How does fingolimod (gilenya(®)) fit in the treatment algorithm for highly active relapsing-remitting multiple sclerosis?

Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, disease-modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya(®)) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.

Recommendations for the use of prolonged-release fampridine in patients with multiple sclerosis (MS).

Prolonged-release fampridine (fampridine PR) is a potassium channel blocker that improves conductivity of signal on demyelinated axons in central nervous system. Fampridine PR has been approved to improve speed of walking in patients with multiple sclerosis. This statement provides a brief summary of data on fampridine PR and recommendations on practical use of the medication in clinical practice, prediction, and evaluation of response to treatment and patient management.

Natalizumab in the treatment of pediatric multiple sclerosis.

Pediatric cerebrospinal multiple sclerosis (MS) constitutes about 2-5% of all MS cases. The International Pediatric MS Study Group (IPMSSG) applies diagnostic criteria for adults to MS in childhood and adolescence. Recent publications highlight an increasing number of MS in children resistant to the first-line treatment, i.e. disease modifying therapy (DMT). Furthermore, the number of published case studies on children with highly active MS treated with natalizumab also rises, whereas long-term risks as well as therapeutic potential of this therapy in pediatric population have been at the centre of attention. This paper presents a group of 5 children in whom natalizumab was selected to manage highly active disease or resistance to conventional MS treatment and provided very good clinical as well as MRI results.

Fingolimod in the treatment algorithm of relapsing remitting multiple sclerosis: a statement of the Central and East European (CEE) MS Expert Group.

Fingolimod is the first oral treatment of multiple sclerosis. It is the first-in-class sphingosine 1-phosphate receptor modulator that binds to sphingosine 1-phophate receptors on lymphocytes and via downregulation of the receptor prevents lymphocyte egress from lymphoid tissues into the circulation. This mechanism reduces the infiltration of potentially auto-aggressive lymphocytes into the central nervous system. Two large phase III studies with fingolimod have shown superior efficacy of the drug in two dosages compared to placebo and to weekly intramuscular injections of Interferon beta-1a. Among possible side effects of the drug is a transient bradycardia after the first dose of fingolimod including possible AV blockade and therefore monitoring of pulse rate and blood pressure for 6 h following the first application is needed. During treatment, attention has to be given to specific infections, elevated liver enzymes, and ophthalmologic changes. Recommendations on the use of fingolimod including safety aspects are given in this article.

Marburg variant multiple sclerosis - a case report.

In this case report we describe the case of a 24 year-old female with a fulminant demyelinating disease of white matter. Disease progression was most probably consistent with the Marburg variant (malignant form) of multiple sclerosis with rapid deterioration of the patient's clinical condition, including bulbar symptoms and epileptic paroxysms and ending with persistent coma and tetraparesis, over the course of 6 months from first symptoms. Repeated Magnetic Resonance Imaging (MRI) examination showed progression of multiple demyelinating lesions culminating in a contiguous focal disorder of the white matter extending both supratentorially and infratentorially. The serial MRI changes closely mapped the deterioration in the patients clinical status. Our patient showed no response to repeated pulse corticotherapy, administration of intravenous immunoglobulins, serial plasmapheresis, and combined high-dose pulse immunosuppression (specify what was used here) and mitoxantrone.

An electrophysiological study of visual processing in spinocerebellar ataxia type 2 (SCA2).

Reports of visual functional impairment in spinocerebellar ataxia type 2 (SCA2) have been studied previously using pattern reversal visually evoked potentials (VEPs) with contradictory results. To provide additional evidence to this area, visual functions were studied using VEPs and event-related potentials (ERPs) in a group of ten patients with genetically verified SCA2. The electrophysiological examination included pattern reversal and motion-onset VEPs as well as visually driven oddball ERPs with an evaluation of a target and a pre-attentive response. In six patients, we found abnormal visual/cognitive processing that differed from normal values in latency, but not in the amplitude of the dominant VEP/ERP peaks. Among the VEPs/ERPs used, the motion-onset VEPs exhibited the highest sensitivity and showed a strong Spearman correlation to SCA2 duration (from r = 0.82 to r = 0.90, p < 0.001) and clinical state assessed by Brief Ataxia Rating Scale (from r = 0.71 (p = 0.022) to r = 0.80 (p < 0.001)). None of the VEP/ERP latencies showed a correlation to the triplet repeats of the SCA2 gene. In three patients, we did not find any visual/cognitive pathology, and one subject showed only a single subtle prolongation of the VEP peak. The observed visual/cognitive deficit was related to the subjects' clinical state and the illness duration, but no relationship to the genetic marker of SCA2 was found. From the VEP/ERP types used, the motion-onset VEPs seems to be the most promising candidate for clinical state monitoring rather than a tool for early diagnostic use.

Abnormalities of tau-protein and beta-amyloid in brain ventricle cerebrospinal fluid.

OBJECTIVE: Determination of various biomarkers, such as beta-amyloid, tau-protein, phosphorylated tau-protein in CSF and their sensitivity and specificity in neurodegenerative brain processes, in particular Alzheimer Dementia (AD), has been recently investigated to monitor their abnormalities in the CSF at early stages of diseases before the clinical manifestation. DESIGN AND SETTING: In the pilot group of our patients (10 men / 5 women) who underwent a drainage neurosurgical procedure for diagnosis of hydrocephalus, CSF was obtained from the brain ventricles and the influence of a different compartment of the CSF on the level of biomarkers, tau-protein and beta-amyloid, was investigated. RESULTS: The mean tau-protein level for all 15 patients was 812.0 pg/ml, with median value 363.7 pg/ml; while mean beta-amyloid level for all 15 patients was 526.7 pg/ml, with median value 239.5 pg/ml, respectively. The abnormal tau-protein and beta-amyloid levels were found in the subgroup of patients in whom hydrocephalus was caused by a severe pathological process, such as brain tumor. The beta-amyloid values were significantly lower also in comparison with our previously published results in patients with AD in the CSF obtained by lumbar puncture in the spinal canal. CONCLUSIONS: CSF in the brain ventricles is theoretically more stable and the values in this CSF probably provide more reliable informations for clinical diagnostic procedure than those for the CSF obtained by lumbar puncture in the spinal canal.

Tau protein, phosphorylated tau protein and beta-amyloid42 in the cerebrospinal fluid of multiple sclerosis patients.

OBJECTIVES: The presented study focuses on the importance of measurement of beta-amyloid42 (Abeta-42) levels, total tau protein, and phosphorylated tau (p-tau) protein in the cerebrospinal fluid (CSF) of cerebrospinal multiple sclerosis (MS) and clinically isolated syndrome (CIS) which represents an early phase of multiple sclerosis. METHODS: A total of 23 patients with clinically isolated syndrome and suspected MS were enrolled into the study. Of this number, 14 patients met the criteria for definitive MS according to McDonald. The control group consisted of 40 patients examined for the possibility of organic damage to the brain, which was not confirmed. We used method of enzyme immunoanalysis to examine concentrations of tau protein, p- tau protein, and beta amyloid42. Differences between the respective groups were examined by test statistics. In addition, dependence of the total tau protein, p-tau protein, and beta-amyloid42 levels on demographic variables, diagnosis and duration of disease was examined by correlation analysis. Correlation of the concentrations obtained in the measurements was evaluated based on the calculated correlation coefficient (r) and level of significance (p). RESULTS: Compared to the control group, no statistically significant difference was found in the levels of tau protein and p-tau protein between the CIS group and definitive MS group. A significant increase was found only for beta-amyloid42 levels in patients with diagnosed MS vs. control group. We demonstrated no correlation between the beta-amyloid42 and tau protein levels, p-tau protein and age of patients and duration of disease in patients with MS, CIS and the control group. CONCLUSION: Results of our study show that use of tau protein, p-tau protein and beta-amyloid42 in the diagnosis of multiple sclerosis seems to be non-beneficial. We confirmed no importance for the differential diagnosis of an early stage MS.