Nasal spray desmopressin treatment of bladder dysfunction in patients with multiple sclerosis

Bladder dysfunction with increased voiding frequency and incontinence is a common problem in patients with multiple sclerosis (MS). In the present study, the effect of the synthetic vasopressin analogue, desmopressin, was evaluated on the voiding frequency in 26 patients with MS suffering from socially handicapping voidings and incontinence problems during daytime. A two-week run-in observation period to establish normal voiding patterns was followed by a double-blind, placebo-controlled cross-over study with 20 μg intranasal desmopressin during daily activities. There was a significant decrease in the number of voidings during the 6-h period after intranasal intake of desmopressin. Side effects were well tolerated and there was no hyponatremia or hypertension registered. Intranasal desmopressin is an efficient and well-tolerated treatment of voiding problems in patients with MS during daily activities.     

Desmopressin in the treatment of daytime urinary frequency in patients with multiple sclerosis

Twenty two patients with multiple sclerosis, complaining offrequency of day time micturition, completed a double blind crossover trial of desmopressin (DDAVP nasal spray) versus placebo. There was asignificant decrease in micturition frequency in the 6 hour post-treatment period from 3.1 voids after placebo to 2.4 voids and asignificant reduction in urinary volume after desmopressin. Eighty percent of patients preferred the active treatment phase. Mean 24 hoururinary volume did not differ between active and placebo treatments andpatients did not complain of increased night time frequency. Transientsymptoms of hyponatraemia occurred in one patient but these resolvedwithin 48 hours of stopping desmopressin. There were otherwise no sideeffects and mean serum sodium concentrations of the groupremained unchanged throughout the study. The clinical indications forprescribing daytime desmopressin are discussed and the importance ofpatient compliance stressed.

     

Intranasal administration of desmopressin acetate (DDAVP) to hemophiliacs

The intravenous infusion of desmopressin acetate (DDAVP), a synthetic vasopressin analogue, has been shown to cause a sustained increase in all Factor VIII related properties (VIII-C, VIIIR-Ag, VIIIR-WF) in patients with mild to moderate hemophilia and von Willebrand's disease. This study examines the effect of high doses of intranasal DDAVP (0.4 μg/kg BiD) in four patients with hemophilia A and one patient with von Willebrand's disease. In spite of a physiologic response with a decrease in urine volume and increase in urine osmolality, there was no effect on the Factor VIII complex.     

Diferencias en la tasa de atrofia global y regional y del volumen lesional entre género en esclerosis múltiple

Introduction

Previous studies showed gender-associated clinical and MRI differences in multiple sclerosis (MS) evolution. However, only few studies were done with non conventional MRI techniques and no one was done in a South American MS population. The aim of this study was to investigate gender differences according to nonconventional MRI measures in patients with MS from Buenos Aires, Argentina.

Methods

Relapsing-remitting MS patients (RRMS) with at least 6 years of follow up and an MRI at onset and at 6 years were included. Patients were assessed using nonconventional MRI measures: total brain volume (TBV), neocortical grey brain volume (GBV), white brain volume (WBV), lesion load (LL), % of brain volume change between onset and year 6 (% BVC) and regional brain volume change. Gender-related MRI differences were investigated using general linear model analysis.

Results

The 45 patients were included (25 female). Mean follow up time was 7.3±0.2 years. No differences in age, EDSS at onset, DMD treatment, TBV, GBV, WBV neither LL were found between gender at baseline. Six years later, males showed a decrease in TBV (P=.002) and GBV (P≤0.001) and an increase in LL (P=.02) and % BVC (P<.001) vs. females. Female patients showed a decrease in the volume of frontal subcortical region.

Discussion

This is the first study showing differences in brain volume changes between gender in MS patients from South America. Future studies will confirm our initial findings.     

Effect of MRI coregistration on serial short-term brain volume changes in multiple sclerosis

OBJECTIVE: To test the effect of serial magnetic resonance (MR) coregistration on short-term brain volume changes using different semiautomated and automated brain volume techniques in patients with relapsing-remitting (RR) multiple sclerosis (MS). Coregistration is frequently used to increase precision in serial MR imaging (MRI) analyses. However, the effect of coregistration on measurement of whole brain volume changes from serial scans in the short term has not been tested in MS patients. METHODS: Twenty-eight patients with RR MS [mean disease duration: 4.9 years, mean age: 34.4 years and mean expanded disability status scale (EDSS): 1.4] were scanned at baseline and monthly for a period of 3 months with 2D spin-echo T1-weighted sequences obtained with nongapped 3 mm axial slices. Percent brain parenchymal fraction change (PBPFC) was calculated by a semiautomated (Buffalo) and, separately, by two automated (Buffalo automated and SIENAX) techniques, whereas percent brain volume change (PBVC) was calculated by the SIENA technique. For coregistration of serial images we used a robust, fully automated linear image coregistration tool. PBPFC and PBVC were calculated before and after coregistration, comparing scans from the following time periods: (1) baseline to month 3; (2) baseline to month 1; (3) month 1 to 2 and (4) month 2 to 3. RESULTS: The highest median PBPFCs measured on non-coregistered images were detected for the baseline-to-month-3 time period and ranged from -0.11% for Buffalo semiautomated to -0.45% for Buffalo automated (p = ns). On coregistered images, the highest PBPFCs were detected for the baseline-to-month-3 time period and ranged from 0.3% for Buffalo semiautomated, -0.3% for Buffalo automated, 0.02% for SIENAX and -0.02% for SIENA (PBVC). At all time points of the study, no significant differences of median volume changes were measured on coregistered and non-coregistered images when comparing the results among the segmentation algorithms. CONCLUSIONS: Over a 3 month period we did not detect short-term changes in normalized brain volumes using different measurement techniques. A longer observation period is needed to assess whether coregistration can affect the measurement of long-term brain volume changes.     

Renal effects of long-term lithium therapy in the elderly: a cross-sectional study

OBJECTIVES: To determine the effect of long-term lithium therapy on glomerular filtration rate (GFR) and maximum renal concentrating capacity (Umax) in the elderly, to identify possible risk factors, to determine the clinical impact of a reduced Umax in this population and in case of polyuria to establish a diagnosis. METHODS: This is a cross-sectional study with 48 outpatients of 65 years or over (mean 74.8 years), who were treated with lithium for more than 6 months (mean 9.2 years). The GFR was determined with the Cockcroft-Gault formula (GFR-CG) and the Umax was measured in a urine sample collected between 3 and 5 h after the patients received 40 microg desmopressin (DDAVP) intranasally. RESULTS: No relation was found between duration of lithium treatment and GFR-CG, but there was a significant negative relation between duration of lithium treatment and Umax (B -0.73; CI: -1.249/-0.212); 73% of the patients had a moderate to severe concentrating defect. No other risk factors than duration of lithium therapy were identified. A reduced Umax caused polyuria (>2500 mL/24 h) in 33% but did not cause significant more thirst, incontinence or disturbed sleep. CONCLUSIONS: In this geriatric population a negative relation was found between duration of lithium treatment and Umax. But a reduced Umax did not result in significant more clinical symptoms. In case of polyuria other mechanisms beside nephrogenic diabetes insipidus were found to play a role in this age group.     

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.     

Desmopressin has no beneficial effect on excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass.

Cardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding. Following a non-randomized study suggesting that desmopressin acetate (desmopressin) reduced blood product requirements in these patients, we conducted a double-blind, placebo-controlled randomized trial of desmopressin (0.3 micrograms/kg, i. v.) in 92 patients with overt bleeding and a prolonged bleeding time. Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups (582 vs 465 ml, respectively; p = 0.15). Red-cell (p = 0.76), fresh frozen plasma (r = 0.66) and platelet unit (p = 0.74) requirements were also similar. The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor (vWF) and a reduced bleeding time. In our study, vWF and factor VIII:C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and, although vWF and factor VIII:C levels were slightly higher in desmopressin-treated patients at 90 min, the difference was not significant. Thrombin-antithrombin III complex, fibrinogen degradation product and tissue plasminogen activator levels, reflecting activation of the coagulation and fibrinolytic systems, respectively, decreased uniformly in both groups. We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding.     

MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a

The aim of this study was to investigate changes of brain volume as measured by magnetic resonance imaging (MRI) in relapsing-remitting multiple sclerosis (MS) patients under treatment with interferon beta-1a. Moreover, the relationship between brain volume changes and standard MR or clinical outcome variables was determined. After a 6-month pretreatment period, 52 patients with relapsing-remitting MS were assigned to receive interferon beta-1a (Rebif-Serono) during a 24-month treatment period MRI scans were performed monthly during the 6-month pretreatment period and for the first 9 months of the treatment period. A final MRI scan was also performed at the end of the 12- and 24-month treatment period. Over 24 months of IFNbeta-1a treatment, a significant decrease of hyperintense lesion volume was found (-18.0%; p<0.0001) compared to the last pretreatment scan, while T1 hypointense volume showed a slight nonsignificant increase (+2.2%), and brain volume showed a significant decrease (-2.2%; p<0.0001). The mean volume of enhancing lesions over the 6-month pretreatment period was significantly related to absolute (p=0.02; r=-0.32) and per cent change (p=0.03; r=-0.30) of brain volume during 24-month treatment period. No correlations between changes in brain volume and changes in T2 hyperintense volume or T1 hypointense volume were observed. Neither was there a relationship between brain volume and changes of Expanded Disability Status Scale (EDSS) or frequency in clinical relapses. Of the group in whom was detected a significant decrease of brain volume, 13 out of 26 (50%) had a sustained change in EDSS while in the group that did not have a significant decrease of brain volume, only 3 out of 26 (11.5%) had a sustained EDSS change (p=0.02). In this study a decrease of brain volume was found in relapsing-remitting MS patients treated with IFNbeta-1a over 2 years. The only parameter that predicted brain volume decrease by 2 years of IFNbeta-1a treatment was the mean volume of enhancing lesions over the 6-month pretreatment period.     

Relationship of urinary myelin basic protein-like material with cranial magnetic resonance imaging in advanced multiple sclerosis

BACKGROUND: A significant correlation exists between disability and the volume of black holes (BHL VOL), defined as hypointense lesions on T1-weighted cranial magnetic resonance imaging. A consistent correlation has also been reported between urinary myelin basic protein-like material (MBPLM) and the transition toward secondary progression (SP) from relapsing-remitting (RR) multiple sclerosis (MS). OBJECTIVE: To improve the management of MS through a noninvasive and cost-effective test for monitoring disease activity or disease status. DESIGN AND METHODS: From 662 patients with MS (86 with RR MS, 259 with SP MS without continued attacks, and 317 with SP MS with continued attacks), 24-hour urine samples were obtained at enrollment in the phase 3 Linomide (roquinimex) drug study. The urine specimens were analyzed for MBPLM and correlated with clinical features and findings on cranial magnetic resonance imaging. RESULTS: Significant but weak correlations existed between urinary MBPLM and BHL VOL in all patients with MS (r = 0.114, P =.003; n = 662), patients with SP MS without attacks (r = 0.185, P =.003; n = 259), and all patients with SP MS (r = 0.122, P =.003; n = 576). No significant correlations were detected in the RR MS group or any of the disease groups or subgroups whose Expanded Disability Status Scale score was 5.0 or lower. In subgroup analysis, the most significant correlation was detected between urinary MBPLM after adjustment for creatinine and BHL VOL in patients with SP MS with an Expanded Disability Status Scale score of 5.5 or higher but without continued relapses (r = 0.417, P<.001; n = 138). CONCLUSIONS: In patients with advanced SP MS, urinary MBPLM may possibly serve as an indicator of failed remission and axonal damage. Urinary MBPLM correlates with disease status in MS, especially the transition of RR MS to SP MS with advancing disability.     

Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder

Lithium (Li) carbonate has been reported to be able to cause some reversible functional changes in the kidney. In this study, the authors aimed to investigate whether the duration of Li treatment is the primary determinant of the changes in renal functioning due to the Li treatment. For this purpose, 10 Li-na?ve (mean age+/-S.D.: 34.50+/-4.85), 10 short-term (mean age+/-S.D.: 31.77+/-7.61) and 10 long-term (mean age+/-S.D.: 36.60+/-10.15) Li-treated bipolar patients were included in the study. Serum blood urea nitrogen (BUN) and creatinine, urine creatinine levels, creatinine clearance, urine osmolality before and after 8-h water deprivation and urine osmolality after desmopressin injection were measured in all patients. Serum BUN and creatinine levels were within the normal limits and not statistically different among the groups. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-na?ve group and that of the short-term Li-treated group. After 8-h water deprivation and also after desmopressin injection, no difference was found among the groups in terms of urine osmolality. However, when each patient was evaluated individually in terms of their renal concentrating ability, partial nephrogenic diabetes insipidus was diagnosed in four patients on long-term and in two patients on short-term Li treatment. To our surprise, hypothalamic diabetes insipidus was also diagnosed in other two patients on long-term Li treatment. These results demonstrate that long-term Li treatment may cause impairment in renal concentrating ability, some of which may originate from the effects of Li on vasopressin on hypothalamic level, and a decrease in glomerular filtration rate (GFR). In the light of these data, we can conclude that long-term administration of Li may be a risk factor for Li-induced renal impairment, which is a progressive effect in nature.     

Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis

OBJECTIVE: To evaluate the efficacy and safety of interferon-alpha2a (IFN-alpha2a) in relapsing-remitting MS (RRMS). BACKGROUND: Several immune-modulating therapy regimens of IFN-alpha have shown varying results in MS. A recent pilot study suggested benefits from IFN-alpha2a. METHODS: Ninety-seven patients were randomized to receive subcutaneous injections of placebo (33 patients) or 4.5 million international units (mIU) (32 patients) or 9.0 mIU (32 patients) of IFN-alpha2a three times weekly for 6 months, with a further 6 months of follow-up. Monthly gadodiamide-enhanced MRI was the primary method of evaluating efficacy. RESULTS: IFN-alpha2a treatment resulted in fewer new MRI lesions during the treatment period (p < 0.003). The probability of no new lesions during treatment was >2.5 times higher with 9.0 mIU IFN-alpha2a than with placebo (p < 0.005). The median number of lesions at the end of treatment was lower with IFN-alpha2a treatment than with placebo (p = 0.0004), but the difference disappeared during follow-up. The total number of lesions (mean) increased by 4.78 with placebo, 0.86 with 4.5 mIU IFN-alpha2a, and 0.28 with 9.0 mIU IFN-alpha2a during treatment (p = 0.030). No treatment effect on exacerbation rate, progression of disability, or quality of life was detected. Nine patients discontinued treatment, five because of adverse events. CONCLUSIONS: IFN-alpha2a treatment significantly reduced disease activity as measured by MRI, but the efficacy disappeared within 6 months after discontinuation of treatment. A long-term study of more patients using disability as a primary outcome measure is needed to evaluate the clinical impact.     

Prevalence of human herpesvirus U94/REP antibodies and DNA in Tunisian multiple sclerosis patients

Human herpesvirus 6 (HHV-6) has been linked to the pathogenesis of multiple sclerosis (MS). Based on antibody detection and quantitative HHV-6 polymerase chain reaction assay, this study aimed to analyze the possible association between infection with HHV-6 and MS. A total of 131 serum samples were analyzed by ELISA for the presence of specific antibodies to HHV-6 latency-associated U94/REP protein: 68 serum samples from 60 MS patients (20 in relapse and 48 in remission phase) and 63 serum samples from 63 healthy controls. Real-time quantitative PCR for HHV-6 U94/rep DNA was also performed in total blood of MS patients and healthy controls. The serological analysis by ELISA showed that MS patients had increased prevalence and titers of anti-U94/REP immunoglobulins in comparison with control group (seroprevalence 51.47 % versus 28.57 % and mean titer of positive samples 1:248 versus 1:110; p?=?0.0005), with significant difference between relapse and remission phases. HHV-6 DNA was detected in 4 of 60 MS patients (6.66 %) and in 2 of 63 healthy controls (3.17 %), confirming previous data of prevalence obtained by qualitative nested PCR. However, viral load was higher in MS patients compared to controls, and differences were statistically significant (p?=?0.02). The results show that, in spite of the low presence of HHV-6 DNA in peripheral blood, MS patients have increased prevalence and titer of IgGs reacting with HHV-6 latency-associated U94/REP protein.     

Extensive cortical inflammation is associated with epilepsy in multiple sclerosis

INTRODUCTION : Epilepsy is three to six times more frequent in MS than in the general population. Previous studies based on conventional magnetic resonance (MR) imaging have suggested a possible correlation between cortical inflammatory pathology and epileptic seizures. However, pure intracortical lesions (ICLs) are unlikely to be demonstrated with conventional MR. We applied the double inversion recovery (DIR) sequence in relapsing remitting MS (RRMS) patients with or without epileptic seizures in order to clarify the relationship between ICLs and epilepsy in MS in vivo. METHODS : Twenty RRMS patients who had epileptic seizures (RRMS/E) during the course of the disease were studied for the presence of ICLs. A group of 80 RRMS patients with no history of seizures and matched for gender, age, disease duration, Expanded Disability Status Scale (EDSS) grading, and T2 lesion volume (T2-WMLV) was selected as reference population. ICLs were detected by applying the DIR sequence. RESULTS : ICLs were observed in 18/20 (90%) RRMS/E and in 39/80 (48%) RRMS (p = 0.001). RRMS/E showed five times more ICLs (7.2 +/- 8.4) than RRMS (1.5 +/- 2.4; p = 0.015). The total ICLs volume was 6 times larger in RRMS/E than in RRMS (1.2 +/- 1.7 cm3 versus 0.2 +/- 0.2 cm3, p = 0.016). No significant difference was observed between RRMS and RRMS/E with regard to the number and volume of juxtacortical lesions and T2-WMLV. DISCUSSION : Our findings indicate that RRMS/E have more extensive cortical inflammation than RRMS patients with no history of epilepsy. Inflammatory ICLs may be responsible for epilepsy in MS.     

Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H.

BACKGROUND: To assess the long-term effect of the lymphocyte-depleting humanized monoclonal antibody Campath 1H on MR markers of disease activity and progression in secondary progressive MS patients. METHODS: Twenty-five patients participated in a crossover treatment trial with monthly run-in MR scans for 3 months, followed (after a single pulse of Campath 1H) by monthly MR scans from months 1 to 6 and again from months 12 to 18. MR analysis was performed to provide measurements of the number and volume of gadolinium (Gd)-enhancing lesions as well as the hypointense lesion volume on a T1-weighted sequence. In addition, serial measurements of T2 brain lesion volume, brain volume, and spinal cord cross-sectional area were made over the duration of the study. The relationship between clinical and MR measures of disease evolution was also assessed. RESULTS: Treatment was associated with a reduction in the number and volume of Gd-enhancing lesions (p < 0.01). Despite this, a decrease in brain volume was seen in 13 patients during the 18 months post-treatment. The mean pretreatment Gd-enhancing lesion volume was predictive of subsequent reduction in brain volume (r = 0.77, p = 0.002). Reduction in brain volume also correlated with the change in T1 hypointense lesion volume after treatment (r = 0.53, p < 0.01). A reduction in spinal cord area was also seen throughout the study duration, and this correlated with an increase in disability (r = 0.65, p = 0.01). CONCLUSION: Campath 1H treatment was associated with a sustained and marked reduction in the volume of Gd enhancement, indicating suppression of active inflammation. Nevertheless, many patients developed increasing brain and spinal cord atrophy, T1 hypointensity, and disability. This study highlights the potential role for novel MR techniques in monitoring the effect of treatment on the pathologic process in MS.     

Glial toxicity in urine and multiple sclerosis.

The biochemical and biological characterization of a cytotoxic activity targeting macroglial cells (oligodendrocytes and astrocytes), in moncyte cultures and in CSF of a patient with multiple sclerosis, has previously been described. In further studies, cell-based tests have shown a good correlation between this glial cytotoxic (gliotoxic) activity, in CSF or in urine, and MS. We now present results obtained with urine samples from 102 MS patients, 51 patients with other neurological disease and 35 healthy subjects using a bioassay set up for the detection of an apoptosis-like effect induced in a glial cell-line. Significant gliotoxicity was detected in urine from 74/102 MS patients while only 4/51 neurological controls (P>0.001) and never in healthy subjects (P>0.001). Given the statistical tendency provided by this bioassay and its technical limitations for routine testing, it is now used for monitoring the molecular characterization of this 'gliotoxic factor'. Its replacement by a specific immunoassay could provide more accurate routine techniques for the detection of this biological marker in MS.     

Polymerase chain reaction analysis of human herpesvirus-6 sequences in the sera and cerebrospinal fluid of patients with multiple sclerosis.

Several studies have suggested a possible association of human herpesvirus-6 (HHV-6) with multiple sclerosis (MS), a demyelinating disease with a variable course and progression. To determine whether HHV-6 could be detected in the sera of CSF of patients with different subtypes of MS, we performed nested polymerase chain reaction (PCR) on samples obtained from MS patients as well as samples from normal adults or individuals with other neurological diseases. Ninety-six serum samples from 24 patients with MS, including 13 individuals with relapsing remitting MS, one individual with primary progressive MS, seven individuals with secondary progressive MS and three individuals with an unspecified type were analyzed. Multiple serum samples were examined from individuals over varying periods of time and included samples obtained during exacerbations, remissions, and at different stages of progressive disease. HHV-6 DNA was detected only in one out of 15 serum samples that were collected over a number of years from one individual with secondary progressive MS. No HHV-6 DNA was detected in CSF from six patients with MS or 14 patients with other neurologic disease. These results indicate that the presence of HHV-6 DNA in the serum or CSF of patients with MS is not a common phenomenon, at least within the limits of the sensitivity of our assay.     

Interferon-β-1a in relapsing-remitting multiple sclerosis: effect on hypointense lesion volume on T1 weighted images

OBJECTIVE: Recently, a strong correlation between the increase in hypointense lesion load on T1 weighted spin echo images, and the increase in disability was reported. Although the effect of interferon-beta has been demonstrated both in reducing exacerbation rate, frequency of enhancing lesions, and accumulation of disease burden on T2 weighted images, the impact on the accumulation of hypointense lesions has not yet been evaluated. The aims of the present study were: (a) to assess for the first time the effect of interferon-beta-1a on T1 weighted MRI hypointense lesion volume; and (b) to evaluate the relation between changes on hypointense, hyperintense, and enhancing lesion volume before and during interferon-beta-1a treatment in relapsing-remitting multiple sclerosis. METHODS: After a baseline scan and 6 month pretreatment period, 67 patients with relapsing-remitting multiple sclerosis were treated with interferon-beta-1a by subcutaneous injection three times a week during a 12 month treatment period. All patients had MRI every month during the 6 month pretreatment period and for the first 9 months of the treatment period. A final MRI was also performed at the end of the 12 month treatment period. RESULTS: There was a significant increase in the mean hyperintense lesion volume during the pretreatment phase (6 months) and a slight decrease during the treatment period (12 months), whereas the hypointense lesion volume increased significantly before treatment and remained substantially stable during treatment. There was a significant correlation between changes in hypointense and hyperintense lesion volume during the observation period, but not during treatment. The monthly mean volume of Gadolinium-DTPA enhancing lesions was significantly higher during the pretreatment than the treatment period, and the enhancing lesion volume correlated with changes of hyperintense and hypointense lesion volumes only during the observation period. CONCLUSION: These data suggest that interferon-beta-1a has a stabilising effect on T1 weighted hypointense lesion volume.     

Increased free light chains in the urine from patients with multiple sclerosis

We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity.     

Beta-endorphin concentrations in peripheral blood mononuclear cells of patients with multiple sclerosis: effects of treatment with interferon beta

CONTEXT: It has been reported that the opioid peptide beta-endorphin (BE) has immunosuppressive effects. Interferon beta (IFN-beta) is a well-established therapy for multiple sclerosis (MS), but immunological mechanisms underlying its beneficial effects in MS are partially undefined. OBJECTIVES: To determine BE levels in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting MS during different phases of disease activity and the possible modulating effects of IFN-beta treatment on PBMC BE synthesis in patients with MS. DESIGN: We measured BE levels in blood samples collected from 6 patients with MS who had not experienced clinical changes during the previous 3 months (patients with stable MS) and from 7 patients with MS during a clinical relapse. We also surveyed BE levels in PBMC samples from 8 patients with MS before treatment and for 6 months after the beginning of IFN-beta administration. The control group was 13 healthy subjects. RESULTS: Low PBMC BE levels were detected in patients with stable MS and in those entering IFN-beta treatment compared with control subjects. Increased BE concentrations were observed in MS patients experiencing a clinical relapse compared with patients with stable MS. During IFN-beta treatment, the levels of BE in PBMC samples from patients with MS increased significantly (after 1 month, P =.02; after 3 months, P =.007; and after 6 months, P =.16). CONCLUSIONS: A reduction of BE levels was present in patients with clinically inactive MS. Treatment with IFN-beta seems to induce an increase of this opioid in PBMCs of MS patients. The increase of BE concentration during a clinical relapse may represent a possible control mechanism aimed at counterbalancing the inflammatory phase of the disease. Arch Neurol. 2000;57:1178-1181