Giovanna Borriello

fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis

Functional magnetic resonance imaging (fMRI) data on motor function have shown adaptive functional changes related to brain injury in multiple sclerosis (MS). We investigated whether patients with MS have altered fMRI activation patterns during attention and memory tasks, and whether functional changes in the brain correlate with the extent of overall tissue damage on conventional MRI. Twenty-two right-handed patients with relapsing-remitting MS (RRMS) and no or only mild deficits at neuropsychological testing and 22 matched healthy subjects were scanned during the Paced Auditory Serial Addition Test (PASAT) and a recall task. fMRI data were analyzed using Statistical Parametric Mapping (SPM99). The relation between fMRI changes during both tasks and T2 lesion load was investigated. During both tasks, patients exhibited significantly greater brain activation than controls and recruited additional brain areas. Task-related functional changes were more significant in patients whose performance matched that of controls than in patients with a lower performance. During the PASAT, brain functional changes involved the right supplementary motor area and cingulate, the bilateral prefrontal, temporal and parietal areas, whereas during the recall task they involved the prefrontal and temporal cortex and basal ganglia bilaterally, and the left thalamus. In patients, activation in specific brain areas during performance of both tasks positively correlated with T2 brain lesions. Patients with RRMS exhibit altered patterns of activation during tasks exploring sustained attention, information processing and memory. During these tasks, fMRI activity is greater in patients with better cognitive function than in those with lower cognitive function. Functional changes in specific brain areas increase with increasing tissue damage suggesting that they may also represent adaptive mechanisms that reflect underlying neural disorganization or disinhibition, possibly associated with MS.

One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis

Background and purpose:  To define the predictive value of clinical and magnetic resonance imaging (MRI) characteristics in identifying relapsing‐remitting multiple sclerosis (RR‐MS) patients with sustained disability progression during interferon beta (IFNB) treatment.

Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis

Objective : To determine whether additional physiotherapy increases botulinum toxin type A effects in reducing spasticity in patients with multiple sclerosis. Design : A single-blind, randomized, controlled pilot trial with a 12-week study period. Subjects : Thirty-eight patients with progressive multiple sclerosis affected by focal spasticity and who were observed at the Multiple Sclerosis Centre operating in the S. Andrea Hospital in Rome. Interventions : For intervention all patients received botulinum toxin type A; the treatment group also received additional physiotherapy to optimize management through passive or active exercise and stretching regimens. Main measures : To measure objective and subjective level of spasticity, patients were assessed at baseline, 2, 4 and 12 weeks post treatment by Modified Ashworth Scale and visual analogue scale. Results : When compared with the control group, we found a significant decrease of spasticity by Modified Ashworth Scale (P < 0.01 by t-test) in the treatment group at week 2 (2.73 versus 3.22), week 4 (2.64 versus 3.33) and week 12 (2.68 versus 3.33). The mean (%) difference in Modified Ashworth Scale score between baseline and the end of follow-up was —0.95 (26.1) in the treatment group and —0.28 (7.7) in the control group (P < 0.01). The combined treatment proved also to be more effective by visual analogue scale (P < 0.01) at week 4 (6.95 versus 5.50) and at week 12 (7.86 versus 6.56) but not at week 2 (5.18 versus 5.50; P = 0.41). Conclusions : Our data suggest that physiotherapy in combination with botulinum toxin type A injection can improve overall response to botulinum toxin.

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis

Objective: To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing–remitting multiple sclerosis (RRMS) patients. Methods: In this post-marketing, prospective, observational study in two Italian multiple sclerosis (MS) centres, a total of 285 RRMS patients who failed a first-line treatment with interferon beta (IFNβ) or glatiramer acetate (GA) were considered. Patients were subdivided according to the strategy adopted after the failure (defined as the occurrence of ≥2 relapses or 1 relapse with residual disability): the switching (SWI) group, i.e. those switched among different IFNβ formulations, or from IFNβ to GA and vice versa; and the escalating (ESC) group, i.e. those escalated to natalizumab. Proportions of patients free from different types of disease activity (relapses, sustained disability progression, new active lesions on MRI, or a combination of them) were calculated at 12 and 24 months. Since patients were not randomized to treatment group, propensity score (PS)-adjusted Cox regression models were built to control for several potential confounders. Results: At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. After 24 months we observed greater proportions of patients in the ESC than SWI group free from relapse (p < 0.0001), disability progression (p = 0.0045), MRI activity (p = 0.0003), and combined activity (p < 0.0001). PS-adjusted models confirmed these findings, with hazard ratios ranging from 0.38 to 0.56 favours the ESC group. Conclusion: We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.

Natalizumab treatment in pediatric multiple sclerosis: A case report

Pediatric multiple sclerosis (MS) with manifestations before 16 years of age occurs in 0.4-10.5% of whole MS population. The initial course of the disease is relapsing-remitting with a relapse rate generally higher than that of adults, less than 3% have a primary progressive form. Some recent reports have shown that Interferon beta (IFNbeta) has a strong effect in reducing the relapse rate in children with MS and is well tolerated. We report a 12-year-old girl with MS and a high relapse rate from the onset. Frequent magnetic resonance imaging (MRI) detected persisting inflammatory activity and increase of lesion burden. She continued to present acute relapses and progression of disability in spite of a treatment with IFNbeta-1a at different dosages and the addition of pulse IV steroid treatment. Then, we opted for Natalizumab treatment, recently approved as a monotherapy for patients with MS who experienced inadequate response to other disease modifying therapies and never used till now in pediatric MS. Our patient showed a complete response to Natalizumab with clinical and MRI suppression of disease activity.

Pulse monthly steroids during an elective interruption of natalizumab: A post-marketing study

Background and purpose:  Temporary discontinuation of natalizumab is sometimes considered as the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). However, interruption of natalizumab may result in a re‐start of disease activity.

Observations during an elective interruption of natalizumab treatment: a post-marketing study

In this prospective post-marketing study, 21 patients with multiple sclerosis treated with natalizumab for 24 consecutive months elected a trial of treatment interruption (90–180 days). During a mean duration of treatment interruption of 111.5 days 4 patients (19.0%) experienced a relapse and 9 out of 19 (47.4%) had MRI activity. Number of contrast-enhancing lesions at baseline was lower than during treatment interruption, but the difference was not significant. These findings suggest that disease activity may return after the last infusion of natalizumab. Patients should have regular MRI assessment during treatment interruption to rapidly identify any return of disease activity. The aim of this study was to determine the optimal duration for temporary interruption of natalizumab therapy in patients who have received continuous therapy with natalizumab for 24 months.

Emerging oral drugs for multiple sclerosis

Background: Therapy for multiple sclerosis (MS) has changed dramatically over the past decade, yielding significant progress in the treatment of relapsing/remitting and secondary progressive MS. Disease-modifying treatments are now widely available, and their beneficial effects on relapse rates, MRI outcomes and, in some cases, relapse-related disability have been shown in several clinical studies. However, as these treatments are only partially effective in halting the MS disease process and in clinical practice are frequently associated with injection-related side effects and suboptimal patient adherence, new oral therapeutic approaches are warranted. Objective: The aim of the present paper is to present new promising results from emerging oral drugs for multiple sclerosis. Methods: This review focuses on advances in current and novel oral treatment approaches for MS. Nevertheless, most of the data were obtained from Phase I/II clinical trials, we need further confirmation of their safety and efficacy profile from longer Phase III clinical trials. Results: Several pivotal reports have provided promising results for new oral therapies evaluating the safety and efficacy of new agents including fingolimod, fumaric acid, cladribine, teriflunomide and laquinomid. Conclusions: It is unknown whether these oral drugs could be used as first-line treatment for MS; this will depend mostly on their safety profile. Alternatively, these drugs could be used as add-on treatment for failed first-line therapy, or as an effective induction agent.

Mitoxantrone treatment in multiple sclerosis: A 5-year clinical and MRI follow-up

Mitoxantrone (MTX) is an antineoplastic agent approved for treatment of secondary progressive and rapidly worsening relapsing‐remitting multiple sclerosis (MS). We designed a longitudinal open‐label prospective study to evaluate the efficacy and toxicity of MTX over a 2‐year treatment period with a further 3‐year follow‐up. Fifty consecutive MS patients were included and received MTX intravenously (8 mg/m2 every 2 months for a total of 12 infusions). Efficacy was assessed clinically and by brain MRI performed before MTX therapy, at the end of treatment and at the end of each year of follow‐up. Forty‐nine patients completed the 5‐year study, 44 (89.8%) completed the MTX course, five (10.2%) interrupted the treatment because of side effects. Fifteen (30.6%) patients showed Expanded Disability Status Scale (EDSS) progression on treatment and nine (18.4%) during follow‐up. Seventeen (34.7%) patients had enhancing lesions at baseline, nine (18.4%) at the end of treatment, but none at the end of follow‐up. In conclusion, we observed EDSS progression in about 1/3 of the patients during the treatment period and in 1/5 during the further 3‐year follow‐up period. This evidence suggests a delayed beneficial effect after MTX treatment is completed with only a minority of patients showing disability progression once the drug was suspended.

A Low-Cost Cognitive Rehabilitation With a Commercial Video Game Improves Sustained Attention and Executive Functions in Multiple Sclerosis A Pilot Study

Objective. To evaluate the effectiveness of a home-based cognitive rehabilitation (CR) program based on the video game Dr Kawashima’s Brain Training (DKBT; Nintendo, Japan), in improving attention, processing speed, and working memory of patients with multiple sclerosis (MS). Methods. This was a randomized, wait-list control study. Patients with MS and failure in at least one between Stroop Test (ST), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test (SDMT) were submitted to an 8-week home-based CR program playing DKBT. Patients were evaluated at baseline and after DKBT by the aforementioned tests, by the Modified Fatigue Impact Scale (MFIS) and by the MS Quality of Life-54 questionnaire (MSQoL-54). Results. Fifty-two 52 patients were screened for eligibility; 35 (mean [standard deviation] age of 43.9 [8.4] years, median Expanded Disability Status Scale score of 2.0 (range = 2.0-6.0) were randomly assigned to the intervention group (n = 18) or wait-list control group (n = 17). ANCOVA analysis showed a significant effect of DKBT on ST (F = 5.027; P = .034; F2 = 0.210), SDMT (F = 4.240; P = .049; F2 = 0.177), and on some subscales of MSQoL-54. The PASAT and cognitive subscale of MFIS also showed an improvement, but this was just not significant (F = 4.104, P = .054, F2 = 0.171, and F = 4.226, P = .054, F2 = 0.237, respectively). Conclusion. We suggest that a home-based DKBT program may improve cognitive functions, some aspects of QoL, and cognitive fatigue in patients with MS.