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Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with an extremely poor prognosis in spite of multimodal treatment approaches. The estimated median survival in cases with GBM is about 12-16 months. Those patients who survive =3 years after the initial diagnosis are defined as long-term survivors. In this study, we retrospectively analyze 50 consecutive cases of Bulgarian patients with newly diagnosed GBM surgically treated at our institution for a period of 1 year. Four of them survived for more than 36 months after the initial intervention. The histological re-examination revealed features typical of primary GBM in 3 of these cases, which are described in detail in the present paper. A brief review of the relevant literature is also given.

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UNLABELLED: Meningiomas are the most common slow growing tumors of the central nervous system which arise from the arachnoid cells. One certain group of them--tuberculum sellae (TS), cavernous sinus (CS), anterior clinoid (AC), and planum sphenoidale (PS) meningiomas, a group often called "parasellar", present with monocular or binocular visual deterioration, which is often unrecognized by patients until visual loss is severe and the tumor has reached a significant size. AIM: To describes the type of visual deficit, severity of the symptoms and surgical treatment of tumors with the above mentioned localization. MATERIAL AND METHODS: During the period 2003-2007 year, 93 patients (31 man, 62 women) diagnosed with meningiomas of the TS (31 cases), CS (16 cases), AC (21 cases), PS (17 cases), (see text) - 8, were diagnosed and operated on in the Department of Neurosurgery, University Hospital "St. Ivan Rilsky", Sofia, Bulgaria. Retrospective analysis was done. RESULTS: Age at diagnosis ranged from 12 to 74 years, but the majority of cases were in the 5th and 6th decade of life. Localization of was: TS 33%, CS 17%, AC 24%, PS 18% and with more than one area affected in 8 %. The most common symptom was slowly progressing loss of monocular visual acuity (81% of cases). 68% of patients presented with already severely deteriorated vision (0.1-0). Neuro-ophthalmological examination (see text) the patients. Computed tomography and magnetic resonance imaging were the main diagnostic methods. "Gross" total resection was achieved in 62%, subtotal in 12%, partial in 26% of the cases. There was early improvement in 57% of the patients. Death due to cardio-respiratory insufficiency occurred in one case. CONCLUSION: the progressive monocular visual deficit is often the first clinical symptom of the parasellar menigiomas. The early diagnosis is important for the success of surgery. Close collaboration between different specialists (ophthalmologists, neurologist and neurosurgeons) is essential for treatment of these tumors and prevention of the visual deterioration.

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INTRODUCTION: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. There is an increasing amount of data demonstrating that the routine histological examination has limited value to predict the tumor biological behaviour. AIM: To compare the clinical, histological and cytogenetical findings in a group of six patients with primary GBM surgically treated in the Department of Neurosurgery at University Hospital "St. Ivan Rilski"- Sofia, Bulgaria. MATERIAL AND METHODS: The studied group consisted of three women and three men with average age of 51 years and 6 months. In all patients the diagnosis was histologically confirmed. A microarray comparative genomic hybridization (CGH) analysis of fresh-frozen tumor tissue samples was also made. RESULTS: In two of the patients the tumor was localized in frontotemporal region, in another two- in frontoparietal, and in the other two- in parietal and occipital respectively. The onset was with headache in three of the cases. The median time between the onset and admission in the clinic was 70 days. Gross-total tumor removal was performed in one patient. In the other five subtotal excision was made. Three of the patients improved after the intervention. One patient deteriorated after the surgery. All patients demonstrated typical histological findings except one who had giant cell subtype of GBM. The microarray CGH analysis determined chromosome 10 monosomy in five patients, trisomy 7 - in four, trisomy 20 - in three, 3q23 deletion - in three, and Yp11.2 deletion - in three. CONCLUSION: GBMs are genetically heterogeneous tumors with different clinical response to standard multimodal treatment regimens. The microarray CGH analysis is a powerful method which can demonstrate the presence of a number of molecular markers with possible predictive value.

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INTRODUCTION: Orbital lymphomas are neoplasms with increasing incidence in recent years in immunocompromised, as well as immunocompetent patients, which defines their social importance. AIM: To describe and analyze the experience of the University hospital "'Sv. Ivan Rilski" with the treatment of this pathology for the period 1997-2008. MATERIAL AND METHODS: Fourteen patients (8 females, 6 males - 13 primary orbital lymphomas, 1 systemic lymphoma). Mean age at diagnosis was 65.6 years (from 50 to 80 years). In 2/3 of the patients the lesion was localized in left eye, without a case with bilateral orbital involvement. Seven cases the diagnosis was made 6 months from the onset of symptoms, 5 cases - 1 year and 2 cases - more than one year. The most common clinical symptoms were exophthalmus (12 case), tumor or bulging mass of the eyelid - 8, diplopy - 6, decreased visual acuity - 5. Intraconal localization of the tumor was in 6 cases, extraconal - 2. intra-extraconal - 6. The diagnosis was made by neuro-ophthalmologist and precised with the aid of CT and MRI. All the patients were operated on with the following approaches - fronto-orbital - 9 cases, lateral - 3, anterior orbitotomy (without bone resection) - 2 cases. In six cases "'gross total" resection was achieved, in the rest of the cases the resection was partial. On histological examination, a high grade lymphoma was established in 2 cases with primary orbital lymphoma and one case with systemic lymphoma. All other cases were diagnosed as low-grade B-call small lymphocytic non-Hodgkin's lymphoma. Long-term survival (over 5 years) was observed in 4 cases with primary lymphoma, whereas the patient with systemic form of the disease died 10 months after the operation.

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Cerebellar lesions have classically been considered not to cause epilepsy. However, previous reports have attributed seizures, beginning as hemifacial spasms to lesions of the cerebellar peduncles. We report an example of paroxysmal facial contractions associated with a cerebellar gangliocytoma. The seizures began on the first day of life and consisted of paroxysmal contractions involving the left orbicularis oculi, often the left forehead and lower facial muscles, sometimes accompanied by nystagmoid eye movements to the right and by head deviation to the left. Video-EEG monitoring showed only artifacts from muscle contractions. Magnetic resonance imaging showed a mass arising from the left superior cerebellar peduncle and partially occupying the fourth ventricle. The lesion was removed subtotally and partial seizure control was achieved. The neuropathological findings were consistent with a gangliocytoma. The literature in the association of cerebellar lesions with hemifacial spasms is reviewed and its possible mechanisms discussed.

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AIMS: The application of endoscope-assisted microsurgery in the treatment of small or medium-sized vestibular schwannomas is of proven value. The goal of our study is to evaluate its usefulness in cases of large schwannomas. PATIENTS AND METHODS: Eighteen patients were included in this prospective study. Their average tumor diameter was 3.9 cm. The retrosigmoid approach was used in all cases. The endoscope was applied during all stages of tumor removal. RESULTS: The facial nerve was visualized endoscopically at early stages of surgery in 9 patients and the abducent nerve in 7 patients. The source of bleeding was identified in 1 case. Tumor remnants in the region of the fundus of the internal auditory canal after apparently total removal were identified in 2 cases. Exposed and unobliterated temporal bone air cells were not observed. DISCUSSION: Even in cases of large schwannomas, the location of the facial nerve can be determined endoscopically early in the procedure. The application of endoscope-assisted microsurgery increases the rate of cranial nerve preservation and of total tumor removal. Although the application of the endoscope did not provide useful information in some cases, it is a safe procedure that did not lead to any complications and/or to considerable prolongation of the operative time. Its application is justified in all cases.

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AIM: The aim of this study is to present the clinical picture of patients with cerebellopontine angle meningiomas and analyze the results of their operative treatment. METHODS: A retrospective study of patients with cerebellopontine angle meningiomas operated consecutively in our department over an 11-year period has been carried out. Data regarding their clinical features, surgical treatment, morbidity, mortality and outcome have been analyzed. Forty-four patients with cerebellopontine angle meningiomas were operated during the period 1991-2001 (intervention: tumor removal via the retrosigmoid suboccipital approach). MAIN OUTCOME MEASURES: clinical condition, MRI/ CT imaging. RESULTS: The median duration of symptoms prior to diagnosis was 44.5 months. The most frequent initial complaints were hearing loss, tinnitus and headache. Most frequent symptoms and signs at presentation were cerebellar, followed by hearing loss and trigeminal nerve symptoms. In 98% of the cases the operative approach used was the retrosigmoidal suboccipital. Total tumor removal was achieved in 55%. After total tumor removal no recurrences have been observed. The mortality rate was 2%. CONCLUSION: The application of different classification schemes complicates the comparison between published series. The outcome depends on their location, consistency, size and relation to the surrounding neurovascular structures. In our experience the retrosigmoid suboccipital approach is most appropriate for their surgical treatment. It offers the possibility to remove completely even large meningiomas and avoids the risk of recurrences.

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Eighty five patients suffering from trigeminal neuralgia resistant to medical therapy underwent surgical treatment for relief of pain at the Department of Neurosurgery University Alexander Hospital Sofia from 1981 until 1997. Microvascular decompression at the root entry zone of the V(th) nerve has been performed using the technique of Jannetta. The operative exploration of the parapontine root entry zone disclosed neurovascular conflicts in 87.1% of the cases. They represented displacement and/or distortion, sometimes pressure grooves, discoloration, altered vascularity of the V(th) nerve. The analysis of early postoperative results have shown an excellent outcome in 90.6% of the cases, good in 3.5% and poor in 2.4% with mortality of 3.5% early in these series when no postoperative monitoring was available. The follow up study one year after surgery revealed 90.2% excellent and 3.7% good results and poor outcome and recurrences in 6.1% of the cases. Patients with long lasting trigeminal neuralgia, previous destructive procedures, venous compression, lack of convincible evidences for neurovascular conflicts had less favorable outcome or recurrences. In the last years partial sensory rhizotomy was performed in cases when no neurovascular conflicts were found out. Patients with unquestionable arterial compression leading to displacement associated with distortion and pressure grooves had excellent outcomes. Early recurrences were associated with missed pathology at the entry zones. During reexplorations for late recurrences new arterial compression was found in less than half of the cases.

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In 15 adult cats the bridging draining into the superior sagittal sinus as well as their main tributaries were dissected under surgical microscope and ligated. Samples of tissue from cerebral cortex (CC) and subcortical white matter (SWM) with presumed disturbances of venous outflow were investigated by means of electron microscopy following different survival times (ranging from 3 to 15 days). The examination of the ultrathin sections from the CC and SWM disclosed signs of severe oedema: extensive areas of oedema fluid accumulation, swollen dendrited and synaptic endings, neurones with mitochondria destruction, disorganised endoplasmic reticulum and polysomal aggregates, prominent number of vacuoles, dendrites undergoing correspondent changes, degenerating axons and synaptic endings. The conspicuous presence of erythrocytes usually in perivascular zones of the neuropil, occluded, ruptured or collapsed capillaries having vacuoles in their endothelial cells were frequently encountered. These findings confirm the light microscopial observations demonstrating haemorrhagic infarctions after venous occlusions. They provide ultrastructural details about the CC and SWM changes resulting from venous hypertension and hypoperfusion.

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A 20-year-old pregnant woman (8th month of gestation) developed signs of intracranial hypertension and coordination disorders. The CT examination demonstrated hydrocephalus, occlusion of the IV ventricle and hyperdense mass lesion in the right cerebellar hemisphere. Following ventricular drainage cesarean section was performed and then total removal of cerebellar hemangioblastoma, which resulted in rapid and complete reversal of neurological abnormalities of the mother and the child.

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Five hundred and five operations for intracranial meningiomas were complicated by 18 postoperative hematomas (POH)--3.56%. The POH were more frequently encountered in older patients and/or patients with atherosclerosis, arterial hypertension and diabetes. Longer lasting operations especially cases with intraoperative fall of blood pressure were more often complicated by POH. The POH were more frequently observed following total excision than partial removal and after convexity meningioma operations than other locations. The outcome of the operations complicated by POH was related to the time of their clinical manifestation and removal.

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The synaptic organization of the subthalamic nucleus (Sth) of the cat has been investigated by means of electron microscopy. On the basis of the following criteria: the size and the shape of the synaptic boutons, their origin, the size and the shape of the synaptic vesicles, the distribution and density of the vesicular population, and the characteristics of the active synaptic zones, several types of synaptic boutons have been discriminated: F1, F2, SR, LR1, LR2, d.c.v., and "d" profiles. The F1 and F2 types have pleomorphic vesicles and form symmetrical synapses with the neuronal perikarya, the proximal dendrites and their spines, as well as with the initial axonal segments. The SR, LR1 and LR2 types contain round or oval vesicles and form asymmetrical synapses mainly with middle sized and small dendrites, and their spines. The d.c.v. boutons contain a mixed population of clear synaptic vesicles and dense core vesicles. The d.c.v. type forms asymmetrical synapses. The "d" profiles share identical features with the vesicle containing dendrites. The F2, SR, LR1, LR2, and "d" profiles take part in synaptic diads and/or triads, and occasionally participate in the synaptic glomeruli. The LR1 and LR2 take part in glomeruluslike formations. The Sth has a distinct synaptic pattern that permits its discrimination as a separate ultrastructural entity. The Sth seems to share some common ultrastructural features with the thalamic nuclei. On the other hand, the ultrastructural aspects of the Sth are much more different from its closest embryological allies: the both pallidal segments, and the zona reticulata of the substantia nigra.

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The fine structure of the neurons in the subthalamic nucleus (Sth) of the cat has been studied. On the basis of the following criteria: the size and the shape of the neuronal perikarya, the ultrastructural characteristics of their organelles, the presence and quantity of somatic spines and their afferentation, three categories of neuronal perikarya were discriminated: large, medium and small neurons. The large neurons have a diameter above 18 microns and nucleocytoplasmic ratio above 1:1,8. These neurons are the richest in organelles, possess the most numerous spines, and are most afferented. According to their shape, the large neurons were subdivided in multipolar, fusiform, and irregular types. The medium sized neurons have a mean diameter between 16 and 13 microns and nucleocytoplasmic ratio 1:1,5-1:1,3. Their cytoplasm contains a lesser number of organelles that are more loosely distributed. The medium neurons possess a small number of somatic spines and are less afferented. The small neurons have a mean diameter below 12 microns and their nucleocytoplasmic ratio is below 1:1,2. Their cytoplasm is poor in organelles and they usually lack spines. The small neurons are remarkably oligoafferented. The large neurons constitute approximately 25%, the medium sized - about 50%, and the small neurons - less than 5% of the neuronal population. The remaining neuronal perikarya do not offer reliable electron microscopical criteria that could allow an unequivocal discrimination.

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Synaptic boutons emanating from axons of nucleus tegmenti pedunculopontinus origin were identified by electron microscopy in the neuropil of the subthalamic nucleus. Such boutons measure 1.5-3 microns, contain round synaptic vesicles and make asymmetrical axodendritic and axosomatic synaptic contacts with large subthalamic neurons. Very few contacts with vesicle-containing dendrites, and no contacts with the perikarya of the small neurons were observed. The present findings, in keeping with the relevant light microscopic and electrophysiologic data, furnish evidence for a substantial bilateral tegmenti pedunculopontinofugal projection that excites monosynaptically the relay subthalamic neurons.

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Young adult cats were subjected to unilateral ablation of the frontal and prefrontal cerebral cortex and were allowed to survive for 4 to 5 days. Routine electron microscopic technique was employed to examine orthograde degenerative changes in the ipsilateral and contralateral substantia nigra (Ni). A moderate number of degenerating synaptic boutons (d. s. b.) were observed in the ipsilateral Ni-pars comacta, and only very few d.s.b. were observed in the ipsilateral Ni-pars reticulata. The d. s. b. exhibited features attributed to the dark degeneration type, and might be referred to two main categories; "small-round-vesicle bouton" and "large-round-vesicle bouton" (Hajdu et al., 1973; Hassler et al. 1975). The d. s. b. performed asymmetrical synapses with dendrites of varying size, much more rarely -- with the neuronal perikarya, and extremely rarely -- with initial axonal segments. No degeneration was observed in the contralateral Ni.

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Our study of the synaptic organization of the baboon subthalamic nucleus has revealed at least nine different types of synapses. Most frequently encountered is the type I (F) axo-dendritic or axo-somatic synapse. It is characterized by scattered flat vesicles and many large mitochondria. The axon terminal is either elongated, tubule shaped (type IF en passant), and undergoes many short button-like en passant junctions with a parallel running dendrite, or it is spindle shaped with similar synaptic contacts (type IFa). In other cases a more compact bouton forms many short junctions at the same time with a dendrite and a beak-shaped spine springing from it. A smaller bouton with flat vesicles, which show a tendency to fuse together (type IIF) usually undergoes slightly asymmetric contacts with two vesicles-free dendrites between which they frequently appear wedged. Three types of boutons with small, round vesicles have extended asymmetric contacts forming elongated (type III), star-shaped (type IV), or oval (type V) synapses. The latter form contacts mostly with dendritic terminals or spines. Another type of synapses contain larger, pale, pleomorphic vesicles (VI (SO)): The bouton is more compact and often in contact with a dendritic terminal. Type VII (LO) shows a looser arrangement of vesicles intermingled with more dense core vesicles. Type VIII (F) is a dendritic terminal with loosely arranged, flat vesicles and is in contact either with a type VI or with a type VII P bouton. Finally, there is an axo-spinous microsynapse type IX, which partly degenerates after contralateral pallidum externum coagulation. A few axon preterminals filled with dense core vesicles do not undergo synaptic contacts.

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The present study demonstrates the existence in the baboon of a powerful ipsilateral pallido-subthalamic projection, composed of myelinated fibers. These axons give rise to type I (F) terminals, including all subtypes identified by Hassler et al. (1982), and terminate on the perikarya of the subthalamic relay neurons, on proximal dendrites, and on somatic and dendritic spines. Endings on subthalamic interneurons could not be found. Following experimental lesions in the pallidum externum, these pallido-subthalamic neurons undergo distinctive changes characterized as "pale", "intermediate" and "dark" degeneration, the form of the degeneration depending on the survival times of 3, 4 and 5 days. The ratios between the individual types of degeneration may vary. The ultrastructural features of the pallido-subthalamic terminals, which are believed to be GABA-ergic (Fonnum et al., 1978), are different from those of the GABA-ergic striato-nigral connections (Kim et al., 1971). After pallidum externum lesions, the pale form of degeneration is found in a few instances in the contralateral subthalamic nucleus in the type IX mini-synapses and the type I (F) beak-shaped synapses. There is a considerable convergence of different afferents with specialized synapses on the somata, stem dendrites, and dendritic spines of the neurons of the subthalamic nucleus.

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Modifications of the selective silver impregnation methods of Nauta and Fink-Heimer are described. Both procedures were tested in wide variety of species: from reptiles to carnivores, as well as in human autoptic cases. The modified Nauta procedure is recommended as a method of choice for tracing axonal trajectories due to an improved impregnation selectivity of the degenerating axoplasm. Its use for the demonstration of monoaminergic (NA, DA, 5-HT) pathways, however, remains limited. The modified Fink-Heimer procedure demonstrates successfully the degeneration of axons, and especially--the thin preterminal arborizations, as well as the terminal boutons in many fiber systems studied, including the nigrostriatal, raphe-nigral, and coerulocortical tracts. Both methods provide an additional cytoarchitectonic orientation due to a counterstain of nerve cell bodies with cresylechtviolett.

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The degenerative changes within the cat's subthalamic nucleus (Sth) following lesions of the external pallidum were studied by electron microscopy. Four to five days following pallidal lesions a great number of terminals undergoing degenerative changes were encountered in the ipsilateral Sth. The contralateral Sth was free of degeneration. The degenerating terminals show predominantly the light degenerative type, less frequently the dark degenerative pattern, and occasionally exhibit signs of filamentous hyperplasia. The degenerated boutons usually insert on perikarya of the large Sth neurons, on proximal dendrites, and more rarely contact dendritic spines. They were observed neither to perform synaptic contacts with the perikarya of the small Sth neurons nor with other vesicle-containing profiles. On the basis of the ultrastructural aspect of the degenerating terminals, they were identified as F1 terminals, discriminated in a previous study (Romansky et al., 1978). The normal appearance, the synaptic relationships, and the degenerative features of the F1 terminials in the Sth closely resemble the entopeduncular terminals in the thalamus described by Rinvik and Grofová (1974a), and Grofová and Rinvik (1974). The possible contribution of the interrupted passing fibers to the observed degeneration is discussed. The present findings corroborate the relevant morphological, physiological, neurochemical, and neuropharmacological data in the literature.

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