December 28, 2012 Utilization of Services A study in Canada found that compared to the general population, there is high rates of physician services utilization at least five years before multiple sclerosis diagnosis. This could be related to the diagnosis process and needs to be better understood. The number of visits peaked the year of MS diagnosis, decreasing thereafter, but remaining elevated versus the pre-diagnosis period. Multiple Sclerosis Journal, December 21, 2012 Smoking and MS This study found that smoking as a risk factor for multiple sclerosis. Elevated cotinine levels (≥10 ng/ml) in the blood were associated with a significantly increased risk for multiple sclerosis. This association was only present in young individuals ( <26.4 years). Multiple Sclerosis Journal, Dec. 20, 2012 Cutaneous adverse events associated with disease-modifying treatment A systematic literature search of published studies and articles on disease-modifying treatment found that up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation presented cutaneous adverse effect. The most frequently reported were lipoatrophy, cutaneous necrosis and ulcers, and various immune- mediated inflammatory skin diseases.. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of the disease-modifying treatment. Multiple Sclerosis Journal, Dec. 18, 2012
The study found that MS patients with fatigue were impaired in working memory, but did not show greater fatigability, whereas MS participants with self-reported sleep problems showed fatigability, which could be improved with a restorative rest period. The data therefore do not support the compensation theory of fatigue. Multiple Sclerosis Journal December 8, 2012 Alzheimer or memory deficit in secondary progressive MS patients. Episodic memory deficits appeared in the long-term course of secondary progressive MS. These deficits were associated with deterioration of executive function, but not impairment of memory storage as recognition was preserved in secondary progressive MS in contrast to the patients with Alzheimer. In neuropsychological testing, MS-related episodic memory impairment due to deteriorated executive function can be distinguished from Alzheimer related encoding and storage deficits. Multiple Sclerosis Journal, November 19, 2012 Endurance exercise and MS An exercise-induced increase in core temperature is associated with increased number and severity of perceived symptoms in heat-sensitive persons with MS. Based on these findings it is expected that heat-sensitive persons with MS do tolerate resistance excessive better than endurance exercise. Multiple Sclerosis Journal, Nov. 12, 2012 Reproductive decision making after the diagnosis of multiple sclerosis This study reported the findings of a self-administered questionnaire on reproductive practices mailed to registrants of the North American Research Committee on Multiple Sclerosis (NARCOMS) database who met inclusion criteria. The majority of respondents (79%) did not become pregnant following diagnosis of MS. The most common MS-related reasons were symptoms interfering with parenting (71%), followed by concerns of burdening partner (51%) and of children inheriting MS (35%). The most common reason unrelated to MS for not having children was that they already have a “completed family” (56%). Multiple Sclerosis Journal Nov. 6, 2012 primary progressive multiple sclerosis and McDonald 2010 criteria This study proposed that an alternative criterion requiring two of: i) MRI of the brain with one or more lesions in two of three regions typical for demyelination; ii) the presence of one T2 -weighted spinal cord plaque (typical for demyelination); iii) cerebro spinal fluid oligobands could increase the diagnostic sensitivity for PPMS from 64% to 77%. Multiple Sclerosis Journal, Nov. 6, 2012 Epstein–Barr virus, latitude, and multiple sclerosis This study, based on the well-known association between MS prevalence and latitude, investigated whether EBV seropositivity also increases with distance from the equator. They found that the proportion of EBV positive individuals is positively associated with latitude independently of MS status. Latitude-related factors may be implicated in the immune response to EBV and its role in MS etiology. Multiple Sclerosis Journal, Nov. 1, 2012
This case study reported the history of 7 children with ADEM that was followed by ON, a rare but distinct clinical phenotype among pediatric patients. Further studies are needed to allow recommendations on treatment or prognosis. Multiple Sclerosis Journal Nov.11, 2012 Time to secondary progression with first generation immune modulating drugs This study used data from the Swedish National MS Registry from 730 patients who had disease onset between 1995 to 2004. They reported that the DMD-treated patients still exhibited a longer time to secondary progressive than the controls. The authors suggested that this effect was not solely driven by the inclusion of benign cases, and it was at least partly due to the long-term immune modulating therapy given. Multiple Sclerosis Journal, Nov. 1, 2012 2010 McDonald criteria in children with a clinically isolated syndrome The study did a retrospective analysis of brain and spinal cord magnetic resonance imaging scans from 52 children with a clinically isolated syndrome applying the McDonald criteria. The 2010 McDonald dissemination in space criteria were more sensitive (85% versus 74%) but less specific (80% versus 100%) compared to the 2005 McDonald criteria. The Callen criteria were more accurate (89%) compared to the 2010 McDonald (85%), the 2005 McDonald criteria for dissemination in space (81%), the KIDMUS criteria (46%) and the Canadian Pediatric Demyelinating Disease Network criteria (76%). The 2010 McDonald criteria for dissemination in time were more accurate (93%) than the dissemination in space criteria (85%). Inclusion of the spinal cord did not increase the accuracy of the McDonald criteria. Multiple Sclerosis journal published online 18 December 2012 Early treatment with glatiramer acetate in patients with clinically isolated syndrome This study found that early glatiramer acetate treatment reduced the conversion risk to multiple sclerosis by 41% versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to MS, less brain atrophy, fewer new T2 lesions/year and lower T2 lesion volume versus delayed treatment. Adverse events were consistent with the established safety profile of glatiramer acetate. Multiple Sclerosis journal published online 12 December 2012 Cognitive functioning in pediatric transverse mielitis This study is the first to document cognitive deficits in pediatric transverse mielitis and raises questions regarding our understanding of the central nervous system injury associated with transverse mielitis. Results did not suggest a clear association between cognitive problems and depression or medication use but did suggest that fatigue may impact cognitive functioning. Findings warrant further exploration of neuropsychological outcomes in TM to inform appropriate intervention. Multiple Sclerosis journal published online November 11, 2012 From the ECTRIMS (European Commission for Treatment and Research In MS) annual conference in October 2012
"BC CCSVI Registry" (established in December 2011) had interviewed 50 patients using a standardized CCSVI treatment telephone survey. Of those interviewed, 64% reported having relapsing-remitting MS, 10% with primary-progressive MS, 10% with secondary-progressive MS and 16% reported “other”; 34 patients (68%) felt that the treatment met their overall expectations. Five cases (10%) reported procedure-related complications: one required a second incision on the neck as the balloon was unable to get through the leg; one did not have the procedure completed as the vessel was about 90% blocked and three felt pain. Five cases (10%) reported complications within the first month after the procedure: heart attack symptoms, vasovagal reaction (arrhythmia), trouble breathing, swelling in the left arm requiring the use of blood thinner, and pain. Data collection is in progress. CCSVI testing and treatment are not recommended by Canadian MS specialists. (P1089) Cerebrospinal venous insufficiency in other neurologic Echo color doppler exams were carried out prospectively in 78 patients with other neurological diseases patients and 234 Healthy Controls (1:3 matching). Of the 78 other neurological diseases patients, 30 were classified in the neurodegenerative, 25 in the neurological autoimmune disease, 12 in the neuromuscular and 11 in the neurovascular group. The study found that CCSVI prevalence was 53.9% in other neurological diseases patients compared to 29.9% in healthy controls. The sensitivity for CCSVI diagnosis between MS and healthy controls was 55.3%, specificity 67.7%. Our findings are consistent with an increased prevalence of CCSVI in other neurological disease patients but with modest sensitivity/specificity. The study found similar prevalence of CCSVI among different other neurological disease subgroups, comparable to that seen in MS, points against CCSVI having a primary causative role in the development of other neurological diseases or MS. (P633) Heart disease, overweight and cigarette smoking and CCSVI The study included 240 controls that underwent physical and doppler sonography examinations for the presence of intra- and extra-luminal structural and functional abnormalities of the intra-jugular veins, and were assessed with a physical examination and structured. Subjects with heart disease, overweight, and smoking had a significantly increased number of intra-luminal structural venous abnormalities. (Abstract 156408) A systematic review of chronic cerebrospinal venous insufficiency and MS This updated systematic review, supported by the Canadian Institutes of Health Research, was undertaken to examine the evidence of an association between CCSVI and MS using rigorous methods. Literature searches of the electronic databases Ovid MEDLINE (2005- March 2012), the Cochrane Central Register of Controlled Trials (2005-March 2012) and EMBASE (2005-March 2012) were undertaken. Studies had to report original data in a peer- reviewed publication, use either Doppler ultrasonography or magnetic resonance venography, and assess MS patients vs. healthy controls and/or those with other neurological disorders. The study found that a) most MS clinical outcomes could not be interpreted as trials since they were neither randomized nor properly controlled; b) most trials did not follow patients beyond the peri-procedure period but reported a small number of early complications including arrhythmias, hemorrhage and vein wall dissection/ rupture; and c) reports of post- procedure complications have documented stent and cerebral vein thrombosis, accessory nerve injury, hemorrhage and death. At present, results demonstrate only an association between CCSVI and MS, not a causal relationship. (P624) Multiple stenosis or multiple sclerosis? The aim of our study in Budapest was to determine if cerebral venous outflow with two Doppler systems differs significantly in MS patients and controls. The study included 20 patients who were scheduled for a control angiography after interventional therapy of intracerebral aneurysm and had no venous pathology or MS, and 14 MS patients who underwent a CCSVI interventional work-up abroad. The one Doppler examination (DSA) found that 80% of controls had >50% stenosis in the right and 94.7% on the left side; all MS patients also had internal jugular vein stenosis. There was no significant difference in the degree of stenosis between groups. However, none of the patients and controls had internal jugular vein stenosis on power duplex US. Normal venous flow and power duplex US findings proved that the internal jugular vein stenosis shown by DSA was not real. Hemodynamically significant venous stenosis –a key feature of CCSVI, cannot be found in MS patients. (P629) Endovascular treatment (PTA) of CCSVI follow up 1 year This retrospective observation study evaluated the neurological outcomes in forty-two patients with relapsing remitting course of MS who underwent Percutaneous Transluminal Angioplasty (PTA) outside Kuwait following treatment used by Zamboni in the last 2 years. Females constituted 73.8% of the cohort; mean age was 34 and mean disease duration was 7 years; 35.71% of patients stopped their disease modifying therapies. At one year post- PTA, the proportion of relapse-free patients decreased from 85.71% to 66.67% whereas the mean score of the disability scale (EDDS) increased from 2.90 SD±1.64 to 3.24 SD±1.86. The proportion of patients with new MRI activity increased significantly from 16.67% to 42.86%.The study revealed that PTA in relapsing remitting MS patients was not associated with any neurological improvement. However, there was an increase in disease activity evident by MRI parameters irrespective of the adherence to disease modifying drugs. (P635) CCSVI and fatigue This study in the Netherlands investigated the correlation between anomalous cerebrospinal venous outflow and the seriousness of fatigue/depression in fourteen MS patients and age and sex matched healthy controls. Five parameters related to impaired cerebral venous outflow were tested and the patients and volunteers filled in the Fatigue Severity Scale (FSS) and Hospital Anxiety Depression Subscale (HADS). The results of this study barely show impaired cerebral venous outflow in patients with MS (5 out of 14 patients); in addition impaired venous outflow was found in 1 healthy control. Furthermore there was no correlation between fatigue as measured by the FSS and impaired venous outflow in MS patients. No differences were found between HADS scores of the patients with abnormal parameters and those without. We cannot confirm the hypothesized relation between impaired cerebrospinal venous outflow, MS and fatigue/depression. (Abstract 157353) Venous hemodynamics in pediatric-onset multiple sclerosis: Canadian study Twenty- six pediatric MS patients (<=18 years), 26 age-matched healthy controls (HC), and 13 young adults with pediatric-onset MS were evaluated in Canada for each of the five venous hemodynamic parameters of CCSVI the ratio of total venous to arterial flow was calculated as a metric for venous flow redistribution. Normal ultrasound was found in 51 (78%) of the 65 evaluated but only 3 patients with MS met the CCSVI (2 pediatric and 1 young adult). The study concluded that CCSVI is rarely observed in pediatric MS, arguing against CCSVI as an etiologic factor. Venous anatomy and flow ratios shown by vascular MRI indicated that venous outflow is intact in children with MS even in the rare patient with ultrasound criteria for CCSVI. (P1090) Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in pediatric MS The study looked to determine prevalence of CCSVI in patients with pediatric MS, patients with other pediatric neurologic diseases and age- and sex-matched healthy controls (HC), using specific proposed echo-color Doppler (ECD) criteria. Transcranial and extracranial ECD were carried out prospectively in 23 pediatric MS patients, 10 patients with other pediatric neurologic diseases (OND) and 20 age- and sex-matched healthy controls. The mean age was 15.1 in MS, 14.7 in OND and 14.4 in HC. The mean disease duration was 2.3 years in MS and 1.7 years in OND patients. A subject was considered CCSVI positive if >=2 venous hemodynamic (VH) criteria were fulfilled. The study showed similar prevalence of CCSVI between pediatric MS (43.5%) and other neurological diseases patients (40%), and healthy control (30%). These findings point against CCSVI having a primary causative role in the development of MS or OND.
This study assessed lymphocyte and neutrophil counts during and after teriflunomide treatment in the TEMSO study in eligible patients (18–55 years, diagnosed with relapsing MS [McDonald criteria], and Expanded Disability Status Scale score =<5.5). The patients were randomized (1:1:1) to once-daily placebo, teriflunomide 7 mg or 14 mg for approximately 2 years (placebo=360 patients; 7 mg=368 patients; 14 mg=358 patients). At the beginning of the study, the mean (SD) lymphocyte and neutrophil counts were similar across groups and reduction in the counts was observed from 6 weeks on. Two patients treated with teriflunomide 14 mg experienced neutropenia or neutrophil count decrease, reported as serious adverse events. Both patients recovered while continuing treatment with teriflunomide. Mean reductions in lymphocyte and neutrophil counts observed in TEMSO were small in magnitude (not exceeding a 15% reduction) and were reversible after treatment discontinuation or on-treatment in some cases. No other clinically significant complications to blood cytopenias were reported.
In vitro studies indicated that teriflunomide might inhibit and/or induce the activity of cytochrome 2C9 (CYP2C9). Therefore, an in vivo study was undertaken to evaluate the effect of repeated doses of teriflunomide on the pharmacodynamics and pharmacokinetic (PK) profiles of warfarin in 14 healthy male subjects. Subjects received a single oral dose of warfarin 25 mg on Day 1 of Period 1 and on Day 5 of Period 2. After 7 days of washout, oral teriflunomide was administered during Period 2 as a loading dose (70 mg/day) for 3 days followed by a maintenance dose (14 mg/day) for 8 days. Due to the long half-life of teriflunomide, this dosing regimen was used to mimic steady-state therapeutic concentrations. Repeated doses of teriflunomide had no effect on the pharmacokinetics of S- warfarin, indicating that teriflunomide is not an inhibitor or an inducer of CYP2C9. However, a 25% decrease in peak INR was observed when teriflunomide was co-administered with warfarin, compared with warfarin alone. Therefore, when warfarin is co-administered with teriflunomide, close INR follow-up and monitoring is recommended.
This study found that Copaxone has two mechanism of action in MS. One was the known effects on T cells. The other one is a new mechanism of action of GA treatment that augments phagocytic activity of human monocytes in vivo and in vitro in CD14 and 16 cells. (P733) Long-term glatiramer acetate therapy in every-day practice. In this study, 206 Relapsing Remitting MS patients using glatimer acetate were followed demonstrating low annual relapse rate. Of those, 74 were followed during 10 years demonstrating glatimer acetate’s long-term benefits in terms of clinical efficacy (low annual relapse rate and stable EDSS) and tolerability. In contrast, at the 10-year long term follow- up time point, withdrawn patients had greater disability and relapse rate
Germany. First annual results as of May 2012, showed that more than 1850 patients have been enrolled in 475 participating centers and 1093 (86%) of 1279 analyzed patients were relapse- free during the observed period. The mean baseline EDSS was 3.0 and decreased to 2.6 after 12 months; 12% of the enrolled patients had adverse events with lymphopenia (3.5%), leucopenia (1.4%) and elevated liver enzymes (2.4%) as the most common adverse events. (Abstract 155690) Initiation of fingolimod (Gylenia) in MS leads to increased macular volume In this study, neuro-ophthalmologist examined MS patients who had initiated fingolimod and received pretreatment and on-treatment OCT evaluations at the center and compare them to MS patients who had received longitudinal OCT evaluations and had never been exposed to fingolimod was selected by matching based on time between OCT exams. Macular volume increased by 0.025 mm 3x higher (95% CI +0.017 to +0.034, p<0.001) in the 30 MS patients who initiated fingolimod over a mean follow-up time of 5 months (SD 3 months). Macular volume did not significantly change in the comparison group of 30 MS patients never exposed to fingolimod over a mean follow-up time of 6 months. They concluded that initiation of fingolimod in MS is associated with a modest, relatively rapid increase in macular volume. (P992) Severe multiple sclerosis relapse under fingolimod therapy This is a case report of a 30-year-old woman who developed MS in her 18 years. She was treated with glatiramer acetate for four years, then underwent a three series of cyclophosphamide with methylprednisolone as an escalation therapy for disease activity followed by interferon beta treatment for another three years. The treatment was stopped due to positive neutralizing antibodies and MRI progression. The patient refused natalizumab due to JCV positivity, and was treated with IV immunoglobulin for another three years. Then she developed two relapses and MRI showed two enhancing lesions. Assuming lack of treatment efficacy immunoglobulin was stopped, patient was treated with IV steroids and fingolimod was initiated. On tenth day of fingolimod treatment she developed mild left sided hemiparesis, aphasia and bilateral hemianopia. MRI disclosed four active lesions. The CSF findings were normal. Fingolimod was stopped treatment. The patient did not respond to IV steroids but improved after plasma exchange. The authors suggested that initiating fingolimod treatment should be considered only in the period of disease stability. (P975) Second-line use of Fingolimod in RRMS is as effective as natalizumab This is the first study to analyze efficacy of fingolimod as a second line drug in relapsing- remitting MS (RRMS) in comparison to natalizumab. Fingolimod was registered in Europe by the European Medicines Agency (EMEA) only as second line therapy in RRMS. All patients with failing first line treatment and subsequent treatment with either fingolimod or natalizumab were included if the observation period documented was minimum 6 months before and after begin of second line therapy. 142 patients were identified receiving fingolimod (age 40 +9.5, MS duration 11.5 years +7.6), 77 patients received natalizumab (age 39 +8.9, MS duration 11.5 +7.6). Within 6 months prior to initiation, there was a deterioration of mean EDSS and an increase in relapses in the participants. Fingolimod and natalizumab showed a statistically significant decreased relapses within 3 months and even more after 6 months after initiation of therapy, returning relapses to rates before failure of first line therapy. Both drugs stopped further deterioration of EDSS within 3 months of initiation. Natalizumab showed a slight better mean recovery than fingolimod.
This study presents the experience in Nova Scotia (Canada) of 44 patients treated with mitoxantrone. Secondary progressive MS was diagnosed in 56.8% prior to mitoxantrone. Mitoxantrone was stopped for the following reasons: intended dose administered (38.1%), worsening disease (16.7%), fear of adverse events (14.3%), and decreased systolic heart function (11.9%). Overall, the study found that mitoxantrone significantly reduced severe relapses, stabilized disability progression, and preserved quality of life in relapse-onset MS. However, the risk of cardiotoxicity is significant and as such, risks/benefits should be carefully weighed before considering mitoxantrone therapy.
This study found that freedom from disease activity at one year was seen in 46/81 (57%), at two year, in 20/56 (36%), at three years in 13/33 (39%) and 6/15 (40%) still met these criteria four years after commencing treatment with natalizumab. Mean EDSS prior to natalizumab was 3.1; EDSS a year after commencing treatment was 2.5. (P496) Therapeutic decision after JC virus testing Since March 2011, a relevant JC antibodies diagnostic test is available for clinical practice. Consequently, a positive JC antibodies diagnostic test, indicative of a previous exposure to JC virus is now taken into consideration when assessing LEMP risk in patients treated with natalizumab. Among the 292 patients, the anti-JCV test was found positive in 150 patients (51%). Hundred and two of the 150 patients received more than 2 years of treatment. Among these 150 patients, 38 (25.3 %) decide to modify the treatment. Fifteen of these 38 patients received an immunosuppressive drug before natalizumab therapy. The therapeutic alternative was first Gilenya (42%), therapeutic abstention (42%), Copaxone (11%) and Rebif (5%). In most cases, patients were very satisfied with their natalizumab treatment and expressed their desire to continue the treatment, even in patients (n = 23 ; 15%) with two risk factors (duration and JCV positive), for progressive multifocal leucoencephalopathy. A regular monitoring and evaluation including MRI every 6 months due to possible conversion seems necessary in these patients. In negative patients for JCV a one-year control of serology seems also necessary, as about 1-2% of patients may convert to positive serology . (P533) Does the STRATIFY JCV TM antibody test encourage natalizumab cessation? Serum JCv-antibody status may influence treatment decisions of patients receiving natalizumab, but was not the only determining factor in our study. Less than 6% of positive cases opted to stop therapy due to JCv positivity alone. Subjective clinical benefit on natalizumab, and paucity of alternative, safe therapies, may raise risk tolerability. However, regular review of decisions is essential, as risk tolerability may be dynamic, and PML risk increases with treatment duration. (P1098) Functional disability after natalizumab-associated PML in a large cohort of survivors Kurtzke Expanded Disability Status Scale (EDSS) scores for PML survivors previously treated with natalizumab were reported by physicians. Of the 242 cases of PML, 190 (78.5%) survivors and 52 (21.5%) fatal outcomes were reported. Survivors were younger (median 43 vs 52.5 years) with lower pre-PML EDSS scores (median 3.5 vs 5.5) compared with patients with fatal outcomes. Similar to patients with fatal outcomes, survivors had a median natalizumab exposure of 36 months at PML diagnosis. Of the 190 survivors, EDSS scores at PML diagnosis (mean 5.2, median 5.5); 6-9 months post-PML diagnosis (mean 6.3, median 6.4); 10-13 months post-PML diagnosis (mean 6.4, median 6.8); and >=14 months post- PML diagnosis (mean 6.6, median 7.0). The majority of patients appear to sustain moderate to moderate-severe disability throughout the course of PML and recovery.
Azathioprine (AZA) has mainly been used as a second line treatment. The study included patients with relapsing-remitting course and more than 2 relapses in the last 2 years; 150 patients were randomized in two groups (77 AZA, 73 interferon beta) that resulted highly comparable as for clinical and demographic baseline characteristics. Annualized relapse rate in the AZA group was lower than in the interferon (IFN) group. The MRI outcomes analyzed in 97 patients showed that the effect of AZA was at least 73% of the IFNs. The number of patients with an adverse event (lymphocytopenia included) and the number of treatment discontinuations due to adverse events was higher in the AZA group during the first months of treatment whereas in the IFN group discontinuations occurred mainly during the second year. These data indicate that in relapsing remitting MS, AZA is at least as effective as IFNs. Given the convenience of the oral administration and the low cost, AZA should be used as a first line treatment.
Recent studies have found no association between multiple sclerosis (MS) and adverse perinatal outcomes, but the duration of birth hospitalization in mothers with MS and their newborns was not examined. The demographics and duration of the birth hospitalization in mothers and newborns in British Columbia were compared between women with MS (n=432) and the general population (n=2,975) from 1998 to 2009. Compared to the general population, the median duration of the birth hospitalization differed little in mothers with MS (+1.5 hours difference) and their newborns (+2.1 hours difference). The duration of the birth hospitalization was not associated with disease duration or disability. Contrary to some older studies, we found that MS was not associated with a longer birth hospitalization.
This study reviewed the pregnancy outcomes in women with MS who were exposed to interferon beta-1a during pregnancy as reported in Biogen global drug safety database from May 1996 to November 2011. There were 3214 reports of pregnancy, which included 1120 spontaneous and 57 in clinical trial cases with 522 known outcomes. Among the 522 known outcomes were 374 live births (71.6%), 78 induced abortions (14.9%), 66 spontaneous abortions (12.6%), 1 stillbirth (0.2%), and 3 ectopic pregnancies (0.6%). Birth defects were reported in 13 of 522 pregnancy outcomes, representing a total major, and minor congenital malformation rate of 2.5%. There was no pattern of a particular birth defect. (P275) Preliminary evaluation of pregnancy outcomes from the TYSABRI This study evaluated the pregnancy outcomes in three hundred seventy five patients (368 with MS and 7 with Crohn’s Disease) who were exposed to natalizumab at any time within 90 days prior to the first day of the last menstrual period or during pregnancy in Biogen registry. Of the 375 patients, pregnancy was ongoing in 41 patients, 8 patients were lost to follow-up, and 334 outcomes were reported, including 8 women who completed twin pregnancies. There were 286 live births (239 at term, 44 preterm, 3 with term unknown), 34 spontaneous pregnancy losses (defined as <22 weeks’ gestation), 13 elective pregnancy terminations, 1 stillbirth, and no ectopic pregnancies. Data reported as of 23 November 2011 do not suggest any effect of natalizumab exposure on pregnancy outcome. Additional data are required before definite conclusions can be made about the effect of natalizumab exposure on pregnancy outcomes.
The study analyzed prospective pregnancy outcomes in women with MS who were exposed to IM interferon beta-1a within approximately 1 week of conception or during the first trimester of pregnancy in The AVONEX Pregnancy Exposure Registry. There were 302 evaluable pregnant women and 306 evaluable outcomes. Of the 306 outcomes, which included 4 sets of twins counted separately, there were 272 live births, 28 spontaneous abortions, 5 induced abortions, and 1 stillbirth. The rate of spontaneous abortions in women who enrolled prior to 22 weeks of gestation was 10.5%. Birth defects (cases with at least 1 major defect) were reported in 17 of 306 known outcomes. The spontaneous abortion rate observed in the registry is consistent with the 15% spontaneous abortion rate in the US general population. No patterns suggesting an unusual distribution of defects were observed and no specific signals of concern were found.
Women taking glatiramer acetate who were contemplating pregnancy were counseled, as part of our standard care, about the pros and cons of remaining on glatiramer acetate a Category B pregnancy rating while attempting to conceive and during pregnancy. They were told (1) they would have no protection from MS while off medication; (2) pregnancy is associated with lower relapse rate compared to non-pregnancy periods; (3) relapse rate is higher during the post-partum period; and (4) resumption of medication immediately after delivery might not be adequately protective during that more vulnerable period. (P737) Retrospective analysis of the teriflunomide (Aubagio) in pregnancy A total of 43 pregnancies were reported in female study patients (aged 22–45 years) across seven teriflunomide clinical trial database (data cut-off: 27 April 2012). Upon learning of her pregnancy, the patient was instructed to discontinue her study treatment and did an elimination procedure (cholestyramine or activated charcoal). The outcomes were as follows: induced abortion, n=20; spontaneous abortion, n=8; healthy newborn, n=12; ongoing pregnancy, n=2; outcome pending, n=1. In the healthy newborns, no structural defects or functional deficits have been reported to date. Although there were no structural or functional deficits reported in newborns with prenatal teriflunomide exposure following rapid elimination, more prospective data are needed with respect to pregnancy outcomes.
An historical cohort was assembled from the database maintained by the MS Clinic at Centre Hospitalier Université de Montréal covered 122 women who contributed one pregnancy and 27 women who contributed two. The study found that predictors of early post-pregnancy relapse were: relapse in immediate pre-pregnancy time period; age <25 at delivery; EDSS greater than 0. These data suggest that recommending delay of pregnancy until after the age of 25 years and for 3 months after a relapse would reduce the risk of post-pregnancy relapse. Women with a high risk for post-pregnancy relapse may consider MS treatment immediately after birth to reduce their risk. (P461) Disease modifying drug and vaccination This study investigated the immune response to H1N1 vaccination among 131 MS patients and 216 health care workers (controls) during the pandemic of 2009. They recorded demographic variables (age, sex, and disease onset), clinical variables, and treatment (interferon beta, glatiramer acetate, natalizumab and mitoxantrone). Only 25.6% of MS patients that received immunomodulatory treatment had protection from the vaccine after 10 months, compared to 43.5% of the controls after 12 months. MS patients that receive glatiramer acetate (19.5%), natalizumab (22.2%) and mitoxantrone (8.3%) had reduced long-term protection after H1N1 vaccination. Interferon beta treated patients had a normal vaccine response. These preliminary findings suggest that MS patients on other therapy than interferon beta should receive two doses of vaccines in a new pandemic of influenza. (P677) Subcutaneous interferon-beta-1a in paediatric patients with multiple sclerosis: This was an international study of patients who had received >=1 injection of sc IFN beta-1a for demyelinating events when aged <18 years. Data were obtained retrospectively from medical records of 307 patients (USA 139; other countries 168). Irrespective of the region, subcutaneous interferon-beta-1a was well tolerated and associated with a reduction in clinical attacks in pediatric MS patients. Regional differences in baseline characteristics and treatment patterns suggested that USA patients had more aggressive disease (a shorter median time from first demyelinating event to first disease-modifying drug (DMD) treatment and more likely to have change after the first year to another treatment), possibly explaining the regional variation in clinical outcomes.
multiple sclerosis Vitamin D insufficiency is common in adults with MS but there are few data pertaining to vitamin D status and metabolism in pediatric MS. :Children and adolescents (<20y) were enrolled from Argentina, Canada, Finland, Italy, Russia, and the United States between 2003 and 2005. Serum was available from 121 children with MS (all countries) and 119 control participants (Argentina, Canada, and US). Overall, 72.1% of participants were vitamin D insufficient. Children with MS did not differ from control participants in terms of seasonally adjusted vitamin D status or prevalence of vitamin D insufficiency. The authors concluded that there is a high prevalence of vitamin D insufficiency in this multinational cohort of children, irrespective of MS diagnosis.
Fifty-five subjects were included (mean age=14.4 ± 2.6 years).After treatment initiation, patients were reassessed clinically every month; brain MRI was performed at baseline and every six months. Patients received a mean number of 23.5 ± 12.7 infusions, 30 subjects were treated for 24 months or more, receiving a mean of 32.9 infusions. In the whole group, three relapses occurred during the follow up. One girl continued to deteriorate in cognitive functioning. The mean EDSS decreased from 2.7 to 1.9 at the last visit (p<0.001). At baseline, 45/55 subjects showed Gd-enhancing lesions (mean number 4.5,range=1-25). During the follow up 35/55 (65%) patients remained free from MRI activity. Transient and mild clinical adverse events which resolved spontaneously occurred in 20 patients, mild hematological abnormalities occurred in 7 cases. Anti-JCV antibodies were detected in 19/50 subjects (38 %). This study provided class IV evidence that NA is effective and well tolerated in pediatric MS with active disease. A strong suppression of disease activity was observed in the large majority of subjects during the whole follow up duration.
and clinical correlations This study used six questionnaires related to sexual dysfunction to evaluate sexual disorders. Inclusion criteria were: age comprised between 20 and 60, disability inferior to 7.0 measured by Expended Disability Status Scale (EDSS), no cognitive impairment and relapsing remitting MS. Out of three hundred eight eligible patients, hundred and forty one returned the questionnaires achieving a response level of 45. 7%. Sixty-eight patients (55%) suffered from sexual dysfunction; 50% of women reported sexual dysfunction with the most frequent complains being decreased libido as primary sexual dysfunction, problems with concentration as secondary, and low self –esteem and deteriorated body image as tertiary. Sexual dysfunction was found in 82% of men. The most frequent primary sexual dysfunction was erectile dysfunction, problems of concentration as secondary sexual dysfunction, and not satisfies their sexual partner as tertiary symptom. The study showed that sexual disorders are frequent and correlated with disability. Depression is most frequent for women with sexual disorders. Quality of life is altered in patients with sexual disorders.
While menopause influences the incidence and course of other neurologic and autoimmune diseases, its impact on multiple sclerosis (MS) remains understudied. Retrospective studies have suggested patient-reported worsening of symptoms at menopause, but limited prospective data on clinical outcomes exist. In this study, a questionnaire assessing women's reproductive history was obtained from 133 women aged 20-75 treated at a large regional Northeastern United States MS referral center. Median age at menarche for all women was 12, and 60% reported ever use of hormonal contraception. At time of study, 51% menstruating, 6% peri-menopausal and 43% postmenopausal (following surgery in 15% and chemotherapy in 5%). The study found a significant effect of menopause on slope of EDSS change in the primary analysis, along with variable results when an alternative model was used, suggesting that larger prospective studies are warranted to clarify the role of menopause, and exogenous hormonal exposures, on the course of MS.
Few studies concerning language functions in multiple sclerosis (MS) have been previously published. Their review indicated that when the tests are done, language disorders can be found. Twenty-three relapsing remitting MS patients were compared to 23 healthy subjects matched for age, sex, and educational level. The majority of MS patients had linguistic complaints (74%). When comparing the 2 groups, the language performances were lower in the MS groups compared with healthy subjects for: time of naming, syllabic fluency, word definition, antonyms, synonyms, concatenation of sentences, explanation of proverbs, management of the implicit and interpretation of advertisements and funny drawings. MS patients that have frequent linguistic complaints, need specific assessment material and thus an appropriate speech therapy. Further studies are now needed to confirm these results.
Alemtuzumab showed efficacy superior to interferon beta administered subcutaneously in two Phase 3 trials and one Phase 2 trial but demonstrated increased risk of some autoimmune disorders. As of December 2011, there were 1485 alemtuzumab-treated patients (1216 with 12mg/day, 269 with 24mg/day). Thyroid adverse effects were observed in 36.4% of them, the most common were hyperthyroidism (8.0%) and hypothyroidism (7.0%). Overall incidence of immune thrombocytopenia purple (ITP) was 1.5% (22 cases) with one fatal case in the Phase 2 study. A case of autoimmune pancytopenia with subsequent medication noncompliance led to a fatal outcome. Two cases of anti–glomerular basement membrane (anti-GBM) antibody disease, a rare autoimmune disorder that results in renal damage, and two cases of autoimmune hemolytic anemia were detected early and treated. The safety monitoring program typically allowed for early detection and management.
in relapsing-remitting multiple sclerosis: results of the SELECT trial The study used monthly, subcutaneous (SC) DAC HYP as monotherapy in RRMS. Patients (n=621) with RRMS (age 18-55 years, McDonald criteria-defined RRMS, EDSS 0-5.5). Patients treated with DAC HYP had reductions in the percent change in volume of both T1- hypointense and T2-hyperintense lesions over 52 weeks of treatment versus increases in these lesions in the placebo group.
October 10, 2012 Increase in multiple sclerosis activity after assisted reproduction technology Sixteen patients with relapsing-remitting MS subjected to 26 ART treatment cycles receiving gonadotropin-releasing hormone (GnRH) agonists and recombinant follicle-stimulating hormone were studied prospectively. The baseline study period encompassed 12 months prior to the first cycle and 9 months after final ART cycle. ART was associated with a 7-fold increase in risk of MS exacerbation, and a 9-fold increase in risk of enhanced disease activity on MRI. Reproductive hormones appear to exert an important role in regulating immune responses during the course of autoimmune diseases.Ann Neurol. 2012 Oct 3. doi: 10.1002 /ana.23745. Fingolimod treatment after natalizumab Fingolimod was started 3-4 months after natalizumab was stopped to help immune surveillance reconstitution and reduce the risk of postnatalizumab MS reactivation.However, all patients developed severe MS reactivation 16 days, 19 days and 6 days after starting fingolimod. More experience is needed to decide on the correct timing of switching patients from natalizumab to fingolimod. Neurology. 2012 Oct 3. [Epub ahead of print] Subcortical atrophy and cognition: Sex effects in MS This Swedish study found that six years post-diagnosis almost all subcortical gray structures were affected by MS, especially in men. Cognition was most severely affected in male patients. They also found that certain areas with atrophy affected sex performance. The patient cohort had relatively mild disability and low lesion load. 170 subjects were included in this study, of which there were 50 healthy controls and 120 who had relapsing-remitting MS. Neurology. 2012 Sep 26. [Epub ahead of print] LDX and cognitive problems Lisdexamfetamine dimesylate (LDX) is an inactive amphetamine prodrug which is currently approved for attention deficit disorder. Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study. There was a high proportion of adverse events reported in both the LDX-treated and placebo-treated subjects. Neurol. 2012 Sep 23. Significance of anti-natalizumab antibodies A study found that there is a correlation between low serum natalizumab concentration and high titer of antinatalizumab antibodies in multiple sclerosis associated with relapses and gadolinium-enhancing lesions on MRI. Mult Scler. 2012 Sep 19. [Epub ahead of print] oral BG-12 for relapsing multiple sclerosis. In patients with relapsing-remitting multiple sclerosis, both BG-12 regimens, as compared with placebo, significantly reduced the proportion of patients who had a relapse, the annualized relapse rate, the rate of disability progression, and the number of lesions on MRI. Adverse events associated with BG-12 included flushing and gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain, as well as decreased lymphocyte counts and elevated liver aminotransferase levels. N Engl J Med. 2012 Sep 20;367(12):1098-1107 Interferon β for secondary progressive MS A systematic review of 5 trials (3082 patients) showed that a 3 year treatment with IFNβ does not delay permanent disability in SPMS, indicating that the anti-inflammatory effect of IFNβ is unable to prevent MS progression once it has become established. J Neurol Neurosurg Psychiatry. 2012 Sep 5.
In a randomized placebo-controlled trial including 59 persons receiving placebo and 61 with ginkgo 120 mg twice a day for 12 weeks did not improve cognitive performance in persons with MS. Neurology. 2012 Sep 5. September 10, 2012 FDA approves Aubagio (teriflunomide) as the second oral drug for MS treatment. Vitamin D levels are inversely associated with MS activity on brain MRI. These results provide further support for a randomized trial of vitamin D supplementation. Annals of Neurology 72:234-240 Disease-modifying drugs in pregnancy The authors reviewed fifteen studies with 761 interferon β-, 97 glatiramer acetate-, and 35 natalizumab -exposed pregnancies. Interferon β exposure was associated with lower mean birth weight, shorter mean birth length, and preterm birth (<37 weeks), but not low birth weight (<2,500 g), cesarean delivery, congenital anomaly (including malformation), or spontaneous abortion. Glatiramer acetate exposure nor natalizumab exposure was not associated with lower mean birth weight, congenital anomaly, preterm birth, or spontaneous abortion. Neurology. 2012 Aug 29. [Epub ahead of print] Circadian rhythmicity of inflammatory serum parameters These data indicated that increased awareness of diurnal serum concentration changes of biomarkers may be needed when interpreting data from research using biomarkers. J Neurol. 2012 Aug 9. [Epub ahead of print] Chronic cerebrospinal venous insufficiency is not specific to MS The authors found that although CCSVI was associated with cerebral hemodynamic anomalies, that the changes are equally seen in healthy controls and are not related to severity of disability related to MS. Radiology. 2012 Aug 21. [Epub ahead of print] Fampridine improves severe dysarthria in secondary-progressive multiple sclerosis. Multiple Sclerosis Journal August 30, 2012 Neuropathic pruritus seems to be a common, but under-recognised symptom of myelitis associated with NMO. Multiple Sclerosis Journal August 30, 2012 This study indicates that aquatic training can be an effective training method during rehabilitation. Multiple Sclerosis Journal August 30, 2012, Treatment of sleep disorders can improve fatigue Multiple Sclerosis Journal August 22, 2012, Impaired heart rate variability in multiple sclerosis. These results suggest that MS causes cardiovascular autonomic dysfunction (CAD) manifested as long-term Heart Rate Variability abnormalities. This illness seems to cause a dysfunction in parasympathetic cardiovascular tone. Act Neurol Belg. 2011 Jun;111(2):116- 20. A simple score for estimating the long-term risk of fracture in patients with MS This interesting study describes a novel risk stratification tool for predicting long term risks of fractures in people with MS. The new risk score contains several new risk factors that have been linked with fracture, which include MS, use of antidepressants, use of anticonvulsants, history of falling and history of fatigue. The authors validated the new scoring system at predicting 5 and 10 year risk and it proved particularly good for predicting hip fractures. Neurology. 2012 Aug 15. [Epub ahead of print] Sleep-disordered breathing in multiple sclerosis. This new cross-sectional study assessed that there is a greater disposition for obstructive sleep apnea and central apneas in people with MS. These alterations in the sleep-pattern were confirmed with a laboratory-based overnight polysomnography. Neurology. 2012 Aug 15. [Epub ahead of print]
This study conclude that compared with White people with MS higher lesion volume accumulation in African Americans rather than loss of brain volume is likely to account for the more rapid disease progression of the disease in African Americans. PLoS One. 2012;7(8):e43061. Epub 2012 Aug 10.
This study aimed to evaluate the relationship between grey matter and white matter tissue damage and obsessive-compulsive disorder (OCD) in patients with MS. Using an MRI with 1.5 T, 16 patients with MS and OCD showed structural brain changes with reduced grey matter volume, compared with the control group of MS patients with no psychiatric symptoms. These changes suggested that OCD in MS may be caused by damage in the right frontotemporal cortex. Am J Neuroradiol. 2012 Jul 19. For more information on the anatomy of the brain Warning on effect of fingolimod withdrawal This report informed of the effect of fingolimod suspension in 6 patients who participated in a study. Within three months from fingolimod suspension, five of six subjects returned to pre-treatment disease activity; one patient, however, exhibited a clear rebound of clinical and MRI activity. The authors suggested that it is important to identify subjects who are at higher risk of rebound and to define effective management strategies in these subjects. Multiple Sclerosis Journal 2012 Jul 24. Cholesterol drugs interfere with interferon-beta This study suggested that MS patients treated with interferon-b, who concurrently take a statin, show a dose dependent inhibition of interferon. The data suggested that high dose add-on statin therapy significantly reduces interferon-beta function and type 1 interferon responses in RRMS patients and provided a putative mechanism for how statins could counteract the beneficial effects of interferon-beta and worsen disease. Arch Neurol. 2012 Jul 16:1-7. MS and extract of cannabis: results of the MUSEC trial. This is a report from the Multiple Sclerosis and Extract of Cannabis (MUSEC) study, a multicenter, double blinded, placebo controlled, phase III study with 279 patients aimed at substantiating previous studies of efficacy of cannabinoid extract for spasticity and evaluating physical and psychological impact, and walking ability. Relief from muscle stiffness was twice as high in the treatment group after 12 weeks of treatment, suggesting that cannabinoid extract is superior to placebo for the management of spasticity in MS. Adverse effects were consistent with the known side effects of cannabinoids. No new safety concerns were observed. J Neurol Neurosurg Psychiatry. 2012 Jul 12. stress management for the prevention of new brain lesions in MS. A total of 121 patients with relapsing forms of MS were randomized to receive stress management therapy for MS (SMT-MS) or control therapy. 76% of the participants remained free of Gd+ lesions during the treatment compared to 54% of the control group; 69% of participants remaining free of new T2 lesions compared to 42% of the control group. This benefit was not sustained beyond 24 weeks of therapy, and there were no clinical benefits. Neurology. 2012 Jul 31;79(5):412-9. Epub 2012 Jul 11. FDA Drug Safety Communication: Seizure risk for multiple sclerosis patients who take Ampyra (dalfampridine). The majority of seizures happened within days to weeks after starting the recommended dose and occurred in patients having no history of seizures. Side effects, including seizures, are more frequent at higher doses. Do not take Ampyra if you have ever had a seizure. Safety Announcement 7-23-2012 July 16, 2012 Mitochondria and tissue repair in MS. Axonal injury is a key feature of multiple sclerosis (MS) pathology and is currently seen as the main correlate for permanent clinical disability. Although little is known about the pathogenic mechanisms that drive axonal damage and loss, there is accumulating evidence highlighting the central role of mitochondrial in axonal degeneration and associated neurodegeneration. New hope in developing therapeutic strategies aimed at improving mitochondrial metabolism and function under neuroinflammatory conditions. Mult Scler. 2012 Jun 21. Cancer risk in multiple sclerosis: British Columbia, Canada This study looks at the risk of the development of cancer in 6,820 patients with MS and compares that risk to the population risk of cancer, matched for sex, age, site of cancer and year of cancer diagnosis. The patient with MS has lower risk for cancer but they were diagnosed when the tumor was big. The authors also suggest that the fact that cancers are generally larger in people with MS at the time of diagnosis suggests that appropriate investigations for cancer symptoms may be delayed in people with MS, perhaps as a consequence of the other symptoms that they experience clouding warning signs for cancer. The importance of investigating new symptoms, and ensuring people with MS are able to attend cancer screening programs was emphasized. Brain. 2012 Jun 21. Term pregnancies and multiple sclerosis A prospective study of women in childbearing age found that long term disability related to MS was not affected by term pregnancies but rather by the years the person had been diagnosed with the disease. J Neurol Neurosurg Psychiatry. 2012 May 23 Sleep Disorders and Multiple Sclerosis This study found that sleep disturbances (SD) and excessive daytime sleepiness (EDS) is more frequent in MS than the general population. Objective assessment of vigilance and sleep can be challenging but MS patients who are poor sleepers should receive immediate assessment and treatment in order to improve QoL. Eur Neurol. 2012 May 23;68(1):8-15
Twenty-three patients with Targeted botulinum toxin type A injections significantly improve arm tremor and tremor-related disability in patients with MS. Neurology July 3, 2012 vol. 79 no. 1 92-99
In vitro fertilization and relapses This French study reported a significant increase in the annualized relapse rate during the three month period following in vitro fertilization treatments. This increase was associated with the use of gonadotrophin releasing hormone (GnRH) agonists as well as IVF failure. J Neurol Neurosurg Psychiatry. 2012 Jun 11.
A study done in the Netherlands showed that lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology. 2012 Jun 13.
Using the Spectral-domain Optical Coherence Tomography (OCT), the researchers in the USA showed that there are changes in retinal nerve fiber layer (RNFL) thickness in patients with clinically isolated syndromes despite no prior clinically evident optic neuritis when compared to healthy controls. The greatest loss of retinal axons was seen in patients with primary and secondary progressive MS. PLoS One. 2012;7(5):e36847. Epub 2012 May 23.
I chose the most relevant abstracts from the conference by topics. That is studied or found something different from what is already published. Cognitive and depression (CG03) Demyelinating lesions and behavioral changes The results of this study suggested that the location of demyelinative plaques in the brain, specially the prefrontal and cingulate gyrus areas, are associated with behavioral symptoms of MS patients. (refer to MS anatomy) (CG05) Physical activity and cognition Maintaining and/or increasing physical activity behavior is associated with improving cognitive dysfunction in persons with MS. (CG11) Characteristics of depression The researchers suggested that the majority of patients with MS had more than one psychiatric condition including major depression and anxiety disorders. This data suggested the importance of identifying and treating depression and other conditions that may be present. (CG16) Depression in MS Diagnosing, and managing depression in multiple sclerosis (MS) patients is often difficult, since MS-related disruption in the central nervous system (CNS) can mimic symptoms of depression; and conversely, symptoms reflecting major depression can be falsely attributed to MS progression, and left undiagnosed and untreated. This study aimed to provide a way to know which signs and symptoms are indicative of a major depressive disorder, and which are indicative of MS-related damage to CNS nerves. (CG21) Pain and depression This study found that pain had a direct relationship with anxiety, fatigue, and sleep disturbance; anxiety has a direct relationship with depression; sleep disturbance had a direct relationship with fatigue and depression; and fatigue had a direct relationship depression. Results suggest a need to evaluate all problems to reach treatment that may be more effective than depression treatment alone or pain treatment alone. (CG24) Negative feelings A study done in Cuba found that the main negative feelings among caregivers were anxiety, depression, anguish, uncertainty, pity, unhappiness, obligation, and frustration. (CG35) Damage in brain and cognitive function Thalamic and hippocampal atrophy in the brain have been demonstrated in relapsing- remitting multiple sclerosis patients and are associated with cognitive dysfunction and episodic memory impairment (See MS anatomy). (CG36) Predictors of dual task cost* This study found that mobility and cognitive impairment were both independent predictors of dual task cost during walking in persons with MS. This raises the possibility that dual task costs could be reduced with improvements in either mobility or cognition. (*Dual task cost- when two tasks are done simultaneously, one suffers due to problems in the other) (CG37) “Bening” MS Benign multiple sclerosis (MS)” is typically “defined” as both a disease duration of >10 years and an Expanded Disability Status Scale (EDSS) score of <3. This study found those patients reported depression, higher likelihood of fatigue, had cognitive impairment in three cognitive domains, and unemployment. These patients should not be considered to have benign disease. Computerized cognitive testing provides valuable clinical information not obtained from EDSS alone. (CG38) Driving with relapsing-remitting The ability to drive is often affected in many individuals with multiple sclerosis (MS) due to the motor, visual, or cognitive deficits commonly associated with the condition. Performance on a combination of four of the tests (ie, the time to complete the dots subtest of the Stroop test, the Direction, Compass, and Road Sign Recognition tests) took 30 minutes and together explained predicted participants’ performance with 86% accuracy, 80% sensitivity, and 88% specificity. Disease Management (DX87) Clinical efficacy of BG-12 A total of 1417 patients received treatment and showed that BG-12 given twice a day reduce the annual rate of relapses by 34% (P <.0020) and given three times a day by 45% (P < .0001) at 2 years compared to glatimer acetate that reduced by 29% (P = .00097). The incidence of adverse events and serious adverse events was similar across all groups, including placebo. (DX88) Restore Study: effects of natalizumab interruption RESTORE data confirmed a high rate of MRI and clinical MS disease activity recurrence after natalizumab cessation; the majority was seen at 16–20 weeks after natalizumab treatment was stoped. (DX91) Alemtuzumab Compared to interferon beta1-a, alemtuzumab significantly improved disability as measured by specific tests designed to measure functions in MS. (DX92) Alemtuzumab in patients who failed prior therapy Alemtuzumab significantly reduced both relapses and the accumulation of disability in a population of RRMS patients who had relapsed on prior therapy (glatimer acetate and interferon beta). (SC10) Genetic susceptibility in the Ashkenazi Jewish population The strongest genetic risk for MS in Europeans, HLA-DRB1*1501, however this was significantly less frequent in Ashkenazi Jewish cases. The study found that four genes outside the HLA in particular underlie the increased genetic risk of Ashkenazi cases to develop MS: CD58, CD6, IL7R, and IL12A. Rehabilitation (RH09) Activity Based rehabilitation Activity-based restorative therapy (ABRT) includes functional electrical stimulation (FES), locomotor training, weight loading, and patterned and non-patterned motor and sensory activation above and below the level of spinal lesions. A one year program of ABRT found that it may help preserve or improve neurological function in progressive MS.. (RH10) Impact of hip flexion A large number of patients with multiple sclerosis experience chronic gait disturbance in the course of their disease. Hip flexor weakness is a major cause of foot drop. Devices such as the ankle-foot orthosis do not compensate for hip flexor weakness. The Hip Flexion Assist Device (HFAD) is a lightweight device that augments active hip flexion while walking. Results of an uncontrolled pilot study suggest that the HFAD is safe and effective in improving walking performance. Interestingly, lower-extremity strength output increased during the study period. (RH27) Weight status and disability The study found that being overweight or more specific BMI did not predict disability. The prevalence of overweight and obesity was considerable and should be the focus of subsequent intervention in MS for its risk of heart diseases or diabetes. (RH36) Balance training This pilot study compared the effects of Nintendo Wii Fit game play (WII), conventional balance training (TRAD), and control (CON) on balance and mobility outcomes among home- dwelling persons with MS. The results suggested that balance rehabilitation training using WII and TRAD may both be effective in improving balance, confidence, perceived walking ability, and fatigue when compared to CON, with TRAD being potentially more effective than WII for this subset of individuals with MS. Symptom management (SX19) Tobacco use Tobacco use is estimated at over 60% in persons with multiple sclerosis. Exacerbation of disease progression and an increase in other diseases, especially obesity and coronary artery disease (CAD), have been strongly linked to smoking in MS. These preliminary findings suggested that tobacco use may exacerbate certain symptoms compared to non-tobacco users in RRMS (SX25) Migraine Migraine was commonly found in all groups of MS patients regardless of race and ethnic background. While chronic migraine was more prevalent among Hispanics than non- Hispanic whites with MS, socioeconomic differences or level of disability did not seem to impact this
com/2012/index.html
Research presented at the American Academy of Neurology, 4-2012 This document contains some of the MS research presented at the annual conference of the AAN. It will be updated as its Spanish version is updated with the translated material.
Fatigue and gait problems The energy consumed during walking by gait-impaired people with mild multiple sclerosis is important and influences the fatigue scores. The authors therefore suggest that developing rehabilitation strategies to address impaired gait parameters may be useful for management of fatigue. Neurorehabil Neural Repair. 2012 Mar 30. More on Fingolimod effect on MS Treatment with fingolimod 0•5 mg was associated with significantly lower annual relapse rate (ARR) versus placebo across all subgroups except for patients aged over 40 years. Larger reductions in ARR were seen in men compared to women. Lancet Neurol. 2012 Apr 5. Interferon beta and survival in MS This newly published data examined the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 MS patients who participated in the pivotal (IFNβ) -1b randomised clinical trial. 81 deaths were reported in the median 21 year follow up. The data from this study provide class 3 evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing remitting multiple sclerosis. Neurology. 2012 Apr 11. CCSVI Turkish researchers could not verify previous reports of ultrasonographically detectable differences in the extracranial venous drainage in people with MS compared to healthy controls by ultrasound. However, the vertebral vein blood flow was found to be higher on the right than the left side in people with MS. Eur Radiol. 2012 May;(5):970-9.
The results suggested that odor identification is more strongly affected than odor threshold and odor discrimination by lesions in areas with high FA values. J Neurol Sci. 316(1-2):56-60
The data from the study don’t support the hypothesis that vitamin D levels in the cerebrospinal fluid regulate production of igG in MS. Acta Neurol Scand. 125(6):e28-e31
This open label study of the experimental orally administered drug, CS-0777, a selective sphingosine 1-phosphate receptor-1 modulator, reported data from a pilot study in 25 people with multiple sclerosis. A clear dose dependent decrease in lymphocytes and CD4 T cell subsets was seen, returning to baseline within 4 weeks of final dose. No serious adverse events were reported. J Neuroimmunol. 2012 May 15;246(1-2):100-7.
clinical trial. Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with interferon beta-1a. Serious infections and thyroid problems were seen more in alemtuzumab patients compare to interferon beta-1. Immune thrombocytopenia occurred in alemtuzumab patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab. Neurology. 2012 Mar 21 Severe haematological complications during treatment with natalizumab Two cases, one of immune-mediated acute hemolytic anemia (IAHA) and another of immune thrombocytopenic purpura during treatment with natalizumab were reported. The temporal relationship between drug administration and the nature of the hematological complications suggested that natalizumab is the most probable cause for these adverse events and are severe enough to justify a close and careful monitoring for all patients with multiple sclerosis treated with an immunosuppressant treatment. Multiple Sclerosis March 2012 Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis Parents of patients with MS did not have a significantly altered immune mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn’s disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset. This may not be due to shared genetic factors or surveillance bias. A modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics. Multiple Sclerosis March 2012
Neurology. 2012 Mar The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have revised prescribing information for the oral MS therapy Gilenya (fingolimod, Novartis). National MS Society update Biogen Idec announced that the company has submitted a New Drug Application to the U. S. Food and Drug Administration for approval to market oral BG-12 (dimethyl fumarate) for the treatment of MS, based on positive results from several clinical trials involving people with relapsing-remitting MS. Biogen Idec, press release Feb 28, 2012 Avonex will have now two separate dosing: AVONEX PEN, the first intramuscular (IM) autoinjector approved for MS, incorporates a smaller needle and easier administration to help patients reduce anxiety about AVONEX self-injection, and a new dose titration regimen, which gradually escalates the dose of AVONEX at treatment initiation, reduces the incidence and severity of flu-like symptoms that can occur at the beginning of therapy. Biogen Idec, press release March3
year cohort study (follow-up) of the pivotal interferon β-1b trial in multiple sclerosis suggested that long term outcome in MS may be largely determined early by behavior and control of the disease course. Journal Neurol Neurosurg Psychiatry. 2012 Mar 83(3):282-287 Study findings in Iran suggest that MS-related physical disability, fatigue, and depression affect the quality of life of people with MS independently of each other. It concludes that effective interventions that target fatigue and depression may help improve the QoL of patients, regardless of their disease type and level of disability. European Journal Neurology. 2012 Mar 19(3):431-7
of vitamin D3 supplementation on relapses, disease progression and measures of function in persons with multiple sclerosis found that vitamin D3 had no significant difference on those values or clinically meaningful effect. Multiple Sclerosis. 2012 Feb 21. The development of anti-GA antibodies was observed in all patients treated with GA, but this was not related with measures of cellular immunity, clinical or MRI disease activity. Multiple Sclerosis March 2012 vol. 18 no. 3 305-313
confirm the association between fatigue and depressive symptoms in MS. They also highlight the difficulties of fatigue assessment in the pediatric population and provide few clues to further research in the field. Multiple Sclerosis March 2012 vol. 18 no. 3 329-334 Although Self-reported fatigue measured by the Rochester Fatigue Diary scores were affected by time of day with significant differences between morning and noon/afternoon, no changes in walking capacity were found in any subgroup. Additional analyses on subgroups distinguished by diurnal change in self-reported fatigue failed to reveal analogous changes in walking capacity. Multiple Sclerosis March 2012 vol. 18 no. 3 351-357 In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS. Multiple Sclerosis March 2012 vol. 18 no. 3 358-363 An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of starting a controlled clinical trial that will establish the safety and efficacy of autologous Hematopoyetic Stem Cell Transplant in comparison with approved therapies in a specific subset of highly active RRMS. Multiple Sclerosis March 1, 2012, doi: 10.1177/1352458512438454 Consistent with the cognitive reserve hypothesis, lifetime intellectual enrichment protects RRMS patients from cognitive impairment. This study showed that intellectual enrichment also protects SPMS patients from cognitive impairment. Multiple Sclerosis March 2, 2012 1352458512440205
frequently associated with local injection site reactions and described a wide spectrum of cutaneous adverse events; the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT. Multiple Sclerosis February 27, 2012 1352458512438239
as a PML Risk Factor. Read bulletin
taking the first dose of Gilenya (fingolimod). The patient had completed 6 hours of monitoring after the first dose without incident, but died less than 24 hours after the first dose. The exact cause of death has not been established. FDA is working closely with the manufacturer of Gilenya (Novartis Pharmaceuticals) to evaluate the post-market report of death. The patient was also treated with metoprolol, a beta blocker, and amlodipine, a calcium channel blocker. At this time, FDA cannot conclude whether the drug resulted in the patient's death. FDA is continuing to evaluate the case and will communicate any new information that results from this investigation. Read more in FDA Drug Safety. Possible role for certain proteins (tau, GFAP, MOG and NFL) found in the cerebral fluid as biomarkers identifying the different subtypes of multiple sclerosis. Multiple Sclerosis Journal January 17, 2012 Two patients with highly active relapsing MS who were treated with subcutaneos alemtuzumab, had significant improvement and tolerated subcutaneos alemtuzumab well without the typical infusion-associated adverse events. Multiple Sclerosis Journal January 17, 2012 Patients with secondary progressive multiple sclerosis involving the visual pathways (expanded disability status score 5.5-6.5) participated in the UK in a research using intravenous infusion of autologous bone-marrow-derived mesenchymal stem cells. One patient developed a transient rash shortly after treatment; two patients had self-limiting bacterial infections 3-4 weeks after treatment. There were no serious adverse events. There was some improvement after treatment in visual acuity and visual evoked response latency but no significant effects on color vision, visual fields, macular volume, or retinal nerve fiber layer thickness. Lancet Neurology. 2012 Jan 9. A systematic review of data from both randomized controlled trials and observational settings on the tolerability and adherence of multiple sclerosis disease-modifying therapies, revealed that the most common adverse events were flu-like symptoms (interferon therapies only) and injection-site reactions. A total of 151 papers were selected for analysis; 33% were classified as randomized controlled trials and 62% as observational studies. Most of the papers concerned interferon preparations and glatiramer acetate; the limited available information on mitoxantrone and natalizumab precluded extensive examination of these. There were no marked differences in tolerability or adherence data from randomized controlled trials and observational studies, but the incidence of adverse events remained high in lengthy studies and discontinuations accumulated with time. Multiple Sclerosis Journal January 16, 2012 In multiple sclerosis, iron accumulation in brain tissue may reflect a multiplicity of pathological processes. Hence, iron may have the unique potential to serve as an in vivo magnetic resonance imaging tracer of disease pathology. Two patients with multiple sclerosis and one non-multiple sclerosis donor were studied with 7 Tesla magnetic resonance imaging scanner and a 3D multi-gradient echo sequence. The study showed that this echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may be seen in apparently normal tissue. Brain. 2011 Dec
clinical measures contribute to unemployment in MS. A total of 101 individuals with MS underwent a brief neuropsychological battery and completed questionnaires related to vocation, mood, fatigue, and personality. Neurological impairment was measured with the Expanded Disability Status Scale (EDSS). It was found that EDSS and performance on measures assessing information processing speed (Symbol Digit Modalities Test (SDMT)), and persistence were the strongest predictors of employment status. Multiple Sclerosis Dec 19
The course of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients and cessation of the drug associated with recurrence of disease activity are related to clearance of the drug. Specific features of this IgG4 antibody (i.e. halfantibody exchange) may result in underestimated drug levels. The study showed that natalizumab levels in 10 patients with relapsing MS, using a recently developed sensitive assay was detectable up to 200 days after cessation of therapy. Multiple Sclerosis December 19 A study found that obstructive sleep apnea was frequent in MS and associated with fatigue but not sleepiness and independent of MS-related disability. Multiple Sclerosis Dec. 19 The purpose of this study was to determine predictors of severe (versus mild/moderate) relapses and poor or fair (versus complete) recovery in patients aged 18 years or less with MS or clinically isolated syndrome (CIS). It was found that optic nerve involvement was associated with a severe initial demyelinating event, while non-White race , localization to the cerebral hemispheres, or encephalopathy showed a trend towards increased severity of the initial demyelinating event. A similar association with race was found for severe second events. A severe IDE initial demyelinating event was associated with incomplete recovery, with similar trends for second and third events. Incomplete recovery from the first event predicted Endurance exercise and MS An exercise-induced increase in core temperature is associated with increased number and severity of perceived symptoms in heat-sensitive persons with MS. Based on these findings it is expected that heat-sensitive persons with MS do tolerate resistance excessive better than endurance exerciseincomplete second event recovery. Multiple Sclerosis Dec. 19 |
Maria A Reyes-Velarde, MD, MPH hablemosdeeem.com |
Latest News 2012
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©2001-2013 maria a.
reyes-velarde
Permission to use/copy any
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ESCLEROSIS MULTIPLE" must
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reyes-velarde
Permission to use/copy any
part of the site "HABLEMOS DE
ESCLEROSIS MULTIPLE" must
be granted by the author
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Hablemos de esclerosis multiple by Maria Adelita Reyes-Velarde, MD, MPH is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.
| Hablemos de esclerosis multiple ©2001-2013maria a. reyes-velarde All rights reserved |
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