Clinical Neuroscience

[EVEN VISITING SCIENTISTS COULD MAKE DISCOVERIES IN MONTREAL]

LÁZÁR György

MARCH 30, 2014

Clinical Neuroscience - 2014;67(03-04)

[This publication summarizes the scientific adventure with Professor Selye, and focuses on the specific effect of rare metal salts on reticuloendothelial functions. Rare earth metal ions markedly affect the functions of cells involved in inflammatory and immunological phenomena. The Kupffer cell blockade induced by GdCl3 is a generally accepted method for investigation of the physiological and pathophysiological roles of Kupffer cells. Potential beneficial effects of macrophage blockade have been demonstrated in different shock states, liver injury and obstructive jaundice.]

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Clinical Neuroscience

[CENTRAL NEUROENDOCRINE MECHANISMS OF GASTROPROTECTION]

GYIRES Klára

[Selye recognized the importance of activation of hypothalamic- pituitary-adrenal axis during stress and the connection between central nervous system and neuroendocrine regulation. This concept basically contributed to initiation of the studies, which revealed the importance of brain gut axis in regulation of gastric mucosal integrity. Several neuropeptides, such as thyreotrop releasing hormones, adrenomedullin, peptide YY, amylin, opioid peptides, nociceptin, nocisatin, substance P, ghrelin, leptin, orexin-A, angiotensin II were shown to induce gastroprotective effect injected centrally. Though the involvement of dorsal vagal complex and vagal nerves in conveying the central action to the periphery has been well documented, additional mechanisms have also been raised. The interaction between neuropeptides further component that may modify the gastric mucosal resistance to noxious stimulus.]

Clinical Neuroscience

[HANS SELYE 70 YEARS LATER: STEROIDS, STRESS ULCERS & H. PYLORI]

SZABÓ Sándor

[Although Hans Selye is mostly known for his discovery & development of the stress concept, he also introduced the first physiologically sound, structure-activity classification of steroids that was also based on the chemical structure of steroids in 1943. He not only introduced the names of glucocorticoids & mineralocorticoids but discovered the anti- & pro-inflammatory properties, respectively, of these steroids in animal models. Furthermore, he not only described the first stress-induced gastric ulcers in rats (1936) & characterized the first human ‘stress ulcers’ during the air-raids in London during World War II (1943). Thus, Selye was a much more productive & creative scientist than it is generally considered.]

Clinical Neuroscience

[Validation of the Hungarian MDS-UPDRS: Why do we need a new Parkinson scale?]

HORVÁTH Krisztina, ASCHERMANN Zsuzsanna, ÁCS Péter, BOSNYÁK Edit, DELI Gabriella, PÁL Endre, KÉSMÁRKI Ildikó, HORVÁTH A. Réka, TAKÁCS Katalin, KOMOLY Sámuel, BOKOR Magdolna, RIGÓ Eszter, LAJTOS Júlia, KLIVÉNYI Péter, DIBÓ György, VÉCSEI László, TAKÁTS Annamária, TÓTH Adrián, IMRE Piroska, NAGY Ferenc, HERCEG Mihály, HIDASI Eszter, KOVÁCS Norbert

[Background - The Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non- English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian. Methods - Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson’s disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥0.90 compared to the English-language version. Results - For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥0.94. Conclusion - The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDSUPDRS in the CFA; therefore, this version was designated as the ‘OFFICIAL HUNGARIAN VERSION OF THE MDSUPDRS.’]

Clinical Neuroscience

[HANS SELYE: AN INSPIRING TEACHER]

GIULIO Gabbiani

[The souvenirs of Hans Selye as a teacher of graduate and post graduate students are presented and discussed. The main aim of his teaching was to orient the student toward importance and originality of findings.]

Clinical Neuroscience

[HANS SELYE AND THE STRESS RESPONSE: FROM “THE FIRST MEDIATOR” TO THE IDENTIFICATION OF THE HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR]

TACHÉ Yvette

[Selye pioneered the stress concept that is ingrained in the vocabulary of daily life. This was originally build on experimental observations that divers noxious agents can trigger a similar triad of endocrine (adrenal enlargement), immune (involution of thymus) and gut (gastric erosion formation) responses as reported in a letter to Nature in 1936. Subsequently, he articulated the underlying mechanisms and hypothesized the existence of a “first mediator” in the hypothalamus able to orchestrate this bodily changes. However he took two generations to identify this mediator. The Nobel Laureate, Roger Guillemin, a former Selye’s PhD student, demonstrated in 1955 the existence of a hypothalamic factor that elicited adrenocorticotropic hormone release from the rat pituitary and named it corticotropin releasing factor (CRF). In 1981, Wylie Vale, a former Guillemin’s Ph Student, characterized CRF as 41 amino acid and cloned the CRF1 and CRF2 receptors. This paves the way to experimental studies establishing that the activation of the CRF signaling pathways in the brain plays a key role in mediating the stress-related endocrine, behavioral, autonomic and visceral responses. The unraveling of the biochemical coding of stress is rooted in Selye legacy continues to have increasing impact on the scientific community.]

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[Interventional radiology of multiple biliary stenoses]

ROSTÁS Tamás, BATTYÁNY István, HADJIEV Janaki

[INTRODUCTION - In palliative treatment of malignant bile duct obstruction the endoscopic and the percutaneous methods are the possible options. In multiple lesions the percutaneous method must be preferable. Decrease of the bilirubin level to normal gives an opportunity for further treatment of the oncology patients. CASE REPORT - Authors report three patients’ case history, when following an unsuccessful endoscopic retrograde cholangiopancreatography, percutaneous cholangiography revealed multiple biliary stenoses. In all cases successful stent implantations were performed (three stents in one patient, two stents in two patients). The bilirubin levels decreased rapidly and the quality of life improved in all cases. Following the stent implantation selective cytostatic treatment (one patient) and systemic cytostatic treatment (one patient) were performed. The mean survival time was 300 days. CONCLUSION - In the case of multiple biliary stenoses the percutaneous stent implantation is an acceptable palliative method, which permit the possibilities of further interventional radiological or oncological treatments.]

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

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.]

LAM KID

[New findings in the cortical bone biology and its role in bone fractures]

BALOGH Ádám, BHATTOA Harjit Pál

[The authors surveyed the already known factors responsible for the osteoporotic bone fragility. Then the results of using modern imaging techniques (micro-CT, high-resolution peripheral computed quantitative tomograph - HR-pQCT) and advanced computer analytic methods (finite element analysis, FEA) are presented. These data - beyond the already known fracture risk factors (age, risk of falling, bone mineral density - BMD, and fine structure damage of trabecular bone) are stressing the importance of the (micro)damage of cortical bone as a fracture risk factor, which has been still underrated. The cortical thickening and increased porosity - verified on various population samples - are increasing the risk of fractures in certain subgroups of subjects having identical BMD values, even among those, who are considered only osteopenic by the earlier classification based on BMD values. Backed with modern software batteries, the new imaging techniques are expected to enter clinical application in the near future. Pharmacologic agents with stronger cortical effect are already available and research is continuing to find new drugs to use in the management of osteoporotic patients of high fracture risk.]