Lege Artis Medicinae

[Addictions in the focus - Readers’ questions answered by dr. János Szemelyácz]

SZEMELYÁCZ János

JULY 14, 2007

Lege Artis Medicinae - 2007;17(06-07)

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Lege Artis Medicinae

[THE USE OF DIRECT VASODILATORS AND DIGITALIS IN CHRONIC HEART FAILURE]

DÉKÁNY Miklós

[For the optimal treatment of heart failure patients with systolic dysfunction, supplementation of the standard diuretics plus neurohormonal antagonists treatment with the direct vasodilator combination dihydralazine+nitrate, as well as with digitalis may be necessary. Addition of hydralazine/dihydralazine+nitrate to the treatment of chronic heart failure is recommended if ACE-inhibitors or angiotensin-receptor blockers cannot be administered. Beta blockers should also be used in these cases. If symptoms persist or worsen, addition of this combination to the standard therapy is reasonable. Supplementation with digitalis, mostly digoxin should be considered in similar conditions. It can be especially beneficial for patients with high-ventricular-rate atrial fibrillation. To achieve maximal survival benefit, the dose of digoxin must not exceed 0.125 mg/day. Low body weight or muscle mass, significantly reduced renal function may make further dose reduction necessary. If renal function is severely limited, digitoxin instead of digoxin may be used.]

Lege Artis Medicinae

[More Effective Metabolic Control – Better Quality of Life]

WINKLER Gábor

Lege Artis Medicinae

[Medicine: a Ship on the Sea of Culture – The “Cheap Drug Debate” and its Cultural Aspects]

BÁNFALVI Attila

Lege Artis Medicinae

[RECENT TRENDS IN THE PHARMACOLOGICAL TREATMENT OF EPILEPSY]

SZUPERA Zoltán

[Over the last decades, drug therapy for epilepsy has changed substantially, which generated new expectations. The first-line therapy of epilepsies is pharmacological treatment, which is effective in 60 to 70% of patients. Despite this favourable result, even today's drug therapy cannot yet be considered optimal. Prior to 1990, only six major antiepileptics were available for the clinicians, while since then more than ten new drugs have been introduced into the market. The older drugs have the advantage of long-term experience, known efficacy, and lower cost. These first generation drugs, while effective in patients with newly diagnosed epilepsy, share some unfavourable properties. They do not control many patients adequately, while with their long-term use chronic side effects develop. The purpose of this paper is to summarize recent data on the efficacy, safety, and administration of the older and new antiepileptic drugs. The main factors to consider when choosing a drug for treatment include syndromatological classification of the disease, efficacy and tolerability of the drug, and individual patient considerations. Of the first generation antiepileptics, carbamapezine, valproate, ethosuximide, and to some extent the clobazam and clonazepam are still widely used (benzodiazepines only as adjunctive therapy). The use of phenobarbitals, primidone, phenytoin, and sulthiam has diminished because of their side effects and inadequate efficacy. New antiepileptics are more efficient primarily in the therapy of West syndrome, Lennox-Gastaut syndrome, and in idiopathic generalized epilepsies. The pharmacokinetic properties of gabapentin, lamotrigine, levetiracetam, and oxcarbazepine are favourable, and their clinical use is safe. The use of felbamate, vigabatrin, and topiramate requires close attention because of their side effects.]

Lege Artis Medicinae

[Meditation]

DONÁTH Tibor

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Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

[Advanced Parkinson’s disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]

TAKÁTS Annamária, ASCHERMANN Zsuzsanna, VÉCSEI László, KLIVÉNYI Péter, DÉZSI Lívia, ZÁDORI Dénes, VALIKOVICS Attila, VARANNAI Lajos, ONUK Koray, KINCZEL Beatrix, KOVÁCS Norbert

[The majority of patients with advanced Parkinson’s disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson’s disease; the proportion of Parkinson’s patients with advanced Parkinson’s disease, the referral process, and the clinical features used to characterize advanced Parkinson’s disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson’s patients identified as advanced patients according to physician’s judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson’s disease status was assessed with Unified Parkinson’s Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson’s disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. Overall, 2627 patients with Parkinson’s disease from 126 sites were documented. In Hungary, 100 patients with Parkinson’s disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson’s disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson’s disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). Physicians in Hungarian movement disorder centers assessed that half of the Parkinson’s patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson’s disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.]

Clinical Neuroscience

The methylation status of NKCC1 and KCC2 in the patients with refractory temporal lobe epilepsy

UNAL Yasemin, KARA Murat, GENC Fatma, OZTURK Aslan Dilek, GÖMCELI Bicer Yasemin, KAYNAR Taner, TOSUN Kursad, KUTLU Gülnihal

Purpose - Methylation is a key epigenetic modification of DNA and regarding its impact on epilepsy, it is argued that “DNA methylation may play an important role in seizure susceptibility and maintenance of the disorder”. DNA methylation status of KCC2 (SCL12A5) and NKCC1 (SCL12A2) associated with refractory temporal lobe epilepsy was investigated in our study. Materials and methods - Thirty-eight patients with temporal lobe epilepsy (TLE) who were diagnosed by video EEG monitoring and 32 healthy control subjects were included in the study. Twenty-three patients in TLE group were men and the remaining 15 were women. Among them, 27 had unilateral temporal focus (9 with right; 18 with left) and 11 patients had bilateral TLE. We analyzed promoter region methylation status of the KCC2 (SCL12A5) and NKCC1 (SCL12A2) genes in the case and control groups. Gene regions of interest were amplified through PCR and sequencing was accomplished with pyro-sequencing. Results - We found a significant relationship between TLE and methylation on the NKCC1. However, there was no association between TLE and methylation on the KCC2 gene. Also, we found no association between right or left and unilateral or bilateral foci of TLE. There was no relationship between TLE and methylation on the NKCC1and KCC2 genes in terms of mesial temporal sclerosis in cranial MRI, head trauma or febrile convulsions. Conclusion - The methylation of NKCC1 can be a mecha­nism of refractory temporal lobe epilepsy. There are limited findings about DNA methylation in TLE. Therefore, further studies with large sample sizes are necessary.

Lege Artis Medicinae

[The Private Physician and State Advisor of Tzar Alexander I János Orlay, a Polymath Physician ]

MOLNÁR László

Clinical Neuroscience

[Family planning in multiple sclerosis: conception, pregnancy, breastfeeding]

RÓZSA Csilla

[Family planning is an exceptionally important question in multiple sclerosis, as women of childbearing age are the ones most often affected. Although it is proven that pregnancy does not worsen the long-term prognosis of relapsing-remitting multiple sclerosis, many patients are still doubtful about having children. This question is further complicated by the fact that patients – and often even doctors – are not sufficiently informed about how the ever-increasing number of available disease-modifying treatments affect pregnancies. Breastfeeding is an even less clear topic. Patients usually look to their neurologists first for answers concerning these matters. It falls to the neurologist to rationally evaluate the risks and benefits of contraception, pregnancy, assisted reproduction, childbirth, breastfeeding and disease modifying treatments, to inform patients about these, and then together come to a decision about the best possible therapeutic approach, taking the patients’ individual family plans into consideration. Here we present a review of relevant literature adhering to international guidelines on the topics of conception, pregnancy and breastfeeding, with a special focus on the applicability of approved disease modifying treatments during pregnancy and breastfeeding. The goal of this article is to provide clinicians involved in the care of MS patients with up-to-date information that they can utilize in their day-to-day clinical practice. ]