Prevalence of multiple sclerosis in Csongrád County, Hungary.

OBJECTIVE: Recent epidemiological studies were mainly based on the Poser or other diagnostic criteria. There have been no previous data from Hungary, which were assessed with the more up-to-date McDonald criteria and which give comparable standardized data from the region. MATERIALS AND METHODS: Data were collected from the MS Register of the Department of Neurology at the University of Szeged. All possible and definitive patients with MS living in the county on the prevalence day were included in the study. Direct standardization was based on the European standard population. RESULTS: On 1 January 2013, 379 registered patients with MS were alive in the county, that is, a crude MS prevalence of 89.8/100,000, 46.6/100,000 in males and 128.6/100,000 in females; standardized prevalence: 83.7/100,000 (42.3/100,000 for males, 122.6/100,000 for females). The distribution of the clinical forms: 11% clinically isolated syndrome, 69% relapsing-remitting form, 14% secondary progressive form, 6% primary progressive form. Patients with no or only mild symptoms comprised 91.9% of the relapsing-remitting population. CONCLUSIONS: This is the first standardized epidemiological study based on the McDonald criteria in Central Europe. Hungary is a medium-risk country as concerns the prevalence of MS. The crude prevalence appears to have increased relative to previous reports from the county.

Fundamental interstrain differences in cortical activity between Wistar and Sprague-Dawley rats during global ischemia.

Four-vessel occlusion (4VO), a frequently used model of global cerebral ischemia in rats, results in a dysfunction in wide brain areas, including the cerebral cortex and hippocampus. However, there are pronounced differences in response to global ischemia between the laboratory rat strains used in these studies. In the present work, the immediate acute effects of 4VO-induced global ischemia on the spontaneous electrocorticogram (ECoG) signals were analyzed in Wistar and Sprague-Dawley rats. The ECoG was isoelectric during the 10 min of global cerebral ischemia in Wistar rats and the first burst (FB) was seen 10-13 min after the start of reperfusion. In Sprague-Dawley rats, the FB was detected immediately after the start of 4VO or a few seconds later. The burst suppression ratio (BSR) in Wistar rats decreased to 45% in 5 min after FB, and after 25 min it was approximately 40%. In Sprague-Dawley rats, the BSR was 55% immediately after the FB and it decreased steeply to reach 0% by 10 min. There was also a significant difference between the two strains in the frequency composition of the ECoG pattern. The power spectral densities of the two strains differed virtually throughout the post-ischemic state. The histological results (Evans Blue, Cresyl Violet and Fluoro Jade C stainings) supplemented the electrophysiological data: the neuronal damage in the CA1 pyramids in Wistar rats was severe, whereas in the Sprague-Dawley animals it was only partial. These observations clearly demonstrate that the use of different rat strains (e.g. Wistar vs. Sprague-Dawley) can be a source of considerable variability in the results of acute experiments on global ischemia and it is important that the laboratory rats used in such experiments should be carefully chosen.

Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning.

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a therapeutic tool for neurorehabilitation, particularly after stroke, because of its potential to modulate local excitability and therefore promote functional plasticity. Previous studies suggest that timing is important in determining the behavioural effects of brain stimulation. Regulatory metaplastic mechanisms exist to modulate the effects of a stimulation intervention in a manner dependent on prior cortical excitability, thereby preventing destabilization of existing cortical networks. The importance of such timing dependence has not yet been fully explored for tDCS. Here, we describe the results of a series of behavioural experiments in healthy controls to determine the importance of the relative timing of tDCS for motor performance. Application of tDCS during an explicit sequence-learning task led to modulation of behaviour in a polarity specific manner: relative to sham stimulation, anodal tDCS was associated with faster learning and cathodal tDCS with slower learning. Application of tDCS prior to performance of the sequence-learning task led to slower learning after both anodal and cathodal tDCS. By contrast, regardless of the polarity of stimulation, tDCS had no significant effect on performance of a simple reaction time task. These results are consistent with the idea that anodal tDCS interacts with subsequent motor learning in a metaplastic manner and suggest that anodal stimulation modulates cortical excitability in a manner similar to motor learning.

Lesion probability mapping to explain clinical deficits and cognitive performance in multiple sclerosis.

BACKGROUND: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and disability is only modest, however. Strategic lesion location might at least partially account for this 'clinico-radiologic paradox'. OBJECTIVES: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing-remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions. RESULTS: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location. CONCLUSIONS: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent.

Modulation of movement-associated cortical activation by transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) is currently attracting increasing interest as a tool for neurorehabilitation. However, local and distant effects of tDCS on motor-related cortical activation patterns remain poorly defined, limiting the rationale for its use. Here we describe the results of a functional magnetic resonance imaging (MRI) experiment designed to characterize local and distant effects on cortical motor activity following excitatory anodal stimulation and inhibitory cathodal stimulation. Fifteen right-handed subjects performed a visually cued serial reaction time task with their right hand in a 3-T MRI scanner both before and after 10 min of 1-mA tDCS applied to the left primary motor cortex (M1). Relative to sham stimulation, anodal tDCS led to short-lived activation increases in the M1 and the supplementary motor area (SMA) within the stimulated hemisphere. The increase in activation in the SMA with anodal stimulation was found also when directly comparing anodal with cathodal stimulation. Relative to sham stimulation, cathodal tDCS led to an increase in activation in the contralateral M1 and dorsal premotor cortex (PMd), as well as an increase in functional connectivity between these areas and the stimulated left M1. These increases were also found when directly comparing cathodal with anodal stimulation. Significant within-session linear decreases in activation occurred in all scan sessions. The after-effects of anodal tDCS arose primarily from a change in the slope of these decreases. In addition, following sham stimulation compared with baseline, a between-session decrease in task-related activity was found. The effects of cathodal tDCS arose primarily from a reduction of this normal decrease.

Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation.

Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.

Reproducibility of fMRI in the clinical setting: implications for trial designs.

With expanding potential clinical applications of functional magnetic resonance imaging (fMRI) it is important to test how reliable different measures of fMRI activation are between subjects and sessions and between centres. This study compared variability across 17 patients with multiple sclerosis (MS) and 22 age-matched healthy controls (HC) in 5 European centres performing an fMRI block design with hand tapping. We recruited subjects from sites using 1.5 T scanners from different manufacturers. 5 healthy volunteers also were studied at each of 4 of the centres. We found that reproducibility between runs and sessions for single individuals was consistently much greater than between individuals. There was greater run-to-run variability for MS patients than for HC. Measurements of maximum signal change (MSC) appeared to provide higher reproducibility within individuals and greater sensitivity to differences between individuals than region of interest (ROI) suprathreshold voxel counts. The variability in measurements between centres was not as great as that between individuals. Consistent with these observations, we estimated that power should not be reduced substantially with use of multi-, as opposed to single-, centre study designs with similar numbers of subjects. Multi-centre interventional studies in which fMRI is used as an outcome measure thus appear practical even when implemented in conventional clinical environments.

Dopaminergic contributions to the visual categorization of natural scenes: evidence from Parkinson's disease.

Recent evidence raised the possibility that dopaminergic mechanisms in the neostriatum play an important role in categorization. In this study, we examined the electrophysiological correlates of natural scene categorization in Parkinson's disease (PD), which is characterized by the depletion of dopamine in the neostriatum. Event-related potentials (ERPs) were recorded in PD patients and age-matched control subjects using a natural scene categorization task. Subjects had to decide whether a briefly presented image contained animals or non-animals. In the control group, the mean amplitudes of N1 (150-250 ms) and N2 components (400-600 ms) were more negative for non-animal scenes as compared with stimuli containing animals, whereas P2 (250-350 ms) was more positive for animals. In contrast, in the PD group the mean amplitudes of N1 and N2 components were similar for both animal and non-animal stimuli, and the P2 amplitudes were reduced. In the case of N1 peak latency, there was no between-group difference, whereas the N2 and P2 components were significantly delayed in the PD group. These results suggest that both perceptual (N1) and semantic (N2) processes related to the categorization of natural scenes are specifically impaired in PD. In the temporal domain, the slowed semantic processing is preceded by a relatively normally paced perceptual analysis. These findings are in agreement with the hypothesis emphasizing the importance of striatal dopaminergic mechanisms in classification functions.

Comparison of calcium and alfacalcidol supplement in the prevention of osteopenia after kidney transplantation.

The aim of this observational study was to compare the effect of calcium and alfacalcidol supplementation on the regression of hyperparathyroidism and on prevention of osteopenia in patients up to 3 years after renal transplantation. Two historical cohorts were compared for that purpose. One hundred and fifty-nine patients received calcium carbonate supplement (group 1), while 81 patients were treated with alfacalcidol (group 2). Serum Ca, phosphate (P), Mg, creatinine, alkaline phosphatase (AP) and parathyroid hormone (PTH) levels were determined before and after transplantation in the two groups, for 3 years. Femoral neck and lumbar spine bone mineral density (BMD) was measured only at 3 and 6 months and 1, 2 and 3 years after transplantation. At baseline there was no difference in age or sex ratio, but prevalence in post-menopausal women was higher in group 1 (6.9% versus 1.2%). Duration on dialysis was comparable but prevalence of interstitial and undetermined nephropathies was higher in group 1. Baseline serum concentrations of PTH, Ca and P were comparable in both groups. After transplantation, plasma creatinine decreased to comparable levels in both groups. Immunosuppression by triple therapy was more prevalent in group 2, so that cumulative dose of steroid was higher in group 1, especially at 1 month because of higher incidence of acute rejections (51% versus 13%). Mean intact PTH levels decreased in both groups, from 18 pmol/l to 8.4 and 7.9 at 3 years, but the decrease was significantly greater with alfacalcidol at 6 and 12 months. At 3 months, BMD were comparable at both sites. From 3 months to 3 years after kidney transplantation, mean lumbar spine BMD significantly increased from 0.963 to 1.054 g/cm(2) in group 1, whereas there was no significant decrease (1.048 to 1.006 g/cm(2)) in group 2, the difference in changes being significant ( P<0.05). Femoral neck BMD was not significantly increased in either group (0.932 to 0.993 g/cm(2) in group 1, and 0.850 to 0.907 g/cm(2) in group 2). Expressed as percentages, these changes were +9.4% and -4% for lumbar BMD and +6.5% and +6.7% for femoral neck, for groups 1 and 2, respectively. Prevalence of osteopenia was not significantly lower at 3 years in group 1 (45% and 51%) than in group 2. During the follow-up period, osteonecrosis was diagnosed in six patients (3.8%) in group 1 and in nine (11%) in group 2. In conclusion, alfacalcidol compared to CaCO3 supplement suppressed hyperparathyroidism more rapidly and strongly. In spite of higher osteopenia risk in the CaCO3 group, lumbar BMD increase was greater and incidence of osteonecrosis higher in this group, suggesting better bone protection with CaCO3 than with alfacalcidol.

[Surgical treatment of colonic diverticulitis]. / A vastagbél diverticulitisek sebészi kezelése.

Diverticulitis is one of the most common benign diseases of the colon, which usually occurs in elderly. Authors assay the surgical treatment of inflammatory complications of colon diverticulitis in the last 19 years. Most frequently inflammation occurs, which in lot of cases leads to acute abdominal disease. Results of 61 acute and 10 elective operations are analysed. Beside the complications and surgical possibilities authors issue the definitive indications of elective operation.

[Complications of laparoscopic cholecystectomy]. / Laparoszkópos cholecystectomiák szövódményei.

Number of bile duct injuries is rising with the spreading of laparoscopic cholecystectomy. Authors analyse the complications in the last 8 years, especially the bile duct injuries. During this period 1657 laparoscopic cholecystectomies were performed. Complication occurred in 28 cases during the intra- and postoperative period (1.68%). Main bile duct injury was detected in 7 cases (0.42%), while leakage from a Luschka's duct appeared in 10 patients. Three bleeding complications, 2 injuries of the duodenum and in 3 cases severe intraabdominal infection was observed. Four patients died (0.24%).

[Acute pancreatitis after kidney transplantation]. / Vesetranszplantált betegek akut hasnyálmirigy-gyulladása.

UNLABELLED: Pancreatitis following kidney transplantation was first described by Starzl in 1964 [19]. The incidence rate of the disease involving severe complications ranges from 1.2 to 6.8%. The number of risk factors, besides those of the normal population, is increased by a number of other factors, i.e. uremia, disorder of lipid metabolism, polycystic kidney, immunosuppressive drugs, cytomegalovirus infection, etc. The mortality of acute pancreatitis in a kidney transplant patient is, in spite of treatment with the most up-to-date methods, is much higher (53-60%) than that for a non-transplant patient. In the period between 27 June 1991 and 31 December 2000 the number of cadaver kidney transplants performed in the Transplantation Division of the 1st Department of Surgery of the Medical and Health-Science Centre of the University of Debrecen was 349. During this period 9 incidences of acute pancreatitis were found in 8 patients. The frequency of incidence was 2.56%. In the present communication we analyse the prognosis of 9 kidney transplant patients, with special respect to immunosuppression. RISK FACTORS: One patient was administered Cyclosporin alone, four were given Cyclosporin and Steroids, a further one Cyclosporin, Steroids and Azathioprine, the remaining three were treated with Cyclosporin, steroids and Mycophenolate Mophetil. In six cases out of nine multiorgan insufficiency (kidney, lung, liver) was encountered on presentation, three cases were accompanied by peritonitis. In spite of early jejunal nutrition, intensive therapy, antibiotic treatment, CT monitoring, if needed, necrectomy and oncotomy, three of our patients died from multiorgan insufficiency induced by septico-toxic state (mortality 33.3%). Other six patients recovered. CONCLUSIONS: The mortality rate of acute pancreatitis is much higher in immunosuppressed patients. The role of the etiological factors is not unequivocal in the development of pancreatitis. Nevertheless, all possible risk factors have to be taken into consideration when starting the immunosuppressive treatment of transplant patients and during their follow-up. By optimally adjusting the immunosuppressants we can decrease the risk of pancreatitis, however, the prognosis of the diseases, in agreement with the data in the literature, cannot be considerably improved even with the most up-to-date methods.

[Changes in calcium metabolism after kidney transplantation]. / Változások a calcium anyagcserében vesetranszplantációt követóen.

Prospective study was performed to measure the changes in calcium metabolism after kidney transplantation. 139 recipients received calcium substitution (1st group) and 81 patients were treated with alfacalcidol (2nd group). Serum Ca, P, Mg, alkaline phosphatase (AP) and intact PTH levels were determined before transplantation and at 1, 3, 6, 12 and 24 months thereafter in the two groups. Femoral and vertebral bone mineral density was measured with bone densitometer at the same period. The serum Ca level elevated and the serum P concentration decreased significantly in both group. The mean serum Mg and AP concentration changed in the normal range after the transplantation. The intact PTH level decreased significantly in both group at 2 years following transplantation. The intact PTH concentration changed from 17.1 pmol/l to 9.3 pmol/l in the 1st group, and it is decreased from 17.7 pmol/l to 7.9 pmol/l in the 2nd group. Bone densitometry showed osteoporosis in both group. At 12 months and at 24 months after kidney transplantation bone mineral density (BMD) of lumbar spine was 90.8% and 86.9% in the 1st group and 85.3% and 81% in the 2nd group. At the same time BMD of the femoral region was 84.4% and 85.5% in the 1st group and 82.0% and 81.3% in the 2nd group. The BMD did not changed significantly in the 1st compared to the 2nd group. During this period osteonecrosis was diagnosed in 6 patients in the 1st group and in 9 cases in the 2nd group. In conclusion, the serum Ca and P levels were in the normal range after kidney transplantation. The alfacalcidol treatment significantly decreased the intact PTH concentration compared to the calcium substitution. Moderate osteopenia was observed in both groups after the transplantation, despite of the administration of alfacalcidol treatment.

The importance of obesity and hyperlipidaemia in patients with renal transplants.

The authors studied dyslipidaemia and "obesity" in 137 patients (87 males and 50 females) following cadaver renal transplantation with regard to the applied immunosuppressive treatment and the patients' hypertension. The most extreme dyslipidaemic values, the highest levels of total cholesterol, LDL and Apo were found 6 to 18 months after successful transplantation; these values were significantly higher in women than in men. While in the dialysis programme only 21.89% of the patients had BMI values higher than 25.1 kg/m2, after transplantation their proportion was 36.49%. In addition to hyperlipidaemia, hyperuricaemia was encountered in 39.42%, erythrocytosis in 8.76% and diabetes mellitus in 9.48%, respectively. In the group of patients treated only with Cyclosporine-A the incidence of hyperlipidaemia and hypertension was significantly lower than in those receiving a combination of either corticosteroids and Cyclosporine-A or corticosteroids, Cyclosporine-A and azathioprine. There was a close relationship between the unfavourable tendency of obesity and the measured hyperlipidaemia. On the other hand, the extent of proteinuria did not always have a positive correlation with the increase of BMI and body weight, the severity of hypertension and hyperlipidaemia. The authors emphasize the importance of a systematic control of the lipid levels, the significance of a diet with an adequate carbohydrate and lipid content, and the necessity of avoiding obesity by selecting the optimal immunosuppressive treatment.

Fluvastatin (Lescol) treatment of hyperlipidaemia in patients with renal transplants.

Hyperlipidaemia of 18 male and 20 female patients following successful renal transplantation was treated with daily 20 mg fluvastatin (Lescol) for 12 weeks. The patients were several months after transplantation, and their total cholesterol levels exceeded 6.5 mmol/l following an 8-week diet. The effect of fluvastatin on the levels of total cholesterol, HDL, LDL, triglyceride, Apo A1 and Apo B, as well as of lipoprotein(a) was examined. Furthermore, changes of the renal function (GFR-urea, creatinine, uric acid) and hepatic function (bilirubin, GOT, GPT, CPK, ALP) were followed up, together with the body weight and blood pressure. The results of the examinations are summarized as follows: Fluvastatin may be administered effectively and without side effects in a daily dose of 20 mg in appropriately selected renal transplant patients. The average total cholesterol values, which were 7.91 mmol/l in men and 7.78 mmol/l in women following the diet, were reduced by 22-25% (p < 0.001) after 6 and 12 weeks, respectively, of fluvastatin treatment. The levels of LDL also decreased significantly (p < 0.001): in response to a 20 mg evening dosage, reduction of more than 25% was observed in 78% of men and 65% of women. Reductions of the Apo B levels were more pronounced in the females (18.3% men vs. 21.2% women). The ratio C/HDL-C decreased both in men (from 5.49 to 4.19) and in women (from 4.83 to 4.02). The ratio Apo B/Apo A1 also decreased (men: from 0.86 to 0.73, women: from 0.73 to 0.66). The concentrations of HDL and Apo A1 did not increase significantly, the reductions in the levels of triglyceride and lipoprotein(a) were not considerable either. An increase in the levels of hepatic enzymes and CPK was not encountered during the administration of fluvastatin. In two patients the levels of serum bilirubin increased by 2-4 micromol/l. Three patients complained about temporary myalgias of the sacroiliac or lumbar region which, however, were not accompanied by elevated CPK levels. The monitored levels of cyclosporine, urea and creatinine did not increase significantly during the 12 weeks of treatment. Two patients had temporary gastric complaints.

Dyslipidaemia and hyperlipidaemia following renal transplantation.

The lipid metabolism of 93 patients with renal transplantation was prospectively studied. It was characterized by the serum levels of cholesterol, HDL, LDL, triglyceride, apolipoprotein Al, Apo B and lipoprotein (a) as well as by lipid electrophoresis. In addition to the examination of lipid concentrations, the authors looked for correlations with other metabolic changes, immunosuppressive treatment and the changes of body weight and hypertension following transplantation. Their conclusion is that hyperlipidaemic and dyslipidaemic changes, as reflected by the levels of total cholesterol, LDL and Apo B, are more considerable in women than in men. The levels of pre-beta and beta lipoprotein were not significantly lower in men than in women. With the passing of time after transplantation and with the reduction of the doses of cyclosporine and corticosteroids, the values of hypertension, hyperlipidaemia and dyslipidaemia decreased. According to the follow-up results, the lipid values measured in the winter and autumn months are higher than those found in the summer. The importance of early and follow-up examinations and of the reduction of pathological metabolic alterations is emphasized.

[Epidural administration of a morphine-adrenaline-bupivacaine mixture in obstetric anesthesia]. / Epidurálisan adott morfin-adrenalin-bupivacain keverék a szülészeti fájdalomcsillapításban.

Pain relieving effect of epidurally given epinephrine-morphine-bupivacaine drug combination was studied in 50 primiparous women during labour. The double-blind, randomised clinical evaluation showed that the components of our drug combination act synergistically. The total dose and the mg min-1 dose of bupivacaine was significantly less following epinephrine-morphine pretreatment than the dose required when only bupivacaine was used for pain relief. The duration of analgesic effect of separate top-up doses was also significantly prolonged when the drug combination was used. It was established that this method of obstetric pain relief uses about 30% less bupivacaine than the classical method. This means decreased drug exposure of mother and fetus alike. In addition to this the use of this drug combination provides also a long-lasting postpartum analgesia.