Clinical Neuroscience

[Prognostic significance of invasion in glioblastoma]

SZIVÓS László1, VIRGA József2, HORTOBÁGYI Tibor3, ZAHUCZKY Gábor4, URAY Iván2, JENEI Adrienn1, BOGNÁR László1, ÁRKOSY Péter2, KLEKNER Álmos1

SEPTEMBER 30, 2020

Clinical Neuroscience - 2020;73(09-10)


[Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness – mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.]


  1. Debreceni Egyetem Klinikai Központ, Idegsebészeti Klinika, Debrecen
  2. Debreceni Egyetem Klinikai Központ, Onkológiai Klinikai, Debrecen
  3. Debreceni Egyetem Klinikai Központ, Neuro-Patológiai Tanszék, Debrecen
  4. UD-Genomed Kft., Debrecen



Further articles in this publication

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 role of sleep in the relational memory processes ]

CSÁBI Eszter, ZÁMBÓ Ágnes, PROKECZ Lídia

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]

Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

Acute effect of sphenopalatine ganglion block with lidocaine in a patient with SUNCT


Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing/short-lasting unilateral neuralgiform headache with cranial autonomic features (SUNCT/SUNA) is a rare severe headache. At the time of an attack, it can hinder a patient from eating and requires acute intervention. The sphenopalatine ganglion is an extracranial parasympathetic ganglion with both sensory and autonomic fibers. Sphenopalatine ganglion block has long been used in the treatment of headache, particularly when conventional methods have failed. Here, we present a patient who was resistant to intravenous lidocaine, but responded rapidly to sphenopalatine ganglion block during an acute episode of SUNCT/SUNA.

Clinical Neuroscience

A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?

ÖKTEM Özdemir Ece, ÇANKAYA Şeyda, UYKUR Burak Abdullah, ERDEN Simsek Nazan, YULUG Burak

Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still un­clear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of genera­lised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.

All articles in the issue

Related contents

Lege Artis Medicinae

[Changing tendencies in retinal surgery]


[Retinal detachment, a disease caused by pathologic alteration of the vitreoretinal relationship, may decrease vision to blindness without treatment. Although some of the patients with retinal detachment become blind for the time being, last two decades produced significant improvement both in diagnosis and treatment. As a result of new surgical techniques we can perform successful surgery even in cases that were earlier inoperable. Recent methods are significantly less traumatic to the eye than they were 20 years ago. Dramatically reduced bedrest before and after surgery, regional or even topical anaesthesia instead of general anaesthesia, short term hospitalisation or one day surgery, short term restriction of physical activity after surgery are the most important consequences of the new wave of retinal detachment repair. According to recent recommendations of the prophylactic treatment of peripheral retinal lesions we treat only horse tears with sudden retinal complaints.]

Lege Artis Medicinae

[The relevancy of measuring the level of D-dimer test in clinical practice]


[Plasma levels of D-dimer may rise in a number of pathological conditions, which might be relevant for diagnosis as well as for prognosis. Its concentration increases with age, perhaps because of the wide-spread co-morbidity. In this article we demonstrate the diagnostic role of Ddimer in the well-known thromboembolic diseases. Beyond that, we highlight the importance of measuring D-dimer levels in other, lesser-known conditions, about which important findings have been published, such as cardiovascular, inflammatory or malignant diseases. It seems that in these disorders - provided that appropriate clinical conditions are available -, measuring D-dimer levels might have a role not only in diagnosis but in the prognosis as well. Furthermore, our aim was to discourage inappropriate clinical practice. Ignoring to measure the D-dimer levels (for fear of it being high) might lead to diagnostic errors. On the other hand, routinely performing the D-dimer test without clinical consideration (in the hope of it being negative) might cause diagnostic confusion in case of unexpected positivity and - mostly because of false interpretation - lead to further, unnecessary examinations.]

Clinical Neuroscience

[Prognosis and classification of hypertensive striatocapsular haemorrhages]


[Introduction - Nontraumatic intracerebral haemorrhage accounts for 10 to 15% of all cases of stroke. Patients and method - In our study hypertensive striatocapsular haemorrhages were divided into six types on the basis of arterial territories: posterolateral, lateral, posteromedial, middle, anterior and massive (where the origin of the hemorrhage can not be defined due to the extensive damage of the striatocapsular region) type. We analysed laboratory data, clinical presentations and risk factors as alcoholism, smoking and hypertension of 111 cases. The size of the hematoma, midline shift and severity of ventricular propagation were measured on the acute CT-scan. The effect on the 30-day clinical outcome of these parameters were examined Results and conclusion - According to our results, the most important risk factor of hypertensive intracerebral haemorrhage was chronic alcoholism. Blood cholesterol, triglyceride levels and coagulation status had no effect on the prognosis, but high blood glucose levels Significantly worsen the clinical outcome. In our study, lateral striatocapsular haemorrhage was the most common while middle one was the least common type. The overall mortality is 42%, but differs by the type. The 30-day outcome significantly depends on the type of the haemorrhage, the initial level of consiousness, the size of the haematoma, the severity of ventricular propagation, the midline shift and the blood glucose levels. The clinical outcome proved to be the best in the anterior type, good in the posteromedial and lateral types. The prognosis of the massive type is poor. In our study, the classes and the mortality of the striatocapsular haemorrhages was different from the literature data. The higher mortality in our cohort could be due to the longer follow-up and the severe accompanying diseases of our patients.]

Clinical Neuroscience

[The future in danger: a survey of the changes in the number of neurologists and a prognosis for 2010 in Hungary]

BERECZKI Dániel, CSIBA László, KOMOLY Sámuel, VÉCSEI László

[Lack of neurologists has become an obvious problem recently in Hungary, not only in small hospitals, but in major health care centers and also in university hospitals. With the current survey we set forth to estimate the number of board certified neurologists, and to evaluate the foreseeable changes in the next decade. In the beginning of 2010 there were 1310 physicians in Hungary with an official license to practice neurology. During 2009 neurological performance at least once during the year was claimed to the National Health Insurance Fund by 948 board certified neurologists. The number of those neurologists who are routinely involved in neurological patient care was estimated to be around 750. The lack of the young generation is characteristic for the age distribution of neurologists. In nine out of the 19 counties of Hungary the number of neurologists below the age of 35 is one or nil. In the ten-year period of 2000-2009 the annual mean number of new board certifications in neurology was 22. This number is much lower than that needed to replace those who get employed abroad and who leave the system for other reasons. The number of neurologists in the age range of 40-60 years will drop to 2/3 of the current number by 2020 even if emigration of neurologists will completely halt. If emigration will continue at the current rate and the number of those in neurological training will not increase considerably, then by 2020 only about 300 neurologists will have to cover neurological services throughout Hungary. As this number is insufficient for the task, and the tendency is clearly foreseeable, the health care government should urgently react to this situation to ensure an acceptable level of neurological services in the near future for the population of Hungary.]

Clinical Neuroscience

[Epilepsy in the elderly]

NIKL János

[The incidence of epilepsy is higher among the elderly, the most rapidly growing segment of the population, than in any other age group. New-onset seizures in elderly patients are typically symptomatic or cryptogenic partial seizures that require long-term treatment. Epilepsy in the elderly is a frequently occuring pathology, differing in etiology, clinical presentation and prognosis from those of young people. Establishing the diagnosis of epilepsy in old age can be more difficult than in younger patients due to the extensive range of differential diagnoses and a higher prevalence of concomitant disease. Beyond a certain age physiological and pathophysiological changes can affect the pharmacokinetics and pharmacodynamics of antiepileptic drugs(AEDs), increasing the risk of pharmacological interactions due to polypharmacy. Furthermore, the elderly people are sensitive to advers events of AEDs, as for example, to cognitive disturbances, osteoporosis. Several of newer AEDs have good safety and cognitive effect profiles and have no interactions with other drugs. The treatment strategies are demanding: they must take into consideration the co-morbidity, co-medication, alterations in drug metabolism, and the effects on aging body. These factors make the management of epilepsy in the elderly particulary challenging, but with appropiate pharmacological treatment most elderly people with epilepsy will remain seizurefree.]