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Clinical Neuroscience

NOVEMBER 20, 2015

[Hyperglycaemic hemiballismus: implications from connectivity analysis for cognitive impairments]

KINCSES Tamás Zsigmond, VADÁSZ Dávid, NÉMETH Dezsõ, JANACSEK Karolina, SZABÓ Nikoletta, DÉZSI Lívia, BABOS Magor, VÖRÖS Erika, VÉCSEI László

[Hyperglycaemia induced movement disorders, such as hemiballism are rare disorders. The syndrome is characterised by the triad of hemiballism, contralateral T1-hyperintense striatal lesion and non-ketotic hyperglycaemia. Here we report a patient with untreated diabetes presenting with acute onset of hemiballism. MRI revealed T1 hyperintensity of the head of the caudate nucleus and the anterior putamen. The patient also had acantocytosis. Based on the detailed examination of the neuroradiological results and earlier findings we will imply on the pathomechanism. Based on previous findings microhemorrhages, extensive mineralisation, gemistocytic astrocytosis might play role in the development of the imaging signs. The connectivity pattern of the striatal lesion showed extensive connections to the frontal cortex. In coexistence with that the most severe impairment was found on the phonemic verbal fluency task measuring frontal executive functions. ]

Clinical Neuroscience

JANUARY 30, 2016

Facial virus inoculations infect vestibular and auditory neurons in rats

HELFFERICH Frigyes, LOURMET Guillaume, SZABÓ Rebeka Éva, BOLDOGKŐI Zsolt, PALKOVITS Miklós

Background and purpose – There is growing evidence for the viral origin of the Bell’s facial palsy, vestibular neuritis and sudden sensorineural hearing loss, however their exact pathophysiology is still unknown. We investigated the possibility of brainstem infections following peripheral viral inoculations in rats. Methods – Pseudorabies virus, a commonly used neurotropic viral retrograde tracer was injected into the nasolabial region of rats. Five and 6 days after injections, infected brainstem nuclei were demonstrated by immunohistochemical techniques. Results – Infected neurons were found in the motor facial, the medial vestibular, and the sensory trigeminal nuclei, as well as in the medial nucleus of the trapezoid body. Conclusion – Pseudorabies virus infects auditory and vestibular sensory neurons in the brainstem through facial inoculation. The possible routes of infections: 1. trans-synaptic spread constituted by facio-vestibular anastomoses: primarily infected motor facial neuron infects neurons in the medial vestibular nucleus, 2. via trigeminal sensory nerves: the sensory trigeminal complex innervated by GABAergic medial vestibular neurons, and 3. one bisynaptical route: infected facial motoneurons may receive indirect input from the medial vestibular nucleus and the trapezoid body via connecting neurons in the sensory trigeminal complex. We may assume that latent infections of these areas may precede the infections of the peripheral organs and the reactivation of the virus exerts the symptoms.

Clinical Neuroscience

NOVEMBER 30, 2018

[Comparison of subthalamic nucleus planning coordinates in 1Tesla and 3Tesla MRI for deep brain stimulation targeting ]

JUHÁSZ Annamária, KOVÁCS Norbert, PERLAKI Gábor, BÜKI András, KOMOLY Sámuel, KÖVÉR Ferenc, BALÁS István

[Backgroud - Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. Methods - In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. Results - The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). Conclusion - Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.]

Clinical Neuroscience

SEPTEMBER 23, 2011

[Role of deep brain stimulation in epilepsy]

JANSZKY József, BALÁS István, KOVÁCS Norbert

[The deep brain stimulation (DBS) is an emerging treatment option in brain disorders in which randomized multicenter trials proved its efficacy leading to licensing different DBS methods in various brain diseases. More recently more and more brain structures have become candidates for being “target” in a possible DBS treatment of epilepsy. At present, only the DBS of the anterior nucleus of the thalamus (ANT) can be considered as a proved method for epilepsy treatment. Other potential targets for DBS treatment in epilepsy are the subthalamic nuclei, and the amygdala- hippocampus complex. There are some ongoing randomized studies to investigating their therapeutical role. The therapeutical outcome of ANT-DBS treatment in drug-resistant epilepsy seems to be better than the new antiepileptic drugs, but much worse than the results of a potential epilepsy surgery. At about 10% of patients may become seizure-free and 50% of patients may have a significant improvement. Nowadays ANT-DBS should be considered as an “ultima ratio” in those adult drug-resistant epilepsy patients with normal intelligence in which neither new antiepileptic drugs nor resective epilepsy surgery are a reasonable therapeutical options.]

Clinical Neuroscience

MARCH 20, 2007

[EFFECT OF LOCAL (INTRACEREBRAL AND INTRACEREBROVENTRICULAR) ADMINISTRATION OF TYROSINE HYDROXYLASE INHIBITOR ON THE NEUROENDOCRINE DOPAMINERGIC NEURONS AND PROLACTIN RELEASE]

BODNÁR Ibolya, HECHTL Dániel, SZÉKÁCS Dániel, OLÁH Márk, NAGY M. György

[Background and purpose - Hypothalamic dopamine (DA), the physiological regulator of pituitary prolactin (PRL) secretion, is synthesized in the neuroendocrine DAergic neurons that projects to the median eminence and the neurointermediate lobe of the pituitary gland. The rate-limiting step of DA biosynthesis is catalyzed by the phosphorylated, therefore activated, tyrosine hydroxylase (TH) that produces L-3,4-dihydroxy- phenylalanine from tyrosine. The aims of our present study were to investigate 1. the effect of local inhibition of the DA biosynthesis in the hypothalamic arcuate nucleus on PRL release, and to get 2. some information whether the phosphorylated TH is the target of enzyme inhibition or not. Methods - A TH inhibitor, α-methyl-p-tyrosine was injected either intracerebro-ventricularly or into the arcuate nucleus of freely moving rats and plasma PRL concentration was measured. Immunohistochemistry, using antibodies raised against to native as well as phosphorylated TH were used to compare their distributions in the arcuate nucleus-median eminence region. Results - Intracerebro-ventricular administration of α-methyl-p-tyrosine has no effect, unlike the intra-arcuatus injection of enzyme inhibitor resulted in a slight but significant elevation in plasma PRL. Parallel with this, the level of DA and DOPAC were reduced in the neurointermediate lobe while no change in norepinephrine concentration can be detected indicating a reduced biosynthesis of dopamine following TH inhibition. On the other hand, systematic application of the α-methyl-p-tyrosine that inhibits TH activity located in DA terminals of the median eminence and the neurointermediate lobe, resulted in the most significant elevation of PRL. Conclusion - Our results suggest that α-methyl-p-tyrosine administered close to the neuroendocrine DAergic neurons was able to inhibit only a small proportion of the TH. Moreover, it also indicate that the majority of the activated TH can be found in the axon terminals of DAergic neurons, therefore, the DA released into the pituitary portal circulation is synthesized at this site.]

Clinical Neuroscience

AUGUST 20, 2002

[Parkinson's syndrome and cognitive disorders]

SZIRMAI Imre, KOVÁCS Tibor

[The cognitive (executive) ability of patients with Parkinson’s-disease (PD) deteriorates gradually during the progression of the disease. Fluency of speech, word finding, working memory, ability to plan the future and flexibility decline. Cognitive disturbance was found to be proportional with the speech, posture, gait and balance problems and can not be influenced by L-dopa substitution. Apart the dorsal and ventral mesolimbic dopaminergic systems the coerulo-cortical noradrenergic, serotoninergic and cholinergic systems are also impaired in PD. Subcortical dementia in PD can also be explained by the functional dysability of dorsolateral and anterior cingular circuits. Attention deficit can be explained by the dopamine depletion of cingular cortex. Cortical Lewy bodies, neurofibrillary tangles, neurit plaques and additional vascular pathology should also play a role in cognitive impairment of PD. In several systemic degenerative diseases associating with Parkinson’s syndrome (PS) ie. progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA) dementia can be detected with various severity, therefore the question arises concerning the correlation between cognitive disability and PS. Parkinson syndrome can also develop in frontotemporal dementias (FTD), Alzheimer’s disease and cortical Lewy body disease (CLBD) but no correlation exists between motor disability and severity of dementia. In CLBD dementia can be the initial symptom in 18% of cases but PS can also preceedes the dementia. In PSP profound depletion of other monoaminergic neurotransmitter system was also reported. In FTDs associated with PS degeneration of substantia nigra, locus coeruleus and basal nucleus of Meynert has been reported with increased number of neurofibrillary tangles. In patients with vascular PS (VP) there is generally no tremor and rigidity, but pseudobulbar palsy, dementia, gate disturbance, incontinency appeares; L-dopa treatment is generally ineffective. In VP no cellular loss can be found within the substantia nigra, but leukoaraiosis, lacunae in the white matter and basal ganglia are commonly demonstrated.]

Clinical Neuroscience

MARCH 20, 2007

[MOLECULAR ARCHITECTURE OF THE CANNABINOID SIGNALING SYSTEM IN THE CORE OF THE NUCLEUS ACCUMBENS]

MÁTYÁS Ferenc, WATANABE Masahiko, MACKIE Ken, KATONA István, FREUND F. Tamás

[Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, and these plastic changes may contribute to the establishment of addiction- related behaviour. Glutamatergic synapses of the prefrontal cortical projections to the nucleus accumbens (nAcb) - which are suggested to be under endocannabinoid (eCB) control - play a central role in the addiction process. The most abundant eCB in the brain is 2-arachidonoyl- glycerol (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-α), and exerts its action via type 1 cannabinoid receptors (CB1). However, the precise localization of DGL-α and CB1 - i.e. the sites of synthesis and action of 2AG - is still unknown. At the light microscopic level, immunocytochemistry revealed a granular pattern of DGL-α distribution in the core of the nAcb. Electron microscopic analysis confirmed that these granules corresponded to the heads of dendritic spines. On the other hand, presynaptic axon terminals forming excitatory synapses on these spineheads were found to express CB1 receptors. Our results demonstrate that the molecular constituents for a retrograde endocannabinoid control of glutamatergic transmission are available in the core of the nAcb, and their relative subcellular location is consistent with a role of 2-AG in addiction-related plasticity of cortical excitatory synapses in this reward area.]

Clinical Neuroscience

MARCH 20, 2007

[PROJECTIONS OF VIP/PHI NEURONS OF THE INTERSTITIAL NUCLEUS OF CAJAL IN THE RAT]

FODOR Mariann, WILLIAM Rostène, ANNE Berod, BENCZE Viktória, PALKOVITS Miklós

[Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Cajal. Unilateral surgical cut through the medial forebrain bundle failed to influence VIP/PHI mRNA expression in the Cajal nucleus while brainstem hemisection or unilateral transection of the medial longitudinal fascicle reduced it markedly, ipsilateral to the knife cuts. Thus, in contrast to forebrain projecting VIP neurons in the rostral periaqueductal gray, VIP/PHI neurons in the Cajal nucleus project downwards, to the lower brainstem.]

Lege Artis Medicinae

OCTOBER 20, 2009

[In vitro sensitivity of human anaerobic pathogenic bacteria for tigecycline and comparative antibiotics in Hungary - Prospective multicentre trial]

NAGY Erzsébet, URBÁN Edit, JAKAB Gabriella, SZIKRA Lenke, MISZTI Cecília, SZABÓ Judit

[INTRODUCTION - Tigecycline, the first member of the glycylcycline family of antibiotics, is a semisynthetic derivative of minocycline. The modified tetracycline nucleus is protected against the resistance mechanisms that inactivate tetracyclines, thus tigecycline is expected to be effective against tetracycline- resistant strains. The aim of this multicenter survey, performed in 2007 and 2008 by three Hungarian laboratories, was to examine the efficiency of this drug against antianaerobic bacteria in vitro. MATERIALS AND METHODS - The participating laboratories isolated 540 strains of Gram-positive and Gram-negative anaerobic bacteria from various infectious sites. These sites represent the classes of infections for which tigecycline was recently approved as a treatment option (skin and soft tissue and intra-abdominalinfections), or for which it will be licensed in the near future (lower respiratory tract infections). Evaluation of antibiotic susceptibility was performed by Etest, and the efficiencies of six antibiotics were determined using MIC values. RESULTS - The 540 strains belonged to 33 different species. Of the 104 strains of Gram-positive anaerobic cocci, 100% proved to be susceptible to tigecycline. Similarly, 98% of the examined Clostridium strains showed susceptibility to this antibiotic. Two of the 56 Prevotella strains were resistant against tigecycline. MIC50 and MIC90 values in the 280 Bacteroides strains were 0.5 μg/ml and 1 μg/ml, respectively, whereas only 1.8% of the tested strains showed low resistance. CONCLUSION - Similarly to the findings of international surveys, our results show that tigecycline is effective against the great majority (97.4% susceptibility) of relevant anaerobic bacteria that are isolated from skin and soft tissue, intra-abdominal and lower respiratory tract infections. Thus, empiric use of tigecycline is recommended in any infections where anaerobic bacteria alone or a mixed flora of aerobic and anaerobic bacteria are likely to be present.]

Clinical Neuroscience

MARCH 20, 2007

[CHARACTERIZATION OF SPECIFIC SUCCINATE BINDING SITE IN BRAIN SYNAPTIC MEMBRANES]

MOLNÁR Tünde, FEKETE Kútiné Erzsébet, KARDOS Julianna, PALKOVITS Miklós

[A synaptic receptor for gamma-hydroxybutyric acid (GHB) - a naturally occuring metabolite of succinic acid1 - interacting succinate has been disclosed in rat and human nucleus accumbens (NA) subcellular fractions2, but the molecular properties of this recognition site were not characterised. To address the presumed recognition site for succinate, the pharmacological profile of [3H]succinate binding to synaptic membranes prepared from rat forebrain and human NA samples has been investigated. Specific [3H]succinate binding sites in the human NA synaptic membrane fraction showed a strong pH-dependence and were characterized by binding of succinate (IC50,SUCC=2.9±0.6 µM), GHB (IC50,GHB=2.1±1.3 µM) and gap junction blocker carbenoxolone (IC50,CBX=7.1±5.8 µM). A similar [3H]succinate binding profile was found in rat forebrain synaptic membrane fractions. We conclude the existence of a pHo-dependent synaptic membrane binding site for the intermediary metabolite succinate. The pharmacological properties of this recognition site may possibly suggest the existence of a hemichannel-like target protein for succinate.]