Clinical Neuroscience

[NOVEL CELL-BIOLOGICAL IDEAS DEDUCIBLE FROM MORPHOLOGICAL OBSERVATIONS ON “DARK” NEURONS REVISITED]

GALLYAS Ferenc

MAY 20, 2007

Clinical Neuroscience - 2007;60(05-06)

[The origin, nature and fate of ”dark“ (dramatically shrunken and hyperbasophilic) neurons are century-old problems in both human and experimental neuropathology. Until a few years ago, hardly any cell-biological conclusion had been drawn from their histological investigation. On the basis of light and electron microscopic findings in animal experiments performed during the past few years, my research team has put forward novel ideas concerning 1. the nature of ”dark“ neurons (malfunction of an energystoring gel-structure that is ubiquitously present in all intracellular spaces between the ultrastructural elements), 2. the mechanism of their formation (non-programmed initiation of a whole-cell phase-transition in this gel-structure), 3. their capability of recovery (programmed for some physiological purpose), 4. their death mode (neither necrotic nor apoptotic), and 5. their relationship with the apoptotic cell death (the gel structure in question is programmed for the morphological execution of ontogenetic apoptosis). Based on morphological observations, this paper revisits these ideas in order to bring them to the attention of researchers who are in a position to investigate their validity by means of experimental paradigms other than those used here.]

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Clinical Neuroscience

[Determining the term of schizencephaly]

KENÉZ József, LEEL-ŐSSY Lóránt

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[CONGRESS CALENDAR]

Clinical Neuroscience

[PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY]

PÁL Endre, ASCHERMANN Zsuzsanna, GÖMÖRI Éva, KOVÁCS Gábor Géza, SIMON Gábor, MARÓDI László, KOMOLY Sámuel, ILLÉS Zsolt

[Progressive multifocal leukoencephalopathy is a rare disease caused by the reactivation of an opportunistic agent, JC virus almost in every cases in immunodeficient conditions. The disease is characterized by multifocal demyelinating lesions of the central nervous system and causes death within a few months. The authors report two patients: a 67 year-old male treated because of chronic lymphoid leukemia, and a 19 year-old male having a hereditary immunodeficiency, X-linked hyper IgM syndrome. In both cases continuously progressive right, later both hemispheric signs were detected. Cerebrospinal fluid was not helpful. Brain MRI showed bilateral large, white matter lesion. The progression was not influenced by the treatment, finally both patient died ten and six weeks after the appearance of first complaints. The diagnosis was confirmed by brain biopsy and autopsy in both cases. Our cases demonstrate that progressive multifocal leukoencephalopathy can develop in various immunodeficiencies.]

Clinical Neuroscience

[SLEEP DISORDERS IN PARKINSON SYNDROMES]

SZŰCS Anna, KOVÁCS Gábor Géza, NARULA Lalit, HALÁSZ Péter

[About 90% of neurodegenerative diseases with parkinsonism are associated with sleep disorders including daytime sleepiness, sleep-related breathing disorders and parasomnias. It is hard to define what ratio of insomnia and daytime hypersomnia is caused by the antiparkinsonian tratment, by the somatic and mentalemotional symptoms of the neurodegenerativ disease and by the neurodegenerative brain process itself. Recent research suggests that the latter group is more important than expected. In Parkinson syndromes the structures included in sleep regulation - mainly within the brainstem - are also affected resulting in specific sleep disorders being the primary biological symptoms of these diseases. The recently described parasomnia - REM sleep behavior disorder - has a specific significance in this respect: it may prevent by several years a high ratio of the parkinsonian disorders - especially synucleinopathies - offering the possibility of prevention by identifying the affected individuals. There seems to exist a similar although less clarified association between daytime sleepiness and Parkinson disease. Analysing the behavior of the orexin system in neurodegenerative diseases may help to learn more about this, recently described neurohumoral system and may clear the association of narcolepsy with neurodegeneration. By understanding the associations of parkinsonian disorders and sleep disorders new therapeutical strategies may be invented and may offer new aspects to understand the mechanism of them.]

Clinical Neuroscience

[TREATMENT OF SPASTIC UPPER LIMB WITH BOTULINUS TOXIN]

DÉNES Zoltán, FEHÉR Miklós, VÁRKONYI Andrea

[Objective - Examination of the effect of local botulinus toxin treatment on spastic upper limb, on patients with different brain injury. Patients and method - Prospective study in Traumatic Brain Injury Rehabilitation Unit of the National Institute for Medical Rehabilitation in the year 2003 and 2004. Thirteen patients (eight with stroke and five with traumatic brain injury) were treated locally on the spastic upper limb with 100 units botulinus A toxin. Results - Spasticity decreased one or two level on Modified Ashworth Scale, and in nine cases the good result were observed still at the end of 3rd month. No local or other complication was detected. Conclusions - Local treatment with botulinus toxin is an effective and safe method to decrease spasticity on upper limb in patients with different brain injury.]

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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

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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

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

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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

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Clinical Neuroscience

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CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein agglutination, disialosyl antibodies) syndrome is a rare polyneuropathy. IgM paraproteins react with ganglioside-containing disialylated epitopes resulting in dorsal root ganglionopathy and B-lymphocyte infiltration of cranial and peripheral nerves. Clinical features include ataxia, slight muscle weakness, areflexia, sensory- and cranial nerve symptoms. Case studies have reported the efficacy of rituximab and intravenous immunoglobulin (IVIg) treatments. We present the case of a 57-year-old man, who had difficulty walking, with numbness and clumsiness in all limbs. He had areflexia, vibratory sensation loss and ataxia. Laboratory tests showed IgM monoclonal components and disialosyl antibodies in the serum. Nerve conduction studies indicated severe sensorimotor demyelinating polyneuroradiculopathy. Despite IVIg and rituximab treatments, the patient’s disease course gradually worsened and he died of respiratory failure. Neuropathological examination revealed dorsal column- and dorsal root atrophy with mixed mononuclear cell infiltration. This article aims to draw attention to this syndrome, and the use of early potent immunosuppressive treatment to improve patients’ quality of life.