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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon’s horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE.During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Epileptic activity evokes profound alterations of hippocampal organization and function. Genomic responses may reflect immediate consequences of excitatory stimulation as well as sustained molecular processes related to neuronal plasticity and structural remodeling. Using oligonucleotide microarrays with 8799 sequences, we determined subregional gene expression profiles in rats subjected to pilocarpine-induced epilepsy (U34A arrays, Affymetrix, Santa Clara, CA, USA; P 〈 0.05, twofold change, n = 3 per stage). Patterns of gene expression corresponded to distinct stages of epilepsy development. The highest number of differentially expressed genes (dentate gyrus, approx. 400 genes and CA1, approx. 700 genes) was observed 3 days after status epilepticus. The majority of up-regulated genes was associated with mechanisms of cellular stress and injury – 14 days after status epilepticus, numerous transcription factors and genes linked to cytoskeletal and synaptic reorganization were differentially expressed and, in the stage of chronic spontaneous seizures, distinct changes were observed in the transcription of genes involved in various neurotransmission pathways and between animals with low vs. high seizure frequency. A number of genes (n = 18) differentially expressed during the chronic epileptic stage showed corresponding expression patterns in hippocampal subfields of patients with pharmacoresistant temporal lobe epilepsy (n = 5 temporal lobe epilepsy patients; U133A microarrays, Affymetrix; covering 22 284 human sequences). These data provide novel insights into the molecular mechanisms of epileptogenesis and seizure-associated cellular and structural remodeling of the hippocampus.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Neurosurgical review 20 (1997), S. 19-23 
    ISSN: 1437-2320
    Keywords: Computerized tomography ; skull fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During a five-year-period (January 1990 to December 1994) a total of 67 patients were operated on for frontobasal skull fractures. The indication for surgical treatment was based on the evidence of fractures encroaching paranasal sinuses or the cribriform plate on high-resolution axial or coronal CT scans. The following clinical signs indicating frontobasal trauma were observed: 25 patients (37%) showed rhinoliquorrhea, 14 (21%) had racoon's eyes, and 2 (3%) had meningitis. Distinct dura laceration was observed intraoperatively in 64 of 67 patients (96%). In our experience, high resolution CT has proven to be a sensitive diagnostic tool for frontobasal skull fractures. With respect to the high coincidence of fractures and dura lacerations, the indication for surgical treatment based on CT findings seems to be justified.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1437-2320
    Keywords: Brainstem acoustic evoked potentials ; click polarity ; cerebellopontine angle ; intraoperative monitoring ; posterior fossa surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The configuration of brainstem acoustic evoked potentials (BAEP) is influenced by the type of click stimuli used and may thus affect detectability of abnormalities. In a group of 19 patients with lesions in the posterior fossa BAEP were recorded pre- and intraoperatively. Repeat recordings were performed in each patient in two alternating series with rarefaction and condensation click stimuli. The findings demonstrated that intraoperative potential changes in latency and amplitude were different between the two stimulation modes, but did not vary significantly in their incidence. It was also not possible to predict from the preoperative BAEP which click polarity would demonstrate intraoperative changes more markedly, taking latency and amplitude as parameters. Two conclusions are drawn from this study: None of the two stimulation modes is superior in detecting intraoperative changes and therefore no recommendation can be made which click polarity to use. When working with only one click polarity it is recommended to use occasional control recordings with the other click polarity.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Neurosurgical review 20 (1997), S. 87-93 
    ISSN: 1437-2320
    Keywords: Brain-stem cavernoma ; microsurgery ; monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present a series of seven patients who were operated on for symptomatic brain-stem cavernomas. The following approaches were used: medial suboccipital (N = 4), lateral suboccipital (N = 1), subtemporal-transtentorial (N = 1), and frontal transcortical-transventricular-subchorioidaltrans velum interpositum (N = 1). Intraoperative motor (N = 4) and somatosensory (N = 1) evoked potential monitoring revealed temporary changes in 3 patients. Immediately postoperatively, the following additional deficits were observed in 6 patients: oculomotor nerve paresis (N = 2), abducens nerve paresis (N = 3), facial nerve paresis (N = 2), deafness (N = 1), and increased ataxia (N = 3). One patient died due to septic complications not related to surgery. After a mean observation time of 2 years, 2 patients had improved, 3 were unchanged, and 1 patient deteriorated as compared to his preoperative status. In conclusion, surgical treatment of brain-stem cavernomas, although carrying a significant risk of temporary neurological deterioration is recommended in symptomatic patients in whom the cavernoma seems to reach the surface of the brain-stem. Intraoperative functional topographic mapping and monitoring have proven useful tools lowering the surgical risks in these patients.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1437-2320
    Keywords: Cervical ventral fusion ; operative technique ; titanium implant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new titanium intervertebral disc for fusion in anterior cervical discectomy is described. The advantages of the device, apart from avoidance of graft explanation, include biocompatibility, simple instrumentation, availability of different forms and sizes, and restoration of physiologic lordosis. Following extensive biochemical testing and implantation in animals, first long-term experience in 15 patients with an average follow-up of three years (28–73 month) are described. Infections, anterior angulation deformities, and graft extrusions were not observed in this series.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Key words Excitatory amino acids ; Therapy-refractory epilepsy ; Ammon’s horn sclerosis ; Quantitative image analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-d-aspartate (NMDA) receptor subunit NMDAR1 and for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon’s horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0533
    Keywords: Key words Ammon’s horn sclerosis ; Calcium-binding proteins ; Cajal-Retzius cells ; Development ; Hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Numerous studies indicate that initial precipitating injuries (IPI) such as febrile seizures during early childhood may play a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon’s horn sclerosis (AHS). Previous data demonstrate an increase of horizontally oriented neurons in molecular layers of hippocampal subfields, which are immunoreactive for calretinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells are transiently expressed in the murine developing hippocampus and are critically involved in neuronal pattern formation. Here we investigated a potential relationship between the distribution of horizontally oriented calretinin-immunoreactive neurons and the clinical history of TLE patients with AHS. Horizontally oriented neurons in the molecular layer of the hippocampal formation have been visualized by antibodies against the calcium-binding proteins calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients with AHS were compared with autopsy specimens from developing and adult normal human hippocampus (n = 26). During ontogeny, CR-ir cells showed a marked perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML) followed by a gradual postnatal decline. In hippocampal specimens from TLE patients with AHS and seizure onset before the age of 4 years, significantly higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P 〈 0.05) were encountered than in AHS patients without precipitating seizures or with an uneventful early medical history. However, all three groups had higher levels of CR-ir neurons compared to adult controls obtained at autopsy (P 〈 0.01). In addition, AHS specimens showed increased CR-ir neuropil staining throughout the DG-ML compared with the restricted distribution of CR-ir fibers within the superficial granule cell layer visible in controls. These findings suggest that a condsiderable number of TLE patients with AHS display signs of impaired hippocampal maturation and circuitry formation as indicated by increased numbers of Cajal-Retzius like cells. It remains to be elucidated, how these changes contribute to the pathogenesis of TLE.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Stem cell ; Tumor ; Malformation ; Epilepsy ; Ganglioglioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The etiology and pathogenesis of complex focal lesions associated with chronic, intractable epilepsy are largely unknown. Some data indicate that malformative changes of the central nervous system may preceed the development of gangliogliomas and other epilepsy-associated neoplasms. In the present immunhistochemical study, we have examined epilepsy-associated lesions for CD34, a stem cell marker transiently expressed during early neurulation. Surprisingly, most tissue samples from patients with chronic epilepsy (n = 262) revealed neural cells immunoreactive for CD34. Prominent immunoreactivity was detected in gangliogliomas (74%), low-grade astrocytomas (62%) and oligodendrogliomas (59%). Only 52% of non-neoplastic, malformative pathologies, such as glio-neuronal hamartias or hamartomas showed solitary or small clusters of CD34-immunoreactive cells. None of the adult control tissues (n = 22), none of the specimens obtained from the developing human brain (n = 44) and none of those tumor samples from patients without epilepsy (n = 63) contained CD34-immunoreactive neural cells. However, a malignant teratoma with microscopic features of early neural differentiation displayed a focal CD34-immunoreactive staining pattern. The majority of CD34-immunoreactive cells co-localized with S-100 protein and a small subpopulation was also immunoreactive for neuronal antigens. CD34 may, thus, represent a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathological changes in epilepsy patients. The CD34 immunoreactivity of these lesions indicates an origin from dysplastic or atypically differentiated neural precursors. Further studies may elucidate the functional significance of CD34 expression during the pathogenesis of epilepsy-related focal lesions as well as during neurogenesis.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0533
    Keywords: Key words: Ganglioglioma ; Hamartia ; Proliferation ; Ki-67 ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gangliogliomas are tumors composed of intimately admixed neuronal and glial components and account for approximately 1   % of all brain tumors. Here we report the histopathological findings in 61 gangliogliomas. Epilepsy was the most common presenting symptom. Most gangliogliomas were located in the temporal lobes (74 %). Thirteen percent of the gangliogliomas were associated with glioneuronal hamartias. There was considerable variation in neuronal size and density, presence of binucleated neurons, calcifications, desmoplasia, lymphocytic infiltrate, pilocytic differentiation, Rosenthal fibers, location, or histological uniformity. Fifteen percent of the gangliogliomas contained areas of purely astrocytic differentiation. All tumors were examined immunohistochemically for an aberrant p53 tumor suppressor gene product and for the presence of nuclear antigens associated with cell proliferation (Ki-67, Ki-S1, proliferating cell nuclear antigen). In 45 of 61 cases (74   %) labeling indices for Ki-67 were less than 1   %. Nuclear labeling for Ki-67 was observed exclusively in the astrocytic component. Gangliogliomas with very large neurons had higher Ki-67 labeling indices and occurred in younger patients than gangliogliomas with small – or intermediate – sized neurons. None of the tumors had an aberrant expression of p53. The observations suggest that gangliogliomas may arise from glioneuronal hamartias through neoplastic transformation of the astrocytic component.
    Type of Medium: Electronic Resource
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