A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia.

The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.

Late-onset and young-onset relapsing-remitting multiple sclerosis: evidence from a retrospective long-term follow-up study.

BACKGROUND AND PURPOSE: Late-onset multiple sclerosis (MS) has a prevalence of about 10-20% in natural history MS studies. Few data have been published about the long-term disease trajectory in the cohort of late-onset relapsing-remitting MS (LORRMS). The aim of this study was to identify the risk factors for reaching an Expanded Disability Status Scale (EDSS) score of 6.0 in LORRMS (onset at >40 years of age) and young-onset relapsing-remitting MS (YORRMS) (onset between 18 and 40 years of age). METHODS: Clinical and radiological [magnetic resonance imaging (MRI) of the brain] follow-up data were collected. Disability was assessed by EDSS score. A Cox proportional hazards model was used to evaluate the demographic and clinical predictors of reaching an EDSS score of 6.0 in the two cohorts. RESULTS: A total of 671 patients with relapsing-remitting MS were enrolled, 143 (21.3%) with LORRMS and 528 (78.7%) with YORRMS. In LORRMS, age at onset was 47.8 ± 5.3 (mean ± SD) years and duration of follow-up was 120.7 ± 52.7 months. In YORRMS, age at onset was 27 ± 2.7 years and duration of follow-up was 149.9 ± 92.7 months. The survival curve analyses showed a higher probability of reaching an EDSS score of 6.0 for LORRMS in a shorter time (months) than for YORRMS (94.2 vs. 103.2 months; log-rank 8.8; P < 0.05). On MRI, YORRMS showed more brain inflammatory features than LORRMS. In the multivariate Cox model, age at onset [Exp(B) value, 6.5; 95% confidence interval, 1.9-22.6; P < 0.001] and male gender [Exp(B) value, 1.7; 95% confidence interval, 1.0-2.8; P < 0.05] were the strongest predictors of reaching an EDSS score of 6.0. CONCLUSIONS: The male population with LORRMS reached severe disability faster than those with YORRMS, even when YORRMS showed more brain inflammatory features on MRI.

Lateral switch to IFN beta-1a 44 mcg may be effective as escalation switch to fingolimod in selected persons with relapsing remitting multiple sclerosis: a real-world setting experience.

BACKGROUND: The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. RESEARCH DESIGN AND METHODS: retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e.g. age and gender) and disease (e.g. timing of pre-switch relapse) characteristics. Switching-time was considered the starting-time of the observation. RESULTS: 43 pwRRMS on IFN beta-1a 44 mcg and 49 pwRRMS on fingolimod were included. Baseline characteristics differed for EDSS score and number of T2 lesions (higher in group on fingolimod). At 24 months of follow up, both groups showed no differences in the survival curves of reaching a first new relapse, new T2 and Gd+ MRI brain lesions, even corrected for the propensity score covariate adjustment. CONCLUSIONS: lateral switch to IFN beta-1a 44 mcg and escalation switch to fingolimod showed same ability in influencing RRMS disease activity at 24 months.

The epidemiology of amyotrophic lateral sclerosis in the Mount Etna region: a possible pathogenic role of volcanogenic metals.

BACKGROUND AND PURPOSE: Trace elements (TEs) may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and volcanic degassing is the major natural source of TEs. Mount Etna, in the province of Catania, is the largest active volcano in Europe. Our aim was to assess the incidence of ALS in the province of Catania during 2005-2010 and its spatial distribution with respect to volcanic gas deposition. METHODS: Cases from all neurological centres of the province of Catania and of the boundary provinces were retrospectively collected. Patients who had onset during 2005-2010 and fulfilled the El Escorial revised diagnostic criteria were included. The incidence of ALS was estimated for the entire province and separately for the population living on the eastern and western flank of Mount Etna, respectively, the most and least exposed areas to volcanogenic TEs, considered as a possible risk factor for ALS. RESULTS: One hundred and twenty-six (57 men) ALS patients were enrolled. The mean annual crude incidence rate was 2.0/100 000 person-years (95% confidence interval 1.7-2.4). A higher incidence rate was found in the population living on the eastern flank compared to the western flank (2.4/100 000 and 0.9/100 000 respectively) with a relative risk of 2.75 (95% confidence interval 1.64-4.89; P < 0.001). CONCLUSIONS: The incidence of ALS in the province of Catania is close to those reported worldwide. The incidence was higher amongst the population living on the eastern flank of Mount Etna, which could be interpreted as a possible role of volcanogenic TEs. Further research on TEs and genetic factors is necessary to support this assumption.

Negative prognostic impact of MRI spinal lesions in the early stages of relapsing-remitting multiple sclerosis.

BACKGROUND: The presence of spinal cord (SC) magnetic resonance imaging (MRI) lesions can be expected to affect the mobility of people with relapsing-remitting MS (pwRRMS), but reports are ambiguous. OBJECTIVE: The objective of this paper is to determine whether the presence of SC MRI lesions in early diagnosed pwRRMS could be considered a predictor of long-term disability. METHODS: pwRRMS with an SC MRI performed within two years from the onset of symptoms and followed up for at least seven years were included. Patients were grouped into: (a) pwRRMs with at least one SC T2 MRI lesion, and (b) pwRRMs without SC T2 MRI lesions. The primary end point was to evaluate the effects of independent factors on reaching an Expanded Disability Status Score (EDSS) of 4.0. RESULTS: A total of 239 pwRRMS matched the required criteria: 116 in the group with SC lesions and 123 in the group without SC lesions. At baseline, there were no statistical differences between the two groups. The presence of SC lesions (Exp(b) 4.4, CI 2.1-9.0, p < 0.001) and higher basal EDSS (Exp(b) 3.3, CI 2.3-4.8, p < 0.001) proved to be the best predictors of reaching EDSS 4.0. CONCLUSION: The presence of T2 SC MRI lesions detected early from MS onset of RRMS predicts a worse prognosis.

Restless legs syndrome and multiple sclerosis: a population based case-control study in Catania, Sicily.

BACKGROUND AND PURPOSE: A population-based case-control study in the city of Catania, Sicily, was carried out to determine restless legs syndrome (RLS) prevalence and its association with multiple sclerosis (MS). METHODS: Patients were randomly selected from a cohort of MS patients resident in the study area and a group of age and sex matched controls was enrolled from the general population. RLS was diagnosed according to the International Restless Legs Syndrome Study Group criteria. RESULTS: In total, 152 MS patients and 431 controls were included in the study. A significantly higher prevalence of RLS amongst MS patients (14.5%) compared with controls (6.0%) was detected, corresponding to an almost threefold increased risk (odds ratio 2.7, 95% confidence interval 1.4-5.0) of developing RLS. Spinal cord lesions in MS patients were associated with a higher risk of RLS (odds ratio 3.7, 95% confidence interval 1.1-13.5). CONCLUSION: RLS was strongly associated with MS, with a significantly higher risk in patients presenting spinal cord lesions.

Pregnancy outcomes in multiple sclerosis patients previously treated with cyclophosphamide.

BACKGROUND: Cyclophosphamide (Cyc) can induce ovarian failure and can have teratogenic effect. Few case reports of successful pregnancies after Cyc treatment in women with autoimmune diseases and malignancies have been described. To date, there are no data about Cyc effect on pregnancy outcomes in MS patients. AIM OF THE STUDY: To describe pregnancy outcomes in multiple sclerosis (MS) patients treated with Cyc before conception. METHODS: We reviewed retrospectively the medical records of all MS patients who received Cyc from 1st of January 1997 to 31st of March 2012, referring to the MS centre of the University of Catania. All pregnancies, occurred during the follow-up period after Cyc treatment, were recorded according to a computerized and standardized protocol (iMED). RESULTS: We found a total of 105 MS women of childbearing age; eleven patients experienced a pregnancy (10.4%); 10 of them had a successful delivery; and one experienced a voluntary abortion. Five women had a preterm delivery. One child was small for gestational age. CONCLUSIONS: Although the favourable pregnancy outcomes, Cyc should be avoided in young women planning a pregnancy. However, Cyc might be considered as a possible alternative to licensed therapies in few selected cases of very aggressive MS, including women of childbearing age.

Frequency and severity of headache is worsened by Interferon-ß therapy in patients with multiple sclerosis.

BACKGROUND: The relationship between multiple sclerosis (MS) and headache (HA) is not well known. It was reported that interferon-beta (IFNß) could induce or worsen HA. OBJECTIVE: To evaluate the impact of IFNß treatment on HA and the relationship between HA and the various commercial preparations of IFNß in mildly disabled patients with MS. METHODS: A specific questionnaire was administered to 357 relapsing-remitting MS patients. Characteristics of HAs were considered, including the temporal relationships with IFNß administration. RESULTS: One hundred and seventeen patients were treated with weekly intramuscular injections of interferon IFNß-1a (Avonex(®)), 84 with subcutaneous injections of IFNß-1b (Betaferon(®)) every other day, 48 and 108 with three times weekly subcutaneous injections of IFNß-1a (Rebif(®)) 22 mcg or IFNß-1a (Rebif(®)) 44 mcg, respectively. Three hundred and fourteen patients were affected by HA, and among them, 219 patients suffered of pre-existing HA. In this latter group, 121 subjects (55%) noted a worsening of their HA after starting IFNß therapy; this was more frequently reported by patients treated with Avonex(®) and Rebif(®) 44. Ninety-five patients experienced new HA. CONCLUSION: IFNß treatment could worsen HA in patients with pre-existing HA or cause the appearance of new HA. Among different IFNß preparations, Rebif(®) 44 and Avonex(®) seemed to be more cephalalgic than the other drugs.

Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis.

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score

Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study.

BACKGROUND: Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing-remitting (RR) MS is unclear. OBJECTIVES: To study the prevalence of cognitive impairment and its relation with MRI disease measures in mildly disabled patients with RRMS. METHODS: Patients aged 18-50 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score or=3 cognitive tests) was present in approximately 20% of all patients and in the subgroup who underwent MRI. T2 hyperintense and T1 hypointense lesion volumes were significantly higher in patients with cognitive impairment (defined as impaired performance on at least three tests of the Rao's battery) than those without. EDSS score was also significantly higher in cognitively impaired than in cognitively preserved patients. Disease duration, depression, and years in formal education did not differ significantly between cognitively impaired and cognitively preserved patients. T2 lesion volume, performance intelligence quotient, and age were significant predictors of cognitive impairment in this population. Weak correlations were found between performance on individual cognitive tests and specific MRI measures, with T1 and T2 lesion volumes correlating with performance on most cognitive tests. CONCLUSIONS: Cognitive impairment occurs in approximately one-fifth of mildly disabled patients with MS and is associated with specific MRI disease measures. Assessment of cognitive function at diagnosis could facilitate the identification of patients who may benefit from therapeutic intervention with disease-modifying therapies to prevent further lesion development.

Fifteen-year experience in treating blepharospasm with Botox or Dysport: same toxin, two drugs.

OBJECTIVES: To compare the clinical characteristics and the long-term outcome of a large series of patients with blepharospasm (BS) treated with the two most used brands of BoNT-A over the last 15 years. METHODS: We have reviewed the clinical charts of 128 patients with BS who received botulinum neurotoxin (BoNT) in 1341 treatments (Botox in 1009, Dysport in 332) over the last 15 years. RESULTS: Mean dose per session was 34U +/- 15 for Botox and 152U +/- 54 for Dysport. Mean latency of clinical effect was 4.5 +/- 4.6 days for Botox and 5.0 +/- 5.7 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher for Dysport than Botox: 80.1 +/- 36.3 and 66.2 +/- 39.8 days, respectively (P < 0.01). In a six-point scale (0: no efficacy, 6: remission of BS), the mean efficacy of both treatments was 3.60 +/- 1.3; 3.51 +/- 1.4 (Botox) and 3.85 +/- 1.2 (Dysport), P < 0.01. The doses of Botox (beta = 0.40) and Dysport (beta = 0.16) were significantly increased over time. Side effects occurred in 325 out of 1341 treatments (24.2%): 21.8% of the patients who had received Botox, and in 31.6% of those who had received Dysport (P < 0.01). CONCLUSIONS: Both brands are effective and safe in treating blepharospasm; efficacy is long lasting. The differences in outcome and side effects suggest that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.

Outcome predictors, efficacy and safety of Botox and Dysport in the long-term treatment of hemifacial spasm.

BACKGROUND AND PURPOSE: To review the clinical characteristics and the long-term outcome of patients with hemifacial spasm (HFS) who received botulinum neurotoxin (BoNT) over the past 10 years. RESULTS: A total of 108 patients received 665 treatments. Mean latency of clinical effect was 5.4 +/- 5.3 days for Botox and 4.9 +/- 4.6 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher after the injection of Dysport than Botox: 105.9 +/- 54.2 and 85.4 +/- 41.6 days respectively (P < 0.01). The percentage of treatment failures was 6.5% for Botox and 4.6% for Dysport (P > 0.05). The doses of Botox significantly increased over time (beta = 0.35, P < 0. 001) whilst Dysport dose remained unchanged (beta = 0.16, n.s.). The duration of clinical benefit slightly increased with Botox (beta = 0.12; P < 0.01), but remained constant for Dysport. Side effects occurred in 17.4% of treatments: 16.7% of patients who had received Botox, and in 19.7% who had received Dysport (P > 0.05). The most common side effects were palpebral ptosis and lacrimation; ptosis and lagophtalmos was more common in Dysport treatments (P < 0.005). CONCLUSIONS: Both brands are effective and safe in treating HFS; efficacy is long-lasting. The differences in outcome and side effects confirm that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.

Headache and multiple sclerosis: a population-based case-control study in Catania, Sicily.

We carried out a population-based case-control study to evaluate the association between multiple sclerosis (MS) and headache. We had previously determined the incidence of MS during 1990-1999 in Catania, Sicily, identifying 155 incident MS patients; these subjects underwent a telephone interview using a standardized questionnaire for headache. Diagnosis and classification of headaches were made according to International Headache Society criteria (1988). A control group was selected from the general population through random digit dialling. One hundred and one (65.2%) MS patients, of the 155 identified, and 101 controls were screened for headaches. Fifty-eight (57.4%) MS patients and 38 (37.2%) controls fulfilled the diagnostic criteria of headache. A significant association between MS and headache was found with an adjusted odds ratio, estimated by logistic regression, of 2.18 (95% confidence interval 1.27, 3.93). Frequency of headaches in our MS population is higher than in the general population, supporting the hypothesis of a possible association between these two conditions.

Is in utero early-exposure to interferon beta a risk factor for pregnancy outcomes in multiple sclerosis?

OBJECTIVE: There exist controversial and discrepant results on the risk of spontaneous abortions and teratogenesis induced by interferon treatment in people with MS.Aim of this study is to evaluate risks of the administration of INFbeta related not only to the foetus, but also to children development up to 12-months developmental milestones. METHODS: The study design is retrospective with a follow-up of babies until 18-months of their life. Thirty-eight women out of 240 with MS followed-up at Clinic MS Center of the University Hospital of Catania, Italy became pregnant in the period june 1997-may 2006. Patients were grouped into three arms: in utero exposed to INFbeta, never treated and patients who discontinued INFbeta before starting conception. Pregnancy outcomes, birth weight, 12-month developmental milestones were collected with an ad hoc questionnaire. RESULTS: Newborns of in utero exposed to INFbeta patients were little smaller for birth weight (3079.6 +/- 313.3 g), but not statistically significant, if compared with the other groups. Developmental milestones appeared within the normal range in all groups. CONCLUSIONS: Our results were particularly favourable on pregnancy outcomes, because we observed only a smaller birth weight which was not detrimental for the further development of children. We believe that INFbeta therapy might not be considered to be a reason for interruption of an intact pregnancy once the drug has been discontinued until delivery.

Frequency of celiac disease is not increased among multiple sclerosis patients.

We evaluated the presence of IgA and IgG celiac disease-related antibodies in a sample of 217 patients with multiple sclerosis (MS) and in a sample of 200 controls not affected by neurological disorders. None of the 217 patients with MS presented IgG and IgA anti-gliadin, anti-endomysial antibodies, anti-tissue transglutaminase and anti-reticulin, whereas only one of the selected controls presented specific antibodies; this subject resulted to be effectively affected by celiac disease. Our data did not show an increased frequency of celiac disease among patients with MS.

Possible increasing risk of multiple sclerosis in Catania, Sicily.

OBJECTIVE: To update prevalence and incidence rates of multiple sclerosis (MS) in Catania, Italy during 1990 to 1999 and evaluate their temporal profiles to assess a possible increase in the MS risk in our study population. METHODS: We studied the frequency of MS in Catania, Italy (population of 313,110 as reported in the 2001 census). The primary sources for the case ascertainment were the neurologic and motor-rehabilitation departments, the MS centers, the Italian MS Association, private neurologists, and family doctors. We considered as prevalent and incident cases all patients who satisfied Poser's criteria for clinically definite MS (CDMS), laboratory-supported definite MS (LSDMS), clinically probable MS (CPMS), and laboratory-supported probable MS (LSPMS). RESULTS: We found 288 subjects with MS who had onset of disease before December 31, 1999 (prevalence day) in a population of 313,110 inhabitants. The prevalence rate was 92.0/100,000 (95% CI 81.8 to 103.2) and was higher in women (102.4/100,000) than in men (80.4/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 years (208.2/100,000). From 1990 to 1999, 155 patients with MS had the clinical onset of the disease. The mean annual incidence was 4.7/100,000 (95% CI 4.0 to 5.5). Age-specific incidence showed a peak in the group aged 25 to 34 years (11.7/100,000). Mean annual incidence for 5-year intervals increased from 3.9/100,000 during 1990 to 1994 to 5.5/100,000 during 1995 to 1999. CONCLUSIONS: Prevalence and incidence rates of multiple sclerosis have further increased during the last decade.

Prevalence and incidence of multiple sclerosis in Catania, Sicily.

OBJECTIVE: An epidemiologic survey was conducted to determine the prevalence and incidence of MS in the city of Catania, Sicily, Italy. Prevalence rate was calculated as point prevalence at January 1,1995, and incidence during 1974 to 1995. METHODS: The authors studied the frequency of MS in the community of Catania in a population of 333,075 inhabitants according to the 1991 census. The primary sources for the case ascertainment were the neurologic and motor rehabilitation departments, the MS Center, the Italian MS Association, private neurologists, and family doctors. All patients who satisfied the Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS, and laboratory-supported probable MS were considered prevalent and incident cases. RESULTS: One hundred ninety-five patients with MS who had had the onset of disease on prevalence day in a population of 333,075 inhabitants were detected. The prevalence rate was 58.5 per 100,000 (95% CI 50.7 to 67.5). Prevalence was higher in women (62.0/100,000) than in men (54.8/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 (145.1/100,000). From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence was 2.3 per 100,000 (95% CI 2.0 to 2.6). Age-specific incidence showed a peak in the group aged 25 to 34 (6.32/100,000). Incidence for 5-year intervals increased from 1.3 during 1975 to 1979 to 3.9 during 1990 to 1994. CONCLUSIONS: These prevalence and incidence rates are close to those reported in other similar surveys carried out in Italy and southern Europe.