Tumor cells are characterized by aberrant glycosylation of the cell surface glycoconjugates. Gangliosides are sialylated glycosphingolipids highly abundant in neural tissue and considered as tumor ...markers and therapeutic targets. In this study, a detailed characterization of native ganglioside mixtures from glioblastoma multiforme, corresponding peritumoral tissue and healthy human brain was performed using mass spectrometry and high performance thin layer chromatography in order to elucidate their roles as tumor-associated antigens. Distinctive changes in ganglioside expression were determined in glioblastoma compared to healthy brain tissue showing 5 times lower total ganglioside content and higher abundance of simple gangliosides. Glioblastoma gangliosides were characterized by highly diverse ceramide composition with fatty acyl chains varying from 16 to 24 carbon atoms, while in normal and peritumoral tissue mostly C18 chains were found. The most abundant ganglioside in glioblastoma was GD3 (d18:1/18:0), followed by GD3 (d18:1/24:0) that was exclusively detected in glioblastoma tissue. Peritumoral tissue expressed higher abundance of GD3- and nLM1/GM1-species while lower GT1-species vs. normal brain. O-Ac-GD1, known as neurostatin, was detected in normal and peritumoral tissue, but not in glioblastoma. O-Ac-GD3 species were found exclusively in glioblastoma; MS structural characterization of the isomeric form possessing the O-acetylation at the inner sialic acid residue confirmed our previous finding that this isomer is glioma-associated. This, to our knowledge, the most detailed characterization of ganglioside composition in glioblastoma and peritumoral tissue, especially addressing the ceramide variability and O-acetylation of tumor-associated gangliosides, could contribute to recognition of new molecular targets for glioblastoma treatment and sub-classification.
•Gangliosides were analyzed in glioblastoma, peritumoral tissue and healthy brain.•Glioblastoma gangliosides expressed ceramide variability and changed O-acetylation.•The most abundant gangliosides in glioblastoma were GD3 with variable ceramides.•Higher abundance of GD3- and nLM1/GM1 was found in peritumoral than normal tissue.•Mass spectrometry confirmed O-Ac-GD3 from glioblastoma as glioma-associated isomer.
In this study, we developed a high-resolution tandem mass spectrometry (HR MS) approach to assess presumed changes in gangliosidome of a human hippocampus affected by temporal lobe epilepsy (TLE) in ...comparison with a normal hippocampus. Gangliosides, membrane glycolipids, are particularly diverse and abundant in the human brain, and participate in ion transport and modulation of neuronal excitability. Changes in structural ganglioside pattern potentially linked to TLE molecular pathogenesis have not been explored in detail. Aiming to characterize TLE-specific gangliosidome, we analyzed the native gangliosides purified from a human hippocampal tissue sample affected by TLE and a control hippocampus using HR MS. Marked differences of ganglioside expression were shown in TLE vs. control, particularly with respect to the sialylation degree of components, discovered as a characteristic feature of TLE. Another major finding is the occurrence of tetrasialofucogangliosides in TLE and species modified by either O-acetylation or CH3COO−. Structural analysis by higher-energy collisional dissociation (HCD) MS/MS gave rise to fragmentation patterns implying that the GQ1b (d18:1/18:0) isomer is specifically associated with TLE. Further investigation in a larger sample is needed in order to confirm the discovery of ganglioside structures specifically expressed in human TLE and to provide information on the probable role of gangliosides in the molecular events underlying seizures.
Gangliosides serve as antitumor therapy targets and aberrations in their composition strongly correlate with tumor growth and invasiveness. Anaplastic ganglioglioma is a rare, poorly characterized, ...malignant neuronal–glial tumor type. We present the first comparative characterization of ganglioside composition in anaplastic ganglioglioma vs. peritumoral and healthy brain tissues by combining mass spectrometry and thin-layer chromatography. Anaplastic ganglioglioma ganglioside composition was highly distinguishable from both peritumoral and healthy tissue despite having five to six times lower total content. Ten out of twelve MS-identified ganglioside classes, defined by unique glycan residues, were represented by a large number and considerable abundance of individual species with different fatty acid residues (C16–C24) in ceramide portions. The major structurally identified class was tumor-associated GD3 (>50%) with 11 species; GD3 (d18:1/24:0) being the most abundant. The dominant sphingoid base residue in ganglioside ceramides was sphingosine (d18:1), followed by eicosasphingosine (d20:1). The peritumoral tissue ganglioside composition was estimated as normal. Specific ganglioside composition and large variability of ganglioside ceramide structures determined in anaplastic ganglioglioma demonstrate realistic ganglioside expression patterns and correspond to the profile of high-grade malignancy brain tumors.
Intracranial aneurysms located on distal arterial branches are sporadic and scarce. They account for 2%-7% of the middle cerebral artery and 0.7%-2.3% of the posterior cerebral artery aneurysms, ...where they mainly arise distally from the P2-related sites. Such aneurysms usually remain asymptomatic prior to rupture, making their diagnosis and management really demanding. Endovascular treatment comprising of different neurointerventional techniques is becoming the most operational up-to-date routine to approach distal cerebral branch aneurysms. In this single-institution case series, endovascular selective coiling and/or parent vessel occlusion resulted in successful and total aneurysmal exclusion from cerebral circulation, which brought good recovery. Hereby, we present an illustrative case series of distal arterial branch intracranial aneurysms, discussing their possible etiology and various endovascular management modalities. We also provide a literature retrospection concerned with this rare entity. In conclusion, due to their predisposition for rupture, distal branch intracranial aneurysms should be treated early and aggressively. We do believe that endovascular selective coil occlusion is the management method of choice, while parent vessel occlusion (with liquid embolics) is optimal when aneurysmal coiling cannot be achieved, or when distal cortical territory is well vascularized by strong collateral cerebral circulation.
Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. ...Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke. Metabolomics has been shown as a promising tool for biomarker discovery since many post-ischemic metabolites can be found in the plasma or serum of the patient. In this research, we performed a comparative targeted metabolomic analysis of stroke thrombi, stroke patient serums, and healthy control serums in order to determine the alteration in the patients’ metabolomes, which might serve as biomarkers for early prediction or stroke prevention. The most statistically altered metabolites characterized in the patient serums compared with the control serums were glutamate and serotonin, followed by phospholipids and triacylglycerols. In stroke thrombi compared with the patients’ serums, the most significantly altered metabolites were classified as lipids, with choline-containing phospholipids and sphingomyelins having the highest discriminatory score. The results of this preliminary study could help in understanding the roles of different metabolic changes that occur during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers for ischemic stroke.
Intraventricular meningiomas are rare and make up between 0.5% and 3% of all intracranial meningiomas, representing one of the most challenging tumors in neurosurgery due to their difficult location. ...Being initially asymptomatic, such tumors usually attain large size before clinical presentation and diagnostic detection. Available literature concerned with their surgical management remains scarce. Herein, we present a case of microsurgical resection of incidental intraventricular meningioma in a 32-year-old female patient who was admitted to the hospital due to the sudden loss of consciousness, retrograde amnesia, and nausea following a head trauma. Routine brain magnetic resonance imaging revealed an irregular expansive formation located in the occipital horn of the right lateral ventricle showing heterogeneous contrast enhancement. The patient underwent right-side temporal osteoplastic craniotomy with total tumor microsurgical resection followed by external ventricular drainage, and recovered fully afterwards. Histopathologic analysis of tumor tissue samples confirmed the tumor as meningioma WHO grade I. Postoperative brain computed tomography confirmed complete tumor resection. In conclusion, intraventricular meningiomas are rather rare extra-axial tumors and may present with various symptoms depending on their size and difficult location. The development of most modern neuroimaging methods offers the opportunity of their precise and accurate diagnosis, better surgical planning, and favorable outcome. Microsurgical gross resection utilizing intraoperative neuromonitoring and cutting-edge neurosurgical armamentarium remains the treatment of choice for these location-challenging and surgically demanding, predominantly benign intracranial tumors.
Neoplastic etiology of intracranial cerebral aneurysm is rare. Yet, the risk of its development is higher in malignant tumor patients receiving radiation therapy. Due to the possible negative effects ...of irradiation on intracranial vessel walls, the risk of aneurysm formation after radiation therapy, which is crucial for some types of breast cancer patients, continues to be a matter of debate. The aim of this study was to evaluate the hazard of multiple intracranial aneurysm development in patients with malignant disease undergoing radiation therapy. It is based on literature review and case report of a 77-year-old female patient who underwent surgery for multifocal invasive hormone-receptor positive ductal breast carcinoma of no special type, followed by chemotherapy, adjuvant radiation and hormone therapy. Her comorbidity included arterial hypertension and type 2 diabetes. Six unruptured intracranial aneurysms of different bilateral locations were diagnosed incidentally by multi-slice computed tomography angiography and digital subtraction angiography of cerebral vessels. Due to the bilateral aneurysm multiplicity, tumor characteristics and prognosis, comorbidity and relatively advanced age, the patient was not selected for active endovascular or microsurgical aneurysm treatment but only periodical clinical, oncologic and radiological follow-up was advised. In conclusion, the risk of multiple intracranial aneurysm formation in patients with breast cancer undergoing radiation therapy is low, but still possible. Long-term follow-up and regular cerebral angiographic check-up studies are necessary in selected malignant patients to decrease such a risk and to evade the worst outcome associated with aneurysm rupture.
Dysembryoplastic neuroepithelial tumors (DNETs) are benign neoplasms classified in the category of glioneuronal tumors. The estimated incidence of DNETs is 0.03
per
100,000 person
per
year with the ...age peak in a range between 10 and 14 years, and decreasing dramatically with increasing age. They are seldom diagnosed in persons above 20 years of age, being a cause of tumor-related intractable epilepsy that begins in childhood or adolescence. They have been proven to be the second most common type of epileptogenic tumors in pediatric population. These rare tumors cause chronic drug-resistant partial complex seizures with or without secondary generalization. Herein, we provide institutional case series of six adult patients with temporal lobe DNET presenting with complex partial seizures. Lesionectomy was performed with tumor resection
in toto
in three patients. In another three, partial resection was performed, whereas tumor remnant was left intact to avoid possible basal ganglia damage. All patients were seizure free postoperatively. Lesionectomy alone in temporal lobe epilepsy was associated with less favorable outcome than anterior temporal lobectomy. Total tumor removal is considered a major prognostic factor in most studies.
Spontaneous subarachnoid hemorrhage (SAH) can occur unexpectedly and independently of the classic risk factors. Several different factors could affect intracranial aneurysm (IA) rupture, such as ...morphological and hemodynamic factors. The aim of this study was to establish the potential association of meteorological data such as temperature, atmospheric pressure, and humidity, and the onset of clinical symptoms preceding hospital admission of patients with acute SAH due to IA rupture. This retrospective study included 130 consecutive patients admitted for non-traumatic SAH with a determinable onset of SAH symptoms. The effects of meteorological parameters of atmospheric pressure, ambient temperature, and relative air humidity on the day of acute SAH onset and 24 hours prior to the onset of symptoms were recorded and analyzed in each patient. Spearman rank correlation analysis was used to assess the risks of incident SAH on the basis of daily meteorological data. Seasonal incidence of acute SAH showed the peak incidence in winter and a trough in summer, with monthly incidence peak in January and December. The circadian rhythm analysis showed the peak incidence of SAH in the forenoon, followed by the evening. Acute SAH incidence showed moderate positive association with daily atmospheric pressure (p<0.05), while no association was found with ambient temperature and relative air humidity. Our results suggested no significant association of changes in ambient temperature and relative humidity with the risk of SAH. Increases in atmospheric pressure were weakly associated with a higher SAH risk. Additional studies are needed to establish in detail both meteorological and morphological factors important to predict IA rupture and SAH.
Infected intracranial aneurysms are a rare type of inflammatory vascular lesions that occur due to infection of intracranial arterial wall. Brain aneurysms of distal arterial branches are equally ...rare and frequently multiple, including those situated at the peripheral middle cerebral artery segments. Although both types represent a small percentage of all intracranial aneurysms, they may bring about high mortality in case of rupture. The management of such aneurysms includes conservative treatment with broad-spectrum antibiotics, and microsurgical or endovascular treatment, which is gaining more prominence for both asymptomatic and ruptured aneurysms. Herein, we present a case of a 61-year-old male patient with a history of cardiac infective disease and multiple bilateral aneurysms of infected distal branch middle cerebral arteries, discussing the efficacy of available endovascular treatment modalities and reviewing the literature. In conclusion, selective endovascular coiling is a preferable method in the current management of distal branch infected ruptured intracranial aneurysms, which may bring a favorable outcome.
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