Relation between plasmatic and cerebrospinal fluid oxidative stress biomarkers and intrathecal Ig synthesis in Multiple Sclerosis patients.

The aim of this study was to evaluate if cerebrospinal fluid (CSF) oxidative stress biomarkers were related to plasmatic levels and to intrathecal Ig synthesis in 51 patients with Multiple Sclerosis (MS) or clinically isolated syndrome (CIS). Plasmatic and CSF ferric reducing ability (FRA) showed a significant positive correlation (ρ 0.28, p=0.04), while advanced oxidation protein products (AOPPs) did not. A negative correlation was found between IgG synthesis index and CSF FRA levels. No difference in CSF AOPPs or FRA was observed between patients with and without intrathecal IgM synthesis. Our results indicate that plasmatic and CSF FRA are strictly linked, while CSF oxidative stress biomarkers are not related to intrathecal Ig synthesis.

A clinical and laboratory study evaluating the profile of cytokine levels in relapsing remitting and secondary progressive multiple sclerosis.

The main aim of the study was to evaluate levels of cytokines IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-alfa, TGB-beta1 and IFN-gamma in 30 patients with relapsing remitting (RRMS) compared to 30 secondary progressive multiple sclerosis (SPMS) in a peripheral blood sample. Statistical analysis showed significant higher levels of IL-17 and INF-gamma, which are cytokines with pro-inflammatory properties, and lower levels of TGF-beta1, a molecule with immunosuppressant activity, in RRMS compared to SPMS. These results underline the existence of a different cytokines dysregulation in RRMS compared to SPMS phases with higher pro-inflammatory activity in RRMS.

Plasmatic oxidative stress biomarkers in multiple sclerosis: relation with clinical and demographic characteristics.

OBJECTIVES: In multiple sclerosis (MS) oxidative injury likely plays a major role in disease progression and in damaging tissue in the central nervous system (CNS), although with different mechanisms in the initial and the progressive disease stages. We compared the biomarker levels of plasmatic oxidative stress in patients with relapsing remitting (RR) and secondary progressive (SP) MS in order to correlate biomarker levels with demographic and clinical variables. DESIGN AND METHODS: We included 60 consecutive MS patients (30 with RR-MS and 30 with SP-MS) and a control group of 81 healthy subjects. All patients underwent clinical assessment, including disability, fatigue and sleepiness evaluations and blood sample collection for advanced oxidation protein products (AOPPs), plasmatic ferric reducing ability (FRA) and thiol group dosage. RESULTS: Plasmatic AOPPs were significantly higher while FRA and thiol levels were lower in MS patients compared to healthy controls. No difference was found in oxidative stress biomarker values in RR and SP-MS patients. However, in patients with "active" disease, FRA levels and thiol groups (expression of antioxidant power) were significantly lower. No significant correlation was found with demographic and clinical characteristics of patients, including age, disease duration, disability, fatigue, and daytime sleepiness. CONCLUSIONS: Plasmatic AOPPs, FRA and thiol groups show oxidative damage and reduced antioxidant capability in MS. Although their power to characterize different courses of the disease is limited, they seem to be related to disease activity.

Paternal therapy with disease modifying drugs in multiple sclerosis and pregnancy outcomes: a prospective observational multicentric study.

BACKGROUND: Most of Multiple Sclerosis (MS) patients undergo disease modifying drug (DMD) therapy at childbearing age. The objective of this prospective, collaborative study, was to assess outcomes of pregnancies fathered by MS patients undergoing DMD. METHODS: Structured interviews on pregnancies fathered by MS patients gathered in the Italian Pregnancy Dataset were collected; pregnancies were divided according to father exposure or unexposure to DMD at time of procreation. Treatment were compared with multivariable logistic and linear models. RESULTS: Seventy-eight pregnancies fathered by MS patients were tracked. Forty-five patients were taking DMD at time of conception (39 beta-interferons, 6 glatiramer acetate), while 33 pregnancies were unexposed to DMD. Seventy-five pregnancies ended in live-births, 44 in the exposed and 31 in the unexposed group. No significant differences between the two groups were found in the risk of spontaneous abortion or malformations (p > 0.454), mean gestational age (p = 0.513), frequency of cesarean delivery (p = 0.644), birth weight (p = 0.821) and birth length (p = 0.649). In comparison with data of the Italian general population, the proportion of spontaneous abortion and caesarean delivery in exposed pregnancies fell within the estimates, while the proportion of pre-term delivery in the exposed group was higher than expected. CONCLUSIONS: Our data indicate no association between paternal DMD exposure at time of conception and risk of spontaneous abortion, adverse fetal outcomes and congenital malformations. Further studies clarifying the role of DMD fathers intake prior and during pregnancy are desirable, to supply guidelines for clinical practice.

Tongue's motor evoked potentials in the diagnosis of primary lateral sclerosis (PLS): preliminary report.

BACKGROUND: Primary Lateral Sclerosis (PLS) is an adult-onset neurodegenerative disorder due to a selective loss of precentral pyramidal neurons. Our purpose was to evaluate preferential impairment of pyramidal tract to bulbar muscles in patients with PLS and identify a valuable electrophysiological method to help clinicians in the differential diagnosis from Amyotrophic Lateral Sclerosis (ALS). MATERIALS AND METHODS: We recorded Motor Evoked Potentials (MEPs) from tongue's and anterior tibialis muscles in six patients with PLS and compared the results, in terms of Central Motor Conduction Time (CMCT), amplitude of MEPs and duration of controlateral silent period (cSP), with those obtained both from ten age-matched healthy volunteers and ten patients affected by ALS. RESULTS: For lower limbs, CMCT resulted significantly increased in PLS and ALS samples compared with healthy subjects (p<0.01); we did not disclose any difference between ALS and PLS groups (p=0.417). Instead for tongue's recordings, CMCT, absolute amplitude of MEPs and cSP were significantly altered in PLS patients towards both ALS patients and healthy volunteers. CONCLUSIONS: We showed that tongue's MEPs are selectively impaired in PLS. This technique could be helpful to differentiate patients with PLS from those affected by upper motor neuron-predominant variants of ALS. Tongue's MEPs could represent an interesting electrodiagnostic test, potentially useful for the diagnosis of PLS.

Differential motor neuron impairment and axonal regeneration in sporadic and familiar amyotrophic lateral sclerosis with SOD-1 mutations: lessons from neurophysiology.

UNLABELLED: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O(-2)) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females) were enrolled in the study and examined basally (T0) and every 4 months (T1, T2, and T3). Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females). We used Macro-EMG and Motor Unit Number Estimation (MUNE) in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. RESULTS AND DISCUSSION: SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS.