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Biomedical subjects

M G Yasargil

Publications and source records attributed to M G Yasargil.

At least 19 recordsLinked to original sources

Neuropathological findings in 224 patients with temporal lobe epilepsy.

During the period between 1976 and 1990, 247 patients with pharmaco-resistant complex partial seizures and a documented unilateral epileptogenic area in the mediobasal temporal lobe underwent a selective amygdalo-hippocampectomy procedure at our institution. Biopsy specimens from 224 patients (91% of the total) were available for a retrospective histopathological and immunohistochemical review. The tissue specimens of 23 patients without evidence for a macroscopic lesion have been used for neurochemical studies and could not be evaluated histopathologically. The most common temporal lobe pathology were neoplasms in 126 patients, i.e. 56%. Tumor entities observed included 23 astrocytomas (18% of all tumors), 17 gangliogliomas (13%), 15 oligodendrogliomas (12%), 15 cases of glioblastoma multiforme (12%), 13 pilocytic astrocytomas (10%), 12 oligo-astrocytomas (10%), 11 anaplastic astrocytomas (9%) and 20 tumors of various other histologies. In 23 specimens (10%), small foci of oligodendroglia-like clear cells were found. The frequent association of these foci with low-grade gliomas or neural hamartomas raises the possibility that these structures may serve as precursor lesion for neuroepithelial tumors of the temporal lobe. In 98 cases, pathological changes of non-neoplastic origin were encountered. The most common diagnoses in this group included hippocampal gliosis/sclerosis (49 cases, 22%) and vascular malformations (20 cases, 9%). Hamartomas, i.e. focal accumulations of dysplastic neuro-glial cells were diagnosed in 14 patients (6%). In only four cases have we not been able to detect any microscopic pathology. These results indicate that a high proportion of pharmaco-therapy-resistant complex-partial seizures are caused by neoplasms of the temporal lobe, some of which appear to be strikingly overrepresented in this group of patients.

Adolescent

Expression of the epidermal growth factor receptor in astrocytic tumours is specifically associated with glioblastoma multiforme.

Epidermal growth factor and its receptor (EGFR) constitute an important and well-characterized mitogenic system in various ectodermal tissues including glial cells. Over-expression of the EGFR due to gene amplification has been reported in primary brain tumours of glial origin. Using a monoclonal antibody to the EGFR and immunohistochemical analysis, we examined the expression and distribution of EGFR in 103 astrocytic tumours. In addition, selected tumours were studied by Western blotting using a polyclonal antibody to EGFR and by Southern blot analysis. Glioblastomas (WHO grade IV) showed EGFR expression in 37% of cases, whereas pilocytic (WHO grade I), low-grade (WHO grade II) or anaplastic astrocytoma (WHO grade III) were invariably EGFR negative. Generally, there was a close correlation between the presence of EGFR gene amplification and over-expression of receptor protein. Different patterns of immunoreactive cells and significant intratumour heterogeneity of EGFR expression were observed in glioblastomas. The specific association of EGFR over-expression with glioblastoma may provide a useful diagnostic tool for distinguishing anaplastic astrocytoma (WHO grade III) and glioblastoma multiforme (WHO grade IV).

Astrocytoma

Central neurocytoma: histopathological variants and therapeutic approaches.

The central neurocytoma has recently been added to the differential diagnosis of intraventricular tumors. Histopathologically, this tumor is characterized by a uniform neoplastic cell population with features of neuronal differentiation. Central neurocytomas occur in young adults, develop in the area of the foramen of Monro, and are usually associated with the septum pellucidum. Initial reports appeared to indicate that these tumors are benign lesions with a favorable postoperative prognosis. The authors present clinical and neuropathological findings in a series of eight patients with central neurocytoma. An anterior transcallosal microneurosurgical approach yielded good outcomes. Postoperative radiation therapy was restricted to two patients with a malignant variant of central neurocytoma and one patient with a recurrent tumor. Observations of anaplastic variants of this neoplasm in two cases and local tumor recurrences in three indicate that the biological behavior and postoperative prognosis of central neurocytoma may not always be as favorable as previously assumed.

Adult

p53 mutations in nonastrocytic human brain tumors.

Genomic DNA from 51 primary human brain tumors was screened for the presence of mutations in the tumor suppressor gene, p53, using the polymerase chain reaction and single strand conformation polymorphism analysis, followed by direct DNA sequencing. Mutations leading to an amino acid change were found in 2 of 17 (12%) oligodendrogliomas and 2 of 19 (11%) medulloblastomas but none of 15 ependymomas. Sites of mutations were in exon 5 (codon 141), exon 6 (codon 193 and 213), and exon 7 (codon 246). In addition, there were silent mutations in exon 6 (codon 213) in one oligodendroglioma and in one ependymoma. This study points to the possible role of the p53 tumor suppressor gene in some central nervous system neoplasms of divergent histogenesis.

Adult

Cerebellar medullomyoblastoma with advanced neuronal differentiation and hamartomatous component.

This report describes an unusual medullomyoblastoma which developed in the cerebellar vermis of a 6-year-old girl. Histological investigation showed a highly cellular and predominantly undifferentiated tumor. Myogenic differentiation was prominent in clusters of large tumor cells with eosinophilic cytoplasm and immunoreactivity for desmin and myoglobin. Electron microscopy revealed the presence of immature Z-bands. Immunohistochemically, numerous cells showed incipient expression of myoblastic marker antigens, supporting the view that medulloblastomas and related primitive neuroectodermal tumors possess the potential for non-neural differentiation. In addition, there was evidence of advanced neuronal differentiation, with expression of neuron-specific enolase, synaptophysin, retinal S-antigen, and the formation of ganglioid tumor cells. Occassional neoplastic cells expressed glial fibrillary acidic protein without morphologically detectable astrocytic differentiation. Associated with the neoplasm was brain tissue containing clusters of neuronal cells and focal accumulations of immature oligodendroglia-like cells which expressed neuronal marker antigens. This unusual component resembled a hamartomatous lesion and would support the hypothesis that the cerebellar medullomyoblastoma originated from a teratomatous or malformative lesion. Alternatively, this component may constitute the end stage of advanced neuronal differentiation of a primitive neuroectodermal tumor.

Cell Differentiation

Conservative treatment of patients with acoustic tumors.

Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Histogenesis and differentiation potential of central neurocytomas.

The central neurocytoma, a recently identified rare supratentorial brain tumor in young adults, is characterized by intraventricular location and a usually benign clinical course. In order to elucidate the histogenesis and differentiation potential of this neoplasm, we have undertaken an immunocytochemical and molecular biological study of four central neurocytomas. It was found by immunocytochemistry and immunoblotting that all tumors express neuron-specific enolase and synaptophysin. Western blots also revealed expression of the synaptic vesicle protein, synapsin I, neurofilament protein and glial fibrillary acidic protein in several neurocytomas which failed to exhibit immunoreactivity to these marker antigens on paraffin sections. Immunocytochemical reactions with antibodies to synaptophysin and glial fibrillary acidic protein on adjacent sections demonstrated coexpression in individual tumor cells. The neuronal form of the pp60src protein-tyrosine kinase, an oncogene-product specifically expressed in central nervous system neurons, was not detectable in two central neurocytomas investigated. N-myc, a proto-oncogene frequently amplified in childhood neuroblastomas, was present as a single copy gene in all central neurocytomas, indicating that amplification of this gene is not involved in the pathogenesis of the central neurocytoma. In accordance with ultrastructural evidence of synaptogenesis, we conclude that the central neurocytoma is a neuroectodermal tumor with consistent commitment for neuronal differentiation. Since these tumors retain a potential for additional glial differentiation, we propose an origin from bipotential progenitor cells in the periventricular matrix, which in the mammalian brain persists throughout adult life.

Adult

Brain tumors: detection of B-cell stimulatory factor-2/interleukin-6 in the absence of oligoclonal bands of immunoglobulins.

24 patients with neoplasia of the central nervous system (CNS-N) were investigated for the presence of B-cell stimulatory factor-2/interleukin-6 (IL-6) in the cerebrospinal fluid (CSF). Whereas IL-6 was detected in 21 (88%) of these CSF samples, only 6% of CSF from non-inflammatory brain diseases and 12% of the samples from multiple sclerosis patients were positive. IL-6 was found in both primary and secondary CNS-N. The presence of IL-6, a cytokine which activates B-lymphocytes to produce high-rate immunoglobulin (Ig) synthesis, is in contrast to the ineffective intrathecal B-cell activation as suggested by the failure to detect oligoclonal bands of Igs in CNS-N.

Adolescent

Experimental transclival exposure and repair of the abducens nerve in cats.

Operations were carried out on eight cats using a transcervical, transclival approach to expose the sixth cranial nerve just beside the basilar artery. In one case 5 mm of the nerve were resected; three months later no reinnervation was seen. In another cat the nerve ends were merely adapted, and good regeneration was seen despite slight neuroma formation. In a third case TabotampR and Aron-Alpha R were used to repair the skull base; this resulted in a neuroma and in atrophy of the sixth cranial nerve with scar adhesions rendering regeneration impossible. In five cases the transsected nerves were glued together with a fibrin adhesive, with excellent results: very good regeneration and reinnervation occurred within three months with ideal parallel alignment of the nerve fibres at the site of the lesion.

Abducens Nerve

Intracranial repair of the oculomotor nerve in cats.

A total of 21 cats survived experimental microsurgical craniotomies with demonstration of the third cranial nerve via a previously described subtemporal route. In one cat the nerve was resected and no adequate regeneration was observed after three months. In five cases the nerve stumps of the transected third nerve were glued together with Aron Alpha. The results were unfavourable due to atrophy and scar adhesions. Ten cats were treated with lateral slit silicone cuffs around the transected third nerve to keep the stumps together. Good results were obtained after three months. Fibrin glue was used for approximation of the stumps of the third nerve in five additional cases. This was followed by superior results with good regeneration and reinnervation. In 19 cases clinical investigation, photographic records, EMG and caloric nystagmus tests, as well as histological and necropsy studies, proved regeneration after primary repair of the cut third cranial nerve.

Animals

[Experimental microsurgical exposure of cranial nerves III, IV and VI in the cat].

The operative techniques for experimental microsurgical studies on the third, fourth and sixth cranial nerves in the cat are described. We have found that the oculomotor nerve is best reached by a subtemporal approach. The trochlear nerve is easily exposed by a posterior temporal craniotomy while the abducens nerve should be approached through the clivus.

Abducens Nerve

Microsurgical anatomy of spinal subarachnoid space.

The anatomy of the spinal subarachnoid space is reviewed with special reference to the work of Key and Retzius, the authors' own cadaver dissections, and experience from operative cases. It appears that despite some variations in the spinal arachnoid anatomy, there are many consistent features that can serve to guide the operating neurosurgeon.

Adult

[Ophthalmic artery aneurysms].

True saccular aneurysms of the ophthalmic artery are extremely rare; they may produce severe conduction disorders of the optic nerve by compression or hemorrhage. Carotid-ophthalmic artery aneurysms, which originate on the medial or superomedial surface of the internal carotid artery at or near the origin of the ophthalmic artery, are much more frequent. This paper describes signs and symptoms as well as modern microsurgical treatment, and reports the results obtained in a group of 33 patients with a total of 40 carotid-ophthalmic artery aneurysms.

Aneurysm