Clinical Neuroscience

[Single dose irradiation of defined region of rat brain with stereotactic BrainLab system]

FARKAS Róbert, KALINCSÁK Judit, KOVÁCS Péter, ARADI Mihály, BELLYEI Szabolcs, WEICZNER Roland, SEBESTYÉN Zsolt, PLANGÁR Imola, HIDEGHÉTY Katalin

JULY 30, 2014

Clinical Neuroscience - 2014;67(07-08)

[Background and purpose of our study was to develop a precise dose delivery technique for partial brain irradiation of two rats simultaneously. Methods - Using a self-developed frame stereotactic radiotherapy with single doses of 30-90 Gy was delivered to the frontal lobe of 22 animals. Tolerability and reproducibility of the method were evaluated and dosimetric measurements were conducted to verify the treatment plans. 2, 4 and 6 months after the irradiation magnetic resonance imaging (MRI) scans and histopathological examinations were performed to detect late radiation induced biological changes. Results - Immobilization device provided excellent reproducibility and tolerability. Dosimetry revealed good corres - pondence with planned dose distribution, but the measured absorbed dose was 30% lower than the planned dose. During the 6 months follow-up period the procedure related death of subject animals after 30 Gy, 70 Gy and 90 Gy were 0%, 20% and 100% respectively. T2 signal and structural changes on MRI scans found to be dose and time dependent. While 30 Gy caused no detectable structural changes, 70 Gy lead to cystic necrosis in 2 cases after 4 month. Histopathology revealed signs of necrosis on macroscopic examination after 70 Gy in the high dose region involving both frontal lobes, and no obvious microscopic changes in the surrounding area were detectable. Conclusion - Our technique of rat cranial irradiation using human stereotactic system provided high accuracy of single dose delivery for a pair of small animals, resulting in brain injury in the defined area. This method proved to be a reproducible model for preclinical studies on radiation effects.]

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Clinical Neuroscience

[Natalizumab therapy, 2013]

KARÁCSONY Mária, BENCSIK Krisztina, VÉCSEI László

[Multiple sclerosis (MS) is the most common chronic disease of the central nervous system in young adults. No curative therapy is known. Currently, six drugs are available that can reduce the activity of MS. The first-line drugs can completely reduce the activity of the disease in nearly two-thirds of the patients. In the remainder, who suffer from breakthrough disease, the condition of the patient worsens, and secondline therapies must be used. The second-line drug natalizumab exhibits almost double efficacy of the first-line drugs, but also have less favourable adverse effects. As a severe side-effect for instance, natalizumab carries the risk of the development of progressive multifocal leucoencephalopathy (PML), caused by a polyoma virus, the JC virus. There are three major risk factors for PML: an anti-JCV antibody status, a long duration of natalizumab treatment and prior immunosuppressant therapy. The lowest-risk group (1:14 286) comprises of patients who are anti-JCV antibody-negative, in whom the prior immunosuppressant use and duration of natalizumab therapy do not influence the risk of PML. With no prior immunosuppressant treatment, the incidence of PML increases to 1 in 192 patients after 2 years among those who are anti-JCV antibody-positive. These data may lead the physician to decide to discontinue natalizumab treatment. The half-life of natalizumab is three months; during this time other therapies can not be administered and the patients encounter the rebound effect: as the patients receiving natalizumab therapy displayed a high disease activity before treatment, the rebound effect can lead to relapses. After the termination of natalizumab secondline disease-modifying therapy with fingolimod may be introduce; no PML cases occur in response to fingolimod treatment. In the large majority of patients taking natalizumab who do not develop PML, this drug is highly effective and can prevent the progression of MS. The benefit of therapy and the risk of PML must be considered on an individual basis, with regard to the disease activity, the progression and the MRI activity, before natalizumab therapy is implemented.]

Clinical Neuroscience

[Depression in Parkinson’s disease]

RIHMER Zoltán, GONDA Xénia, DÖME Péter

[The prevalence of major and minor depression in Parkinson’s disease is around 30-40% but, unfortunately, depression remains frequently underrecognized and often undertreated. However, recognition and appropriate treatment of depression in patients with Parkinson’s disease is essential for improving the cross-sectional picture and longitudinal course. This review focuses on the epidemiology, pathophysiology and different treatment modalities of depression in Parkinson’s disease.]

Clinical Neuroscience

[Maybe it hurts more than you think! - Neonatal pain]

MIKOS Borbála

[Neonatal pain is often undertreated. This is based on the assumption that because of the immature nervous system and the lack of the myelinisation preterm and newborn does not feel pain. It is confirmed by a number of articles that the fetus and neonate can experience and respond to painful events. This publication gives a brief overview of the ontogeny of the pain, short-and long-term postnatal consequences, as well as the perception of the possibility of a particularly frail child population: premature infants and neonates, based on animal and human studies.]

Clinical Neuroscience

[The impact of levodopa-carbidopa intestinal gel on health-related quality of life in Parkinson’s disease]

KOVÁCS Norbert, ASCHERMANN Zsuzsanna, ÁCS Péter, BOSNYÁK Edit, DELI Gabriella, JANSZKY József, KOMOLY Sámuel

[Background - The levodopa/carbidopa intestinal gel (LCIG) therapy can improve the severe fluctuations associated with advanced Parkinson’s disease (PD). Our aim was to assess the improvement in the health related quality of life of PD patients treated with LCIG at University of Pécs. Methods - Eight PD patients were evaluated (age: 68.1±4.4 years, disease duration: 14,5±6,2 years, duration of fluctuations: 8.9±3.1 years). Before the initiation of LCIG treatment and 6 and 12 months later, the health-related quality of life (PDQ-39 and EQ-5D-5L), severity of PDrelated symptoms (MDS-UPDRS, Hoehn-Yahr Scale, Clinical Global Improvement - Severity) and major non-motor symptoms (PD Sleep Scale 2nd version: PDSS-2, Epworth Scale and Beck Depression Inventory: BDI) were assessed. Results - Health-related quality life improved after LCIG treatment measured by both EQ-5D-5L (from 0.257 to 0.662, p=0.009) and PDQ-39 (from 34 to 26 points, p=0.038). Meanwhile PD-related symptoms (MDS-UPDRS total score: from 105 points to 68 points, p<0.05) sleep quality (PDSS-2: from 25 to 22 points, p<0.05), daytime sleepiness (Epworth: from 12 to 7 points, p<0.05) and depression (BDI: from 20 to 15 points, p<0.05) also improved. Median ON time improved form 4.5 hours to 10.0 hours; whereas, the OFF time decreased from 4.5 to 0.5 hours (p<0.05). Conclusion - Both the quality of life and the clinical features of PD can be improved by LCIG treatment in advanced PD.]

Clinical Neuroscience

[Examining the diagnostic accuracy of a new migraine screener]

CSÉPÁNY Éva, BOZSIK György, KELLERMANN István, HAJNAL Boglárka, SCHEIDL Erika, PALÁSTI Ágnes, TÓTH Marianna, GYÜRE Tamás, ERTSEY Csaba

[Background - Migraine affects more than 10% of the Hungarian population, causes significant disability and severely affects patients’ generic and condition-specific quality of life. Despite these facts, a significant proportion of patients is not diagnosed and not treated adequately. Headache centres can provide care for only a fraction of all patients. The task of primary care providers would be greatly simplified by a reliable self-administered migraine screening questionnaire. Objective - To develop a short and reliable questionnaire as a migraine screening tool. Methods - Outpatients at the Headache Service, Department of Neurology, Semmelweis University completed a self-administered questionnaire which contained 9 yes/no questions about their headaches’ characteristics. The number of ’yes’ answers (the patients’ total score) was evaluated in connection with the diagnosis based on the International Headache Society criteria. We calculated the sensitivity, specificity, positive and negative predictive value as well as the misclassification rate for each total score value and used these to establish the final cutoff value of the questionnaire. 306 patients (242 females, mean age 39.1±13.3 years) were enrolled. The diagnosis was migraine in 244. Results - Completing the questionnaire did not pose any difficulty for the patients. At a cutoff value of 5 points the questionnaire’s sensitivity was 0.96 and specificity was 0.61. The positive predictive value was 0.91 and the negative predictive value was 0.81. The misclassification rate was 0.11. Discussion - Our results show that the questionnaire may help the diagnosis of migraine. In order to use it in medical practice, its further evaluation is necessary on a large representative sample of the Hungarian population.]

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Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

[The connection between the socioeconomic status and stroke in Budapest]

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[The well-known gap bet­ween stroke mortality of Eastern and Western Euro­pean countries may reflect the effect of socioeconomic diffe­rences. Such a gap may be present between neighborhoods of different wealth within one city. We set forth to compare age distribution, incidence, case fatality, mortality, and risk factor profile of stroke patients of the poorest (District 8) and wealthiest (District 12) districts of Budapest. We synthesize the results of our former comparative epidemiological investigations focusing on the association of socioeconomic background and features of stroke in two districts of the capital city of Hungary. The “Budapest District 8–12 project” pointed out the younger age of stroke patients of the poorer district, and established that the prevalence of smoking, alcohol-consumption, and untreated hypertension is also higher in District 8. The “Six Years in Two Districts” project involving 4779 patients with a 10-year follow-up revealed higher incidence, case fatality and mortality of stroke in the less wealthy district. The younger patients of the poorer region show higher risk-factor prevalence, die younger and their fatality grows faster during long-term follow-up. The higher prevalence of risk factors and the higher fatality of the younger age groups in the socioeconomically deprived district reflect the higher vulnerability of the population in District 8. The missing link between poverty and stroke outcome seems to be lifestyle risk-factors and lack of adherence to primary preventive efforts. Public health campaigns on stroke prevention should focus on the young generation of socioeconomi­cally deprived neighborhoods. ]

Lege Artis Medicinae

[Thiazide- or thiazide-like diuretics should be used in the treatment of patients with hypertension? Particularities of the situation in Hungary]

VÁLYI Péter

[Diuretics have remained the cornerstone of the antihypertensive treatment since their widespreading in the 1960s. According to the 2018 ESC/ESH Guidelines for the management of arterial hypertension, in the absence of evidence from direct comparator trials and recognizing that many of the approved single-pill combinations are based on hydrochlorothiazide, this drug and thiazide-like indapamide can be considered suitable antihypertensive agents. In the 2018 Hungarian guidelines indapamide is named as the most efficacious diuretic in the treatment of patients with hypertension. The aim of the publication is redefining thiazide- and thiazide-like diuretic use in the treatment of hypertensive patients, with particular attention to presently available hydrochlorothia­zide and indapamide, and their combination drugs in Hungary.]

Lege Artis Medicinae

[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]

FARSANG Csaba

[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]

Lege Artis Medicinae

[LAM 30: 1990–2020. Facing the mirror: Three decades of LAM, the Hungarian medicine and health care system]

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