Clinical Neuroscience

[Volumetric changes following 125 I interstitial irradiation of low grade gliomas]

JULOW Jenő, VIOLA Árpád, MAJOR Tibor, MANGEL László, BAJZIK Gábor, REPA Imre, SÁGI Sarolta, VALÁLIK István, EMRI Miklós, TRÓN Lajos, NÉMETH György

MARCH 10, 2005

Clinical Neuroscience - 2005;58(03-04)

[Background - Image fusion permits quantitative analysis of the consequences of 125 Iodine interstitial irradiation of brain tumors. The volume of tumor necrosis, reactive zone and edema can be compared to the dosimetric data. Patients and method - Nineteen patients with low grade glioma were analyzed on the average 14.5 months following 125 Iodine interstitial irradiation. Dose planning and image fusion were performed with the Target 1.19 (BrainLab) software. The CT/MR images showing the so called “triple ring” (necrosis, reactive ring and edema) developing after the interstitial irradiation of brain tumors were fused with the planning images and the isodose curves. The volume of the three regions was measured. Values at the intersections of isodose curves and necrosis borders were averaged and used for calculation of tumor necrosis. The volume of normal brain tissue irradiated by given dose values, as well as homogeneity and conformality indices were also determined. Results - The relative volumes of the different parts of the “triple-ring” compared to the reference dose volume were the following: necrosis 54.9%, reactive zone 59.7%, and edema 445.3% . Tumor necrosis developed at 71.9 Gy dose. At the irradiation of an average size glioma with a volume of 12.7 cm3, 5 to 7 cm3 normal brain tissue around the tumor received 60-70 Gy dose. The average homogeneity and conformality indices were 0.24 and 0.57, respectively. Conclusion - The analysis of changes in the volume of edema, reactive ring and necrosis caused by interstitial irradiation, and their correlation with the dozimetric data using the image fusion method provide useful information for patient follow-up, clinical management and further therapeutic decisions.]



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Clinical Neuroscience

[Clinical neurosciences for efficient treatment - 2nd Live Issue of Clinical Neuroscience/ Ideggyógyászati Szemle]


[Clinical neurosciences for efficient treatment - 2nd Live Issue of Clinical Neuroscience/ Ideggyógyászati Szemle 2005;58(03-04)]

Clinical Neuroscience



[Pathologically, Binswanger’s disease is subcortical periventricular leucoencephalopathy sparing the U fibers. Clinically it is characterised by executive dysfunction, gait problems, urinary incontinence, pseudobulbar palsy, mood disturbances and dementia. The pathomechanism of Binswanger’s disease is unclear. It is hypothesized that it results from an ischemic-hypoxic injury of the periventricular white matter, which, in turn, can be caused by a sclerotic elongation of the medullary arteries, widening of the perivascular spaces or decreased brain perfusion due to hypotension or heart disease. The symptoms of Binswanger’s disease frequently overlap with those of normal pressure hydrocephalus, vascular parkinsonism and Alzheimer’s disease. A diagnostic criterion of Binswanger’s disease is radiologically demonstrated leukoaraiosis, which, on the other hand, is not equivalent with Binswanger’s disease. A good clinical response after lumbar puncture or shunt implantation might lead to confusion with normal pressure hydrocephalus, which further complicates the clinical diagnosis. It is likely that among the above mentioned disorders there are a number of transitional forms and overlaps, which might be explained by the common pathomechanism of disturbance in cerebrospinal fluid circulation.]

Clinical Neuroscience

[Supplementary sensory-motor seizures - symptomatology, etiology, and surgical management with illustrative case reports]

HALÁSZ Péter, JUHOS Vera, ERÕSS Loránd, TÓTH Szabolcs, BALOGH Attila, GYÖRGY Ilona, BARSI Péter, KELEMEN Anna, BARCS Gábor

[In the past decade, owing to the advance of epilepsy surgery, growing knowledge has accumulated on the role of the supplementary motor area, described by Penfield and coworkers in the early fifties, in movement regulation and on the characteristics of seizures involving this area. In the Hungarian neurological literature this topic - despite its neurophysiological and practical clinical importance - has been hardly touched. The authors, based on their own experience obtained from surgeries performed within the framework of the "Co-operative Epilepsy Surgery Program", describe the electrophysiological features of this area, its role in movement regulation and the symptoms of epileptic seizures stemmed from or spread onto this area. Using cases as illustrations, they demonstrate the reasoning and various algorithms of the multidisciplinary examination necessary to explore the seizure onset zone and the pathways of seizure spread. Details of the surgical solution are also described.]

Clinical Neuroscience

[Primary prevention program of the Hungarian Spine Society - Part I. Scientific background of the posture correction exercise scheme]

GARDI Zsuzsa, FESZTHAMMER Artúrné, DARABOSNÉ Tim Irma, TÓTHNÉ Steinhausz Viktória, SOMHEGYI Annamária, VARGA Péter Pál

[The primary prevention program of the Hungarian Spine Society aims to increase awareness of the need to develop and automatically maintain a biomechanically correct posture for all school children. The biomechanically correct posture is a dynamic balance based on a correct middle position of the pelvis and on muscle balance. In this position three important anatomical points - the left and right anterior superior iliac spines and the upper medial point of the pubic bone - form one frontal plane. From side-view the imaginary weight median of the body crosses the 2nd to 5th lumbar and the 2nd to 5th cervical vertebral bodies. When the muscles involved in posture are in balance, their strength and flexibility are just appropriate for the almost continuous work required against gravity. In case of static and/or dynamic under- or overload tonic muscles become shortened, and phasic muscles become stretched, and are no longer able to work optimally. Since many muscles and muscle parts that are involved in normal posture maintenance are not satisfactorily challenged in regular physical exercises and sport activities, the preventive exercise scheme of the Hungarian Spine Society aimed to involve these rarely used muscles in special strengthening and stretching exercises. The scheme is based on 12 test exercises that assess the strength and flexibility of postural muscles. A person who is able to do all test exercises correctly has no problem with his or her muscle balance. In order to counteract the harm caused by sedentary lifestyle already in childhood, regular use of this posture correction scheme in physical education starting from preschool throughout the school-years is recommended for all children.]

Clinical Neuroscience

[Application of the Multiple Sclerosis Functional Composite in Debrecen]


[Introduction - The Multiple Sclerosis Functional Composite (MSFC) has been recommended by the National Multiple Sclerosis Society as a new clinical outcome measure. It is based on measurements in three clinical dimensions: leg function/ambulation (timed 25-foot walk), arm function (9-hole peg test), and cognitive function (paced auditory serial addition test). Scores on component measures are converted to standard scores (Z-scores) that reflect patient performance. This method has not yet been introduced into routine clinical practice. Patients and method - MSFC calculation was applied to 17 patients with relapsing-remitting multiple sclerosis (age mean: 37.4±10.8 years; duration of the disease: 5.5±4.9 years, EDSS: 2.7±1.4) seen at the neuroimmunological outpatient clinic to evaluate its usefulness and its correlation with the traditionally applied Expanded Disability Status Scale (EDSS) and with patient-reported quality of life. Fifteen patients received immunomodulatory treatment (interferon beta and glatiramer acetate). MSFC and EDSS were measured at 0, 3, 6, 9, 12, 18 months, and questionnaires on quality of life were filled in by the patients at 0, 6, 12, 18 months of follow- up. Results - The prospective study confirmed a strong correlation between EDSS and MSFC (Spearman correlation test, p=0.03, 0.004, 0.002, 0.004, 0.0008, 0.002; R=-0.54, -0.66, -0.68, -0.65, -0.73, -0.69) in multiple sclerosis. The MSFC was more sensitive to clinical changes than EDSS. The extent of changes on the two scales correlated only after 18 months (p<0.005, R=-0.65). The arm/hand function was the most sensitive measure for disease progression. There was no correlation between the quality of life and either of the two other clinical parameters. Conclusion - MSFC is a simple method, suitable for followup of multiple sclerosis patients in everyday clinical practice.]

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Clinical Neuroscience

Wnt pathway markers in low-grade and high-grade gliomas

NAGY Ádám, TOMPA Márton, KRABÓTH Zoltán, GARZULY Ferenc , MARÁCZI Alexandra , KÁLMÁN Bernadette

Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes. Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations. In the normal brain – grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas. These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.

Clinical Neuroscience

[Role of the intraoperative electrical brain stimulation in conserving the speech and language function in neurosurgical operations of awake patients]

ERÕSS Loránd, FEKETE Gábor, ENTZ László, FABÓ Dániel, BORBÉLY Csaba, KOZÁK Lajos Rudolf, ANDREJKOVICS Mónika, CZIRJÁK Sándor, FEDORCSÁK Imre, NOVÁK László, BOGNÁR László

[Aim of the study - To summarize the results gained with awake craniotomies, which were performed in either low grade glioma patients or epilepsy surgical patients whose tumor or epileptogenic zone, was in the vicinity of eloquent, mostly language, cortices. Patient selection and methods - In our retrospective study we selected 16 patients who were operated awake between 1999-2011 at the Neurosurgical Department of MÁV Kórház Budapest, or at the National Institute of Neurosciences in Budapest, or at the Neurosurgical Department of the University of Debrecen in Debrecen. In the presurgical evaluation if it was possible we performed functional magnetic resonance imaging, tractography and detailed neuropsychological testing. At the National Institute of Neurosciences all patients were operated with the aid of MR guided neuronavigation. Results - Anesthesia was carried out without complications in all of the 16 cases. Monitoring of sleep deepness has significantly contributed to the safety of anesthesia during the superficial anesthezied states of the operation. The intraoperative neuropsychological tasks used for testing language were sensitive enough to judge the little disturbances in speech during stimulation. Stimulation evoked seizures could be adequately managed during surgery and did not influence the outcome of the procedures. The use of neuronavigation helped significantly by planning the optimal place for the craniotomy and by intraoperative orientation. Conclusions - Awake craniotomies require well practiced surgical teams, which requires the cooperation of neuro-anesthesiologits, neurosurgeons, neuropsychologist and electrophysiologists. It has two goals, first to reduce the time of surgery to minimize surgical complications, secondly the detailed intraoperative mapping of cognitive and motor functions to avoid any neurological deficit. The intraoperative anatomical data provided by the neuronavigation and the functional data provided by awake intraoperative stimulation of the patient together serve the safety of the patient which is essential in the neurologically minimal invasive neurosurgical approach of the 21st century.]

Clinical Neuroscience

[Prognosis of neuroepithelial tumours by means of cell proliferation studies]


[Cell-kinetic analysis of tumours has recently been widely used in clinical oncology for prognosis of patients treated with malignant neoplasms and for controlling the efficiency of treatment protocols. Definition of biological nature of neuroepithelial tumours was based on grading depending on the severity of cellular anaplasia. Neuroepithelial tumours can be characterized not only by the histological features but also by the DNA content and abnormalities of the cell proliferation – though the relationship between histological malignancy, proliferative activity and cellular aneuploidity was found to be rather controversial according to the literature. In this review article the clinical value of cell cycle analysis such as distribution of DNA content, DNA index; S-phase fraction; proliferation-markers [MIB 1 antibody, bromdeoxy uridin labelling index, mitotic index, definition of nucleolar organization region) are discussed on the basis of personal experience and review of the appropriate literature. Flow cytometry and examination of proliferation markers have a significant role in the definition of prognosis of patients suffering from WHO grade II and III neuroepithelial tumours. Gliomas giving rise to recidivism have a rapid cell cycle already at their first occurrence, which is characterized by raised proliferation indices, and occurrence of aneuploid cell clones. An unfavourable outcome can be prognosed in patients suffering from a WHO grade II or III glioma if the DNA index is above or below 1+0.1 if the value of the S phase fraction is above 6%, if more than 1 mitosis is found in 10 large magnification field, and if the number of cells labelled with MIB 1 antibody exceeds 3 in 1 large magnification field. The literature confirms our notion that further studies of proliferation characteristics may help in the production of a malignity score of gliomas that could support the efficiency of traditional histological grading in prognosis and control of complex therapy of these tumours.]

Clinical Neuroscience

[Image fusion guided brachytherapy of brain tumors]


[The paper is the summary of mostly published works of the clinical results of intracavitary Yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas, and Iodine-125 interstitial irradiation of gliomas, pinealomas, brainstem tumors, recurrent meningeomas, solid craniopharyngiomas and metastases. It concisely demonstrates the usefulness of image fusion in the verification of isotope seeds and catheters, the comparison of 125 Iodine stereotactic brachytherapy and LINAC radiosurgery modalities on physical dose distribution and radiobiological efficacy, and the analysis of volumetric changes after interstitial irradiation of gliomas. Results of the immunohistochemical study deal with the role of microglia/macrophage system in the tissue response to I- 125 interstitial brachytherapy of cerebral gliomas. Due to financial reasons, gamma knife and Linac are not available to many countries and neurosurgical institutes. In the absence of the above mentioned radiosurgical methods, we have shown brachytherapy as an alternative solution in the treatment of different types of inoperable or recurrent brain tumors. The observed results may be noticable at LINAC and gamma knife irradiation too.]

Clinical Neuroscience

[125I brachytherapy of pineal parenchymal tumours]

JULOW Jenő, VIOLA Árpád, MAJOR Tibor, VALÁLIK István, SÁGI Sarolta, MANGEL László, KOVÁCS Rita Beáta, HÁVEL János, KISS Tibor

[Introduction - Pineal parenchymal tumours make up 0,3% of all brain tumours. Stereotactic biopsy has by now become an indispensable method to detect these tumours and it can be safely performed. Patients and method - Two patients with pineoblastoma were treated with 125I brachytherapy. The MRI and CT images taken 15 and 18 months after irradiation showed significant tumour shrinkage. Results - Tumour volume was 0.76 cm3 in the control CT image in Case 1, a shrinkage by 73% compared to 2.87 cm3 measured at the time of planning the interstitial irradiation. In Case 2, tumour volume measured on the control MRI examination was 0.29 cm3 as opposed to 1.27 cm3 of original tumour volume, which represents a 77% shrinkage. Conclusion - The insertion of isotope seeds was performed at the same time as the biopsy, because thus the knowledge of the histological diagnosis could spare the patients from a second stereotactic intervention. The CT- and image fusion guided 125I stereotactical brachytherapy is a procedure that can be dosimetrically precisely planned and surgically accurately and safely performed.]