Clinical Neuroscience

[Pathology of CNS tumors]

BÁLINT Katalin, JULOW Jenő

SEPTEMBER 30, 2010

Clinical Neuroscience - 2010;63(09-10)

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Clinical Neuroscience

[The concept of epileptic networks. Part 1.]

HALÁSZ Péter

[In this paper we investigate evidences supporting the network concept of epilepsies from different approaches. Firstly the functions of cortical networks in which most of the epileptic networks are embedded, are treated. Then the tentative characteristics of an epileptic network are enumerated and the conversion mechanisms from physiological to epileptic networks are analyzed. Later the role of neuronal oscillations in epileptic networks and aspects of epilepsies provoked by sensory and cognitive tasks is studied. Lastly new fMRI data in mapping BOLD networks underlying spike and seizure discharges are used as arguments in favour of the epileptic network hypothesis. In a second part the well-known epilepsies related, or probably related to physiological networks are shown. Finally consequences of the network approach for creating a new unified epilepsy classification are discussed.]

Clinical Neuroscience

[Examining the psychometric properties of a new quality of life questionnaire in migraineurs]

MANHALTER Nóra, PALÁSTI Ágnes, BOZSIK György, ÁFRA Judit, ERTSEY Csaba

[Background - The deleterious effect of primary headaches on the sufferers’ quality of life (QOL) has been abundantly documented using both generic and headache-specific instruments. The currently used questionnaires focus on a limited number of factors and therefore may not be sensitive enough to detect the effect of headache type and headache characteristics on QOL, despite the obvious clinical differences. We have devised a comprehensive questionnaire that may be more sensitive to the burden of headache. Objective - To assess the psychometric properties of the new questionnaire on a group of migraineurs. Patients and method - We studied 117 migraineurs who completed the validated Hungarian version of the SF-36 generic QOL measure and our new, 25-item questionnaire. Reliability was assessed by internal consistency, measured by Cronbach’s a of all items. Content validity was exam- ined by calculating the correlation of the items with subscales of the SF-36 measure. The correlation of the patients’ migraine characteristics with the questionnaire’s items was used to assess criterion validity. Results - The questionnaire was quick and easy to administer. The questionnaire demonstrated good reliability, with Cronbach’s alpha being 0.893. Content validity was adequate; most “physical” items of the new questionnaire showed significant correlations with the bodily pain and role physical SF-36 subscales and most “psychical” and “social” items were correlated with mental health and social functioning SF-36 subscales. Criterion validity was adequate, with headache severity being correlated with most of the items. Discussion - In this study the new headache-specific quality of life instrument showed adequate psychometric properties.]

Clinical Neuroscience

[Analysis of antiparkinsonian drug reduction after bilateral subthalamic deep brain stimulation]

FEHÉR Georgina, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ASCHERMANN Zsuzsanna, BALÁZS Éva, NAGY Ferenc, KOVÁCS Norbert

[Background - Bilateral deep brain stimulation of the subthalamic nuclei (STN) is a well-established and cost-effective treatment in advanced PD. Objectives - To quantitatively analyze the change in use of antiparkinsonian drugs one year after subthalamic deep brain stimulator (DBS) implantation in patients with idiopathic Parkinson’s disease (PD). Patients and methods - Eighteen consecutive patients with advanced PD underwent bilateral STN DBS implantation were involved in the study. The stimulation achieved a stable and clear clinical benefit in all of the cases. One year after the implantation, drug usage of patients was analyzed and correlated with the postoperative symptomatic improvement measured by the modified Hoehn-Yahr, Schwab and England, and Unified Parkinson’s Disease Rating Scales. Because none of the investigated variables followed the normal distribution, non-parametric Wilcoxon signed-rank, McNemar and Kendell’s τ tests were applied. Results - Preoperatively, the patients used 12.05±4.57 tablets a day out of 3.19±0.97 different antiparkinsonian drugs, which was significantly reduced by deep brain stimulation to the application of 7.00±2.96 tablets out of 1-3 (1.84±0.76) drugs (p<0.001). Meanwhile, the usage of amantadine, MAO-B and COMT inhibitors was also significantly decreased (p<0.05). The dosage of dopaminerg medication was significantly lowered from 1136 mg to 706 mg expressed in levodopa equivalent dosage (p<0.001) whereas the UPDRS-III also improved by 48.6%. Conclusion - Our study is in accordance with previously published international findings that antiparkinsonian medication can be significantly lowered after bilateral STN DBS. Because not only the dosage, but also the applied number of tablets were decreased, it may have resulted in a better compliance and quality of life.]

Clinical Neuroscience

[Devic syndrome - case report, diagnostic and therapeutic principles]

ILJICSOV Anna, BARSI Péter, VÁRALLYAY György, TÁTRAI Erika, SOMFAI Gábor Márk, BERECZKI Dániel, RUDAS Gábor, SIMÓ Magdolna

[Neuromyelitis optica (NMO, Devic-syndrome) is a rare, relapsing autoimmun disease of the central nervous system, which is distinguished from other demyelinating disorders by a recently identified, specific autoantibody. By demonstrating the anti-aquaporin-4 IgG in the serum, a heterogenous group of syndromes can be defined, called NMO-spectrum. In the future, optical coherence tomography may support this diagnosis besides the clinical features, imaging examinations and presence of serum antibody. Early recognition and treatment can improve clinical outcome even in serious condition. Long-term immunosuppressive therapy is advised to prevent further relapses and to stabilize or improve clinical status. Hereby, we report a case of a 51-year-old woman, under treatment for 1.5 years. We summarize the up-to-date knowledge about the pathomechanism, diagnostic strategy and therapy of neuromyelitis optica. We review recent findings and the diagnostic value of a new, non-invasive ophtalmological examination, the optical coherence tomography. According to the first results, this method may be helpful in the early differential diagnosis of optic neuritis.]

Clinical Neuroscience

[Genetic risk factors in Alzheimer’s disease]

FEHÉR Ágnes

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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

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

[Rehabilitation possibilities and results after neurosurgical intervention of brain tumors ]

DÉNES Zoltán, TARJÁNYI Szilvia, NAGY Helga

[Objectives - Authors examined the rehabilitation possi­bi­lities, necessities, and results of patients after operation with brain tumor, and report their experiences. Method - Retrospective, descriptive study at the Brain Injury Rehabilitation Unit, in National Institute for Medical Rehabilitation. Patients - Patients were admitted consecutively after rehabilitation consultation, from different hospitals, following surgical intervention of brain tumors, between 01 January 2001 and 31 December 2016. Patients participated in a postacute inpatient rehabilitation program, in multidisciplinary team-work, leaded by Physical and Rehabilitation Medicine specialist included the following activities: rehabilitation nursing, physical, occupational, speech, psychological and neuropsychological therapy. Results - At the rehabilitation unit, in the sixteen-year period 84 patients were treated after operation with brain tumor. Patients arrived at the unit after an average of 41 days to the time of the surgical intervention (range: 10-139 days), and the mean length of rehabilitation stay was 49 days (range: 2-193 days). The mean age of patients was 58 years (20-91), who were 34 men and 50 women. The main symptoms were hemiparesis (64), cognitive problems (26), dysphagia (23), aphasia (16), ataxia (15), tetraparesis (5), and paraparesis (1). The mean Barthel Index at the time of admission was 35 points, whereas this value was 75 points at discharge. After the inpatient rehabilitation, 73 patients improved functionally, the status of 9 patients did not show clinically relevant changes, and 2 patients deteriorated. During the rehabilitation 10 patients required urgent interhospital transfer to brain surgery units, 9 patients continued their oncological treatment, two patients continued rehabilitation treatment at another rehabilitation unit, and after rehabilitation 73 patients were discharged to their homes. Conclusions - Inpatient rehabilitation treatment could be necessary after operation of patients with brain tumor especially when functional disorders (disability) are present. Consultation is obligatory among the neurosurgeon, rehabilitation physician and the patient to set realistic rehabilitation goals and determine place and method of rehabilitation treatment, but even at malignancies cooperation with oncological specialist also needed. Authors’ experience shows benefits of multidisciplinary rehabilitation for patients after brain tumor surgery. ]

Clinical Neuroscience

[Pharmacological and nonpharmacological treatment of insomnias with regard to sleep medicine]

FALUDI Béla, ROZGONYI Renáta

[Insomnia - one of the most prevalent sleep complain - has a great impact on the everyday life. Basically two different form of insomnia can be defined: the insomnia disorder and the co-morbid insomnias. To treat adequately determination of background pathology is essential, which is based on the help of Sleep Medicine Centers. According to the newest guidelines, the treatment of insomnia disorder is based on cognitive behavioural therapies followed by pharmaceutical intervention. In this review we provide the short description of cognitive behavioural therapies and basic principles of hypnotic drugs. Despite the availability of insomnia guidelines the huge variation of the insomnia medication can be seen in the daily practice. Due to the above mentioned reasons we summarize the good clinical practice of hypnotic drug administration for insomnia patients.]

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.