Clinical Neuroscience

[Endogenous psychopharmacology]

BÁNKI M. Csaba

SEPTEMBER 30, 2006

Clinical Neuroscience - 2006;59(09-10)

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Clinical Neuroscience

[MULTIPLE SYSTEM ATROPHY: THE BEGINNING OF A NEW ERA IN THE HISTORY OF NEURODEGENERATIVE DISEASES]

PAPP Mátyás, KOVÁCS Tibor

[Multiple system atrophy (MSA) belongs to the neurodegenerative diseases of the nervous system, but it is different from them in many aspects: it has no familiar form and no genetic factor was identified in the pathomechanism. Its neuropathology is unique too, because oligodendroglial cells are harbouring the main pathological burden. It was described in MSA that there is no elective neuronal degeneration in neurodegenerative disorders: the glial cells show the same patochemical and structural abnormalities as found in the neurones. The discovery of the glial cytoplasmic inclusions, as a pathognostic marker for MSA, has directed attention to the glial cells in other neurodegenerative disorders. As a result of this, there are several neurodegenerative diseases nowadays in which glial inclusions were described, similar to the neuronal inclusions in their structural and biochemical properties and some of them became the diagnostic marker of the disease. In our review we summarize the clinical features, the history and the neuropathology of MSA and we discuss its special features.]

Clinical Neuroscience

[SUDDEN DEATH AND MORTALITY IN EPILEPSY]

SZŰCS Anna, LALIT Narula, RÁSONYI György, BARCS Gábor, BÓNÉ Beáta, HALÁSZ Péter, JANSZKY József

[Mortality in epilepsy is 2-3 times higher than in the age- and sex-matched general population. It is the highest in young male epilepsy patients with generalised tonic-clonic seizures living in low socio-economical situation. The main factors of early mortality unrelated to seizures are the neurological conditions underlying epilepsy. Suicide is an important factor first of all in temporal lobe epilepsy. The group of mortality directly related to epilepsy is made up of the high-mortality grand mal status epilepticus rarely seen in treated epilepsy; the accidents related to seizures and sudden unexpected death (SUDEP). The reasons directly related to epilepsy make up about 40 per cent of epilepsy mortality. There is a 20-24-fold increase of the risk of sudden death in epilepsy compared to sudden death in the general population. The main risk of SUDEP is the “severity” of epilepsy signaled by generalized tonic-clonic seizures, resistance to antiepileptic drugs, polytherapy and frequent drug-modifications in adulthood epilepsy. Seizure-dependent autonomic changes as cardiac rhythm and breathing disturbances as well as some antiepileptic drugs and treatment modifications may contribute to the development of SUDEP. The data suggest that the main tools helping to decrease mortality in epilepsy nowadays are as follows: optimal seizure control, effective tratment of concomitant psychiatric conditions and monitoring for potentially dangerous heart dysrhythmias as well as respiration disorders.]

Clinical Neuroscience

[PREDICTIVE FACTORS OF TEMPORAL LOBE SURGERY]

KELEMEN Anna, RÁSONYI György, SZŰCS Anna, FABÓ Dániel, HALÁSZ Péter

[The most effective type of epilepsy surgery in adults is temporal lobe epilepsy (TLE) surgery. Three quarter of the patients become seizure free, however the remaining patients experience seizures after resection. In our study we analyzed retrospectively the possible electro-clinical, neuroimaging and surgery-related outcome predictors in 94 adult patients who had anterior temporal lobectomy (ATL) from the material of Epilepsy Centre of the National Institute of Psychiatry and Neurology, Budapest since the beginning of the surgery program in 1989 until 2001. Three outcome endpoints were chosen: the seizure status at the last visit, the longest seizure free period and the time to the first non-acute postoperative seizure. The predictors were assessed by multivariate and Cox regression methods. After one year of surgery 72% of the patients were seizure free, after two years 67% and after five years 59%. Factors predicting favorable outcome in TLE surgery were: typical temporomesial aura, strictly unilateral interictal anterotemporal spikes, unilateral ictal onset, slow contralateral propagation, hippocampal sclerosis (HS) as etiology. Factors predicting poor outcome in TLE surgery were: increase in seizure frequency in the last two preoperative years, presence of preoperative psychiatric disturbances, ictal contralateral propagation, MRI lesion distant from the surgery site, incongruency of data of preoperative investigations, postoperative sequels and non-HS type MR residuum.]

Clinical Neuroscience

[We do need change in the education of neurosurgeons]

CSÓKAY András

Clinical Neuroscience

[EFFICACY, SAFETY AND EFFECT ON THE QUALITY OF LIFE OF GABAPENTIN IN ADULT EPILEPSY - RESULTS OF A PROSPECTIVE OPEN-LABEL QUASI NATURALISTIC HUNGARIAN MULTICENTER STUDY (PHASE HUMAN-IV).]

RAJNA Péter, SZÍJÁRTÓ Elvira

[Purpose - To evaluate the efficacy and safety of gabapentin (GBP) in idiopathic or crypto/symptomatic partial epilepsy in adults. Methods - We performed a prospective open label add-on study in pharmacoresistant patients with simple or complex partial or generalized seizures of partial onset (at least four seizures per month). GBP was added to no more than two baseline antiepileptics and the efficacy was rated primarily according to the seizure frequency. The secondary efficacy parameters were the change in the seizure severity scores (measured by the NHS3 scale) and in the quailty of life (measured by the QUOLIE-31 questionnaire). GBP was added up to 1500-1600 mg per day in the titration period than an individual optimalization was allowed in any further visits. The follow-up period was three months. Population - Fourteen Hungarian epilepsy out-patient unit participated in the study. 72 patients were enrolled, GBP was applied in 63 persons (ITT population) and 57 completed the study. Results - A more than 50% decrease in seizure frequency was found in more than 70% of the patients in the third month. Among them just every third patient became seizure-free. Significant improvement appeared also in the severity of seizures and in the total score of the quality of life questionnaire. There was no difference either according to the etiology of the epilepsy or the seizure types. GBP was tolerated excellently. There was no need to decrease of the dosage of GBP and the side effects were mild and of transitory nature. Consequences - GBP appears to be a valuable antiepileptic drug considering its high efficacy and extremely favourable tolerance. While GBP also decreases the severity of the seizures, its complex effects result an improvement in the quality of life of the patients. The positive effects have been durable during the follow-up. Open label naturalistic studies of larger population are needed to clear the special indications of GBP in chronic partial epilepsies.]

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[THE GHRELIN SYSTEM: PHYSIOPATHOLOGICAL INVOLVEMENT IN THE CONTROL OF BODY GROWTH AND ENERGY METABOLISM]

JACQUES Epelbaum

[This short review will summarize some recent findings on the physiopathology of the endogenous ghrelin/obestatin system by focussing on experimental studies aiming at blocking the effects of endogenous ghrelin and clinical studies investigating genotype/phenotype correlations concerning the genes encoding for ghrelin and its cognate receptor.]

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[Assessment of the role of multidrug resistance-associated proteins in MPTP neurotoxicity in mice]

PLANGÁR Imola, ZÁDORI Dénes, SZALÁRDY Levente, VÉCSEI László, KLIVÉNYI Péter

[Goals - The available scientific data indicate that the pathomechanism of Parkinson's disease (PD) involves the accumulation of endogenous and exogenous toxic substances. The disruption of the proper functioning of certain transporters in the blood-brain barrier and in the blood-cerebrospinal fluid barrier in PD would accompany to that accumulation. Although there is an emerging role of the dysfunction of multidrug resistance-associated proteins (MRPs), members of ATP-binding cassette (ABC) transporter superfamily, in neurodegenerative disorders, there is only a few available data as regards PD. So the aim of our study was the assessment of the role of certain MRPs (1,2,4 and 5) in neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods - Following the intraperitoneal administration of silymarin (with MRP1, 2, 4 and 5 inhibitory effects), naringenin (with MRP1, 2 and 4 stimulatory effects), sulfinpyrazone (with MRP1, 4 and 5 inhibitory and MRP2 stimulatory effects) and allopurinol (with MRP4 stimulatory effect) in doses of 100 mg/kg, 100 mg/kg, 100 mg/kg and 60 mg/kg, respectively, for one week before and after the administration of MPTP in C57B/6 mice in acute dosing regimen, the striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid has been measured using high-performance liquid chromatography. Results - Although the results of these experiments showed that neither of these substances exerted significant influence on MPTP-induced striatal depletion of dopamine and its metabolites, naringenin exerted a slight prevention of dopamine decrease, while allopurinol considerably enhanced the MPTP-induced lethality in mice. The explanation of these findings would be that the stimulation of MRP1- and MRP2-mediated transport of glutathione conjugates of toxic substances may have slight beneficial effects, while stimulation of MRP4-mediated efflux of brain urate, which has an important antioxidant potency, may worsen the effects of oxidative stress.]

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[GASTROINTESTINAL COMPLICATIONS OF LOW-DOSE ASPIRIN TREATMENT]

RÁCZ István

[Since its synthesis more than 100 years ago aspirin has become one of the most successful drug. Low-dose, long-term aspirin therapy reduces the risk of myocardial infarction, the frequency of cerebral stroke and also reduces the mortality of peripheral arterial diseases and systemic embolisms. With aspirin therapy becoming more and more widespread current knowledge is also getting more concerned about the gastrointestinal risks and beneficial effects. Aspirin therapy causes gastrointestinal damages by the inhibition of endogenous prostaglandin synthesis. The ion trapping effect and the injury of mucosal barrier as well as the inhibition of platelet aggregation are also responsible for gastrointestinal damages. According to epidemiological studies lowdose aspirin treatment increases the risk of acute upper gastrointestinal bleeding by 1.5-2.0 fold. However, endoscopic studies indicate that gastroduodenal ulcers may develop even in 10 percent of cases on long term aspirin treatment, most frequently in a symptom-free form. Older age as well as Helicobacter pylori infection increase the risk of aspirin induced ulcers. Beside Helicobacter pylori eradication therapy, preventive proton-pump-inhibitor treatment and the widespread of new non-toxic aspirin derivates may decrease the risk of gastrointestinal complications. Capsule endoscopy also seems to be a promising diagnostic tool for detecting aspirin induced small bowel erosions and ulcers. Long-term aspirin treatment increases the risk of acute bleeding from large bowel diverticulas especially with non-steroidal anti-inflammatory drug co-therapy present. Long-term, low-dose aspirin treatment is a promising method for the chemoprevention of colorectal cancers.]

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[A new DPP-IV inhibitor: saxagliptin]

KIS János Tibor, MÉSZÁROS Gabriella

[Saxagliptin is a selective, potent inhibitor of dipeptidyl peptidase-IV (DPP-IV). By inhibiting DPP-IV, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin and decreased glucagon secretion from the pancreas islets. Clinical trials of saxagliptin as monotherapy and as combination therapy with other oral antidiabetic medications including metformin, glibenclamide, glipizide, pioglitazone and rosiglitazone have demonstrated clinical benefits in different glycaemic endpoints. Due to its glucose- dependent mechanism of action, saxagliptin as monotherapy or in combination with metformin results in a very low risk for hypoglycemia. It has also been shown to be generally well-tolerated, with not having any relevant effect on weight. The authors summarize the most important saxagliptin trials.]

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[The antinociceptive effect of kynurenic acid]

KÉKESI Gabriella, HORVÁTH Gyöngyi

[It is well known that glutamate receptors have significant role in the pain transmission. The activation of N-methyl-Daspartate receptors causes persistent pain, therefore the antagonists acting on these receptors cause antinociception in chronic pain states. As the synthetic N-methyl-D-aspartate receptor antagonists have several side effects, they are not used generally in the clinical therapy. The tryptophan metabolite kynurenic acid is an endogenous antagonist of N-methyl-D-aspartate receptors. Although some data proved its neuroprotective effect, only a few studies suggest the antinociceptive potential of kynurenic acid. The goal of this review to summarise the possible role of kynurenic acid in the pain therapy based on the results of animal studies. Data available concerning this subject demonstrated that kynurenic acid is not an appropriate agent for antinociception neither in single nor in continuous administration because of its side-effect resulting in motor deficiency. On the other hand the combination of low doses of kynurenic acid and endomorphin-1 provides effective antinociception without side-effects on inflammatory pain test, thus may offer a new treatment modality in human pain therapy.]