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.

Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons.

AIMS: The crucial step in the pathogenic events that lead to the development and the progression of multiple sclerosis (MS) is the infiltration of autoreactive T cells in the brain. Data from experimental autoimmune encephalomyelitis (EAE) mice indicate that, together with microglia, T cells are responsible for the enhancement of the glutamatergic transmission in central neurons, contributing to glutamate-mediated excitotoxicity, a pathological hallmark of both EAE and MS brains. Here, we addressed the synaptic role of T cells taken from MS patients. METHODS: A chimeric model of human T cells and murine brain slices was established to record, by Patch Clamp technique, the glutamatergic transmission in the presence of T cells isolated from the peripheral blood of healthy subjects (HS), active (a) and nonactive (na) relapsing remitting MS patients. Intracellular staining and flow cytometry were used to assess tumour necrosis factor (TNF) expression in T cells. RESULTS: Chimeric experiments indicated that, compared to HS and naMS, T cells from aMS induced an increase in glutamatergic kinetic properties of striatal neurons. Such alteration, reminiscent of the those induced by EAE T cells, was blocked by incubation of the slices with etanercept, a TNF receptor antagonist. Of note, T cells from aMS expressed more TNF than naMS patients and HS subjects. CONCLUSION: These data highlight the synaptotoxic potential retained by MS T cells, suggesting that during the inflammatory phase of the disease infiltrating T cells could influence the neuronal activity contributing to the TNF-mediated mechanisms of glutamate excitotoxicity in central neurons.

KFLC Index utility in multiple sclerosis diagnosis: Further confirmation.

The Multiple Sclerosis (MS) diagnosis is based on dissemination of focal lesions in time and space. The free light chains (FLCs) determination might be a sensitive alternative to oligoclonal bands assay. The study aim was to redefine sensitivity, specificity of the kFLC Index cut-off. We analyzed serum and cerebrospinal fluid of 176 patients, with different neurological disorders. We obtained a cut off of 12,3 for kFLC Index with a sensitivity and specificity of 93% and 100% respectively. Our data confirm that the kFLC Index is a valid tool in the diagnosis of MS.

Diagnostic tools for assessment of urinary dysfunction in MS patients without urinary disturbances.

Many guidelines are available for the management of lower urinary tract symptoms (LUTSs) in multiple sclerosis (MS) patients, but no agreement exists on the best approach for subjects without LUTSs. The objective of this study was to evaluate whether LUTSs can be detected in MS patients asymptomatic for urinary dysfunction, comparing three different tools [measure of post-void residual volume (PRV), bladder diary (BD), a focused questionnaire (IPSS)], and whether disability, disease duration and signs of pyramidal involvement are linked to their subclinical presence. 178 MS patients (118 women) have been included (mean age 41.2 years, mean disease duration 11.3 years, mean EDSS 2.2), and tested with the above-mentioned tools. PRV was abnormal in 14 subjects (7.8%), associated to abnormal findings at IPSS in 3 cases, at BD in 2 cases, at both in 1. BD was abnormal in 37 subjects (20.8%), with concomitant abnormal PRV in 2, abnormal IPSS in 10 cases, abnormal IPSS and BD in 1. IPSS was ≥ 9 in 43 subjects (24.1%). At least one test was abnormal in 76 patients (42.7%): 1 in 57 patients (32.0%), 2 in 17 (9.5%), and 3 tests in 2 (1.1%). Patients with at least one abnormal urinary variable, compared to patients without urinary abnormalities, had a more frequent pyramidal involvement (69.5 vs. 16.8%, χ(2) = 48.6, p < 0.00001), a more frequent occurrence of EDSS ≥2 (83.1 vs. 23.5%, χ(2) = 56.9, p < 0.00001), and a longer disease duration (15.7 ± 7.3 vs. 9.1 ± 7.1, t = 5.7, p < 0.00001). Asymptomatic LUTS were frequent but none of the tests used permitted to better identify asymptomatic patients.

Risk of acute promyelocytic leukemia in multiple sclerosis: coding variants of DNA repair genes.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ). METHODS: Using MassARRAY high-throughput DNA analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we genotyped patients with sAPL (n=20) developed after treatment of MS (18 out 20 treated with MTZ) for the presence of 210 SNPs of 22 genes mostly involved in DNA repair and drug detoxification. Patients with MS who did not develop sAPL including 41 treated with MTZ (n=253 and 41, respectively) and healthy blood donors (n=310) were also genotyped as controls. RESULTS: We observed risk allele frequency between MS and sAPL for BRCA2 (rs1801406): 6% and 26%, p=0.007; XRCC5 (rs207906): 2.5% and 15%, p=0.016; CYP3A4 (rs2740574): 4.5% and 25%, p=0.0035. The association of homozygous variants of BRCA2 and XRCC5 yielded higher risk of sAPL (MS vs sAPL: 0.4% and 18%, p=0.001). We also observed a significant association between a SNP in the promoter region (rs2740574) of CYP3A4, an enzyme involved in the metabolism of chemotherapeutic agents and development of sAPL. CONCLUSIONS: Increased susceptibility to develop sAPL in patients with MS receiving MTZ may be linked to genetic variants in DNA repair and drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage.

Effects of levetiracetam on chronic pain in multiple sclerosis: results of a pilot, randomized, placebo-controlled study.

BACKGROUND AND PURPOSE: Central neuropathic pain (CNP) is a prevalent and distressing symptom in patients with multiple sclerosis (MS). The anticonvulsant levetiracetam (LEV) has been shown to be efficacious in some types of CNP, but its efficacy in MS-related CNP has not been confirmed. METHODS: To investigate the tolerability and potential effects of LEV against CNP in MS subjects, we performed a single-center, prospective, randomized, single-blind, placebo-controlled study in twenty patients with MS and CNP. Outcomes before and during the 3-month study were assessed using validated measures of pain, depression, disability and quality of life. RESULTS: The medication was well tolerated and analysis revealed a significant difference between the LEV and placebo arm in all study outcomes related to pain (mean pain intensity score, mean pain difference, percentage of patients with a clinically significant pain reduction). Furthermore, the individual quality of life rating improved in treated patients, showing a significant correlation with pain reduction. CONCLUSIONS: These findings suggest that further studies with larger samples of patients be carried out in order to confirm the efficacy of LEV in MS-related CNP population.

[Diagnostic hysteroscopy in the third millennium. Indications and role]. / L'isteroscopia diagnostia nel terzo millennio. Indicazioni e ruolo.

BACKGROUND: The present paper analyses a recent personal series of 284 diagnostic hysteroscopies carried out between May 1999 and December 2001 at the Operating Unit of the University Gynaecology and Obstetrics Department of the Hospital of Avezzano. Emphasis is laid on the description of the indications underlying the investigation and on the hysteroscopic and histological findings in the cases examined. METHODS: The sample was also subdivided into two groups depending on the fertility or postmenopausal status of the patients. In the sample of 284, 89 (31.3%) patients were subjected to local anaesthesia with paracervical block, while the remaining 195 (68.7%) did not receive any form of anaestetic. The hysteroscopies were generally carried out in day surgery, using the commonest and most tried and tested hysteroscopic optic systems and carbon dioxide as a means for distending the uterine cavity. None of the hysteroscopies gave rise to important complications. RESULTS: In both the group of patients in fertile age and in the group of post-menopause patients, the main indication for hysteroscopy was anomalous uterine bleeding (AUB) for which a total of 159/284 hysteroscopies (56%) were carried out, of which 68 (42.8%) in patients in fertile age and 91 (57.2%) in post-menopause patients. In the group of post-menopause patients hysteroscopy was carried out for this indication in 73.4% of cases (91/124) while in fertile age it was performed in 42.5% of cases (68/160). CONCLUSIONS: Underlying AUB in the post-menopause patient endometrial hypo-atrophy was evidenced in 59 of 91 patients examined (64.9%), while in fertile age most of the 68 cases of AUB proved to be of dysfunctional nature: hystological examination showed a proliferative endometrium in 29 cases, secretory in 7 and hyperplastic in 12 cases (11 cases of simple endometrial hyperplasia with atypia and 1 of complex hyperplasia with atypia). Finally, hysteroscopy made it possible to diagnose 6 cases of endometrial adenocarcinoma (6.6% of patients with AUB in post-menopause).

[Pregnancy in adolescence. Consequences and considerations]. / La gravidanza nell'adolescente. Conseguenze e considerazioni.

Many authors have pointed out that sexual activity is starting at an increasingly early age in young adolescents. In 1990 pregnancies in under 15-year-olds in the United States accounted for 3% of the total, a figure that has increased by 13% over the past decade. Moreover, pregnancy in adolescence may result in a number of complications, including pre-term birth, PIH, sexually transmitted diseases. The aim of this study was to evaluate the incidence of adolescent pregnancy in our user basin and to analyse the clinical evolution of these cases. The sample included 61 girls aged between 15.4 and 17.9 years old, mean age 16.7. Of these, 65.6% were students. The majority opted for voluntary abortion (85.2%). Those who chose to continue the pregnancy came from small towns with less than 1000 inhabitants (77.7%). They subsequently married their partners and continued to live with their parents. From an obstetric point of view, only one case of pre-term birth was recorded at week 26, and two cases of IUGR. The fact that the percentage of pregnancies in adolescence has remained unchanged over the years in spite of the numerous health and contraception campaigns represents a strong stimulus to investigate the countless facets of this problem.