Gangliosidome of a Human Hippocampus in Temporal Lobe Epilepsy Resolved by High-Resolution Tandem Mass Spectrometry.

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.

Intermittent tramadol vs tramadol administration via patient-controlled pump after lumbar discectomy: a randomized controlled trial.

AIM: To compare the effect of intermittent tramadol dosing vs tramadol administration via patient-controlled pump on pain after lumbar discectomy. METHODS: This randomized prospective study enrolled 100 patients who underwent elective LIV-LV lumbar discectomy in the neurosurgery department at Sestre Milosrdnice University Hospital Center from May 2016 to July 2017. Patients were randomized to receive either tramadol (600 mg daily) via a patient-controlled analgesia (PCA) pump or intermittently. Pain was evaluated by the Croatian version of Short-Form McGill Pain Questionnaire. RESULTS: Forty percent of patients were women. The median (interquartile range) age of the patients was 51 (40-61) years. The groups did not differ in pain at 7 pm on the day of discectomy. However, in the morning and evening on the first postoperative day and in the morning and evening of the second postoperative day, the PCA group had significantly lower pain (P=0.023, P<0.001, P<0.001, P=0.026, respectively). CONCLUSION: This is the first study that used the Short Form McGill Pain Questionnaire to compare the effect of tramadol administration via PCA pump and intermittent administration on pain after LIV-LV discectomy in a neurosurgery department. Tramadol showed a good analgesic efficacy in lumbar spine surgery; tramadol via PCA controlled pain more effectively than intermittently administered tramadol.

METEOROLOGICAL VARIABLES ASSOCIATED WITH SUBARACHNOID HEMORRHAGE: A SINGLE CENTER STUDY.

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.

MICROSURGICAL MANAGEMENT OF A RARE INCIDENTAL INTRAVENTRICULAR MENINGIOMA: A CASE REPORT AND RELEVANT LITERATURE REVIEW.

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.

Ganglioside Composition Distinguishes Anaplastic Ganglioglioma Tumor Tissue from Peritumoral Brain Tissue: Complementary Mass Spectrometry and Thin-Layer Chromatography Evidence.

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.

SURGICAL AND SEIZURE TREATMENT OUTCOMES IN ADULT DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS: A CASE SERIES.

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.

Prospective randomized appraisal of the best pain relief option after L4/L5 discectomy.

OBJECTIVES: To determine the efficacy of paracetamol and tramadol analgesia via patient controlled pump and intermittent administration using the Short-Form McGill Pain Questionnaire after L4/L5 discectomy in neurosurgical patients. METHODS: Fourteen months prospective quantitative study with 200 neurosurgical patients' participation who underwent elective discectomy of the L4/L5 intervertebral disc extrusion. The study was conducted due to a patient-controlled analgesia pump and intermittent analgesia application. Pain was assessed using the Short-Form McGill Pain Questionnaire in the Croatian language during the zero, first, and second postoperative day. RESULTS: Perception of pain was reduced in patient controlled analgesia pump groups after the second measurement during the first postoperative day [95% CI: -3.89, -0.76], regardless of administered analgesic (p< 0.001). After the final measurement, at 7 PM on the second postoperative day, the differences were not significant (p= 0.070). This study results are registered and allocated in the Australian New Zealand Clinical Trials Registry (ANZCTR). DISCUSSION: Analgesia administration via patient-controlled pump contributes to the alleviation of postoperative pain after L4/L5 disc extrusion surgery regardless of administered analgesic.

ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS ON DISTAL ARTERIAL BRANCHES: ILLUSTRATIVE CASE SERIES AND LITERATURE RETROSPECTION.

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.

CURRENT ENDOVASCULAR MANAGEMENT OF INFECTED DISTAL BRANCH INTRACRANIAL ANEURYSMS: A CASE REPORT AND INSIGHT INTO THE LITERATURE.

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.

THE RISK OF MULTIPLE INTRACRANIAL ANEURYSM FORMATION IN PATIENTS WITH MALIGNANT DISEASE UNDERGOING RADIATION THERAPY: A CASE REPORT AND LITERATURE REVIEW.

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.

Aberrant ganglioside composition in glioblastoma multiforme and peritumoral tissue: A mass spectrometry characterization.

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.

Standard Lumbar Discectomy Versus Microdiscectomy - Differences in Clinical Outcome and Reoperation Rate.

Microdiscectomy (MD) is accepted nowadays as the operative method of choice for lumbar disc herniation, but it is not rare for neurosurgeons to opt for standard discectomy (SD), which does not entail the use of operating microscope. In our study, differences in disc herniation recurrence and clinical outcome of surgical treatment of lumbar disc herniation with and without the use of operating microscope were assessed. Our study included 167 patients undergoing lumbar disc surgery during a three-year period (SD, n=111 and MD, n=56). Clinical outcome assessments were recorded by patients via questionnaire forms filled out by patients at three time points. Operation duration, length of hospital stay and revision surgeries were also recorded. According to study results, after one-year follow up there was no statistically significant difference between the SD and MD groups in functional outcome. However, we recorded a statistically significant difference in leg pain reduction in favor of the MD group. According to the frequency of reoperations with the mean follow up period of 33.4 months, there was a statistically significant difference in favor of the MD group (SD 6.3% vs. MD 3.2%). There appears to be no particular advantage of either technique in terms of functional outcome since both result in good overall outcome. However, we choose MD over SD because it includes significantly lower recurrent disc herniation rate and higher reduction of leg pain.

The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

Epilepsy is the most common neurological complication in pregnancy. Women with epilepsy have a higher risk of complications in pregnancy. In Croatia, women with epilepsy are treated by neurologists at tertiary centers according to the place of residence. We prospectively followed-up pregnancies in women with epilepsy and healthy controls, and analyzed the factors responsible for their delivery outcomes and development of their babies. Healthy pregnant women had a higher level of education and economic status, but pregnant women with epilepsy took folic acid in a higher proportion than controls, possibly due to timely preconception counseling. Complications during pregnancy depended on the number of antiepileptic drugs and epilepsy control. We noticed some behavioral and cognitive aspects in children exposed in utero to valproic acid, which required follow up. The rate of congenital malformations was not increased. In conclusion, women with epilepsy should receive preconception counseling about the risk for pregnancy, but also about the possibilities to minimize that risk. We have introduced a model of integrative management of pregnancy and epilepsy based on close collaboration among different clinical experts in Croatia, in order to provide prompt counseling and timely intervention.

[AWAKE SURGERY FOR A PRIMARY BRAIN TUMOR]. / OPERACIJA PRIMARNOG TUMORA MOZGA U BUDNOM STANJU BOLESNIKA.

Awake brain surgery has been approved as a safe and efficaceous operative procedure with the goal of maximal tumor resection and preservation of neurological function. This case report presents the first full awake primary brain tumor surgical procedure performed in Croatia.

DYSPHONIA AS AN UNCOMMON PRESENTATION OF PONTOCEREBELLAR CHOROID PLEXUS PAPILLOMA.

A case is presented of a patient with dysphonia, hearing loss and ataxia due to vestibulocochlear and vagal nerve compression by choroid plexus papilloma in the cerebellopontine angle. Choroid plexus papillomas are rare tumors usually arising in the lateral and fourth ventricle, and rarely found in the cerebellopontine angle, making the neuroimaging characteristics usually not sufficient for diagnosis. Patients usually present with headache and hydrocephalus but tumors in the cerebellopontine angle can cause vestibulocochlear dysfunction and cerebellar symptoms. Dysphonia along with hearing loss was a dominant symptom in the case presented. After complete surgical removal of the tumor, deterioration of dysphonia was noticed; it could be explained as peripheral vagal nerve neuropathy due to tumor compression and intraoperative manipulation. In this case report, we describe dysphonia as an uncommon presentation of a rare posterior fossa tumor. To our knowledge, a case of choroid plexus papilloma presenting with dysphonia has not been described before. Our case extends the differential diagnosis of dysphonia from the otorhinolaryngological to the neurosurgical field.

Sphenoid sinus aspergilloma in trans-sphenoidal surgery for pituitary adenomas.

BACKGROUND: Simultaneous appearance of sphenoid sinus aspergilloma and pituitary adenoma is a very rare finding. METHODS: Retrospective analysis of patients with sellar and sphenoid sinus mass lesions who underwent trans-sphenoidal surgery was performed. Demographic data, medical history, predisposing factors, clinical picture, neurological status and radiological findings were reviewed. All patients underwent a trans-sphenoidal microsurgical treatment, and acquired specimens underwent both histopathological and microbiological analysis. RESULTS: Sphenoid sinus aspergilloma was encountered in seven patients. Three patients had an isolated sphenoid sinus aspergilloma and four patients with pituitary macroadenoma had a sphenoid aspergilloma as an incidental finding. CONCLUSIONS: Sphenoid sinus aspergilloma can be found during trans-sphenoidal surgery for pituitary adenomas. Sphenoid sinus extirpation followed by adenomectomy is the treatment of choice unless invasive aspergilloma is encountered requiring additional antifungal therapy.

[Minimally invasive surgery in treatment of lumbar intervertebral disc herniation]. / Minimalno invazivna kirurgija slabinske kraljeznice u lijecenju hernije intervertebralnog diska.

Surgical treatment of lumbar intervertebral disc herniation is one of the most common neurosurgical procedures. Besides conventional surgical techniques, in the last more than 30 years, different methods with minimal damage to neuromuscular spine structures are being developed and introduced, all having the purpose of reducing postoperative back pain. The advantages of the minimally invasive spine surgery include: possibility of performing procedures under local anaesthesia, reduced hospital stay, limited blood loss with consecutively reduced fibrous tissue development. Patients are capable of return to work and everyday activities early after surgery. From the economical point of view, this kind of treatment is considered to be a cost-effective intervention. Three methods that are being used for treatment of lumbar intervertebral disc herniation are: percutaneous laser disc decompression (PLDD), microdiscectomy using tubular retractor system and selective endoscopic discectomy (SED). Conducted prospective studies have shown that minimally invasive methods are adequate alternative to classic surgical procedures.

Surgical treatment of prolactinomas--our experience.

The dilemma of whether to apply surgical or drug treatment to prolactinomas has been ongoing for the past 30 years. The aim of this study is to compare the early postoperative values of prolactin (PRL) in two groups of patients with prolactinomas: those who underwent primary surgical-treatment, and those who underwent surgery after a dopamine agonist (DA) therapy. We present the results of surgical treatment on a series of 161 patients with prolactinomas. Surgery was the primary treatment in 65 patients, while 96 patients had surgery following a long-term treatment with a DA. All surgically treated prolactinomas were operated in the standard transsphenoidal, microsurgical approach. The criteria for hyperprolactinemia remission was a PRL level under 25 ng/ml. Early normalization of PRL was achieved in 92% of those patients who underwent primary surgical-treatment, yet it was achieved in only 42% of patients who were operated on after receiving a long-term drug treatment with a DA. The highest prevalence of postoperative normalization of PRL was achieved in a group of patients with microadenomas who were primarily operated on (98%). The worst results in postoperative normalization of PRL were found in the group of patients with macroadenomas who received a long-term drug treatment with a DA first. These results show our surgical experience in treating prolactinomas. Using surgical treatment, the best clinical outcome was achieved with microprolactinomas and intrasellar, well-confined macroprolactinomas. Nevertheless, we stress the need of an individualized approach and recommend treatment in multidisciplinary centres for pituitary diseases.

Complete neurological recovery after surgery for mesencephalic cavernoma: case report.

Cavernous malformations are classified as a group of vascular malformations of the central nervous system. Conservative treatment of brainstem cavernomas is accompanied with poor outcome. Surgery ofbrainstem cavernomas still poses a challenge due to the high risk of neurological damage and respectable morbidity. We report a case of complete neurological recovery in a 24-year-old female patient with mesencephalic cavernoma treated surgically. This case highlights that careful microsurgical treatment with the goal of complete cavernoma excision remains the treatment of choice in cases with de novo or recurrent hemorrhage. Intraoperative neurophysiologic monitoring should be used as the gold standard during brainstem cavernoma operations in order to avoid nuclear and long tract damages.