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



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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 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

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.

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.

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Hungarian Radiology

[Radiologic imaging in the diagnosis and follow up of malignant lymphomas]


[Certain viral infections, gene mutations and immune suppression are likely to play some role in the development of malignant lymphomas. The clinical stage at the time of diagnosis is a decisive factor of prognosis. The evaluation of the nodal and extranodal manifestation of the disease is performed by standardized imaging techniques. Most frequent extranodal manifestation involves the bone marrow, the lung and the gastrointestinal tract. Different imaging techniques are indispensable in monitoring the effectiveness of the treatment and in long term follow up.]

Clinical Neuroscience

[Extracellular matrix of intracerebral tumors with different invasion activity]


[Objectives - Ineffective surgical and radiotherapy of glioblastoma is mainly due to its intensive infiltrating behavior. Contrarily, brain metastases of anaplastic carcinomas are well-circumscribed intracerebral lesions that can be easily exstirpated in most cases. The molecules of the extracellular matrix (ECM) play a pivotal role in the peritumoral infiltration. In this study the mRNA expression of the ECM components was investigated in two types of intracerebral malignoma with different invasion activity. Our aim was to identify the ECM molecules that are responsible for the different intensity of peritumoral infiltration of tumors from different origin. Methods - The mRNA expression of twenty-three ECM molecules was determined by quantitative reverse transcriptase polymerase chain reaction. Four pieces of glioblastoma and four pieces of intracerebral lung adenocarcinoma metastasis from neurosurgical operation were investigated. Immunohistochemical investigations were performed in case of five molecules. Results - The mRNA expression of nine molecules (brevican, neurocan, neuroglycan-C, syndecan-1,2,4, tenascin-C, versican and matrix-metalloproteinase-[MMP]2) differed significantly by comparison of the two tumor types. By immunohistochemistry, neurocan, syndecan, versican and MMP-2 showed alteration in staining intensity according to the mRNA expression, while MMP-9 showed higher staining intensity in the metastatic tumor. Conclusions - The identified molecules can play an important role in the different infiltration activity of tumors from different origin. Thus these ECM-components could serve as targets for anti-invasion therapy in the future.]

Clinical Neuroscience

Isocitrate dehydrogenase mutations in defining the biology of and supporting clinical decision making in glioblastoma


Background and purpose - Oncogenesis is related to a sequential accumulation of somatic mutations. Comprehensive characterizations of the genomic landscapes have been completed recently for several tumors, glioblastoma being among the first ones. Our own translational research studies have been focused on defining molecular subtypes of glioblastoma in the clinical setting because of an expected prognostic and therapeutic utility of the information. Somatic mutations in genes of the isocitrate dehydrogenase (IDH) enzyme family appear to be among the best-defined biomarkers that also influence tumor behavior and confer clinical utility. Methods - We have reviewed the literature including our own results to summarize basic science and clinical correlates of IDH mutations. Results - The surveyed data reveal genomic, transcriptomic, epigenomic and biochemical consequences of IDH mutations in the context of glioblastoma biology and phenotype. In addition, a few studies highlight the therapeutic potential of targeting IDH, although thus far all tests have only been conducted in the preclinical setting. Conclusions - Somatic mutations in isoforms of IDH genes represent important biomarkers that correlate with biochemical, biological and phenotypic features of glioblastoma, and may also facilitate the development of new therapeutic strategies complementing the currently available approved protocols.

Clinical Neuroscience

Extreme delta brush EEG pattern in a case with anti-NMDA receptor encephalitis


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Clinical Neuroscience

[Reversible hepatocerebral degeneration-like syndrome due to portovenous shunts]


[Ataxia and tremor are rare manifestations of hepatocerebral degeneration due to portovenous shunts. Ammonia is a neurotoxin that plays a significant role in the pathogenesis of hepatic encephalopathy. A 58-year old male patient was assessed with the complaints of gait disturbance, hand tremor, and impairment of speech. His neurological examination revealed dysarthric speech and ataxic gait. Bilateral kinetic tremor was noted, and deep tendon reflexes of the patient were hyperactive. Serum ammonia level was found to be 156.9 μg/dL. Cranial magnetic resonance (MR) imaging revealed increased signal intensity in bilateral globus pallidus on T1-weighted axial sections, and bilateral prominent hyperintense lesions in the middle cerebellar peduncles on T2-weighted axial sections. On his abdominal MR portography, multiple portohepatic venous collaterals were noted in the right and left lobes of liver parenchyma in 2D FIESTA axial MR sections. To our knowledge, we reported the first case of acquired hepatocerebral degeneration presenting with cerebral symptoms without any hepatic findings in which clinical improvement was noted, and hyperammonemia disappeared following medical treatment.]