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Background and purpose: In the SELECT study, treatment with daclizumab high-yield process (DAC HYP) versus placebo reduced the frequency of gadolinium-enhancing (Gd+) lesions in patients with relapsing-remitting multiple sclerosis (RRMS). The objective of this post hoc analysis of SELECT was to evaluate the effect of DAC HYP on the evolution of new Gd+ lesions to T1 hypointense lesions (T1 black holes). Methods: SELECT was a randomized double-blind study of subcutaneous DAC HYP 150 or 300 mg or placebo every 4 weeks. Magnetic resonance imaging (MRI) scans were performed at baseline and weeks 24, 36 and 52 in all patients and monthly between weeks 4 and 20 in a subset of patients. MRI scans were evaluated for new Gd+ lesions that evolved to T1 black holes at week 52. Data for the DAC HYP groups were pooled for analysis. Results: Daclizumab high-yield process reduced the number of new Gd+ lesions present at week 24 (P = 0.005) or between weeks 4 and 20 (P = 0.014) that evolved into T1 black holes at week 52 versus placebo. DAC HYP treatment also reduced the percentage of patients with Gd+ lesions evolving to T1 black holes versus placebo. Conclusions: Treatment with DAC HYP reduced the evolution of Gd+ lesions to T1 black holes versus placebo, suggesting that inflammatory lesions that evolved during DAC HYP treatment are less destructive than those evolving during placebo treatment. [ABSTRACT FROM AUTHOR]

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7-36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15-24, all patients receiving fingolimod 5.0mg switched to 1.25mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88-89%) or new T2 lesions (70-78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20-0.21, and 68-73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3-5mmHg) during the first 6months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated bymost patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate if subjective symptoms indicating an impaired deglutition correlate with videofluoroscopic findings in patients with multiple sclerosis (MS). Videofluoroscopic examinations of 18 MS patients were analyzed by a radiologist and a logopedist and compared with the symptoms of these patients. Four patients complained about permanent dysphagia. Six patients reported mild and intermittent difficulties in swallowing, but were asymptomatic at the time of videofluoroscopy. Eight patients had no symptoms regarding their deglutition. All patients ( n=4) who complained of permanent dysphagia showed aspiration. All patients ( n=6) with mild and intermittent difficulties in swallowing showed undercoating of the epiglottis and/or laryngeal penetration. Of those 8 patients without any swallowing symptoms, only 2 had a normal videofluoroscopy. Swallowing abnormalities seem to be much more frequent in patients with MS than generally believed and they may easily be missed clinically as long as the patients do not aspirate. [ABSTRACT FROM AUTHOR]

Forty-nine patients with clinical features of vascular disease in the vertebrobasilar territory were examined to evaluate the diagnostic performance of computed tomography. It provided useful information in the diagnosis of acute vascular lesions in patients in whom a definite episode had occurred not longer than 2 weeks before computed tomography was undertaken. It was of value in both haemorrhagic and thromboembolic groups but in many patients angiography was required to make a substantive diagnosis. It was of less value in patients with vague and ill defined symptoms and of no value in transient ischaemia. [ABSTRACT FROM AUTHOR]

Two patients are described in whom computerised tomography revealed contrast-enhanced lesions in the early stages of multiple sclerosis. Such lesions may be differentiated from tumours by their transient nature, lack of space-occupying effect, and localisation in the white matter. Contrast enhancement in demyelinating disease is probably related to local breakdown of the blood-brain barrier. [ABSTRACT FROM AUTHOR]

A subdural haematoma is described in which a definite computed tomographic (CT) scan diagnosis was made only after contrast enhancement had been achieved by the inhalation of xenon. The different types of enhancement obtained with iodide containing contrast media and with xenon are discussed. The use of xenon to obtain further information in conditions which are inadequately elucidated by conventional CT must be balanced against its anaesthetic effects and relatively high cost. [ABSTRACT FROM AUTHOR]

Oral administration of hydrolytic enzymes (HE), such as bromelain, trypsin and rutosid, may have beneficial effects on the clinical course of neurological symptoms related to multiple sclerosis (MS). This is supported by a complete protection by HE from experimental allergic encephalomyelitis, an animal model related to MS. Three hundred and one patients with relapsing MS were enrolled in a double-blind, placebo-controlled trial. No treatment effect between the placebo and the HE groups was found either for clinical or MRI parameters. [ABSTRACT FROM AUTHOR]

Two different types of retrospective study of the value of CT have been contrasted. In one, the patients were chosen because of the way they presented (with posterior fossa signs or symptoms) or because they were found to have posterior fossa disease; in the other, all were reported as having, or found to have, gliomas or metastases. The first type of study provides a better basis for evaluation of neuroradiological procedures. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss a placebo-controlled trial of fingolimod in patients with relapsing multiple sclerosis (MS). They say that the study assessed fingolimod's efficacy in 1272 relapsing-remitting MS (RRMS) patients, who randomly received oral fingolimod capsules at doses of 0.5 milligrams (mg) or 1.25 mg per day. They conclude that the doses were as effective in RRMS treatment as in placebo, but note that the benefits of fingolimod must be balanced against potential risks.

An abstract of the article "Oral fingolimod (FTY720) in relapsing MS: MRI results of a placebo-controlled phase II study and active drug extension," by E. W. Radue, P. O'Connor, J. Antel, G. Comi, X. Montalban, A. De Vera, D. Tang and L. Kappos is presented.

Background: Reliable prognostic factors are lacking for multiple sclerosis (MS). Gadolinium enhancement in magnetic resonance imaging (MRI) of the brain detects with high sensitivity disturbance of the blood-brain barrier, an early event in the development of inflammatory lesions in MS. To investigate the prognostic value of gadolinium-enhanced MRI, we did a meta-analysis of longitudinal MRI studies.Methods: From the members of MAGNIMS (European Magnetic Resonance Network in Multiple Sclerosis) and additional centres in the USA, we collected data from five natural-course studies and four placebo groups of clinical trials completed between 1992 and 1995. We included a total of 307 patients, 237 with relapsing disease course and 70 with secondary progressive disease course. We investigated by regression analysis the relation between initial count of gadolinium-enhancing lesions and subsequent worsening of disability or impairment as measured by the expanded disability status scale (EDSS) and relapse rate.Findings: The relapse rate in the first year was predicted with moderate ability by the mean number of gadolinium-enhancing lesions in monthly scans during the first 6 months (relative risk per five lesions 1.13, p=0.023). The predictive value of the number of gadolinium-enhancing lesions in one baseline scan was less strong. The best predictor for relapse rate was the variation (SD) of lesion counts in the first six monthly scans which allowed an estimate of relapse in the first year (relative risk 1.2, p=0.020) and in the second year (risk ratio=1.59, p=0.010). Neither the initial scan nor monthly scans over six months were predictive of change in the EDSS in the subsequent 12 months or 24 months. The mean of gadolinium-enhancing-lesion counts in the first six monthly scans was weakly predictive of EDSS change after 1 year (odds ratio=1.34, p=0.082) and 2 years (odds ratio=1.65, p=0.049).Interpretation: Although disturbance of the blood-brain barrier as shown by gadolinium enhancement in MRI is a predictor of the occurrence of relapses, it is not a strong predictor of the development of cumulative impairment or disability. This discrepancy supports the idea that variant pathogenetic mechanisms are operative in the occurrence of relapses and in the development of long-term disability in MS. [ABSTRACT FROM AUTHOR]

An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available., (© 2016 by American Journal of Neuroradiology.)

Background: Brain volume loss occurs in patients with relapsing-remitting MS. Fingolimod reduced brain volume loss in three phase 3 studies., Objective: To evaluate whether the effect of fingolimod on disability progression was mediated by its effects on MRI lesions, relapses or brain volume loss, and the extent of this effect., Methods: Patients (992/1272; 78%) from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study were analyzed. Month-24 percentage brain volume change, month-12 MRI-active lesions and relapse were assessed. The Prentice criteria were used to test surrogate marker validity. The proportion of treatment effect on disability progression explained by each marker was calculated., Results: Two-year disability progression was associated with active T2 lesions (OR = 1.24; p = 0.001) and more relapses during year 1 (OR = 2.90; p < 0.001) and lower percentage brain volume change over two years (OR = 0.78; p < 0.001). Treatment effect on active T2 lesions, relapses and percentage brain volume change explained 46%, 60% and 23% of the fingolimod effect on disability. Multivariate analysis showed the number of relapses during year 1 (OR = 2.62; p < 0.001) and yearly percentage brain volume change over two years (OR = 0.85; p = 0.009) were independent predictors of disability progression, together explaining 73% of fingolimod effect on disability., Conclusions: The treatment effect on relapses and, to a lesser extent, brain volume loss were both predictors of treatment effect on disability; combining these predictors better explained the effect on disability than either factor alone., (© The Author(s), 2015.)

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.