Egon Kurča

Possible extrapyramidal system degradation in Parkinson's disease.

Extrapyramidal system, a rich network of nerve and glial cells consists of subcortical and cortical grey matter. The system serves as an integrator of unaware, automatic, repeated, spontaneous, complicated and purposeful motor samples. Muscle tone regulation and its distribution is another decisive extrapyramidal function. This review article concerns to some degradation mechanisms in extrapyramidal system, as either the programmed cell death or apoptosis. The physiologic extracellular decreasing signals creating apoptosis (nerve growth factor--fall) are either genetically expressed or there are neuropathophysiologic processes that may activate pathways leading to apoptosis, namely oxidative stress, glutamate toxicity and calcium homeostasis disruption. The level of dopamine transporter expression (mRNA, methyl-phenyl-pyridinium) might determine the vulnerability of the nigral neurons to the Parkinsonian insult. The most common clinical picture of extrapyramidal disorder-Parkinsons disease-consists of an active dopamine cell death-apoptosis, which is partially programmed like as programmed cell death and partially accidentally installed chain of events. Without morphological criteria, biochemical indicators such as laddered DNA fragmentation pattern and/or the requirement for macromolecular synthesis merely suggest but do not provide unequivocal evidence for apoptosis. There are either genetic or acquired conditions creating unbalance of Bax/Bcl-2 families-proapoptotic and prooncogenic factors, respectively. The first Bax gene cooperates with other genes coding the new transmembrane proteins into the mitochondrial megapores determinating transition by means of death receptors. Bcl-2 codes prooncogenic mitoses and tissue proliferation. The neuroprotective hypothesis of the dopamine agonist action is a very attractive working hypothesis and some of its tenets are derived from the oxidative stress hypothesis for neurodegeneration, but this hypothesis is still controversial.

Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation

Background: The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). Participants: A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke “expanded disability status scale” (EDSS), the duration of the disorder, VEP – latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann–Whitney, and Spearman correlation analyses. Results: In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = −0.15) and strongly with brain new MRI lesions (r = −0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = −0.3, r = −4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. Conclusion: In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring disease progression in MS patients, independent of the ON history.

Early and delayed auditory oddball ERPs and brain MRI in patients with MTBI

Introduction: Mild traumatic brain injury (MTBI) is a common neurotraumatologic diagnosis. It is possible to confirm objective cognitive impairment in MTBI patients not only by complex neuropsychological testing but also by event-related potentials (ERPs). The most common ERPs used in clinical practice are based on an oddball paradigm. Magnetic resonance imaging (MRI) is not routinely used in MTBI despite its proven greater sensitivity and specificity in comparison with computer tomography (CT). Methods: This study investigated 31 MTBI patients and 31 sex and age-matched healthy controls. Both groups underwent clinical neurological examinations. Auditory oddball ERPs and brain MRI were done early after the injury and 3–7 months later. Results: There were no significant sex, age and education differences between the analysed groups. No significant differences were found in N2 and P3 wave parameters in both ERP examinations. Conclusion: Standard auditory oddball ERPs are not sensitive enough to detect and/or quantify subtle objective neuropsychological changes in selected MTBI patients, especially those with traumatic MRI brain lesions. More complex auditory or other oddball paradigms have to be tested in the future.

Clinical correlations of proton magnetic resonance spectroscopy findings in acute phase after mild traumatic brain injury

Abstaract Introduction: Standard brain magnetic resonance imaging (MRI) is typically normal in most patients after mild traumatic brain injury (MTBI). Proton magnetic resonance spectroscopy (1H-MRS) is more sensitive to detect subtle post-traumatic changes. The aim of the study was to evaluate the clinical correlations of these changes in the acute phase (within 3 days) after MTBI. Methods: Twenty-one patients with MTBI and 22 controls were studied. Both groups underwent neuropsychological testing and single-voxel 1H-MRS examination of both frontal lobes and upper brainstem. Results: Significant decrease in NAA was found in both frontal lobes and in NAA/Cre ratio in the right frontal lobe (p < 0.05). Correlation analysis showed a correlation of NAA in the left frontal lobe with Backward Digit Span (p = 0.022) and Stroop test A (p = 0.0034) and a weak correlation with TMT B time (p = 0.046). The NAA/Cre in the right frontal lobe correlated with Stroop test A (p = 0.007) and with the total score of Digit Span (p = 0.016). Lower NAA was found in the upper brainstem (p = 0.0157) in the sub-group of patients with post-traumatic unconsciousness. Conclusions: This study found a correlation of 1H-MRS metabolite changes with cognitive decline and presence or absence of loss of consciousness in the acute phase after MTBI.

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.

Genetic variants in interleukin 7 receptor α chain (IL-7Ra) are associated with multiple sclerosis risk and disability progression in Central European Slovak population

In this study, we determined the association between rs6897932 in interleukin 7 receptor α (IL7Ra) gene and the risk and disability progression of multiple sclerosis (MS) in 270 MS patients and 303 controls. We found allele C to be associated with the risk of MS and minor allele T to be protective against MS development. Moreover, we revealed for the first time that rs6897932 in IL7Ra gene is associated with the progression of MS, evaluated by MSSS scores. The minor allele T and genotype TT are protective against a rapid disability progression in MS in the Central European Slovak population.

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.

FokI vitamin D receptor gene polymorphism in association with multiple sclerosis risk and disability progression in Slovaks

Abstract Objective: It is still unclear as to why multiple sclerosis (MS) is so devastating and rapidly progressive in one patient and less so in another. Recent data implicate vitamin D in modulation of the risk as well as the clinical course of disease. Since vitamin D acts through the vitamin D receptor (VDR), association of single nucleotide polymorphisms (SNPs) in the VDR gene might account for variations in the MS risk within populations. The aim of our study was to determine the association between FokI gene polymorphism (rs10735810) and the risk of MS in a cohort of Slovak population and to investigate possible correlations of this SNP with the rate of disease disability progression. Methods: FokI SNP was detected in 270 clinically diagnosed MS patients and 303 healthy control subjects. Genotyping was performed by polymerase chain reaction (PCR) and restriction analysis. We used multiple sclerosis severity score (MSSS) for patient’s stratification by the rate of disease disability progression. Results: We observed a significantly higher frequency of Ff genotype of FokI SNP (53·4 vs 43·7%, P  =  0·042) in women with MS compared to women of the control group. There was no significant association between FokI SNP and the rate of disease disability progression. Discussion: Although our findings suggest a weak association between VDR SNP FokI and the MS risk in women, further studies are needed to explore the role of VDR polymorphic alterations in MS disease etiology and pathogenesis.

Unique case of eleven Bell's palsy episodes

Bells palsy (BP) is a peripheral facial nerve paralysis of unknown etiology. It is not a life-threatening condition; however, incomplete recovery may leave an individual stigmatized functionally, occupationally as well as socially. Recurrent paralyses are seldom, noted in 7–8% of all BP cases. More than two BP relapses are even less frequent. Adour et al. (1977) reported only two patients with four BP episodes from 1700 patients. Only one patient with more than four BP recurrences in the group containing 2414 BP cases was reported by Yanagihara et al. (1984). The highest reported number of BP recurrences in the accessible literature has been nine. We are presenting an unusual patient who suffered a total of eleven relapses of an idiopathic facial nerve palsy. Description of the case along with review of the relevant literature are discussed.

Cytokine and chemokine profile changes in patients with lower segment lumbar degenerative spondylolisthesis

BACKGROUND Lumbar degenerative spondylolisthesis (DS) develops as a result of inflammatory and remodeling processes in facet joints (FJs). Several inflammatory cytokines are involved in the osteoarthritic and remodeling changes that occur and in low-back and/or radicular pain, the most prevalent clinical symptom of disease. This study improves knowledge related to the roles that 27 cytokines, chemokines and growth factors play in the pathophysiology of lumbar DS. MATERIAL AND METHODS Cytokine levels were examined using capture sandwich immunoassay using the Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) separately in intervertebral discs (IVDs) and FJ bone tissue. The samples were obtained during primary spinal surgery from 9 patients suffering from lower segment lumbar DS. The pain intensity was assessed using a visual analog scale. The controls were tissue samples collected from both lower lumbar segment levels of 6 male subjects during a multiorgan procurement procedure. RESULTS The Bio-Plex® assay revealed significant differences between the patients and controls in cytokines, chemokines and growth factor profiles: i, The elevated interleukin-6 (IL-6), IL-7, IL-13, tumor necrosis factor α (TNF-α), interferon γ and platelet-derived growth factor levels in lumbar DS samples of subchondral FJ bone. These indicated ongoing inflammation, bone formation and increased fibroblasts activity in the FJ bone. ii, The elevated levels of IL-6, IL-8, TNF-α, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in anulus fibrosus together with increased IL-6, IL-8, TNF-α and eotaxin and decreased IL-1-receptor antagonist in nucleus pulposus confirmed advanced IVD degeneration in the patient samples. CONCLUSION This study identified, for the first time, protective levels of cytokines, chemokines and growth factors in healthy subjects and supported their significant involvement in the pathogenesis of lumbar DS. The control samples and analytical methods used avoided any false changes in the cytokine levels due to secondary factors (e.g., death of donor and limited cytokine stability).