Clinical Neuroscience

[OPTIMAL ALIGNMENT®. NOVEL SOFTWARE PROCEDURE FOR 3D RECONSTRUCTION OF ELECTRONMICROSCOPIC SERIAL SECTIONS]

SIMON László, GARAB Sándor, NOSZEK Annamária, ELIZABETH Römmer, ZÁBORSZKY László

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

[3D reconstruction from electronmicroscopic (EM) serial sections substantially differs from modeling body parts by linking convoluted planes delivered by CT and NMR. Namely, variations both in relative X-Y position and rotation of the target elements between the adjacent images and also additional problems caused by deformed, deteriorated or missing sections can only be overruled by an aligning paradigm, which exploits all the pixel-level information, and results in an optimal fitting with selected precision. This paper presents a complex computer program called Optimal Alignment®, which performs the precise elaboration of X-Y shift and relative rotation of two consecutive images. The required searching process will be customized by setting four independent parameters which relate the span and density of the pixel-scanning basic process. Optimalization of fitting accuracy versus running time can be achieved by a rather short training period. The potential precision of Optimal Alignment based on complex algorythms is far superior to manual aligning of EM photographs with the eye-wrist-mouse facility. The resulted database of alignment orientation parameters can serve as an advanced source for the 3D reconstructing programs. Optimal Alignment® software tool (supported by Hungarian Space Office grant TP 138) will be demonstrated on a basal forebrain NPY+ axonal reconstruction, performed in L. Záborszky’s laboratory (supported by NIH grant NSO23945).]

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Clinical Neuroscience

[FINE STRUCTURE OF THE AREA SUBPOSTREMA IN RAT. OPEN GATE FOR THE MEDULLARY AUTONOMIC CENTERS]

FODOR Mariann, PALKOVITS Miklós, GALLATZ Katalin

[The area subpostrema (ASP) is a V-shaped area, ventral and ventrolateral to the area postrema. It constitutes the upper border zone of the commissural portion of the nucleus of the solitary tract. The ASP is considered as a morphological and functional key area for the medullary autonomic center. The capillaries here, in contrast to the capillaries of the area postrema are not fenestrated but establish a specific staining for acetylcholinaestherase (AChE). The ASP contains a high density of fibers and terminals of several neuropeptides which are known to affect on NTS activity. Receptors of different neuropeptids and cathecholamines and a dense network of GFAP positive glial processes are found also here. The neurons and the glial cells of the ASP are connected with the AP and a bidirectional connection exists between the ASP and NTS.]

Clinical Neuroscience

[USING BRAIN SLICE CULTURES OF MOUSE BRAIN TO ASSESS THE EFFECT OF GROWTH FACTORS ON DIFFERENTIATION OF BONE MARROW DERIVED STEM CELLS]

BRATINCSÁK András, LONYAI Anna, SHAHAR Tal, HANSEN Arne, TÓTH E. Zsuzsanna, MEZEY Éva

[Bone marrow derived stem cells (BMDSCs) have been reported to form neurons and supportive cells in the brain. We describe a technique that combines the simplicity of in vitro studies with many of the advantages of in vivo experiments. We cultured mouse brain slices, deposited GFPtagged BMDSCs evenly distributed on their surfaces, and then added test factors to the culture medium. Addition of both SDF-1 and EGF resulted in morphological changes of BMDSC and in the induction of islet-1, a marker of neuroepithelial progenitors. We conclude that organotypic tissue culture (OTC) may allow us to detect the effects of exogenous factors on the differentiation of BMDSCs (or any other type of stem cells) in an environment that may resemble the CNS after brain injury. Once such factors have been identified they could be evaluated for tissue regeneration in more complex, whole animal models.]

Clinical Neuroscience

[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

[THE SUPRASPINAL INNERVATION OF THE LEFT ADRENAL IS MORE INTENSE THAN THAT OF THE RIGHT ONE]

GERENDAI Ida, WIESEL Ory, BOLDOGKŐI Zsolt, TÓTH E. Ida

[Background and purpose - Previous studies using the viral transneuronal tracing technique demonstrated that central autonomic circuits are involved in the innervation of the adrenal gland. Since increasing number of data indicate laterality in the neuroendocrine system, we aimed to investigate whether the supraspinal innervation of the adrenal gland exhibits asymmetry or not. Methods - The central circuitry involved in the innervation of the left and the right adrenal gland was studied in individual rats by dual transneuronal tracing using isogenic recombinant strains (BDG and BDL) of Bartha strain of pseudorabies virus. Results - Viral infection of brain nuclei (dorsal vagal nucleus, nucleus of the solitary tract, caudal raphe nuclei, A5 cell group, hypothalamic paraventricular nucleus) from the left adrenal was more severe than that from the right organ. Dual-infected neurons from the two adrenals were also detected both in the brain stem and in the hypothalamus. Conclusion - The results indicate a predominance in the supraspinal innervation of the left adrenal gland. Data further suggest that each adrenal gland is innervated both by side-specific neurons and by neurons which project to both organs.]

Clinical Neuroscience

[Dedication]

PALKOVITS Miklós

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Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]

JANSZKY József, HORVÁTH Réka, KOMOLY Sámuel

[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]

Clinical Neuroscience

[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]

RAJNA Péter

[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

Clinical Neuroscience

A case report of Morvan syndrome

AYTAC Emrah, ACAR Türkan

Morvan syndrome is a rare disease characterized by peripheral nerve hyperexcitability, encephalopathy, dys­autonomia and significant insomnia. The patient, who was included in the present study, was followed-up at our clinics for confusion, myokymia, hyperhidrosis, epileptic seizures, tachycardia, agitation, hypokalemia, and hyponatremia. The cranial MRI of the patient demonstrated hyperintensities at the T2 and FLAIR sections of the medial temporal lobe and insular lobes. Electromyography and neurotransmission examination results were concordant with peripheral nerve hyperreactivity. Contactin-associated protein-like 2 antibodies and leucine-rich glioma inactivated protein 1 antibodies were detected as positive. The patient was diagnosed with Morvan syndrome; intravenous immunoglobulin and corticosteroid treatment was started. Almost full remission was achieved. This very rare syndrome implies challenges in diagnosis and treatment; however, remission can be achieved during the follow-up. In addition, caution is needed in the long-term follow-up of these patients regarding the development of malignancies.

Clinical Neuroscience

[Earlier and more efficiently: the role of deep brain stimulation for parkinson’s disease preserving the working capabilities]

DELI Gabriella, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ASCHERMANN Zsuzsanna, NAGY Ferenc, BOSNYÁK Edit, KOVÁCS Norbert

[Background – The recently published “EarlyStim” study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. Methods – We reviewed the data of 39 young (<60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job (“Job+” group, n=15) and retired patients (without active job, “Job-” group, n=24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. Results – As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p<0.01, McNemar test). Conclusion – Although our retrospective study has several limitations, our results fit well with the conclusions of “EarlyStim” study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.]

Clinical Neuroscience

EEG-based connectivity in patients with partial seizures with and without generalization

DÖMÖTÖR Johanna, CLEMENS Béla, EMRI Miklós, PUSKÁS Szilvia, FEKETE István

Objective - to investigate the neurophysiological basis of secondary generalization of partial epileptic seizures. Patients and methods - inter-ictal, resting-state EEG functional connectivity (EEGfC) was evaluated and compared: patients with exclusively simple partial seizures (sp group) were compared to patients with simple partial and secondary generalized seizures (spsg group); patients with exclusively complex partial seizures (cp group) were compared to patients with cp and secondary generalized seizures (cpsg group); the collapsed sp+cp group (spcp) was compared to those who had exclusively secondary generalized seizures (sg group). EEGfC was computed from 21-channel waking EEG. 3 minutes of waking EEG background activity was analyzed by the LORETA Source Correlation (LSC) software. Current source density time series were computed for 23 pre-defined cortical regions (ROI) in each hemisphere, for the 1-25 Hz very narrow bands (1 Hz bandwidth). Thereafter Pearson correlation coefficients were calculated between all pairs of ROI time series in the same hemisphere. Z-scored correlation coefficients were compared at the group level (t-tests and correction for multiple comparisons by local false discovery rate, FDR). Results - Statistically significant (corrected p<0.05) EEGfC differences emerged at specific frequencies (spsg > sg; cpsg > cp), and at many frequencies (sg > spcp). The findings indicated increased coupling between motor cortices and several non-motor areas in patients with partial and sg seizures as compared to patients with partial seizures and no sg seizures. Further findings suggested increased coupling between medial parietal-occipital areas (structural core of the cortex) and lateral hemispheric areas. Conclusion - increased inter-ictal EEGfC is associated with habitual occurrence of secondary generalized seizures.