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Sporadic Creutzfeldt–Jakob disease is a rare and fatal human prion disease characterized by a rapidly progressive dementia, myoclonus, cerebellar, pyramidal, extrapyramidal, visual, and psychiatric symptoms. These findings are all non-specific and making diagnosis is often difficult at the symptoms onset, especially in case of atypical clinical and radiological presentation. This case report describes a woman in her 60s, who presented with rapid cognitive decline, confusion, ataxia and electroencephalographic changes compatible with nonconvulsive status epilepticus. Her symptoms progressively worsened and she died 8 weeks after the onset. The two cerebrospinal fluid analyses were normal and no 14-3-3 protein was detected. The brain MRls revealed areas of cortical restricted diffusion involving the right frontal and parietal lobe. The electroencephalographic findings of continuous periodic generalized bi-triphasic complexes, typical for sporadic Creutzfeldt–Jakob disease, were detected 1 month after the onset. Sporadic Creutzfeldt–Jakob disease was neuropathologically confirmed. Although sporadic Creutzfeldt–Jakob disease is a rare neurodegenerative disease, it should be considered in the differential diagnosis of all cases with unexplained and rapid cognitive decline and confusion, along with ataxia, pyramidal/ extrapyramidal signs, myoclonus and dysphagia.

Аs many other viral pandemics, the current SARS-CoV-2 is also characterized by nervous system involvement, mainly in elderly patients with comorbidities. Recent scientific reports indicate that involvement of the nervous system is manifested by a variety of clinical symptoms related to the severity and extent of brain damage. Encephalopathy, encephalitis and polyneuritis are among the complications reported in patients with SARSCoV- 2. These complications have been morphologically proven. As an immune-privileged structure, neural tissue is particularly vulnerable to autoimmune attacks. Therefore, various neurological diseases such as MS, Guillain-Barre syndrome, as well as autoimmune encephalitis and psychosis have also been reported in patients with SARS-CoV-2 infection. Herein, we present three cases of patients who died after infection with the SARS-CoV-2 virus. We emphasize on the pathomorphological changes found in a detailed study of the brain and cervical spine. The analysis of the inflammatory findings, mainly manifested by perivenous lymphocytic infiltrates, serodiapedesis and erythrocyte depots around the vessels, showed a presence of initial demyelination (in two of the cases). The blood supply of most venous vessels with different size and a pronounced “sludge” phenomenon were the most impressive findings, as in some sections these changes were demonstrated by a presence of thrombosis. Inflammatory manifestations were also observed in the brainstem near to the stem nuclei. The SARS-CoV-2 virus induces a variety of immune system responses. In some patients there is a negligible or no reaction, while in others there is a “cytokine storm” with a system damage of multiple organs – often including the brain.

The article presents a case study of a 58-year-old man with a 1-year history of involuntary movements of the left side of the face and progressive visual blurring. It discusses results of his neurological examination, computed tomography (CT), and magnetic resonance imaging (MRI). The patient was diagnosed with glioblastoma multiforme (GBM) and pituitary adenoma (PA) in association with colorectal carcinoma (CC).

Herein, we report the first case of mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) in Bulgaria. It is a newly recognised clinico-pathological entity with medically intractable focal epilepsy in paediatric patients. The patient of interest is a 9-year-old boy who has been suffering from refractory epilepsy since the age of three. Positron emission tomography revealed a consistent hypometabolism with maximum in the orbitofrontal and fronto-opercular cortex, as well as in the adjacent anterior insula and the anterior temporal regions. A left frontal corticotomy anterior from the precentral sulcus, left insulectomy and temporal disconnection were performed. Pathomorphological examination of the material from the resected brain tissues demonstrated oligodendroglial hyperplasia with blurring of grey-white-matter boundaries and presence of subcortical heterotopic neurones. Eighteen months post-surgically the patient is seizure-free and drug-free. The observed oligodendroglial hyperplasia with increased proliferative activity and heterotopic neurones in the white matter with blurring of grey-white-matter junctions are the histopathological hallmarks of MOGHE. More new cases are needed to establish further data about this distinct entity in frontal lobe epilepsy.

Focal cortical dysplasia (FCD) represents a heterogeneous group of morphological changes in the brain tissue that can predispose the development of pharmacoresistant epilepsy (recurring, unprovoked seizures which cannot be managed with medications). This group of neurological disorders affects not only the cerebral cortex but also the subjacent white matter. This work reviews the literature describing the morphological substrate of pharmacoresistant epilepsy. All illustrations presented in this study are obtained from brain biopsies from refractory epilepsy patients investigated by the authors. Regarding classification, there are three main FCD types, all of which involve cortical dyslamination. The 2022 revision of the International League Against Epilepsy (ILAE) FCD classification includes new histologically defined pathological entities: mild malformation of cortical development (mMCD), mild malformation of cortical development with oligodendroglial hyperplasia in frontal lobe epilepsy (MOGHE), and "no FCD on histopathology". Although the pathomorphological characteristics of the various forms of focal cortical dysplasias are well known, their aetiologic and pathogenetic features remain elusive. The identification of genetic variants in FCD opens an avenue for novel treatment strategies, which are of particular utility in cases where total resection of the epileptogenic area is impossible.

Purpose: to study brain metastases (BM) and their corresponding primary lung cancers (LCs)., Methods: Surgically resected BMs and their corresponding primary LCs from 30 patients (25 men, 83%; age 55±9 years) were studied: 21 adenocarcinomas (ACs), 5 squamous cell carcinomas (SCCs), 4 small cell lung carcinomas (SCLCs). The histological subtype, immunohistochemical expression of TTF1, p63, Ki67 (proliferative activity), CD31, number of intratumoral microvessels, (NIM) and survival were evaluated., Results: There was a different histological structure in 47% of the cases of ACs of the lung in comparison with the corresponding metastasis, but none in SCC and SCLC. TTF-1 was expressed in a greater number of ACs (n=20; 95%), with lower mean expression levels, while the corresponding BM expressed the marker less frequently (n=16;76%) with higher mean expression values (p=0.011). P63 was expressed in all SCCs (p=0.68). Cytokeratin 7 was expressed equally in all ACs. Ki-67 proliferative index (PI) was higher in SCLC than in AC (p=0.008), in SCLC BM than in AC BM (p<0.001), and in SCLC BM than in SCC BM (p=0.008). The Ki-67 PI in BM was higher than in AC (p=0.003), SCC (p=0.048), but without difference in SCLC (p=0.141). CD31 NIM was higher in AC than in SCLC (p=0.003), in SCC than in SCLC (p=0.009), while no difference between AC and SCC was found (p=0.467). There were no differences between LC/BM in the NIM. Survival after surgery for LC was significantly longer in AC than in SCLC (p=0.017). SCLC histology and Ki67>18% were established as negative prognostic factors after surgery for LC. Such factors were not found after surgery for BM., Conclusion: There are differences between primary LC and corresponding BM - in histology, immunohistochemical expression and proliferative activity, but there are no significant differences in vascularization. SCLC histology and Ki67>8% may represent negative prognostic factors after surgery for LC with BM.

Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics-first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGF β , CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM.

Optic nerve glioma (ONG) is associated in 10% of patients with neurofibromatosis (NF) type 1. To date no consensus has been reached regarding the therapeutic approach and prevention of visual impairment in these patients. Reports in the literature vary from a conservative approach (observation) to the use of single treatment modalities or multimodality protocols of surgical removal, radiotherapy, and/or chemotherapy. We present our experience with two siblings with ONG whose mother carries cutaneous stigmata of NF type 1. The younger sister was diagnosed 3 years after the treatment of the older sibling following recommended imaging for screening. Postoperative follow-up for 11 and 15 years, respectively, demonstrated lack of tumor regrowth and preserved vision in the contralateral eye. We discuss the treatment strategy in pediatric patients with orbital ONG associated with NF type 1., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Successful use of high-dose fluorescein-sodium (20mg/kg) with a standard light microscope for resection of high-grade gliomas, meningiomas, hemangioblastoma and metastases was reported. The principle of brain tumor staining by fluorescein-sodium (Fl-Na) consists in the accumulation of fluorescein in brain tumors with impaired blood-brain barrier. The aim of our study was to investigate for the first time the usefulness of high-dose fluorescein in patients operated on for benign neuroepithelial brain tumors (grade I WHO tumors) with contrast enhancement on magnetic resonance imaging., Methods: Our study included 11 patients operated on for benign neuroepithelial primary brain tumors with contrast enhancement on magnetic resonance imaging (MRI): pilocytic astrocytomas (5 patients), dysembrioplastic neuroepithelial tumors (4) and gangliogliomas grade I (2). In all cases, Fl-Na was injected intravenously (20mg/kg) just after the craniotomy using a peripheral venous line. The dural opening was performed 10min later. Microsurgical tumor resection using conventional neurosurgical microscope guided by the fluorescein staining was performed., Results: Complete resection of the yellow-green stained tissue was achieved in 10 patients confirmed by postoperative control MRI study. Subtotal resection of the colored tissue was achieved in one case with fourth ventricle pilocytic astrocytoma because of the involvement of the medial eminence and functional constraints discovered during intraoperative neuromonitoring. Three patients have had a postoperative volume of resection greater than the tumor volume because of the planed perilesionectomy by our epilepsy surgery team. Surrounding tissue not stained by Fl-Na was obtained in these 3 cases. The histopathological examination did not find tumor tissue in the perilesional Fl-Na negative tissue. On the other hand, all 11 Fl-Na positive specimens presented signs of tumor involvement. We did not observe complications related to the use of high dose Fl-Na., Conclusions: High doses intravenous Fl-Na seems to be a useful intraoperative technique for delineation of benign neuroepithelial brain tumors with contrast enhancement. Further larger studies may reveal the real value of high doses Fl-Na as intraoperative method for increasing the extent of resection in these particular indications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Glioblastoma multiforme (GBM) is the most common and malignant tumor in the central nervous system. One of the contemporary hypotheses postulates that its pathogenesis is associated with the cancer stem cells (CSCs) which originate from mutations in the normal neural stem cells residing in their specific "niches." Simultaneously with its aggressive development the tumor suppresses the local immune system by different secreted and/or cell expressed factors. Progesterone-induced blocking factor (PIBF) is an immunomodulatory protein with known role in the regulation of the immune response in the reproductive system. Expression of PIBF has been described in some tumors as one of the factors suppressing the anti-tumor immunity. The aim of the present study was to check for the expression of PIBF from cells isolated from six GBMs. To characterize the cultured cells and to study the PIBF expression confocal microscopy, flow cytometry, ELISA, and real-time PCR were used. The results obtained showed expression of markers typical for cancer CSCs and secretion of interleukin 6 by the GBM-derived cultured cells. The results convincingly prove that PIBF is intracellularly expressed by the cultured cells from the all six GBM samples, and this fact is confirmed by three different methods-flow cytometry, confocal microscopy, and real-time PCR. This paper reports for the first time the expression of PIBF by GBM-derived cells cultured in vitro and reveals a new aspect of the immunosuppressive mechanism used by GBM in escaping the immune control.

Glioblastoma multiforme is the most common primary malignant brain tumor in adults. The actual treatment approach includes surgical excision of the lesion followed by radio- and chemotherapy in standard doses and regimens. In most cases, in spite of aggressive treatment, the survival does not exceed 12-16 months after the initial diagnosis. The present survey provides systematic information about the current treatment modalities for control of the disease as well as the perspectives of introduction of some experimental methods in clinical practice.

Introduction: Ganglioglioma is an uncommon type of primary brain tumors. In most of the cases the tumor demonstrates benign clinical behaviour with long-term patients' survival. We present two cases ofhistologically confirmed anaplastic ganglioglioma in which malignant progression into a glioblastoma multiforme was seen. CASE 1: A 36 year-old female with known Turner syndrome and recent history of single generalized seizure. The contrast-enhanced magnetic resonance imaging (MRI) showed an infiltrating lesion of the left frontal lobe. The tumor was excised partially and the histological result was anaplastic ganglioglioma (World Health Organization - WHO. gr. III). No additional neurological deterioration occurred after the procedure. A postoperative radiotherapy was performed with total dose of 60 Gy. The patient was symptom-free for one year taking her anticonvulsant medications. Control neuroimaging studies (computer tomography - CT, and MRI) were made because of progressive headache, right limbs weakness and speech disturbances. A local tumor recurrence was found and the patient underwent second operative intervention with gross total tumor resection. The histological result was glioblastoma multiforme (WHO gr. IV glioma). The patient improved after the procedure. An involvement of the contralateral cerebral hemisphere was found on control CT-scan ten months later. The patient died after one month, 23 months after her initial diagnosis. CASE 2: A 17 year-old female with recent history of progressive headache and three generalized seizures preceded by involuntary movements of the right limbs. MRI data for large, heterointense tumor lesion in the left frontal lobe was found. A subtotal tumor removal was made. The histological result was anaplastic ganglioglioma (WHO gr. ILL). The patients' headache and right side hemiparesis improved after the intervention. She was seizure-free taking her anticonvulsant medications. Thirty-day-long fractionated radiotherapy was performed with total dose of 60 Gy. The patient remained symptom-free for thirteen months after initial surgical procedure. During the next month the patients, partial motor seizures relapsed. Progressive headache, diplopia, and visual acuity impairment also developed. The ventriculoperitoneal shunt was implanted with neuroimaging data for internal hydrocephalus development. The patients' headache and visual disturbances improved after the procedure. Data for additional local tumor growth was found on control CT-scan one month later. The patient underwent subtotal excision of the lesion and the actual histological result was glioblastoma multiforme. The patient deteriorated after the intervention according to her right limbs paresis and died one month and half later. 20 months after the initial diagnosis., Conclusion: The gangliogliomas are uncommon in clinical practice. The tumor behaviour may vary between the patients in spite of the similar histological characteristics which indicates the possible presence of different tumor subtypes.

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.

Unlabelled: Patients with ischemic mitral incompetence have a high operative risk and the advantage of repair over replacement in those patients is unclear. In cases of moderate mitral regurgitation and coronary artery disease operative strategy continues to be debated between coronary artery bypass grafting (CABG) alone and concomitant valve replacement or repair. The objective of the study is to review our experience with the different surgical treatments and to assess the impact of pre- and intraoperative factors on mortality, morbidity and long-term survival., Methods: From July 1990 to May 2000, 102 patients with ischemic mitral regurgitation > 2 + grade underwent operative treatment. CABG alone was performed in 52 and combined procedures in 50 cases (18 replacements and 32 repairs). Mitral repairs were accomplished by Carpentier or Key techniques and/or ring implantation. All replacements were done with preservation of the posterior mitral valve leaflet., Results: Overall mortality is 11(10.8%)-3 patients (5.8%) in the CABG group and 8 (16%) in the combined group (3-16.7% for replacement and 5-15.6% for repair). There was 7 late deaths in both groups. Five year survival was 78% for CABG, 78% for repair and 76 for replacement., Conclusions: In high risk patients with ejection fraction < 35% and mitral regurgitation < 3 + grade we recommend CABG alone. Valve replacement is the procedure of choice in case of papillary muscle rupture. All patients need complete revascularisation. Good results are obtained with repair techniques and ring implantation.

We investigated the immunohistochemical expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and of its endothelial cell receptor flt-1 in relationship to microcyst formation in meningiomas. Expression of VPF/VEGF was studied in 60 meningiomas (6 microcystic, 38 partially microcystic and 16 with no microcystic areas) and 30 meningiomas from these three subgroups were evaluated for flt-1 expression. VPF/VEGF immunoreactivity was mainly observed in vessel endothelium. Positive vessels were present in 75% (33/44) of meningiomas with any amount of microcystic pattern and in 38% (6/16) of the solid meningiomas (P < 0.02). Densities and percentages of both VPF/VEGF-positive and flt-1-positive vessels were higher in meningiomas with microcystic areas than in solid meningiomas (P /= 0.75, P < 0.0001). A strong positive correlation between VPF/VEGF-positive vessel density and proportion of microcystic pattern in all 60 specimens was found (r = 0.75, P < 0. 0001). We conclude that accumulation of flt-1-bound VPF/VEGF on endothelial cells of meningiomas is associated with microcyst formation that leads to the histologic appearance of microcystic meningiomas.

The morphological investigation in an experimental model of lead (Pb) encephalopathy (according to the method of A. Pentschew, 1966) is presented. Electron microscopy-dense inclusions are found out in the nuclei and cytoplasm of astrocytes and in some ependyma cells in the investigated cortical and subcortical (paraventricular) structure of the brain and spinal cord. This confirms the direct toxic action of Pb on these structures and proves their participation in pathogeneses of the developing encephalopathy. The established inclusions in the ependyma and the data about a disturbance of the blood-brain barrier give a reason to be proposed the possibility for a penetration of Pb in the nervous system not only through a blood but also through a cerebrospinal fluid way.

A case of polypous endocarditis which affects the tricuspid valve and whose genesis remains unclear (a septic state, an idiopathic disease?) is described. Clinically the disease has taken its course as a chronically recurring form of pulmonary thromboembolism. Morphologically it concerns to a massive fibroplastic verrucous endocarditis of the tricuspid valve and a more slightly expressed similar process in the wall of the right atrium and ventricle, combined with a significant fibrosis of the myocardium. The death has come from a massive thrombotic embolism in the two branches of the pulmonary artery on the background of a great number of small thromboembolic and hemorrhagenic infarctions with a different duration in the two lobes of the lung, which lead to an adaptable reconstruction of many lung vessels. The presence of a discrete affection of the aortic valve according to a rheumatic type and the combination of the disease, in the described case, with essential hypertension and thrombophlebitis undergone in the past, give a reason to discuss the possibility of taking into account these diseases in etiopathogenesis of the described myocardiopathy.

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.

A morphological study on experimental model of lead (Pb) neuropathy (by the method of Pentschev, A., 1966) was described. Dense inclusions in Schwann's cells and satellite cells of the sensory ganglia were found by an electron microscope in the examined peripheral nerves (n. ischiadicus) and sensory ganglia (g. lumbale and g. trigeminale--Gasseri). These finding supported direct toxic action of Pb on these structures and proved their participation in the pathogenesis of developing neuropathy.

The authors present one lethal case of primary pulmonary hypertension (PPH) in a male of 40. The pathomorphological examination revealed very characteristic changes in the vessels of the lungs. Often slot-like canals were found, with proliferated myoepithelial cells, connecting the lumena of vessels with thickened walls with thin-wall vessels ("plexiform changes") or with vessels with sinusoidal-cavernous type ("angiomatoid formations"). Those vascular changes are in a strong contrast with the absence of inflammatory alterations in the lungs. The possibilities of developing of similar vascular changes in the lungs, leading to PPH are discussed in accordance with the up-to date literature data.

A case with multiple endocrine neoplasia was reported, including parathyroid adenoma, of the main cells of the gland, multiple small adenomas in the tail of pancreas, (cytologically and electron-microscopically determined as A cellular) and light-cellular adenoma of adrenal. The hyperfunction of parathyroid adenoma was manifested with hypercalcemia (3.75 mmol/l), and morphologically--with the multiple calcium metastases in lungs, kidneys and heart, established at necropsy. The cause for the death was the acutely advanced ischemic disease of myocardium, on the background of chronic pyelonephritis and renal insufficiency. The timely diagnosis of such morbid states is concluded to be important for the clinical practice and could lead to the saving of the patients by operative removal of the tumour.

An enzootic of necrotic dermatosis in hen layers was described. The changes consisted in that they had constant localization and demarkated sites on the skin between the back and the neck. The disease was observed on a farm for 5000 layers in the course of two consecutive years. All birds contracted the disease and in the first year they recovered the 10 months; in second year they recovered for three months. Each bird showed symptoms for 3 weeks. The skin lesions resulted in cicatrization. The etiologic agent (a Pasteurella-like organism) was isolated from the necrotic foci. It proved pathogenic for albino mice and manifested biochemical activity and morphology characteristic of Pasteurella multocida. The disease was successfully reproduced with a broth culture applied on a scarified skin of test birds. Histopathologically, the spontaneous lesions proved undistinguishable from the experimental ones and represented coagulation necrosis of the epidermis, derm, and subcutis. It is supposed that the constant localization was due to the porte d'entrer of the infection, associated with the bad habit of picage on the neck as demonstrated on a large scale by the birds of the infected flock. This is characteristic of some lines of the White Leghorn breed.

A case is presented of a 28-year-old man with Hand-Schüller-Christian's disease whose initial manifestations were skull bones lesions and a diffuse interstitial fibrosis. Three years later the patient developed diabetes insipidus without changes in the hypothalamic-hypophysial region on computed tomography. Some features of the clinical picture are discussed.