Emanuele D’Amico

Multiple Sclerosis and CCSVI: A Population-Based Case Control Study

Background Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS). Objective To evaluate the possible association between CCSVI and MS, using a population-based control design. Methods A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled. Results CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4). Conclusions A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.

Cognitive-motor dual-task interference: a systematic review of neural correlates.

HIGHLIGHTSCMi refers to the simultaneous performance of a cognitive and a motor task as DT.CMi is assessed by various techniques able to measure the related brain activity.FMRI studies showed additive/over‐additive brain activity as multiple resources are needed.Specific loci have been identified, although they may depend on the single components. ABSTRACT Cognitive‐motor interference refers to dual‐tasking (DT) interference (DTi) occurring when the simultaneous performance of a cognitive and a motor task leads to a percentage change in one or both tasks. Several theories exist to explain DTi in humans: the capacity‐sharing, the bottleneck and the cross‐talk theories. Numerous studies investigating whether a specific brain locus is associated with cognitive‐motor DTi have been conducted, but not systematically reviewed. We aimed to review the evidences on brain activity associated with the cognitive‐motor DT, in order to better understand the neurological basis of the CMi. Results were reported according to the technique used to assess brain activity. Twenty‐three articles met the inclusion criteria. Out of them, nine studies used functional magnetic resonance imaging to show an additive, under‐additive, over‐ additive, or a mixed activation pattern of the brain. Seven studies used near‐infrared spectroscopy, and seven neurophysiological instruments. Yet a specific DT locus in the brain cannot be concluded from the overall current literature. Future studies are warranted to overcome the shortcomings identified.

Frequency and severity of headache is worsened by Interferon‐β therapy in patients with multiple sclerosis

Patti F, Nicoletti A, Pappalardo A, Castiglione A, Lo Fermo S, Messina S, D’Amico E, Cimino V, Zappia M. Frequency and severity of headache is worsened by Interferon‐β therapy in patients with multiple sclerosis. 
Acta Neurol Scand: 2012: 125: 91–95. 
© 2011 John Wiley & Sons A/S.

Treatment options of cognitive impairment in multiple sclerosis

Multiple sclerosis (MS) is a progressive disease of the CNS, characterized by the production of widespread lesions in the brain and spinal cord. Inflammatory demyelination has traditionally been seen as the main disease process in MS; however, axonal damage or loss is increasingly being documented to occur early in the disease. Cognitive deficits can occur independently of physical disability, which complicates their identification and recognition. More recently, cortical demyelination has been identified among possible causes of cognitive impairment in MS. Neuropsychological studies have consistently demonstrated that 40–65% of patients with MS experience cognitive dysfunction, particularly in recent memory, information processing speed, and sustained attention. Early detection of cognitive impairment is essential to enable therapeutic intervention to alleviate symptoms or prevent further cognitive decline, although how best to manage MS-related cognitive impairment is currently unclear. Treatment strategies for cognitive impairment in MS are still in their infancy. This article will summarize several pharmacological attempts to enhance cognitive performances in people with MS.

Depressive Symptoms Correlate with Disability and Disease Course in Multiple Sclerosis Patients: An Italian Multi-Center Study Using the Beck Depression Inventory.

Background Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. Methods Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. Results 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0–8.5) and mean disease duration of 10.3 years (range 1–50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20–63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. Conclusions Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

Can we define a rehabilitation strategy for cognitive impairment in progressive multiple sclerosis? A critical appraisal

Cognitive impairment (CI) has been shown to be severe in patients with progressive forms of multiple sclerosis (MS), and the most frequently impaired domains are sustained attention, information processing speed, memory, and executive functions. In contrast to relapsing forms of MS, where studies have shown favorable results from cognitive rehabilitation, there is a lack of data on cognitive rehabilitation in progressive forms of MS. A specific approach in assessing CI and in designing and administering rehabilitation training for patients with progressive forms of MS is needed.

A critical appraisal of daclizumab use as emerging therapy in multiple sclerosis

Introduction: Daclizumab (DAC) is a mAb that binds to CD25, a receptor on the surface of lymphocytes for IL-2, a chemical messenger in the immune system. This prevents activation and proliferation of lymphocytes, which are involved in the immune attack in multiple sclerosis (MS). Areas covered: In this review, we will focus on newly emerging DAC-high-yield process (HYP) therapy for MS. Based on published original articles and citable meeting abstracts, we will discuss its mode of action as well as data on efficacy and safety. Expert opinion: DAC has been observed to have multiple (biological) effects, which may contribute to beneficial effects in immune-related disease and particularly in relapsing-remitting MS. The positive results in the clinical studies represent achievement of an important milestone in the development of DAC-HYP as a potential new treatment option for MS patients. The benefit/risk ratios of this new biological agent in MS therapy are still being evaluated. Soon, DAC-HYP might qualify as MS therapy. A safety monitoring program is recommended in the clinical practice.

Familial clustering in Italian progressive-onset and bout-onset multiple sclerosis

Multiple sclerosis (MS) is a complex disease triggered by environmental and genetic agents, and clinically characterized by bout onset (BOMS) or progressive onset (PrMS). We collected clinical and familial aggregation data in a cohort of 518 Italian PrMS patients, and compared with 400 BOMS cases. An increased prevalence of MS in first-degree relatives of Italian PrMS was found. Familial aggregation is not influenced by probands’ clinical course, and there is no disease course concordance within MS families. These data are useful in counseling MS patients affected with different clinical courses of the disease.

A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs) and Future Perspectives

Using the term of progressive multiple sclerosis (PMS), we considered a combined population of persons with secondary progressive MS (SPMS) and primary progressive MS (PPMS). These forms of MS cannot be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile. We need to achieve more accurate estimates of useful predictors in PMS, including unconventional and qualitative markers which are not yet currently available or practicable routine diagnostics. The evaluation of an individual patient is based on the profile of disease activity.Within the neurology field, PMS is one of the fastest-moving going into the future.

Monoclonal antibody therapy in multiple sclerosis: critical appraisal and new perspectives.

Monoclonal antibodies (mAbs) have been used as experimental treatments of multiple sclerosis (MS) since the 1980s, with the advantage of a high specificity for their target but disadvantages due to their immunogenicity. A literature review of experimental and disposable mAbs in the treatment of MS was performed, putting into perspective the clinical impact that these novel therapies can have and the main challenges facing their use in the daily practice. mAbs therapy resulted in a clear paradigm shift in MS therapeutics. Their use in early, inflammatory phases could have the potential to prevent or delay disability. However, it is still unclear how and when these powerful biological weapons can be used safely in the management of MS. The challenge then is how to obtain the best benefit–risk ratio and how to monitor and prevent emergent safety concerns.