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Hypertension and nephrology

DECEMBER 10, 2013

[Early histopathological changes in new onset diabetes mellitus after renal transplantation]

IBRAHIM Munir Yasmin, BORDA Bernadett, LENGYEL Csaba, VÁRKONYI Tamás, KEMÉNY Éva, SZABÓ Viktor, KUBIK András, LÁZÁR György

[Introduction: New-onset diabetes after transplantation (NODAT) is one of the most common complications following kidney transplantation. The diagnosis of NODAT is often late or missed, therefore it impairs the implanted renal allograft. Patients and methods: Patients were randomized to receive cyclosporine A- or tacrolimusbased immunosuppression. One year after the transplantation, fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following three groups based on the results: normal, impaired fasting glucose/impaired glucose tolerance (IFG/IGT), NODAT. Age, laboratory results, renal function, morphological abnormalities, and changes in the Banff score were evaluated. Results: NODAT developed in 14% of patients receiving cyclosporine A-based immunosuppression and in 26% of patients taking tacrolimus (p=0.0002). Albumin levels were similar, but uric acid level (p=0.002) and the age of the recipient (p=0.003) were significantly different between the diabetic and the normal group. The evaluation of renal function showed no significant differences in case of serum creatinine level, eGFR, and urea level. Evaluation of tissue samples revealed that acute cellular rejection (ACR) and interstitial fibrosis/ tubular atrophy (IF/TA) were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis (“t”) and interstitial inflammation (“i”) (p=0.05). Discussion: The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before any signs of functional impairment.]

Clinical Neuroscience

NOVEMBER 30, 2013

[Diffusion MRI measured white matter microstructure as a biomarker of neurodegeneration in preclinical Huntington’s disease]

KINCSES Tamás Zsigmond, SZABÓ Nikoletta, TÓTH Eszter, ZÁDORI Dénes, FARAGÓ Péter, NÉMETH Dezsõ, JANACSEK Karolina, BABOS Magor, KLIVÉNYI Péter, VÉCSEI László

[Background - Huntington’s disease is a progressive neurodegenerative disease, genetically determined by CAG trinucleotide expansions in the IT15 gene. The onset of the symptoms is related to the number of CAG triplets. Because the patients are asymptomatic in the early phase of the disease, in vivo biomarkers are needed to follow up the neurodegeneration and to test putative neuroprotective approaches. One such promising biomarker is the diffusion MRI measured microstructural alteration of the white matter. Methods - Seven presymtomatic, mutation carriers and ten age-matched healthy controls were included in the study. Diffusion parameters were compared between groups and correlated with measures describing neurodegeneration. In order to reduce the possible misregistration bias due to atrophy the analysis was restricted to the core of each fibre bundles as defined by maximal fractional anisotropy (Tract- Based Spatial Statistics). Results - Decreased fractional anisotropy, along with increased mean, parallel and perpendicular diffusivity was found in white matter tracts, mainly in the corpus callosum. An inverse correlation was detected between the fractional anisotropy and neurodegeneration score (derived from the number of CAG triplets and the patient age) from the areas of the left precentral gyrus, frontal lobe, corpus callosum and the capsula extrema. Altered diffusion parameters are promising biomarkers of the neurodegeneration in Huntington’s disease.]

Clinical Neuroscience

JANUARY 25, 2013

[Sturge-Weber syndrome: clinical and radiological correlates in 86 patients]

FOGARASI András, LODDENKEMPER Tobias, MELLADO Cecilia, TUXHORN Ingrid, EVERS Georg, SARCO Dean, BURGESS C. Richard, HALÁSZ Péter, BARSI Péter, GYORSOK Zsuzsanna, GYIMESI Csilla, KÓBOR Jenõ, SIEGLER Zsuzsanna, JANSZKY József, JAKUS Rita, RÁSONYI György, EBNER Alois, WOERMANN Friedrich, SAHIN Mustafa

[Backgrounds and purpose - To correlate the extent of the leptomeningeal angiomatosis with clinical features in Sturge- Weber syndrome (SWS). Methods - The study group consisted of 86 consecutive patients aged two months to 56 (mean 7.9±10.3) years with SWS and epilepsy. Clinical and MRI data were analyzed. Results - Based on the extent of leptomeningeal angiomatosis, patients were divided into two subgroups: 43 patients had hemispheric angiomatosis and atrophy, whereas, another 43 had focal involvement. Nine of the 43 hemispherial patients (10%) showed bilateral involvement: all of these bilateral cases demonstrated dominance in a single side with hemispheric leptomeningeal angiomatosis and contralateral focal extension. Hemispheric and focal subgroups were clinically different. Patients with hemispheric SWS were younger at the age of epilepsy onset (p<0.001) and age at MRI examination (p<0.05). Neither gender, lateralization, duration of epilepsy, appearance of secondarily generalized seizures, nor seizure frequency revealed a significant difference between subgroups. Conclusion - Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side. The age of epilepsy onset is related to the extent of leptomeningeal angiomatosis. Patients with hemispheric form of SWS presented with earlier age of seizure onset. Focal pial angiomatoses do not tend to progress (a longer duration is not associated with more frequent hemispheric involvement). Other variables including seizure frequency and secondary generalized tonic-clonic seizures are not associated with the extent of angiomatosis.]

Clinical Neuroscience

NOVEMBER 20, 2012

[The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and β-actin genes in rat brain]

KÁLMÁN János, PÁKÁSKI Magdolna, SZŰCS Szabina, KÁLMÁN Sára, FAZEKAS Örsike, SÁNTHA Petra, SZABÓ Gyula, JANKA Zoltán

[Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer’s disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations - also affecting the metabolism of β-actin - can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], β-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n=16), CIS (n=10), 10 mg/kg sertindole (n=5) and 10 mg/kg sertindole + CIS (n=4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal β-actin (p<0.01), MAPK-1 and APP (p<0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in β-actin, MAPK-1 and APP expression (p<0.05). Ours is the first report about CIS induced β-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.]

Clinical Neuroscience

NOVEMBER 20, 2012

[Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis]

SZÉPLAKI Gábor, MERKELY Béla

[Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsingremitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine- 1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.]

Hypertension and nephrology

FEBRUARY 20, 2012

[Functional and morphologic changes in patients with new-onset dyslipidemia after transplantation]

BORDA Bernadett, LENGYEL Csaba, VÁRKONYI Tamás, SZABÓ Viktor, SZEDERKÉNYI Edit, LÁZÁR György

[The principal risk factors for cardiovascular mortality after transplantation are hyperglycemia, hypertriglyceridemia, immunosuppressive therapy, obesity, and smoking. Among 115 patients, we assessed the risk factors for new-onset dyslipidemia, and their effects on the function and histopathology changes in the allografts one year after transplantation. Evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal versus new-onset dyslipidemia patients (p=0.002). The difference in body mass index was significant one year after kidney transplantation when comparing normal with new-onset dyslipidemia patients (p=0.02). The trigliceride levels were significantly higher among those on cyclosporine- A than those on tacrolimus (3.02±1.51 mmol/l vs 2.15±1.57 mmol/l, p=0.004). The difference also proved to be significant for the total cholesterol level: 5.43±1.23 mmol/l versus 4.42±1.31 mmol/l respectively (p=0.001). In regard to allograft function there was no significant difference one year after transplantation between the normal and new-onset dyslipidemia patients. When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy among new-onset dyslipidemia than normal function patients. Disruption of lipid homeostasis is known to severely damage the allograft. Without timely recognition and treatment, these conditions may not only lead to irreversible damage in the allograft, but also increase cardiovascular risk.]

Clinical Neuroscience

NOVEMBER 30, 2011

[Vascular or “lower body parkinsonism”. Rise and fall of one diagnosis]

SZIRMAI Imre

[The “arteriosclerotic parkinsonism”, which is called vascular parkinsonism (VP), was first described by Critchley1. The broad based slow gait, reduced stride lenght, start hesitation, freezing and paratonia was mentioned as “lower body parkinsonism” (LBP) which can be associated by slow speech, dysexecutive syndrome, and hand tremor of predominantly postural character. In VP the DAT-scan proved normal dopamine content of the striatum in contrast with Parkinson’s disease (PD). Additionally, Lewy bodies of brainstem type were not found in VP. Probability of VP increases if central type pathologic gait is prominent; the hands are slightly involved, the MRI indicates transparent periventricular white substance and/or brain atrophy. In some cases differentiation of gait apraxia and parkinsonism could be challenging. There is no rigor of the lower limbs at rest in neither of them, the disturbance of movement is evoked by the gait itself. Three subtypes of “gait ignition failure” has been recently described: (1) ignition apraxia, (2) equilibrium apraxia and (3) mixed gait apraxia. The primary progressive freesing gait was considered as a Parkinson-plus syndrome. Freesing occurs more frequently in diseases with pakinsonism than in PD. The grade of ventricle dilatation and the frontal leukoaraiosis was similar in LBP and gait apraxia. In cases of normal pressure hydrocephalus the impaired gait may mimic PD. Pathologic gait in VP can be explained by the lesions of the senso-motor association pathways in dorsal paramedian white substance within the vulnerable borderzone region. These may be colocalized with the representation of the lower extremities in the posterior third of the supplementer motor area. Rektor2 proposed to change the name of LBP to “cerebrovascular gait disorder”. Notwithstandig central type gait disorder develops also in many degenerative diseases other than cerebro-vascular origin. The neuronal net controling the regulation of movement is widespread, therefore several cortical and subcortical lesions could elicit large variations of pathologic gait, ie.: ataxia, apraxia, ignition failure, akinesis etc. In conclusion: most of the central gait disorders regarding the pathology and their appearance can not be called “parkinsonism”; these are much closer related to the localization of lesions rather than to the diagnostic categories.]

Clinical Neuroscience

JUNE 02, 2009

[99-mTc-HMPAO single photon emission computed tomography examinations in genetically determined neurometabolic disorders]

ARANKA László, AMBRUS Edit, VÖRÖS Erika, SVEKUS András, KÓBOR Jenõ, BEREG Edit, PALATKA János, PÁVICS László

[The aim of our study was to determine regional cerebral blood flow (rCBF) abnormalities in different types of enzymopathies. Patients and methods - Among the patients with genetically determined enzymopathies 3 patients had aminoacidopathies, and 11 had different types of encephalopathies, from which 10 had mitochondrial encephalomyopathy (MEMP), and 1 patient had hyperuricaemic encephalopathy. Besides the mentioned 14 patients, 1 had ceroid lipofuscinosis and another patient had tuberous sclerosis. The further distribution of the MEMP patients’ group was the following - 5 patients had MEMP with lactic acidosis, 5 had Leigh’s disease (subacute necrotizing encephalopathy), from which 1 had cytochrome-c-oxidase deficiency (COX). Additionally in all patients were performed cerebral MRI and SPECT examination 10 min. after intravenous administration of 20 Mbq/kg 99 mTc-HMPAO. Results - Fourteen out of 16 SPECT findings were pathologic, showing decreased focal frontal/temporal/temporoparietal cerebral blood perfusion. Aminoacidopathic group - all the 3 patients revealed pathologic signs from the aminoacidopathic patients’ group. Among them the ornithine transcarbamylase (OTC) heterozygous female patient with left-sided hemiparesis caused by hyperammonemic stroke at 10 month-age, showed right sided temporoparietal, occipital and left frontal hypoperfusion, nearly 6 years after the cerebral vascular attack. This finding might be resulted because of diaschisis. Mitochondrial encephalo-myopathic (MEMP) group - all the four patients with MEMP and lactic acidosis showed focal hypoperfusion in the temporal region, while the perfusion was normal in the COX deficient patient and in 2 Leigh’s disease (subacute necrotizing encephalopathy) patients. In the remaining 1 Leigh’s patient frontotemporal hypoperfusion was found. In all patients there were non specific structural abnormalities detected by MRI - cortical and subcortical atrophy, and scattered demyelination foci. In the case of ceroid lipofuscinosis the MRI showed cerebral atrophy and cerebellar hypoplasia, and the SPECT showed right frontal and occipital hypoperfusion, bilateral parietal physiological riping process. The patient with tuberous sclerosis showed bilateral temporo-occipital hypoperfusion. Conclusion - 1. SPECT images demonstrated hypoperfusion rCBF changes in 14 out of all 16 patients. 2. Regional cerebral/cerebellar hypoperfusion was detected by SPECT in mitochondrial encephalomyopathies, with lactate acidosis and aminoacidopathies giving high informative value about the cerebral perfusion.]

Clinical Neuroscience

SEPTEMBER 30, 2006

[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

DECEMBER 20, 2003

[HIV infection and neurology - long term follow-up of HIV infected children]

KOLLÁR Katalin, JELENIK Zsuzsanna, HEGELSBERGER Edit

[Objectives - Before the widespread introduction of combined antiretroviral therapy (1995) complications from HIV and AIDS in the central nervous system had been reported in larger proportion in infants and children than in adults: 80-90% versus 60-70%. Particular clinical manifestations tend to occur at different stages during the evolution of HIV infection. The authors review the neurological aspects of HIV infection. Method - First, a summary of the protocol of the neurological examinations and related experience is given. Then authors present the evaluation of neuro-psychological development, prevalence of neurological impairment and neuro-imaging of nine HIV infected children (seven boys, two girls) for the period of ten years (1991-2001). Three/ten children had vertically transmitted HIV, six/nine were infected by a nosocomial route in their early childhood. Children were regularly followed up from the diagnosis of HIV. The median follow up time has been 79 month (range: 18-144 month). Four patients died during the study period. The neurological status, the motor and mental development were examined at three month intervals or monthly under one year of age. EEG was performed every six month and CT/MRI once a year. All patients received combined antiretroviral treatment and immunglobulin therapy continuously. Results - Three/nine children have normal development, one/nine has hyperactive and attention deficit disorder with normal IQ range, two/nine have slight, one/nine moderate and two/nine serious mental retardation. Mild neurological signs were found in two children, various moderate and serious neuro/psychological symptoms were found in four patients, one of them was treated with benign epilepsy too. There was also close correlation between the clinical symptoms and the results of EEG examination (diffuse background slowing) and results of neuroimaging studies (cortical atrophy, calcification of the basal ganglia, toxoplasma abscesses). According to the results of different examinations three/nine children were found to be symptom-free, one/nine case showed the static form, two/nine patients showed the plateau form, two/nine the rapid progressive form and one/nine the progressive infantile form of AIDS encephalopathy. The majority of the patients suffered from adapting problems and difficulties of socialisation since their families lives were damaged by isolation and rejection from the community. Conclusion - The regular neurological and psychological examinations completed with EEG, CT/MRI were very informative to follow the course of neuro-psychological problems of HIV infected children. Symptom-free patients have to face psychosocial problems too, which cause much more damage in their mental progress than HIV itself.]