new scenario.
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http://dx.doi.org/10.3389/fneur.2020.00583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308485PMC
June 2020

Exergaming for Quality of Life in persons living with chronic diseases: A systematic review and meta-analysis.

PM R 2020 Jun 26. Epub 2020 Jun 26.

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Objective: To evaluate the evidence of effectiveness of exergame-based rehabilitative interventions on health-related quality of life (HRQoL) in persons with chronic diseases. TYPE: Systematic review and meta-analysis.

Literature Survey: Randomized and non-randomized controlled trials of exergame rehabilitation interventions in populations with chronic diseases reporting HRQoL outcomes were identified by searching PubMed, Scopus, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar, using keywords and MeSH terms for papers published between January 2005 and March 2019.

Methodology: Risk of bias was assessed by using the PEDro scale. The GRADE system was used to score the quality of evidence. Pooled effects were reported as standardized mean differences (SMDs) or weighted mean difference (MDs) and 95% confidence intervals (CIs), using a random-effects model. Heterogeneity was weighted by inconsistency I tests.

Synthesis: Thirty-four trials were identified (1,594 participants). Overall, the evidence was low quality. Exergames significantly improved HRQoL in populations with chronic diseases, with a small effect size (32 studies; 1,544 participants; SMD 0.24; 95% CI 0.1 to 0.4; I = 27%) and specifically in people with neurological disorders (20 studies, 956 participants, SMD 0.22; 95% CI 0.2 to 0.4; I = 49%), rheumatologic diseases (four studies, 210 participants, SMD 0.39; 95% CI 0.1 to 0.7; I = 4%), and cardiorespiratory and chronic metabolic conditions (five studies, 309 participants, SMD 0.23; 95% CI 0.0 to 0.5; I = 0%). Exergaming interventions in health care settings demonstrated similarly small but positive effects (22 studies, 905 participants, SMD 0.30; 95% CI 0.1 to 0.5; I = 41%), whereas those carried out in home-based contexts did not.

Conclusions: Exergame-based rehabilitative interventions performed in health care settings led to small but statistically significant improvements in HRQoL in persons with chronic diseases. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/pmrj.12444DOI Listing
June 2020

Exergames for balance dysfunction in neurological disability: a meta-analysis with meta-regression.

J Neurol 2020 May 23. Epub 2020 May 23.

Rehabilitation Unit 'Mons. L. Novarese' Hospital, Loc. Trompone, 13040, Moncrivello, VC, Italy.

Objective: To evaluate systematically the efficacy of exergames for balance dysfunction in neurological conditions and to identify factors of exergaming protocols that may influence their effects.

Methods: We searched electronic databases for randomized clinical trials investigating the effect of commercial exergames versus alternative interventions on balance dysfunction as assessed by standard clinical scales in adults with acquired neurological disabilities. Standardized mean differences (Hedge's g) were calculated with random-effects models. Subgroup analyses and meta-regression were run to explore potential modifiers of effect size.

Results: Out of 106 screened articles, 41 fulfilled criteria for meta-analysis, with a total of 1223 patients included. Diseases under investigation were stroke, Parkinson's disease, multiple sclerosis, mild cognitive impairment or early Alzheimer's disease, traumatic brain injury, and myelopathy. The pooled effect size of exergames on balance was moderate (g = 0.43, p < 0.001), with higher frequency (number of sessions per week) associated with larger effect (β = 0.24, p = 0.01). There was no effect mediated by the overall duration of the intervention and intensity of a single session. The beneficial effect of exergames could be maintained for at least 4 weeks after discontinuation, but their retention effect was specifically explored in only 11 studies, thus requiring future investigation. Mild to moderate adverse events were reported in a minority of studies. We estimated a low risk of bias, mainly attributable to the lack of double-blindness and not reporting intention-to-treat analysis.

Conclusions: The pooled evidence suggests that exergames improve balance dysfunction and are safe in several neurological conditions. The findings of high-frequency interventions associated with larger effect size, together with a possible sustained effect of exergaming, may guide treatment decisions and inform future research.
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http://dx.doi.org/10.1007/s00415-020-09918-wDOI Listing
May 2020

Local Dynamic Stability of Gait in People With Early Multiple Sclerosis and No-to-Mild Neurological Impairment.

IEEE Trans Neural Syst Rehabil Eng 2020 06 30;28(6):1389-1396. Epub 2020 Apr 30.

Poor dynamic balance, such as poor walking stability, is a hallmark of multiple sclerosis. Instrumental measures of local dynamic stability (LDS, e.g. short-term Lyapunov's exponents, sLyEs) are genuine measures of walking stability and increasingly used as dynamic balance indicators. The current work aims to investigate if people with multiple sclerosis (PWMS) with no clinical evidence of gait impairment suffer poor LDS of gait. Eighty PWMS with minimal impairment (EDSS ≤2.5) and twenty controls completed the Six-Minute Walk Test (6MWT) at their maximum speed, wearing inertial sensors. sLyEs were calculated from trunk vertical, mediolateral and anteroposterior (sLyE) acceleration. PWMS also completed a full clinical assessment including gait, balance and fatigue. Gait speed was lower in PWMS than controls (-15%), while sLyEs were larger in PWMS (+12%), even when adjusting for the different gait speed. High sLyE was associated with low gait speed, high impact of disease (including high fatigue) and poor balance, the three variables returned by a principal component analysis of the dataset of clinical measures. PWMS suffer poor LDS of gait, as indicated by large sLyEs. The association between high sLyE and poor balance supports the validity of sLyE as a dynamic balance measure. The inverse relationship between sLyE and gait speed is in line with the view that good balance is decisive for high gait speed. Finally, these findings are in line with the vicious circle linking poor balance and fatigue in PWMS, with fatigue worsening balance and poor balance leading to fatigue.
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http://dx.doi.org/10.1109/TNSRE.2020.2991636DOI Listing
June 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

Induction Versus Escalation in Multiple Sclerosis: A 10-Year Real World Study.

Neurotherapeutics 2020 07;17(3):994-1004

Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.

In this independent, multicenter, post-marketing study, we directly compare induction immunosuppression versus escalation strategies on the risk of reaching the disability milestone of Expanded Disability Status Scale (EDSS) ≥ 6.0 over 10 years in previously untreated patients with relapsing-remitting multiple sclerosis. We collected data of patients who started interferon beta (escalation) versus mitoxantrone or cyclophosphamide (induction) as initial treatment. Main eligibility criteria included an EDSS score ≤ 4.0 at treatment start and either ≥ 2 relapses or 1 disabling relapse with evidence of ≥ 1 gadolinium-enhancing lesion at magnetic resonance imaging scan in the pre-treatment year. Since patients were not randomized to treatment group, we performed a propensity score (PS)-based matching procedure to select individuals with homogeneous baseline characteristics. Comparisons were then conducted using Cox models stratified by matched pairs. Overall, 75 and 738 patients started with induction and escalation, respectively. Patients in the induction group were older and more disabled than those in the escalation group (p < 0.05). The PS-matching procedure retained 75 patients per group. In the re-sampled population, a lower proportion of patients reached the outcome after induction (21/75, 28.0%) than escalation (29/75, 38.7%) (hazard ratio = 0.48; p = 0.024). Considering the whole sample, serious adverse events occurred more frequently after induction (8/75, 10.7%) than escalation (18/738, 2.4%) (odds ratio = 3.36, p = 0.015). These findings suggest that, in patients with poor prognostic factors, induction was more effective than escalation in reducing the risk of reaching the disability milestone, albeit with a worse safety profile. Future studies are warranted to explore if newer induction agents may provide a more advantageous long-lasting risk:benefit profile.
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http://dx.doi.org/10.1007/s13311-020-00847-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609676PMC
July 2020

Italian translation and psychometric validation of the Manual Ability Measure-36 (MAM-36) and its correlation with an objective measure of upper limb function in patients with multiple sclerosis.

Neurol Sci 2020 Jun 23;41(6):1539-1546. Epub 2020 Jan 23.

Department of Psychology, University of Turin, Turin, Italy.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with an unpredictable course. During its course, deficits affecting upper limb functions may occur. Hence, there is a need for self-administered scales providing a comprehensive assessment of upper limb functions. The Manual Ability Measure-36 (MAM-36), which investigates patients' performance in activities of daily living requiring upper limb function, has not been adapted and validated in the Italian context.

Objectives: We develop an Italian translation and validation of the MAM-36 in a population of people with MS (PwMS), explore its psychometric properties and investigate its associations with clinical data and the Nine Hole Peg Test (9-HPT).

Research Plan And Methods: The multicentre study involved five Italian neurological centres. Subjects were evaluated using EDSS, 9-HPT and the MAM-36 scale. We used confirmatory factor analysis and Rasch analysis to investigate the properties of the MAM-36.

Results: We enrolled 218 PwMS. Results supported the unidimensionality of the MAM-36, and adequate functioning of rating scale and items. Additionally, the MAM-36 showed weak negative associations with age and disease duration, and moderate associations with EDSS and 9-HPT scores.

Discussion: The adapted MAM-36 showed adequate psychometric properties. However, indications of problematic targeting to PwMS with low disability emerged. For this reason, use of the scale appears to be more suitable among patients with moderate-to-severe disability.
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http://dx.doi.org/10.1007/s10072-020-04263-2DOI Listing
June 2020

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis.

J Neurol Neurosurg Psychiatry 2020 03 23;91(3):271-277. Epub 2020 Jan 23.

Multiple Sclerosis Center, San Camillo-Forlanini Hospital, Roma, Italy.

Objective: This study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.

Methods: We retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called 'MAGNIMS score' (: no relapses and <3 new T2 lesions; : no relapses and ≥3 new T2 lesions or 1 relapse and 0-2 new T2 lesions; : 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).

Results: At follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with score (reference category), 57/241 (23.7%) with score (HR=1.94, p=0.002) and 30/110 (27.3%) with score (HR=2.47, p<0.001) after the first year of treatment. In the score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.

Conclusions: Early marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.
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http://dx.doi.org/10.1136/jnnp-2019-322348DOI Listing
March 2020

Premorbid functional reserve modulates the effect of rehabilitation in multiple sclerosis.

Neurol Sci 2020 May 9;41(5):1251-1257. Epub 2020 Jan 9.

S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.

Background: Premorbid physically and intellectually enriching lifestyles have increasingly been recognized as able to mitigate the risk of disease-related disability in patients with multiple sclerosis (MS).

Objective: To explore if premorbid physical activity, cognitive reserve and trait personality act as proxies for functional reserve that contributes to rehabilitation outcome.

Methods: We recruited all patients previously enrolled in two pilot trials investigating the effect of home-based video game training in improving balance (Study 1) and attention (Study 2) for additional assessments with the Historical Leisure Activity Questionnaire (HLAQ; a proxy for premorbid physical activity), Cognitive Reserve Index Questionnaire (CRIQ), and Temperament and Character Inventory (TCI). Hierarchical logistic regression (HLR) analyses tested the association of HLAQ, CRIQ, and TCI with training effect on balance (static posturography) and on attention (Symbol Digit Modalities Test).

Results: We identified 94% (34/36) and 74% (26/35) of patients participating at the original Study 1 and Study 2, respectively. HLR analyses showed an exclusive "intra-modal" modulation of rehabilitation outcome by functional reserve, given that (1) larger training effect on balance was associated with higher HLAQ (OR = 2.03, p = 0.031); (2) larger training effect on attention was associated with higher CRIQ (OR = 1.27, p = 0.033). Furthermore, we found specific personality traits associated with (1) greater training effect on balance (self-directedness; OR = 1.40, p = 0.051) and lower training effect on attention (harm avoidance; OR = 0.66, p = 0.075).

Conclusion: We hypothesize that premorbid physical and intellectual activities not only act as a buffer for limiting the MS-related damage but also as functional reserve that can be retrieved by task-oriented training to promote recovery through rehabilitation.
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http://dx.doi.org/10.1007/s10072-019-04237-zDOI Listing
May 2020

Dalfampridine to Improve Balance in Multiple Sclerosis: Substudy from a Randomized Placebo-Controlled Trial.

Neurotherapeutics 2020 04;17(2):704-709

S. Andrea Hospital, Sapienza University, Via di Grottarossa 1035, 00189, Rome, Italy.

This was a substudy of a randomized, double-blind, placebo-controlled trial originally designed to explore the effect of dalfampridine on information processing speed (2013-002558-64 EU Clinical Trials Register) in patients with multiple sclerosis (MS). A total of 120 patients were originally randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. Here, we sought to explore the effect of dalfampridine on static balance in single-task and dual-task conditions in a subgroup of 41 patients. They underwent static posturography in quiet standing (single-task) and while performing the Stroop test (dual-task) at randomization (baseline), after 12 weeks and after a 4-week wash-out period. Baseline characteristics of active group (n = 27) did not differ from those of placebo group (n = 14). Dalfampridine treatment was associated with better balance control than placebo in both single-task (F = 4.80, p = 0.034) and dual-task (F = 6.42, p = 0.015) conditions, with small-to-moderate effect sizes (Cohen's f = 0.122-0.162). The beneficial effect of dalfampridine was not retained 4 weeks after its discontinuation. The rate of accidental falls per month did not differ between the two groups (p = 0.12). Our preliminary findings suggest that dalfampridine can be considered a potential option to treat balance impairment due to MS. Larger sample sizes are needed to verify if the beneficial effect of dalfampridine on balance can be translated into a reduced risk of accidental falls.
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http://dx.doi.org/10.1007/s13311-019-00813-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283428PMC
April 2020

Cognitive fatigability is a quantifiable distinct phenomenon in multiple sclerosis.

J Neuropsychol 2020 09 14;14(3):370-383. Epub 2019 Nov 14.

Medicine Department, Neurology Unit, San Filippo Neri Hospital, Rome, Italy.

Cognitive fatigability in multiple sclerosis represents the decrease in cognitive performance over time. It is a frequent symptom that negatively affects quality of life and ability to work. There are no objective measures of cognitive fatigability. This study aimed at quantifying cognitive fatigability despite the learning effect and to clarify whether cognitive fatigability represents a free-standing phenomenon rather than an aspect of cognitive impairment. We measured information processing speed with the Symbol Digit Modalities Test, and the number of right answers was recorded every 30 s for 180 s. We approximated the number of right answers as function of time with two logarithmic models, one including a first-order term alone and the other adding also a second-order term. The coefficient of the latter (B) may quantify performance deflection and may represent cognitive fatigability. We tested 173 patients with multiple sclerosis, including 119 cognitively impaired and 54 cognitively preserved patients, and 35 healthy subjects. The performance of cognitively preserved patients showed a deflection at the end of task that was detected neither in controls nor in cognitively impaired patients and needed a second-order term to be approximated (p < .03, F = 14.02). B was explained neither by depression nor fatigue. We proposed for the first time a method to quantify cognitive fatigue via a second-order least square fit model, easily usable in the clinical practice. By using this novel approach, cognitive fatigability results to be a free-standing phenomenon that is more evident in cognitively preserved than in cognitive impaired patients.
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http://dx.doi.org/10.1111/jnp.12197DOI Listing
September 2020

Exit strategies for "needle fatigue" in multiple sclerosis: a propensity score-matched comparison study.

J Neurol 2020 Mar 13;267(3):694-702. Epub 2019 Nov 13.

San Filippo Neri Hospital, ASL Roma 1, Via G. Martinotti 20, 00135, Rome, Italy.

Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called "needle fatigue", i.e., a waning commitment to continue with the prescribed injectable treatment. Therefore, alternative treatment strategies to enhance patients' adherence are warranted. In this independent, multicentre post-marketing study, we sought to directly compare switching to either teriflunomide (TFN), dimethyl fumarate (DMF), or pegylated interferon (PEG) on treatment persistence and time to first relapse over a 12-month follow-up. We analyzed a total of 621 patients who were free of relapses and gadolinium-enhancing lesions in the year prior to switching to DMF (n = 265), TFN (n = 160), or PEG (n = 196). Time to discontinuation and time to first relapse were explored in the whole population by Cox regression models adjusted for baseline variables and after a 1:1:1 ratio propensity score (PS)-based matching procedure. Treatment discontinuation was more frequent after switching to PEG (28.6%) than DMF (14.7%; hazard ratio [HR] = 0.25, p < 0.001) and TFN (16.9%; HR = 0.27, p < 0.001). We found similar results even in the re-sampled cohort of 222 patients (74 per group) derived by the PS-based matching procedure. The highest discontinuation rate observed in PEG recipient was mainly due to poor tolerability (p = 0.005) and pregnancy planning (p = 0.04). The low number of patients who relapsed over the 12-month follow-up (25 out of 621, approximately 4%) prevented any analysis on the short-term risk of relapse. This real-world study suggests that oral drugs are a better switching option than low-frequency interferon for promoting the short-term treatment persistence in stable patients who do not tolerate injectable drugs.
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http://dx.doi.org/10.1007/s00415-019-09625-1DOI Listing
March 2020

Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS.

Mult Scler 2019 09;25(10):1348-1362

Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.

Background: Neural plasticity represents the substrate by which the damaged central nervous system (CNS) re-learns lost behaviors in response to rehabilitation. In persons with multiple sclerosis (MS), rehabilitation can therefore exploit the potential of neural plasticity to restore CNS functions beyond the spontaneous mechanisms of recovery from MS-related damage.

Methods: Here, we reviewed the currently available evidence on the occurrence of mechanisms of structural and functional plasticity following rehabilitation, motor, and/or cognitive training. We presented both data gained from basic laboratory research on animal models and data on persons with MS obtained by advanced magnetic resonance imaging (MRI) techniques.

Results: Studies on physical and environmental enrichment in experimental MS models showed beneficial effects mediated by both immune modulation and activity-dependent plasticity, lowering tissue destruction and restoring of CNS network function. Translational researches in MS people demonstrated structural and/or functional MRI changes after various interventions, but their heterogeneity and small sample sizes (5-42 patients) raise concerns about the interpretation and generalization of the obtained results.

Discussion: We highlighted the limitations of published studies, focusing on the knowledge gaps to be filled in terms of neuropathological correlations between changes detected in animal models and changes detected in vivo by neuroimaging.
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http://dx.doi.org/10.1177/1352458519846096DOI Listing
September 2019

The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray).

PLoS One 2019 30;14(7):e0219670. Epub 2019 Jul 30.

IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.

Background: Nabiximols (THC/CBD Oromucosal Spray, Sativex) is used as an add-on therapy to treat moderate to severe spasticity of Multiple Sclerosis (MS).

Objectives: To examine the impact of physiotherapy (PT) programs on effectiveness and persistence of nabiximols treatment in people with MS-related spasticity.

Methods: This is an observational multicenter study with a follow-up period of 12 weeks, conducted in routine care settings in Italy. Patients with moderate to severe MS-related spasticity who started nabiximols were included. Spasticity was evaluated by the patient-rated 0-10 numerical rating scale (NRS). Clinical data were collected at baseline (T0), 4 weeks (T1) and 12 weeks (T2) months after enrollment.

Results: A total of 297 MS patients were selected, 290 completed the 3 months follow-up period. Mean NRS scores were 7.6 ± 1.1 at T0, 5.8 ± 1.4 at T1 and 5.5 ± 1.5 at T2. At T1, 77% of patients reached ≥20% improvement (initial response, IR); 22% reached ≥30% improvement (clinically relevant response, CRR). At T1, patients undergoing PT had a higher probability to reach CRR (Odds Ratio = 2.6 95% CI 1.3-5.6, p = 0.01). Nabiximols was discontinued in 30/290 (10.3%) patients at T1 (early discontinuers) and in 71/290 (24.5%) patients at T2 (late discontinuers). The probability of being late discontinuers was reduced in patients undergoing PT (Hazard Ratio = 0.41; 95% CI 0.23-0.69, p = 0.001).

Conclusions: Our real-life study confirms nabiximols' effectiveness in MS-related spasticity and suggests that the association of a PT program may improve overall response and persistence to nabiximols treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219670PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667203PMC
February 2020

Effect of dalfampridine on information processing speed impairment in multiple sclerosis.

Neurology 2019 08 22;93(8):e733-e746. Epub 2019 Jul 22.

From the MS Center Sant'Andrea Hospital (L.D.G., F.G., G.B., C.P.), Department of Human Neuroscience (L.D.G., F.D.L., F.G., I.F., C.P.), and Department of Psychology (F.D.L.), Sapienza University of Rome; Department of Neuroscience San Camillo-Forlanini Hospital (L.P., E.Q., C.G.); and Neurological Center of Latium (G.B.), IRCCS Neuromed, Rome, Italy.

Objective: To test a possible benefit of dalfampridine on information processing speed (IPS), a key function for cognitive impairment (CogIm) in multiple sclerosis (MS).

Methods: In this randomized, double-blind, placebo-controlled trial, we included patients with a score on the Symbol Digit Modalities Test (SDMT) under the 10th percentile of the reference value. Patients were randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. They underwent a comprehensive neuropsychological evaluation at screening (T0), at the end of treatment (T1), and after a 4-week follow-up (T2). The primary endpoint was improvement in SDMT.

Results: Out of 208 patients screened, 120 were randomized to receive either dalfampridine (n = 80) or placebo (n = 40). At T1, the dalfampridine group presented an increase of SDMT scores vs placebo group (mean change 9.9 [95% confidence interval (CI) 8.5-11.4] vs 5.2 [95% CI 2.8-7.6], = 0.0018; = 0.60 for raw score; and 0.8 [95% CI 0.6-1] vs 0.3 [95% CI 0.0-0.5], = 0.0013; = 0.61 for scores; by linear mixed model with robust standard error). The improvement was not sustained at T2. A beneficial effect of dalfampridine was observed in the Paced Auditory Serial Addition Test and in cognitive fatigue.

Conclusion: Dalfampridine could be considered as an effective treatment option for IPS impairment in MS.

Trial Registration: 2013-002558-64 EU Clinical Trials Register.

Classification Of Evidence: This study provides Class I evidence that for patients with MS with low scores on the SDMT, dalfampridine improves IPS.
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http://dx.doi.org/10.1212/WNL.0000000000007970DOI Listing
August 2019