Clinical Neuroscience

[Diseased brain, diseased nerves, diseased mind]

RAJNA Péter

MAY 30, 2013

Clinical Neuroscience - 2013;66(05-06)

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Clinical Neuroscience

[Neurorehabilitation, neurology, rehabilitation medicine]

URBÁN Edina, SZÉL István, FÁY Veronika, DÉNES Zoltán, LIPPAI Zoltán, FAZEKAS Gábor

[We have read several publications of great authority on the neurological profession in the last two years in which were expressed assessments of the current situation combined with opinions about neurology and the necessity to reorganize neurological patient care. These articles took up the question of neurorehabilitation too. The authors, who on a daily basis, deal with the rehabilitation of people with disabilities as a consequence of neurological conditions, summarize some important definitions of rehabilitation medicine and the present system of neurological rehabilitation, as it is defined by the rehabilitation profession.]

Clinical Neuroscience

[Targeted nanomedicine in diagnostics and therapy of neurological diseases]

FODOR Bertalan, BARKAI László, VALIKOVICS Attila

[The incidence of neurological diseases increases. The up to date diagnostics and therapeutics approaches require the cost-effective and personalized solutions. The nanomedicine now, - and likely more in the future - opens a new horizon in the treatment of neurological diseases. The nano-size materials have several advantages that make it their use as drug delivery systems, and imaging agent. Very important aspect is that these materials can transfer across the bloodbrain barrier. The functionalization and surface modification of nanomaterials enhances this effect. The authors summarize of neurological application of nanoparticles according to the current data. They provide an overview about the most common used nanomedical materials, targeted drug delivery mechanisms and nano-imaging opportunities.]

Clinical Neuroscience

[Effective, safe stroke prevention with novel oral anticoagulants in patients with atrial fibrillation. Focus on dabigatran]

SZAPÁRY László, FEHÉR Gergely, BOSNYÁK Edit, DELI Gabriella, CSÉCSEI Péter

[Non-valvular AF is the most common cardiac arrhytmia. Its incidence increases with age. AF is an independent risk factor for ischaemic stroke, representing a five times higher risk for it, associated with a high mortality rate. Beside AF, there are several other risk factors which influence the risk of stroke. Stroke risk calculator can be used to assess the risk of patient having a stroke. The most endangered group of patients with AF are those who have already suffered from cerebrovascular event. The only effective medication for prevention of stroke due to AF had been the application of vitamin K antagonists (VKA) which considerably decrease the rate of ischaemic event in a patient with AF providing that the INR is in the therapeutic range. VKA have several limitations of use in clinical practice and the fear of bleeding complications results an underusing of these drugs. Only 50% of all patients treated with VKA reaches the therapeutic range of INR. The breakthrough of prevention of stroke in recent years is undisputedly the coming out of novel oral anticoagulants (NOACs, thrombin and Xa-factor inhibitors). Recent studies suggest that these novel drugs prove the same efficacy as VKA drugs, furthermore dabigatran in a dose of 2×150 mg or apixaban in 2×5mg was statistically superior to warfarin in the prevention of stroke. NOACs have shown a large reduction in intracranial hemorrhage compared with warfarin. They are given as a fixed dose and do not require persistent monitoring making them much more convenient. NOACs at guidelines of European Society of Cardiology act as a preferable drugs in case of ischaemic stroke with AF. Probably the extended use of NOACs in clinical practice will be the mainstream of stroke prevention in the future.]

Clinical Neuroscience

[Spectral, phase-synchronization, and graph theoretical EEG changes related to mental arithmetics]

BOHA Roland, TÓTH Brigitta, GAÁL Zsófia Anna, KARDOS Zsófia, FILE Bálint, MOLNÁR Márk

[During mental arithmetic operations working memory playsan important role, but there are only few studies in which anattempt was made to separate this effect from the process ofarithmetics per se. In this study the effects of arithmetic onthe EEG of young adults (14 participants, six of themwomen, mean age 21.57 years, SD: 2.62) was investigatedduring a subtraction task in the θ(4-8 Hz) frequency band.Besides the power density spectrum analysis phasesynchrony based on recently developed graph theoreticalmethods were used and strength of local connections (clustercoefficient; C) and global interconnectedness of network(characteristic path length; L) were determined. Before thearithmetic task passive viewing (control situation) and anumber recognition paradigms were used. During the arith-metic task compared to the control situation significantlyincreasing phase synchrony and C values were found. L wassignificantly shorter (F(2, 26)=818.77, p<0.0001) only dur-ing the arithmetic task: this fact and the former two resultsimply that the network topology shifted towards the “smallworld” direction. Our findings concerning regionaldifferences confirm those reported earlier in the literature:compared to the control condition significant task-relatedincrease was found in C values in the parietal areas [moreexplicitly in the left side, (F(1, 13)=7.2020, p=0.0188)],which probably corresponds to stronger local connectionsand more synchronized (sub)networks. During the task con-dition significantly increased θband power; (F(1,13)=7.9708, p=0.0144) and decreased L values werefound in the left frontal region compared to the right side(F(1, 13)=6.0734, p=0.0284), which can also be interpret-ed as an indicator of optimized network topology ofinformation processing.]

Clinical Neuroscience

[Possibilities of gene therapy with recombinant adenovirus in the cortex and hippocampus]

KOSKA Péter, VALIKOVICS Attila, KISS-TÓTH Éva, SZALAI Adrienn, NAGY Zoltán, FODOR Bertalan

[Background and purpose - Neurodegenerative diseases eg. ischemic stroke causes lifelong disabilities in cognitive functions and movement, furthermore high frequency of death. Antiapoptotic, or growth factor gene targeting to cortical structures could be a useful tool for neuroprotection in ischemic brain diseases. In present study we examined the feasibility of the gene therapy of the cortex and hippocampus via transfecting brain with recombinant adenovirus containing LacZ reporter gene in normal and postischemic condition. Since translation of proteins can be inhibited following ischemia by the phosphorylation of ribosomal subunit eIF2α, phosphor-eIF2α immunohystochemistry were performed. Methods - Our adenovirus vector was introduced via the cisterna magna into control and postischemic gerbil brain. After 48 hours of transfection the brains were examined for X-gal staining. LacZ expressing cells showed blue colour. Five min. transient global ischemia was induced by clipping the vertebral and carotid arteries of gerbil. Phosphor-eIF2α immunohystochemistry were performed following 48 hours of ischemia. Results - Administration of adenoviral vector resulted in transfection of hippocampal CA1, CA2, CA3 cell layers while gyrus dentatus remained untransfected. Cortical pyramidal cell layers were also transfected. In postischemic brain the lack of LacZ gene expression were detected in the CA1 and CA2 layer of hippocampus. Ischemia caused eIF2α phosphorylation in hippocampal CA1, CA2, CA3 and most neuronal layers in the cortex. Conclusion - Introducing adenovirus vector via the cisterna magna may results in effective gene therapy of cortex and hippocampus. To develop effective gene therapy in postischemic hippocampal CA1 and CA2 cell layers needs further investigation. eIF2α phosphorylation probably doesn’t interfere with transgene expression.]

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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

Creutzfeldt-Jakob Disease: A single center experience and systemic analysis of cases in Turkey

USLU Ilgen Ferda, ELIF Gökçal, GÜRSOY Esra Azize, KOLUKISA Mehmet, YILDIZ Babacan Gulsen

We aimed to analyze the clinical, laboratory and neuroimaging findings in patients with sporadic Creutzfeldt-Jakob disease (CJD) in a single center as well as to review other published cases in Turkey. Between January 1st, 2014 and June 31st, 2017, all CJD cases were evaluated based on clinical findings, differential diagnosis, the previous misdiagnosis, electroencephalography (EEG), cerebrospinal fluid and cranial magnetic resonance imaging (MRI) findings in our center. All published cases in Turkey between 2005-2018 were also reviewed. In a total of 13 patients, progressive cognitive decline was the most common presenting symptom. Two patients had a diagnosis of Heidenhain variant, 1 patient had a diagnosis of Oppenheimer-Brownell variant. Seven patients (53.3%) had been misdiagnosed with depression, vascular dementia, normal pressure hydrocephalus or encephalitis. Eleven patients (87%) had typical MRI findings but only 5 of these were present at baseline. Asymmetrical high signal abnormalities on MRI were observed in 4 patients. Five patients (45.4%) had periodic spike wave complexes on EEG, all appeared during the follow-up. There were 74 published cases in Turkey bet­ween 2005 and 2018, with various clinical presentations. CJD has a variety of clinical features in our patient series as well as in cases reported in Turkey. Although progressive cognitive decline is the most common presenting symptom, unusual manifestations in early stages of the disease might cause misdiagnosis. Variant forms should be kept in mind in patients with isolated visual or cerebellar symptoms. MRI and EEG should be repeated during follow-up period if the clinical suspicion still exists.

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

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.