Antonio Cortese

The prevalence of multiple sclerosis in central Italy

Background: The prevalence of multiple sclerosis varies considerably throughout the world. Objective: To better define the prevalence of MS in central Italy. Methods: This is a population-based study conducted in the province of Frosinone, which is situated in the Lazio region, central Italy. The selected prevalence day was 1 January 2007. A total of 467 patients, with a definite diagnosis of multiple sclerosis, were considered for crude, age- and sex-specific prevalence estimation. Results: The overall crude prevalence rate was 95.0 cases per 100,000 (95% confidence interval (CI) 86.6—104.0). A significantly higher prevalence rate was recorded in females (134.9, 95% CI 121.0—150.1) than in males (53.3, 95% CI 44.4—63.3) (p = 0.001). Age-specific prevalence peaked in the 25—34 year, 35—44 year and 45—54 year age groups; moreover, it was found to increase up to the 35—44 year age group in males and the 45—54 year age group in females, decreasing thereafter. The female to male ratio was 2.6. Conclusions: The results confirm that MS occurs more frequently in central Italy than might be expected on the basis of the geographic-related distribution model, thus supporting the view that this is a high-risk area for the disease.

A dual concurrent mechanism explains trigeminal neuralgia in patients with multiple sclerosis

Objective: In this clinical and neuroimaging study, we sought information on the possible role of neurovascular compression in multiple sclerosis (MS)–related trigeminal neuralgia (TN). Methods: After screening 1,628 consecutive patients with MS, we enrolled 28 patients with definite unilateral MS-related TN. In these patients, we acquired dedicated 3T MRI scans, identified pontine demyelinating plaques, and, using highly specific diagnostic criteria, distinguished possible neurovascular compression. Results: MRI scans in most patients showed a demyelinating plaque in the pontine trigeminal root entry zone on the affected side. The frequency of the neurovascular compression and its association with the pontine demyelinating plaque were higher on the affected than on the unaffected side (54% vs 0%; p = 0.0001). Conclusions: Our observation that in many patients with MS-related TN a pontine demyelinating plaque and neurovascular compression coexist should prompt neurologists to seek possible neurovascular compression in patients with MS-related TN.

Attention-related changes in short-term cortical plasticity help to explain fatigue in multiple sclerosis.

Background: In multiple sclerosis (MS), pathophysiology of fatigue is only partially known. Objective: The aim of this study was to investigate whether the attention-induced modulation on short- and long-term cortical plasticity mechanisms in primary motor area (M1) is abnormal in patients with MS-related fatigue. Methods: All participants underwent 5-Hz repetitive transcranial magnetic stimulation (rTMS), reflecting short-term plasticity, and paired associative stimulation (PAS), reflecting long-term plasticity, and were asked to focus their attention on the hand contralateral to the M1 stimulated. A group of age-matched healthy subjects acted as control. Results: In patients with MS, 5-Hz rTMS and PAS failed to induce the normal increase in motor-evoked potential (MEP). During the attention-demanding condition, 5-Hz rTMS- and PAS-induced responses differed in patients with MS with and without fatigue. Whereas in patients with fatigue neither technique induced the attention-induced MEP increase, in patients without fatigue they both increased the MEP response, although they did so less efficiently than in healthy subjects. Attention-induced changes in short-term cortical plasticity inversely correlated with fatigue severity. Conclusion: Short-term and long-term plasticity mechanisms are abnormal in MS possibly owing to widespread changes in ion-channel expression. Fatigue in MS reflects disrupted cortical attentional networks related to movement control.

Fingolimod vs dimethyl fumarate in multiple sclerosis: A real-world propensity score-matched study

Objective To directly compare fingolimod (FNG) and dimethyl fumarate (DMF) on no evident disease activity (NEDA) status in patients with relapsing-remitting multiple sclerosis (RRMS) from 7 multiple sclerosis outpatient clinics in Central Italy. Methods We analyzed data of patients with RRMS who started an oral agent, namely DMF or FNG, either as first treatment (naives) or after switching from self-injectable drugs (switchers). We performed a propensity score (PS)–based nearest-neighbor matching within a caliper of 0.05 to select patients with homogeneous baseline characteristics. Pairwise censoring was adopted to adjust for difference in length of follow-up between the 2 treatment groups. Comparisons were then conducted in matched samples with Cox models (stratified by center) with NEDA-3 as the main outcome. NEDA-3 was defined as no relapses, no disability worsening, and no MRI activity. Results Overall, 483 and 456 patients eligible for analysis started on FNG and DMF, respectively. The PS-matching procedure retained a total of 550 patients (275 per group). After a median on-study follow-up of 18 months, the proportions of patients with NEDA-3 were similar (FNG 73%, DMF 70%; hazard ratio [HR] 0.74, p = 0.078). Subgroup analyses showed a comparable effectiveness of the 2 drugs in naives (n = 170, HR 1.15, p = 0.689), whereas FNG was superior to DMF in the achievement of NEDA-3 status among switchers (n = 380, HR 0.57, p = 0.007). Conclusion We found no significant difference between FNG and DMF on NEDA-3 status, while subgroup analyses suggest the superiority of FNG over DMF in patients switching from self-injectable drugs. Classification of evidence This study provides Class IV evidence that for patients with RRMS, DMF and FNG have comparable efficacy in treatment-naive patients and that FNG is superior to DMF in patients switching from self-injectable drugs.

The Prevalence of Multiple Sclerosis in the Metropolitan Area of Rome: A Capture-Recapture Analysis

Background: Limited data are available on the prevalence of multiple sclerosis (MS) in central Italy. The objective of this study is to estimate MS prevalence in the metropolitan area of Rome. Methods: We used the capture-recapture method to calculate prevalence estimates in the study area. The selected prevalence day was December 31, 2015. A total of 1,007 patients, with a definite diagnosis of MS according to the revised McDonald’s criteria, were considered for crude, age- and sex-specific prevalence estimation. Results: The overall crude prevalence rate was 146.2 cases per 100,000 (95% CI 119.9–172.5). A higher prevalence rate was recorded in females (194.1, 95% CI 149.6–238.6) than in males (93.0, 95% CI 67.2–118.8) with a female to male ratio of 1.8. Age-specific prevalence peaked in the 25–34 , 35–44 and 45–54 years class; moreover, it was found to increase up to the 45–54 years age group in females and the 35–44 years age group in males, decreasing thereafter. Conclusion: The results confirm that the metropolitan area of Rome is a high-risk area for MS.

Photophobia in multiple sclerosis

BACKGROUND Photophobia has never been investigated in MS. METHODS In this pilot study we used photosensitivity questionnaire assessment (PAQ) to evaluate tolerability to light in 73 MS patients and 62 healthy controls. RESULTS We identified a lower PAQ score and a higher number of photophobic subjects in MS than in controls. Moreover, clinical disability or previous optic neuritis did not predict the photosensitivity profile. CONCLUSION Further studies to investigate the pathophysiological mechanisms underlying photophobia in MS are needed.

JC Virus-DNA Detection Is Associated with CD8 Effector Accumulation in Peripheral Blood of Patients with Multiple Sclerosis under Natalizumab Treatment, Independently from JC Virus Serostatus

Although natalizumab (anti-α4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 (N0), 1–12 (N12), 13–24 (N24), 25–36 (N36), and over 36 (N > 36) infusions. JCV-DNA was detected in plasma and urine. T-lymphocyte phenotype was evaluated with flow cytometry. JCV serostatus was assessed. Ten healthy donors (HD), whose ages and sexes matched with the RRMS patients of the N0 group, were enrolled. CD8 effector (CD8 E) percentages were increased in natalizumab treated patients with detectable JCV-DNA in plasma or urine compared to JCV-DNA negative patients (JCV−) (p < 0.01 and p < 0.001, resp.). Patients with CD8 E percentages above 10.4% tended to show detectable JCV-DNA in plasma and/or urine (ROC curve p = 0.001). The CD8 E was increased when JCV-DNA was detectable in plasma or urine, independently from JCV serology, for N12 and N24 groups (p < 0.01). As long as PML can affect RRMS patients under natalizumab treatment with a negative JCV serology, the assessment of CD8 E could help in the evaluation of JCV reactivation.