2010, Vol 10, No 3
Fingolimod in treatment of multiple sclerosis
AKTUALN NEUROL 2010, 10 (3), p. 145-151
ABSTRACT

Currently immunomodulatory drugs for multiple sclerosis (MS) are injected subcutaneously, intramuscularly or intravenously. This route of drug delivery creates some inconveniences for patients and health care system and there is a need to introduce oral treatment with efficacy superior to available treatments. The first drug of this characteristics is fingolimod (FTY720). This drug is easily absorbed from digestive tract with the maximal concentration in the blood 12-16 hours after ingestion. The mechanism of FTY720 action targets sequestration of mature lymphocytes in lymph nodes and Peyer’s patch, what limits the number of lymphocytes in the blood and inflammatory cuffs. The function of lymphocytes and their activation is not affected. It is suggested that fingolimod slows lymphocyte migration using two independent mechanisms: firstly by diminishing the number of S1P receptors on lymphocytes and blocking signalling for their migration, the second mechanism relies on constant stimulation of those receptors on endothelium in lymph node sinuses to strengthen the barrier limiting lymphocyte migration. Promising results of phase II clinical trials enabled development of two big phase III trials which opened the way to register fingolimod: FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis) and TRANSFORMS (Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis). FREEDOMS study confirmed superiority of fingolimod over placebo in all analyzed endpoints. TRANSFORMS study showed that fingolimod slows MS activity stronger that interferon β-1a. Those data confirm that FTY720 is promising new drug for the treatment of MS.

Keywords: fingolimod, multiple sclerosis, oral treatment, immunomodulation, clinical trials
DOWNLOAD ARTICLE (PDF)
The immunoexpression of LAMP2 protein in central nervous system in sporadic Creutzfeldt-Jakob disease (sCJD)
AKTUALN NEUROL 2010, 10 (3), p. 152-166
ABSTRACT

Introduction: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disease. Based on the status of the codon 129 of the PRNP gene as well as the type of PrP Sc protein, sporadic CJD is divided into 6 subtypes. Each subtype possess both different histochemical phenotype and clinical manifestation. LAMP2 is a membrane protein limiting late endosomes and lysosomes, which acts as a key element in endosomal-lysosomal system (ELS). ELS plays an important role in all major protein degradation systems in eukaryotic cells. It has been recently suggested that disruptions in the function of protein degradation pathways are likely to be main events in almost all neurodegenerative diseases. The main aim for current work was to demonstrate immunoexpression of LAMP2 protein in subtypes of sCJD. Material and methods: The material for current study was 26 brain tissue samples collected from patients with sCJD. The immunoexpression of LAMP2 and PrP Sc proteins was studied by immunohistochemistry and confocal laser scanning microscopy (Olympus FluoView 1000). The studied group was subdivided into subgroups based on the subtype of sCJD. Semiquantitative results of the level of LAMP2 and PrP Sc immunoexpression were analysed using statistical methods. Correlation ratios between levels of immunoexpression of aforementioned proteins were assessed using the Pearson’s correlation test. Group differences in sCJD subtypes and age groups were assessed using ANOVA. Results: The studied group consisted of 7 cases of subtype 1, 9 cases of subtype 2, 2 cases of subtype 3 and 1 case of subtype 5 of sporadic CJD. Pearson’s correlation test showed statistically significant relationship between immunoexpression of LAMP2 and PrP Sc proteins. ANOVA showed significant differences between sCJD subtypes regarding immunoexpression of LAMP2 protein. No significant differences regarding immunoexpression of studied proteins were observed between age groups. Conclusions: 1) A strong positive correlation between levels of immunoexpressions of PrP Sc and LAMP2 may represent up-regulation of the protein processing by endosomal-lysosomal system. 2) Significant differences of immunoexpression of LAMP2 protein were observed between subtypes of sporadic CJD. 3) Confocal laser scanning microscopy results confirmed significant positive relationships between immunoexpression of PrP Sc and LAMP2 proteins.

Keywords: LAMP2, PrP, prion, sCJD, immunoexpression
DOWNLOAD ARTICLE (PDF)
Hypoadiponectinemia in patients with ischaemic stroke
AKTUALN NEUROL 2010, 10 (3), p. 167-171
ABSTRACT

Adiponectin – the peptide with anti-inflammatory, antidiabetic and antiatherogenic effects, is secreted specifically from adipose tissue. Despite adipose tissue is only source of adiponectin, paradoxically its plasma level decreases in obesity. The aim of this study was to investigate the association between the lowering of plasma adiponectin level and presence of ischaemic stroke. To this study were qualified 72 patients with early ischaemic stroke and 29 referents without cerebrovascular diseases. In stroke group we evaluated neurological deficit according to NIHSS, in 1st and 7th day of hospitalization. In every patient we examined: anthropometric parameters (BMI, WC, WHR), blood (adiponectin concentration, lipid pattern, glucose level). On the basis of these parameters we diagnosed the presence of metabolic syndrome according to NCEP 2005. Ultrasonographic scanning of the carotid artery was performed in every patient to evaluate CIMT. There was no significance difference between stroke group and referents. Adiponectin level was significantly lower in patients with hypertension, hyperglycaemia, presence of metabolic syndrome, and abdominal obesity. Adiponectin was negatively correlated with hypertriglyceridaemia and positively correlated with HDL-cholesterol. In this study we did not find association between adiponectin level and CIMT. There was correlation between hypoadiponectinemia and high score of NIHSS. Adiponectin does not have direct association with ischaemic stroke, but rather is the marker of states which predispose to cerebrovascular diseases. The conclusions that adiponectin is the independent marker of stroke are probably premature.

Keywords: adiponectin, stroke, metabolic syndrome, obesity, CIMT
DOWNLOAD ARTICLE (PDF)
Transient neurological deficit due to neurotoxicity of contrast medium used for coronary angiography
AKTUALN NEUROL 2010, 10 (3), p. 172-175
ABSTRACT

Coronary angiography is an invasive procedure and may lead to complications. The most common of them are: myocardial infarction, embolism (e.g. cerebral embolism), dysrhythmia and acute circulatory insufficiency. Damage to the artery and subsequent major bleeding or thrombosis, vasovagal reaction and allergic reactions may also occur. Neurological deficits caused by contrast medium neurotoxicity are very rare complications of percutaneous coronary interventions. Contrast medium infiltrates blood-brain barrier and produces transient disturbances of neural membranes function. The neurotoxicity depends on its ionic properties, osmolality and solubility. Contrast medium neurotoxicity usually concerns occipital lobes and transient cortical blindness is its most common clinical manifestation. Transient pyramidal deficits due to contrast medium neurotoxicity are very rarely observed. The authors present a case of 70-year-old woman who developed left-sided hemiparesis and conjugate deviation of the eyes to the right after coronary angiography with subsequent right coronary artery angioplasty and stenting. Computed tomography (CT) of the brain performed just after occurrence of the neurological deficit revealed hyperintensive areas in sulci of the cerebral convexities and in the right frontal lobe. Control brain CT done after 24 hours did not show hyperintensive areas mentioned above. All symptoms of neurological deficit withdrew during 72 hours. Neurotoxicity of contrast medium seems to be responsible for occurrence of neurological deficit symptoms in a presented case.

Keywords: coronary angiography, complication, contrast medium, neurotoxicity, transient neurological deficit
DOWNLOAD ARTICLE (PDF)
4th Annual Meeting of Society of Vascular and Interventional Neurology: a report from the Fall Practicum and Interactive Laboratory, October 2010, Atlanta, Georgia, USA
AKTUALN NEUROL 2010, 10 (3)
DOWNLOAD ARTICLE (PDF)