Clinical Neuroscience

[László Vécsei: Kynurenines in the Brain: From Experiments to Clinics]

FAZEKAS András

JULY 30, 2006

Clinical Neuroscience - 2006;59(07-08)

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Clinical Neuroscience

[EXECUTIVE DYSFUNCTION IN FRONTAL LESIONS AND FRONTAL EPILEPSY]

TÁRNOK Zsanett, BARSI Péter, GÁDOROS Júlia, HALÁSZ Péter

[Background - To explore the functions of the frontal lobe that are associated with high order cognitive and behavioral aspects such as the organization and execution of thoughts and behavior by neuropsychological methods is difficult. These so called executive functions are in close connection with the prefrontal thalamocortical circuits, damage of which can cause deficits in cognitive functions and even changes in personality. Methods - The aim of this study is to present a neuropsychological battery for testing frontal lobe functions. 31 patients (with frontal epilepsy and/or frontal lesion) and 38 healthy control subjects participated in the study. The control subjects were matched to the patient group in age, gender and education. Results - Comparing to the controls the patient group showed significant deficits in most of the measured executive functions, except two tests which show that the short time selective attention is preserved. We divided the patient group into three subgroups (frontal epilepsy only FLE, frontal lesion only FL, frontal lesion and epilepsy FLE+FL) and we found that except working memory deficits and problems in inhibition, there were no difference between the FLE patients and the control group. We found most frequently perseveration and errors in a strategy making task among the FL (mainly medial) patients. We didn’t find any difference in these tests according to the lateralization of the lesion. Conclusion - In conclusion we found that working memory deficits and problems in inhibition differentiated the frontal patient group from the controls in all cases. We emphasize that in frontal epilepsy (with no reported MR lesion) there are the same type, however more limited neuropsychological alterations as in lesional frontal dysfunction.]

Clinical Neuroscience

[PARALLEL PROCESSING OF VISUAL INFORMATION]

BENEDEK György, JANÁKY Márta, BENEDEK Krisztina, KÉRI Szabolcs

[This is a survey on the function of parallel visual pathway with a special emphasis on its clinical implications. It is based on data in the literature and own results of our group. The paper primarily deals with the X, Y, W pathways and by the magnocellular, parvocellular and koniocellular visual pathways characterized by cells of various size as well as by nerve fibers of various thickness. Electrophysiological, microelectrode recording of single-unit activity makes the distinction between the pathways available in animal modell. Much more difficulties arise if we intend to characterize the pathways in humans or to detect the selective damage of one of these pathways in patients. The non-invasive diagnostic methods that could be used in the diagnosis are detailed here, too. Finally, the neurological, ophtalmological and psychological diseases are discussed in which a selective damage of any visual pathway is suspected. Summing it up, the survey provides evidences for the introduction of the novel concept of parallel pathways into the diagnostic aspects of ophthalmology, neurology and psychiatry.]

Clinical Neuroscience

[THE AUGMENTATION OF CLOZAPINE TREATMENT WITH ELECTROCONVULSIVE THERAPY]

GAZDAG Gábor, KOCSIS-FICZERE Nárcisz, TOLNA Judit

[Objectives - The assessment, in terms of safety and efficacy, of augmenting clozapine monotherapy, as well as combined psychopharmacotherapy involving clozapine, with electroconvulsive therapy (ECT). Method - Reviewed were the charts of patients who received clozapine-ECT treatment in the Department of Psychiatry and Psychotherapy of Semmelweis University between November 1999 and December 2003. Results - During the studied period there were altogether 43 patients treated with the combination of clozapine and electroconvulsive therapy. In the schizoaffective group, the values for post-electroconvulsive therapy CGI were significantly lower than either in the catatonic (Z=-3.72, p<0.01) or in the hebephrenic (Z=-3.17, p<0.01) group. Among the groups created on the basis of the number of augmentation strategies utilized, the clozapine+3 group consisted of patients significantly older than the clozapine+1 group (Z=2.45, p=0.01). In the clozapine monotherapy group, the values for post-electroconvulsive therapy CGI were significantly lower than in any of the groups that had received a combination of augmentations (monotherapy-1 augmentation: Z=-3.01, p<0.01; monotherapy-2 augmentation: Z=-2.89, p<0.01; monotherapy- 3 augmentation: Z=-2.41, p=0.01). Conclusions - According to our examinations, the augmentation of clozapine treatment with electroconvulsive therapy should be tried primarily on schizoaffective patients, in case the clozapine monotherapy is ineffective. The simultaneous use of different augmentation strategies is expected to increase only the side effects not the efficacy of the treatment.]

Clinical Neuroscience

[AIDS-RELATED TOXOPLASMA-ENCEPHALITIS PRESENTING WITH ACUTE PSYCHOTIC EPISODE]

ILNICZKY Sándor, DEBRECZENI Róbert, KOVÁCS Tibor, VÁRKONYI Viktória, BARSI Péter, SZIRMAI Imre

[The most frequent neurological manifestations of the Acquired Immunodeficiency Syndrome- (AIDS) are Cerebral Toxoplasmosis, Primary Central Nervous System Lymphoma (PCNSL), Progressive Multifocal Leukoencephalopathy (PML) and AIDS-encephalitis (AIDS-dementia complex, multinucleated giant cell encephalitis, HIV-encephalopathy). Neurological complications usually occur in the advanced stages of the disease, and they are uncommon in the beginning as presenting illness, but may result in lifethreatening condition or in death. Rarely the disease presents as a neuropsychiatric illness in an undiagnosed AIDS patient, delaying a proper diagnosis. We present the case of a 34 years old patient treated for AIDS-related Toxoplasma-encephalitis in our department. His illness started as an acute psychosis followed by rapid mental and somatic decline, leading to death in three months. His HIV-seropositivity was not known at his admission, and the extraneural manifestations were slight. The diagnosis was established by serology, imaging methods and histopathological investigation. After presenting the medical history and results of autopsy studies of the patient we discuss the problems of the differential diagnosis, especially regarding the findings of the imaging methods.]

Clinical Neuroscience

[APPLICATION OF VERTEBROPLASTY, NEURONAVIGATION AND KYPHOPLASTY IN THE TREATMENT OF MULTIPLEX OSTEOPOROTIC VERTEBRAL FRACTURES - CASE REPORT]

KASÓ Gábor, HORVÁTH Zsolt, KÖVÉR Ferenc, EZER Erzsébet, DÓCZI Tamás

[Vertebroplasty is a therapeutic image-guided procedure, consisting of an injection of acrylic cement through a bone biopsy needle into a vertebral body. Main indication for vertebroplasty is painful vertebral body compression fracture due to osteoporosis. The procedure is an efficient mean with high succes in pain release and prevention of further collapse of the treated vertebrae; however, the technique does not allow to realign the spine. Kyphoplasty was designed to adress the kyphotic deformitiy. It involves the percutaneous placement of an inflatable bone tamp into a vertebral body (VB). Restoration of VB height and kyphosis correction is achieved by inflation of the tamp with contrast material liquid. After deflation a cavitiy is created that eases the cement application. The most modern way of guidance in spinal surgery is neuronavigation - the use of frameless stereotaxy. The system reformats patient-specific CT images acquired prior surgery, performs image fusion with intraoperative plain X-ray. Before the operation, the surgeon may create surgical plan and simulate advancement of a virtual instrument along one or more surgical trajectories. During surgery, the system tracks the position of specialized surgical instruments. All three modalities mentioned above have been applied in the treatment of our patient suffered from multiple osteoporotic vertebral body compression fractures. Using kyphoplasty an almost total VB height restoration could be achieved. The pain relief was more than 50% after both operation.]

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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

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

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm

BÉRES-MOLNÁR Anna Katalin, FOLYOVICH András, SZLOBODA Péter, SZENDREY-KISS Zsolt, BERECZKI Dániel, BAKOS Mária, VÁRALLYAY György, SZABÓ Huba, NYÁRI István

The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Clinical Neuroscience

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report

OTTÓFFY Gábor, KOMÁROMY Hedvig

Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.