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.

A pilot study of lncRNAs expression profile in serum of progressive multiple sclerosis patients.

OBJECTIVE: Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease that affect both white and gray matter. The relapsing and the eventually progressive course of MS is heterogeneous; thus, a confident long-term prediction of individual prognosis is not possible yet. Recent studies have demonstrated the role of long non-coding RNA (lncRNAs) as potential biomarkers that could provide information to predict disease activity and progression. PATIENTS AND METHODS: By qRT-PCR, we analysed the lncRNAs expression in the serum of 16 secondary progressive MS (SP-MS), 12 primary progressive (PP-MS) patients and 8 healthy controls. RESULTS: We found that TUG1 was upregulated in SP-MS, while the comparison of PP-MS vs. controls showed a downregulation of non-protein coding RNA 188 (LRRC75A-AS1) and a significant upregulation of two lncRNAs: long intergenic non-protein coding RNA 293 (LINC00293) and RP11-29G8.3. Moreover, we performed an in-silico analysis using DIANA-LncBase v2 and HMDD v3.0 software, in order to predict the possible interaction of these four lncRNAs with miRNAs. We identified 21 miRNAs prediction targets possibly involved in MS. CONCLUSIONS: Our data indicate a regulatory function of these lncRNAs in autoimmune and inflammatory processes related to MS suggesting their potential role in progressive MS pathogenesis.

Informing MS patients on treatment options: a consensus on the process of consent taking.

In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow patient's empowerment in the decision-making process. AIMS: The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice. RESULTS: The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.

The predictive value of CSF multiple assay in multiple sclerosis: A single center experience.

BACKGROUND: Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, neurodegenerative disorder. Many studies are investigating the potential role of body fluid biomarkers as prognostic factors for early identification of patients presenting with clinical isolated syndrome (CIS) at high risk for conversion to MS or to recognize RRMS patients at high risk for progression. OBJECTIVES: To evaluate the correlation between levels of BAFF, chitinase 3-like 1 (CHI3L1), sCD163, Osteopontin (OPN), both on serum and cerebral spinal fluid (CSF), and the disease activity and progression. We also want to explore a possible relationship between serological and CSF biomarker's levels. PATIENTS AND METHODS: We enrolled 82 patients between June 2014 and June 2016. Seventy-one received a diagnosis of demyelinating disease of CNS (46 RRMS and 25 CIS), while 11 were affected by other neurological diseases. All patients underwent a neural axis MRI, lumbar puncture and blood samples. Levels of BAFF, CHI3L1, sCD163, OPN on serum and CSF were analyzed by Luminex xMAP system, with a kit 11-plex ad hoc. RESULTS: The CSF CHI3L1, sCD163 and OPN levels were significantly higher in MS patients than in controls. We did not find significant differences in serum CHI3L1, sCD163 and OPN levels, nor CSF or serum BAFF levels between patient and control groups. We found significantly higher CSF level of sCD163 and CHI3L1 in all patients' subgroups compared with controls, while OPN was higher in CIS and RR subgroups. We did not find significant differences for serum and CSF levels of all the markers between patients with or without clinical or radiological disease activity. CSF sCD163 and CHI3L1 levels was significant higher in CIS patients who converted to MS (p < 0.05). Using ROC curve analysis, CSF sCD163 resulted the best predictive factor. CSF CHI3L1 and OPN levels resulted useful independent predictors too. Combined ROCs of those three analytes demonstrated a better predictive value, with sCD163 and CHI3L1 resulting as the best combination. CONCLUSIONS: CSF sCD163 CHI3L1 and OPN levels were higher in MS patients whereas serum CHI3L1, sCD163 and OPN levels did not show differences compared with controls. This finding confirms the high CSF specificity with regards to the analysis of processes, inflammatory and non-inflammatory, that occur within the CNS.

Focal muscle vibration, an effective rehabilitative approach in severe gait impairment due to multiple sclerosis.

Gait impairment is one of the most frequent and life-altering consequences of Multiple sclerosis (MS), frequently associated with lower limb spasticity. Focal muscle vibration (fMV) is a technique that applies a vibratory stimulus to a specific muscle or its tendon, reducing spasticity. The aim of our study is to evaluate the efficacy of fMV in ameliorating gait impairment in MS patients with severe lower limb spasticity, measured by Gait Analysis (GA) and objective and patient-oriented scales scores. Fourteen patients affected by Secondary Progressive MS (SPMS) with a lower limb spasticity with a low or no response to antispastic drugs, received repetitive fMV (r-fMV) over the quadriceps and the lumbar paraspinal muscles. The effect of r-fMV on gait was measured by a GA evaluation and objective and patient-oriented scales scores, performed before r-fMV (T0), and 1week (T1) and 1month (T2) after the last session of r-fMV. After the r-fMV the most of spatio-temporal parameters calculated by GA were improved. Moreover, clinical evaluation related results showed an improvement of SM patients' quality of life. In conclusion, r-fMV improves gait function in MS patients affected by severe spasticity of lower limb, non-responsive to common oral antispastic drugs.

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception.

BACKGROUND AND PURPOSE: Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression. The aim of this study was to analyze the influence of disease-related factors, BDNF Val66Met polymorphism and perception of disease on the severity of depression in MS. METHOD: In total, 136 MS patients (88 women) were recruited and genotyped for BDNF rs6265 polymorphism at nucleotide 196 (G/A) using 'high resolution melting'. Depressive symptoms were assessed by the Multiple Sclerosis Depression Rating Scale. Perception of health status was assessed using the SF-36 questionnaire. RESULTS: A multivariable linear regression model showed that the best predictors of depression were the SF-36 General health (ß = -0.209; P = 0.013), Mental health (ß = -0.410; P < 0.001) and Social activity (ß = -0.195; P = 0.035) scores; physical disability (assessed by the Extended Disability Status Scale score) was directly correlated to depression severity on univariate analysis, but it was not a relevant predictor of depression on multivariate analysis; other variables directly related to the disease (treatment, annual relapsing rate) and the BDNF Val66Met polymorphism were not significantly associated with depression. CONCLUSION: Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.

A prospective study on 132 cases of ocular palsy.

OBJECTIVES: In this prospective study, we used one diagnostic protocol to establish an early diagnosis in patients with ocular palsies in absence of other neurological findings. MATERIALS AND METHODS: The study was performed on a consecutive series of 132 patients who visited our Neurological Department for ptosis and/or diplopia in absence of other neurological signs, using the same diagnostic protocol. RESULTS: An etiological diagnosis was made in 74% of cases during a mean time of 17 ± 23 months from symptom onset. Myasthenia gravis was the most common diagnosis (n = 60, 45.5%). Thirty-four cases (26%) remained undiagnosed in spite of a follow-up lasting 32 ± 33 months on average. CONCLUSIONS: Identifying the cause of an isolated ocular palsy can be difficult, and an extended follow-up time does not aid in further establishment of the diagnosis.

Epstein-Barr virus antibodies in serum and cerebrospinal fluid from multiple sclerosis, chronic inflammatory demyelinating polyradiculoneuropathy and amyotrophic lateral sclerosis.

Elevated anti-Epstein-Barr virus (EBV) antibody levels are present in serum of Multiple sclerosis (MS) patients but literature lacks of studies comparing anti-EBV antibody levels between MS and other neurological diseases. We evaluate anti-VCA IgG and IgM, anti-EBNA1 IgG, anti-Cytomegalovirus IgG and IgM titres in serum and cerebrospinal fluid (CSF) of 267 MS, 50 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and 88 Amyotrophic Lateral Sclerosis (ALS) patients. We found increased titres of anti-EBV-IgG in serum and CSF of MS subjects as compared to CIDP and ALS patients thus providing additional evidence for a possible involvement of EBV in MS.

Correlations between peripheral blood mononuclear cell production of BDNF, TNF-alpha, IL-6, IL-10 and cognitive performances in multiple sclerosis patients.

The aim of this study was to investigate the role of Brain Derived Neurotrophic Factor (BDNF) and inflammatory factors in the development of cognitive dysfunctions in Multiple Sclerosis (MS). We correlated peripheral blood mononuclear cell (PBMC) production of BDNF, Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin (IL)-6 and IL-10 with performances on specific neuropsychological tasks in a selected series of MS patients. We studied a sample of 30 patients with relapsing-remitting (RR)MS, segregated by gender and matched for age, education, disease duration, type of immunomodulating therapy, degree of disability and overall cognitive status. We found that low BDNF levels were correlated with increased time of execution on a divided attention and visual scanning task whereas high levels of IL-6 were correlated with low Mini Mental State Examination scores. We did not observe any significant correlations between IL-10, TNF-alpha levels and cognitive performances in our patients. In conclusion our study shows a correlation between low BDNF and high IL-6 production by PBMCs and poorer performances in cognitive tasks in RRMS patients suggesting a possible role of these factors in cognitive impairment in MS.

Multiple sclerosis attacks triggered by hyperprolactinemia.

Multiple sclerosis (MS) is a T-cell autoimmune disease of the central nervous system (CNS). Predominance of women in autoimmune diseases suggests that sex hormones may play a role in disease susceptibility. A possible role for prolactin, a neuroendocrine peptide with powerful immunomodulatory properties, is suggested in MS. We describe the case of a 32-year-old man affected by relapsing-remitting MS who experienced the first MS clinical event during the development of a prolactin-secreting adenoma and the only two MS relapses during adenoma recurrence. Prolactin may have facilitated the inflammatory process and triggered MS clinical attacks, suggesting a role of prolactin in immunomodulation and therefore in autoimmune disease course.

T-bet and pSTAT-1 expression in PBMC from coeliac disease patients: new markers of disease activity.

Coeliac disease (CD) is considered a T cell-mediated autoimmune disease, and up-regulation of T-bet and phosphorylated signal transducers and activators of transcription (pSTAT)1, key transcription factors for the development of T helper type 1 (Th1) cells, has been described in the mucosa of patients with untreated CD. Using transcription factor analysis, we investigated whether T-bet and pSTAT1 expressions are up-regulated in the peripheral blood of CD patients and correlate with disease activity. Using flow cytometry, we analysed T-bet, pSTAT1 and pSTAT3 expression in CD4(+), CD8(+) T cells, CD19(+) B cells and monocytes from peripheral blood of 15 untreated and 15 treated CD patients and 30 controls, and longitudinally in five coeliac patients before and after dietary treatment. We evaluated using enzyme-linked immunosorbent assay (ELISA), interferon (FN)-gamma, interleukin (IL)-17 and IL-10 production by peripheral blood mononuclear cell (PBMC) cultures. T-bet expression in CD4(+), CD8(+) T cells, CD19(+) B cells and monocytes and IFN-gamma production by PBMC was higher in untreated than in treated CD patients and controls. pSTAT1 expression was higher in CD4(+)T cells, B cells and monocytes from untreated than from treated CD patients and controls. pSTAT3 was increased only in monocytes from untreated patients compared with CD-treated patients and controls. The data obtained from the longitudinal evaluation of transcription factors confirmed these results. Flow cytometric analysis of pSTAT1 and T-bet protein expression in peripheral blood mononuclear cells could be useful and sensible markers in the follow-up of CD patients to evaluate disease activity and response to dietary treatment.

Tourettism in multiple sclerosis: a case report.

The term Tourettism refers to Tourette Syndrome (TS)-like symptoms which appear secondary to a variety of both acquired and congenital neurological and neuropsychiatric disorders or following an exposure to several drugs. The association between Tourettism and Multiple Sclerosis (MS) is very rare. Only two cases of patients affected by MS who also showed a simple phonic tic and complex vocal tics respectively have been reported. The case here described reports of a 30 year-old woman affected by secondary-progressive MS who developed, 7 years after the onset of the disease, TS-like symptoms which were responsive to quetiapine. At that time her brain MRI, when compared with the previous scan, showed an increased lesion burden and an increased atrophy in the regions around Sylvian fissures. Considering recent findings on TS, the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. At the same time, the diffuse involvement of the white matter and the progressive brain atrophy which we observed could have impaired the cortico-striato-thalamo-cortical circuits consistently implicated in the pathogenesis of TS. In conclusion, we can hypothesize that in our case Tourettism and MS could be considered causal related more than coincidentally associated.

T-bet, pSTAT1 and pSTAT3 expression in peripheral blood mononuclear cells during pregnancy correlates with post-partum activation of multiple sclerosis.

In pregnant women affected by multiple sclerosis (MS) we observed increased percentages of CD4(+)CD25(+)Foxp3(+) T regulatory cells at the 1st and the 2nd trimester of gestation that was associated with a decreased T-bet expression in CD4(+) T cells. In women showing clinical relapse and/or new lesions at MRI after delivery we found, a higher expression of T-bet, pSTAT1 and pSTAT3 in CD4(+), CD8(+) T cells and CD14(+) cells, associated with an increase of IFNgamma and IL17 production by PBMC at the 3rd trimester of gestation and after delivery. Our data suggest that the expansion of circulating CD4(+)CD25(+)Foxp3(+) regulatory T cells and the lower expression of T-bet in CD4(+) T cells may account for the decreased MS activity during pregnancy. The expression of T-bet, pSTAT1 and pSTAT3 in peripheral blood CD4(+) and CD8(+) T cells and monocytes could be useful to identify MS patients who will develop a relapse after delivery.

Movement disorders in multiple sclerosis: Causal or coincidental association?

Despite the relatively frequent involvement of the basal ganglia and subthalamic nucleus by multiple sclerosis (MS) plaques, movement disorders (MD), other than tremor secondary to cerebellar or brainstem lesions, are uncommon clinical manifestations of MS. MD were present in 12 of 733 patients with MS (1.6%): three patients had parkinsonism, two blepharospasm, five hemifacial spasm, one hemidystonia, and one tourettism. MD in patients with MS are often secondary to demyelinating disease. Also in cases without response to steroid treatment and demyelinating lesions in critical regions, it is not possible to exclude that MD and MS are causally related.