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In 1998, a teleradiology system was established in Croatia. It connects 34 CT, MRI and DSA scanners in 29 hospitals with a referral centre in the neurosurgery department in Zagreb. In the first three years of its use, the network saved more than 400,000 km of patient transportation (i.e. without a teleconsultation, all of the patients would have had to be transported to the nearest referral neurosurgical unit). During the first seven years, an archive with 25,366 expert opinions was collected. A total of 7103 (28%) expert opinions were provided for the distant regional hospitals. The most common diagnoses for patients from regional hospitals were neurotrauma (53%), cerebrovascular diseases (22%) and brain tumours (19%). The teleradiology system was used less often for lumbar disc disease (4%), hydrocephalus or other neurosurgical disorders (2%). The most valuable results from teleradiology were the decisions about proper and effective patient treatment. In Croatia, the national teleradiology network for neurosurgery has speeded up therapy, avoided unnecessary travelling for patients and reduced costs. [ABSTRACT FROM AUTHOR]

Aim: To examine whether changes in biomarker concentrations in patients with idiopathic normal-pressure hydrocephalus (iNPH) during 72 h of external lumbar drainage (ELD) can differentiate between responders and non-responders., Methods: Twenty patients with clinical and neuroradiological signs of iNPH underwent ELD over a period of 72 h. During this period, changes in cerebrospinal fluid (CSF) concentrations of biomarkers (amyloid-β, total and phosphorylated tau proteins) and intracranial pressure were monitored, and the volume of drained CSF was measured. Changes in the concentrations of selected biomarkers at three time points (0, 36, and 72 h) during ELD were tested for association with changes in clinical condition., Results: Ten patients showed significant clinical improvement after ELD, quantified as a difference of two or more points on the Mini-Mental State Examination and/or Japanese iNPH grading scale. The concentration of all tested biomarkers increased during the first 36 h. Respondents had higher Aβ 1-42 at all time points, with a significant difference seen after 72 h. They also had a significantly higher Aβ1-42/Aβ1-40 ratio at all time points., Conclusion: A gradual increase in Aβ 1-42 concentration during three-day ELD represents a possible positive prognostic factor for the placement of permanent CSF drainage in patients with iNPH.

Background:  Nodular fasciitis is a benign neoplasm occurring predominantly in the subcutaneous tissue. There have been nine intraneural occurrences described in the literature., Case Report:  A 37-year-old woman presented with numbness and tenderness in her left shoulder and scapula and a slightly dropped left shoulder, without history of trauma. A magnetic resonance imaging (MRI) of the cervical spine showed a well-circumscribed oval mass deep to the levator scapula muscle. Due to persisting symptoms and an unknown nature of the process, surgical excision was performed, and histopathologic analysis confirmed diagnosis of a benign fibroblastic/myofibroblastic neoplasm, nodular fasciitis. The postoperative course was uneventful and the patient was without symptoms at 4 months of follow-up., Methods:  We reviewed the available literature (PubMed, Google Scholar), with nine published cases of intraneural nodular fasciitis. The reported clinical, radiologic, and histopathologic parameters were evaluated and compared., Discussion:  Most of the cases reported in the literature were symptomatic, with tenderness and palpability being the main symptoms. Six of the reported cases occurred in the forearm, whereas three were in the leg. To the best of our knowledge, ours is the first reported case of nodular fasciitis occurring in the trunk. Ours is the only case to display desmin positivity, which supports the reactive hypothesis of nodular fasciitis., Conclusion:  Intraneural nodular fasciitis is an extremely rare diagnosis. Due to its benign natural course, a multidisciplinary approach with this extremely rare diagnosis in mind is needed to avoid overtreatment., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Reports on petroclival meningioma (PCM) surgical mortality and morbidity often deviate from established standards; as such, a comprehensive summary is lacking., Methods: Eligibility/sources . Peer-reviewed case series of at least 10 PCM patients identified from PubMed, Web of Science, Ovid, or Google Scholar. Outcomes . Primary: mortality, tumor recurrence, any cranial nerve deficit (CND); other: individual CNDs, other complications. Data synthesis . Random-effects meta-analysis/meta-regression [effects: surgical approach (supratentorial, S; infratentorial, I; combined, (C), average age and follow-up, sample size, and percent of patients with gross-total resection (GTR)] of logit-transformed proportions., Results: Data . 73 case-series/3553 patients. Mortality . Adjusted predicted mortalities of 2.4%, 2.5%, and 1.2% (50-month follow-up) for the S, I, and C approaches, respectively, with the upper limits of the 95% credibility intervals at 3.3%, 3.7%, and 3.6%, respectively. Recurrence . Adjusted predicted recurrences of 5.5%, 11.1%, and 12.0% (50-month follow-up and 57% GTR) for the S, I, and C approaches, respectively; recurrence was positively associated with follow-up period and negatively associated with having received GTR. At all covariates at median values but at GTR 90% predictions: 3.1% (95%CI 3.1-9.8), 6.3% (3.8-10.4), and 6.9% (3.4-13.2) with the S, I, and C; prediction credibility intervals 1-4% and 22.4%. Any CND . Adjusted predicted probabilities of 37.2%, 23.4%, and 29.5% (at median covariate values) for the S, I, and C approaches, respectively; prediction credibility intervals ranged from <10% to 78%. Other outcomes . The most common individual CNDs were nVII (14.4%), nV (11.5%), and nIII (10.2%); other common complications included motor deficit (10.8%), infection (9.8%), and CSF leak (7.5%)., Conclusion: This is the first systematic review on PCM surgical mortality, recurrence, and morbidity. Outcomes differ between surgical approaches and reporting quality varies greatly.

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons' excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.

A prospective study was carried out at the Zagreb University Hospital Centre to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and quality of life (QoL) in patients with epilepsy (PE), and its association with depressive symptoms and sexual dysfunction (SD). QoL was assessed by use of the Quality of Life in Epilepsy-31 Inventory (QOLIE-31), SD by the Arizona Sexual Experiences Scale (ASEX), and depressive symptoms by the Hamilton Rating Scale for Depression (HAM-D17). The study included 108 PE (women 63% and men 37% men), mean age 39.54±15.91 years. Focal type epilepsy was diagnosed in 14.8%, generalized type in 35.2%, and both types were present in 40.7% of study patients. Drug-resistant epilepsy (DRE) was present in 44/108 and vagus nerve stimulation (VNS) was implanted in 27/44 patients. The mean response on QOLIE-31 was 62.88±17.21 with no significant differences according to gender, type of epilepsy, and age. A statistically significantly lower QoL was found in the 'Overall QoL' domain (35-55 vs . <35 age group). Patients taking both types of AEDs had a significantly lower QoL compared to those on newer types of AEDs. Higher QoL was associated with less pronounced depressive symptoms (p=0.000). Significant correlations were found between lower QoL and SD (p=0.001). In 27 patients with DRE having undergone VNS, a favorable effect of VNS implantation on the QoL and mood was observed as compared with 18 patients without VNS (p=0.041).

Aim: To compare the effect of adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia vs general anesthesia only on pro-inflammatory cytokine concentrations in patients with non-ruptured brain aneurysms undergoing elective open surgery., Methods: This parallel, randomized, controlled, open-label trial was conducted at Clinical Hospital Center Zagreb between March 2019 and March 2020. At the beginning of anesthesia, lidocaine group received 40 mg of 2% lidocaine for laryngotracheal topical anesthesia and 4 mg/kg for the scalp block. Control group underwent general anesthesia only. Plasma concentrations of IL-6, TNF-α, and IL-1β were measured before anesthesia (S0); at the incision (S1); at the end of surgery (S2); 24 hours postoperatively (S3). Cerebrospinal fluid (CSF) cytokine concentrations were measured at the incision (L1) and the end of surgery (L2)., Results: Forty patients (each group, 20) were randomized; 37 were left in the final analysis. IL-6 plasma concentrations increased significantly compared with baseline at S3 in lidocaine group, and at S2 and S3 in control group. In both groups, changes in TNF-α and IL-1β were not significant. CSF cytokine concentrations in lidocaine group did not change significantly; in control group IL-6 and IL-1β were significantly higher at L2 than at L1. CSF IL-6 in control group significantly increased at L2, but TNF-α and IL-1β did not. No differences in clinical outcome and complication rates were observed., Conclusion: Adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia might attenuate CSF IL-6 concentration increase in patients with brain aneurysm.

Aim: To investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG)., Methods: The study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol - 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks., Results: We observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P=0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P=0.248)., Conclusion: Performing PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Objective: This study aimed to determine the role of brain MRI post-processing method MAP07 (Morphometric Analysis Program) in detecting epileptogenic brain lesions in patients with pharmacoresistant epilepsy (PE). MAP07 is a sophisticated diagnostic program that offers several morphometric maps and facilitates the detection and localization of hippocampal sclerosis (HS), focal cortical dysplasias (FCD), and other types of cortical malformations, which could be undetected by conventional visual MRI analysis (CVA)., Methods: 120 patients aged > 16 years with PE have been recruited. 3 T MRI was performed according to epilepsy imaging protocol followed by image postprocessing with a fully automated MATLAB script, MAP07, by applying SPM5 algorithms. Statistical analysis was performed in IBM SPSS Statistics, version 25.0., Results: Analysis in our patients showed a high sensitivity of MAP07 with low specificity and with a high proportion of false-positive patients. After MRI analysis, out of 120 patients, 32 were found to have no structural abnormalities by conventional visual analysis in whom after MAP07 in 5 patients structural lesions were found (in one HS, in one FCD, in two perinatal vascular lesions, and in one hippocampal hyperintensity). There was a quite high overall coincidence of the findings of MAP07 and MRI for the detection of FCD, HS, perinatal ischemia/chronic vascular lesions, heterotopias, and polymicrogyria (kappa coefficient above 0.700)., Conclusions: MAP07 analysis is a useful, additional, and automated method that may guide re-evaluation of MRI by highlighting suspicious cortical regions, as a complementary method to CVA, by enhancing the visualization of cortical malformations and lesions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Normal pressure hydrocephalus (NPH) is communicating hydrocephalus characterised by normal intraventricular pressures. It presents with the triad of gait impairment, cognitive decline, and urinary incontinence. The term idiopathic normal pressure hydrocephalus (iNPH) is used in cases where the etiology is unknown. The aim of this study was to assess the prevalence and management of iNPH in our institution. Method: This was a retrospective study carried out at a tertiary health care center. Retrospective case series analysis was conducted using the existing electronic medical record data (2009-2017) on patients with hydrocephalus. Results: Forty-two (6.7%) patients with iNPH were identified, mean age 71.5 ± 8.8 years, 21 male (mean age 71.5 ± 9.3 years) and 21 female (mean age 71.5 ± 8.5 years). Ataxia was recorded in 39, symptoms of dementia in 31, and urinary incontinence in 29 patients. Forty patients were treated surgically by placing a ventriculoperitoneal (VP) shunt. One of the two patients treated by endoscopic third ventriculostomy (ETV) was subsequently treated by placing a VP shunt due to clinical deterioration. Significant improvements were noticed in cognitive and urinary symptoms, in the triad symptom sum score on the Japanese NPH scale, as well as in Evans' index and callosal angle (CA) on brain MRI ( p < 0.05). Significant positive correlation was found between age and gait disturbance (Spearman's rho = 49.86% p = 0.0017), age and incontinence (Spearman's rho = 35.22%, p = 0.0351), age and triad symptom sum score (Spearman's rho = 44.67%, p = 0.0056), female gender and dementia (Spearman's rho = 34.94%, p = 0.0367), and among all three variables on the Japanese NPH scale ( p < 0.0001). Conclusions: Treatment of iNPH with VP shunt showed significant improvement. A properly designed study is required to address the efficacy of ETV in the treatment of iNPH.

Background: Neurosurgical treatment is one of important way to cure drug resistant epilepsy. After invasive EEG monitoring and the invasive neurosurgical treatment (resective surgery) there are possible complications (intracranial haemorrhage, cortical lesions and infections), however there are possible neuropsyhologic outcomes such as memory outcomes, language outcomes and psychiatric outcomes. The quality of life in epilepsy (QOLIE-31) scale is a self-completed questionnaire which contains seven subscales which address the following aspects: emotional well-being, social functioning, energy/fatigue, cognitive functioning, seizure worry, medication effects and overall quality of life. Our study aimed to examine the quality of life in patients with drug resistant epilepsy who had undergone invasive EEG monitoring and resective neurosurgical treatment through the application of the QOLIE-31 scale., Subjects and Methods: The study included 9 patients with drug resistant epilepsy who had undergone invasive EEG monitoring followed by resective neurosurgical treatment in the period from 2010 to 2016, and the control group of 15 patients with drug resistant epilepsy who had not undergone neurosurgical procedures. Clinical variables of interest for this study were obtained through phone contact, and the QOLIE-31 scale was applied., Results: In the domaine of seizure worry, patients in the examined group were more concerned about the seizures (54.7) compared to the examined group (80), as well as in the overal quality of life (examined group 57.5; control group 77.5). Patients in the control group complained more in the domain of antiepileptic therapy (score 70.7) than patients in the examined group (score 100). In the other domains: emotional well-being, energy/fatigue, cognitive functioning, and social functioning there were minor deviations between the examined and control groups., Conclusion: There was no statistically significant difference between individual QOLIE-31 questionnaires, as well as between the two groups of respondents.

Background: Acute stent thrombosis is a rare adverse event following endovascular treatment of carotid artery. Experience on the topic is scarce, making the therapeutic approach a clinical challenge. In cases of intraprocedural acute carotid stent thrombosis, thromboaspiration, thrombectomy, and thrombolysis have been used as successful modalities for achieving recanalization., Case Description: We describe a case of carotid artery dissection treated endovascularly and complicated by intraprocedural stent thrombosis, which was ultimately managed by emergent extracranial-intracranial bypass with radial artery graft connecting the external carotid artery to the ipsilateral middle cerebral artery., Conclusions: Neurosurgical management may represent a rescue option for otherwise unmanageable acute carotid stent thrombosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report our experience with 3D customised cranioplasties for large cranial defects. They were made by casting bone cement in custom made moulds at the time of surgery. Between October 2015 and January 2018, 29 patients underwent the procedure; 25 underwent elective cranioplasties for large cranial defects and four were bone tumour resection and reconstruction cases. The majority of patients (96.5%) reported a satisfactory aesthetic outcome. No infections related to the surgical procedure were observed in the follow-up period. The method proved to be effective and affordable.

Aim: To analyze the sex-specific incidence and mortality trends of brain malignancies in Croatia from 2001 to 2014., Methods: Incidence and mortality rates per 100000 population were calculated using data obtained from the Croatian National Cancer Registry and the Croatian Bureau of Statistics. Rates were age-standardized to the European Standard Population, and trends were assessed using joinpoint regression., Results: In the observed period there were 6634 new brain malignancy cases (52% men) and 5379 deaths due to this diagnosis (52% men). Age-standardized incidence rates ranged from 9.2-11.5 per 100000 in men and from 7-8.8 per 100000 in women. Mortality rates ranged from 7.5-8.7 per 100 000 in men and from 5-6.5 in women. Incidence trends in men, mortality in men, and mortality in women were not statistically significant, while a significant trend was observed in incidence in women (annual percent change -1.5; 95% confidence interval -2.3 to -0.6). No joinpoints were observed in any of the joinpoint analyses by sex for incidence and mortality. Age-specific incidence and mortality rates in both sexes indicate a trend shift toward older age. The proportion of morphologically verified cases ranged from 40.2%-62.4% in men and from 38.6%-56.3% in women; the proportion of death-certificate-only cases ranged from 3.3%-9.4% in men and from 3.3%-17.5% in women., Conclusion: Incidence and mortality of brain malignancies in Croatia are among the highest in Europe, while reporting on brain malignancies is still poor. There is a need for improved care of patients with brain malignancies and detailed and accurate data reporting.

Key regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1, DVL2 and DVL3 were used to detect microsatellite instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF1 and LEF1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II (P = 0.008). Collectively, LOHs were more frequent in high-grade tumours than in low grade ones. LOHs of DVL3 gene were significantly associated with grade IV tumours (P = 0.007). The results on protein expressions indicated that high-grade tumours expressed less DVL1 protein as compared with low grade ones. A significant negative correlation was established between DVL1 expression and malignancy grades (P < 0.001). The expression of DVL2 protein was found similar across grades, while DVL3 expression significantly increased with malignancy grades (P < 0.001). The signal strengths of expressed DVL1 and DVL3 were negatively correlated (P = 0.002). However, TCF1 and LEF1 were both significantly upregulated and increasing with astrocytoma grades (P = 0.001). A positive correlation was established between DVL3 and both TCF1 (P = 0.020) and LEF1 (P = 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that DVL1 and DVL2 may be involved during early stages of the disease, while DVL3 may have a role in later phases and together with TCF1 and LEF1 promotes the activation of Wnt signalling., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objectives: Tentorial alignment and dimensions of posterior fossa cisterns are measurements whose variability can decrease surgical freedom if not taken into account when choosing the approach to the pineal region. The aim is to provide quantitative anatomical information regarding these dimensions, and to discuss their relevance in two most commonly used approaches to this region: the occipital transtentorial and supracerebellar-infratentorial approach., Patients and Methods: A retrospective study of midsagittal T1-weighted MRI images of 410 randomly selected healthy subjects was performed. The clivus-tentorium (C-T) angle was measured to assess tentorial alignment. The following distances were used as craniocaudal cisternal measurements: quadrigeminal cistern = superior colliculi - inferior part of the splenium of corpus callosum (SC-ISCC), and superior cerebellar cistern = vermis - inferior part of the splenium of corpus callosum (VER-ISCC)., Results: Median C-T angle value was 19 ± 7°, the quadrigeminal cistern height 6.7 ± 1.6 cm, and the superior cerebellar cistern height 10.4 ± 2.6 cm. The C-T angle was negatively correlated with the SC-ISCC distance (r = -0.271; p <  0.001) and the VER-ISCC distance (r = -0.052, p >  0.001). The SC-ISCC distance was positively correlated with the VER-ISCC distance (r = 0.282; p < 0.001)., Conclusion: Our new method of measuring tentorial alignment provides a simple and effective aid in preoperative planning. For the first time, we present data on craniocaudal dimensions of posterior fossa cisterns, their relationship with tentorial alignment, and discuss their relevance in SCIT and OT approaches., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Background: In some cases when risk of occlusion of a blood vessel is greater than risk of bleeding when patients undergo urgent or unplanned bypass during neurosurgery, the use of eptifibatide may be an option. We describe 2 patients who underwent arterial bypass in whom eptifibatide was used successfully intraoperatively during neurosurgery for prevention of bypass occlusion., Case Description: The first patient presented with a right middle cerebral artery (MCA) aneurysm with subocclusive stenosis of the M1 branch. After right-sided osteoplastic frontotemporal craniotomy, the MCA bifurcation was exposed with a bifurcational 6-mm aneurysm with a wide neck. Prebifurcation stenosis was found, with yellow calcification of the vessel wall, and postbifurcation calcification was found on the upper M2 branch. Superficial temporal artery-MCA bypass and occlusion of the MCA aneurysm was done. Before the bypass, continuous intravenous infusion of eptifibatide 1 μg/kg/minute was administered. The patient recovered normally without hemorrhage or neurologic deficit. The second patient presented with a left-sided lateral sphenoid wing meningioma. Left-sided frontotemporal craniotomy was performed, and the tumor was completely removed from the arachnoid layer. The temporal M3 branch was invaded by the meningioma. As there was no flow through the invaded segment of the aforementioned artery, termino-terminal M3 arterial anastomosis was done. Continuous intravenous infusion of eptifibatide 1 μg/kg/minute was administered. Indocyanine green angiography showed normal flow through the anastomosis, and the patient recovered normally., Conclusions: Future studies are needed to test the safety and potential efficacy of eptifibatide in intraoperative settings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Neuropsychological testing of patients in the course of their recovery from brain injuries enables analysis of cognitive deficiencies and/or emotional changes. The principle study objective was to define organic and/or reactive personality changes and the course of these changes in the function of the time span following brain artery aneurysm surgery in both female and male patients. The study was carried out at the Clinical Department of Neurosurgery, Zagreb University Hospital Center in Zagreb. The data refer to the period from 1989 to 2012 collected in two time intervals, i.e. 11 months and 12-48 months following brain artery aneurysm surgery. Of 72 patients included in the study, there were 28 male and 44 female patients. Neuropsychological testing consisted of clinical interview, clinical assessment of frontal lobe syndrome, Cornell personality questionnaire and Emotional Profile Index. Study results showed evidence of frontal lobe syndrome in 32% of patients on first testing and significant recovery on retesting, when only 17% of patients presented with frontal lobe syndrome. The reactive personality changes found in both testing intervals indicated increased neuroticism. In the first testing period, asthenic syndrome occurred most often, followed by conversion and aggressive-antisocial syndromes, while in the second testing interval asthenic syndrome was most pronounced and conversion and antisocial syndromes showed the same level of expression. The results also showed higher depressive and disorganizing states, which were even more pronounced in the second testing interval. As regards sex differences, the inclination toward cardiovascular somatization and destructiveness was more expressed in females than in males, showing a tendency of aggravation with increasing the time span following surgery. It may be concluded that the study has contributed to better understanding of organic and/or reactive personality changes in patients undergoing brain artery aneurysm surgery.

Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an increased expression level of SFRP3 was identified in the high grade astrocytomas when compared with those of a low grade. This may suggest that SFRP3 acts as an agonist of Wnt signaling and promotes invasive behavior.

Angiofibromas are rare tumors of the head and neck that mostly occur in the sphenopalatine region. We present a case of angiofibroma in a young male patient with an unusual and extremely rare localization, which to our knowledge has not been described before. It was situated in the tentorium and spread to the supratentorial and infratentorial regions. The patient initially presented with symptoms of increased intracranial pressure. After a diagnostic evaluation was done, the whole tumor was successfully removed using the supratentorial and infratentorial approach and the microsurgical technique., (© 2016 S. Karger AG, Basel.)

Background and Importance: We report an unusual case of complex giant and large fusiform aneurysms not amenable for clipping or coiling in a 4-year-old child managed with aneurysm resection and radial artery interposition graft., Clinical Presentation: A 4-year-old child presented with repeated severe headache and vomiting. Computed tomography, magnetic resonance imaging, and magnetic resonance angiography and digital subtraction angiography showed a giant fusiform aneurysm on the right middle cerebral artery (MCA). Because of the complex shape, endovascular treatment or clip reconstruction was not possible, and a bypass procedure was planned. Right frontotemporal craniotomy and orbitotomy was performed. Two aneurysms involving the M1 segment of the MCA were found in line, 1 giant, and the other large in size. The aneurysms were resected and treated with short radial artery interposition graft, which was narrower than the proximal or distal MCA. The child recovered normally, and the bypass was patent after 1 year., Conclusion: Large fusiform MCA aneurysms may be difficult to treat, but there are treatment options that include a bypass procedure. Resection and short interposition radial artery graft is an excellent but rare treatment option in a very young child. This was a very successful treatment in this child.

Introduction: Lafora body disease (LBD) is a rare autosomal recessive disorder characterized by progression to inexorable dementia and frequent occipital seizures, in addition to myoclonus and generalized tonic-clonic seizures (GTCSs). It belongs to the group of progressive myoclonus epilepsies (PMEs), rare inherited neurodegenerative diseases with great clinical and genetic differences, as well as poor prognosis. Since those patients have a pharmacoresistant disease, an adjunctive treatment option is vagus nerve stimulation (VNS). To date, there are four reported cases of the utility of VNS in PME - in Unverricht-Lundborg disease (ULD), myoclonic epilepsy with ragged-red fibers (MERRF), Gaucher's disease, and in one case that remained unclassified., Case Presentation: A 19-year-old male patient had progressive myoclonus, GTCSs that often progressed to status epilepticus (SE), progressive cerebellar and extrapyramidal symptomatology, and dementia, and his disease was pharmacoresistant. We confirmed the diagnosis of LBD by genetic testing. After VNS implantation, in the one-year follow-up period, there was a complete reduction of GTCS and SE, significant regression of myoclonus, and moderate regression of cerebellar symptomatology., Conclusion: To our knowledge, this is the first reported case of the utility of VNS in LBD. Vagus nerve stimulation therapy may be considered a treatment option for different clinical entities of PME. Further studies with a larger number of patients are needed.

In the last 20 years neurological and neurosurgical follow up of our patients with pineal region expansions (118 patients) pointed to certain clinical and neurophysiological regularities. We performed retrospective study which included 84 patients with pineal region expansions in the period from 1992 to 2009. The study included 55 women and 29 men, mean age 30.08 +/- 13.93 years, with positive brain magnetic resonance imaging (MRI)--70 patients (83.4%) had simple pineal gland cysts, and 14 patients (16.67%) had expansive process in pineal region with compressive effect. All patients had headache, while 32 patients (38%) had epileptic phenomena--primary generalized seizures. Patients had common electroencephalography (EEG) pattern with paroxysmal discharges of 3Hz (or more than 3 Hz) spike-and-wave complexes. Operation with supracerebellar infratentorial approach was performed in 70 patients. In most of our patients indication for the operation was established based on the size of the cyst (15 mm or more), with the signs of compression on the quadrigeminal plate and compression of the surrounding veins, which could result in seizures and EEG changes verified in our group of patients. Pathohistological analysis revealed pineocytomas in 11 cases (15.71%), pinealoblastomas in 2 cases (2.86%), one case of teratoma (1.43%), while 56 patients had pineal gland cysts (80%). Following surgery clinical condition improved in all patients--patients became seizure-free and headaches significantly decreased. Other symptoms including diplopiae, nausea, vomiting, vertigo as well as blurred vision also disappeared. There were no complications after surgical procedures. This study points to often appearance of seizures that clinically and neurophysiologically present as primary generalized epilepsy in patients with pineal region expansions. Our hypotheses are that mass effect on the surrounding veins that affects normal perfusion, compressive effect on the quadrigeminal plate and the aqueduct of the midbrain, hemosiderin deposists, as well as secretion disturbances of anticonvulsive agent melatonin can be involved in the pathogenesis of seizures. We suggest to perform high resolution brain MRI with special demonstration of pineal region in all young patients that have seizures and specific EEG changes.

The objective of this study is the management of multiple family members with multiple neurofibromatosis type 2 (NF2) related tumors of the skull base that can be challenging, on purely technical, decision-making, and ethical levels. These issues are addressed in this manuscript based on an experience treating an unique large family with NF2. A retrospective chart review was performed, reviewing clinical, radiological, surgical, and pathological data. A unique family of 17 siblings, whose father was the proband as a sporadic mutation is reported. Over a 4-month period, five of eight affected siblings underwent 12 procedures for resection of 15 different NF2-related tumors. This single family experience of NF2-related skull base tumors underscores the importance of preservation of function and quality of life as the major determinants of treatment success.

Vagus nerve stimulation (VNS) for the treatment of refractory partial epileptic seizures with or without secondary generalisation in patients older than 12 years was approved in Europe in 1994 and in the United States in 1997. We have studied the efficacy of VNS in patients with pharmacoresistant epilepsy hospitalized in the Neurology Department of the University Hospital Centre Zagreb. From 1997 to 2001 we have implanted VNS in 11 patients with pharmacoresistant epilepsy, who were magnetic resonance imaging (MRI) negative and from May 2007 to May 2009 in 11 patients with pharmacoresistant epilepsy, 9 of them were MRI positive, and were inoperable due to localisation of the pathomorphologic changes (ganglioglioma, hamartoma, various types of cortical dysplasia, porencephalic cysts), 2 were MR negative. In the group of MRI negative patients 1 patient had complex partial seizures (CPS), 6 patients had CPS with secondary generalisation, 2 patients had primary generalized epilepsy (PGE) including myoclonic, absence, atonic and tonic-clonic seizures, one patient had PGE and CPS, and 3 patients had Lennox-Gastaut syndrome (LGS). In the group of MRI positive patients one patient had elementary partial seizures (EPS) and CPS, two patients had EPS and CPS with secondary generalisation, one patient had CPS, 3 patients had CPS with secondary generalisation, and 2 patients had CPS with secondary generalisation as well as atonic seizures. After continuous follow-up of 11 MRI negative patients during 5 years and 2 MRI negative patients during one year there was decrease in mean-seizure frequency of 51.67%. After continuous follow-up of 9 MRI positive patients during 2 years there was decrease in mean-seizure frequency of 61.9%. The most frequent side effects were hoarseness, throat pain and cough in the "on phase" of the VNS, but they were mild and transitory. We can conclude that VNS was effective mode of therapy in our group of patients with pharmacoresistant epilepsy.

In this paper, our experience with originally constructed Neurosurgical Endoscopic Contact Ultrasound Probe "NECUP-2" in neuroendoscopy is reported. Between June 1997 and June 2007, 132 neuroendoscopic procedures have been performed: 102 endoscopic thrid ventriculostomies (ETV), 15 arachnoid cysts and 5 intraventricular tumours operations. The "NECUP-2" was applied effectively in all cases in which blunt perforation was not possible: 38/102 ETY, 10/10 septostomies, 15/15 arachnoid cysts. In five cases of intraventricular tumours, neuroendoscopic procedure was combined with open microsurgery for tumour removal with preservation of vascular structures. There were no "NECUP-2" related complications. Of postoperative complications, we had liquorrhea (9 patients), and symptoms of meningitis (6 patients). In the follow-up period (6 months to 6 years), we had a patency rate of 80% (50/63 patients). All patients improved in clinical status. According to the first results, it seems that ultrasonic contact probe NECUP-2 presents a new device in neurosurgical armamentarium that can be used in various fields of neurosurgery. With minimal and controlled lesion that is produced at the tip of the probe, it can be used in highly demanding operations such as third ventriculostomy and tumour resection.

Objective: The purpose of the study is to compare the results of minimally invasive keyhole craniotomy and standard larger craniotomies in the surgical treatment of patients with intracranial aneurysms., Methods: In the past eight years 628 patients were operated by two experienced neurosurgical teams. The first group of 482 patients with 565 aneurysms were operated through a small keyhole craniotomy, using the eyebrow keyhole approach in particular. The remaining 146 patients with 167 aneurysms were operated using a standard craniotomy that included pterional/frontotemporal, frontoparietal parasagittal, and retrosigmoid suboccipital craniotomies. All operations were performed in the standard microsurgical technique using intraoperative evoked potential monitoring and endoscopic assistance in selected cases., Results: Most supratentorial aneurysms and basilar tip aneurysms were successfully operated through an eyebrow keyhole craniotomy. Distal MCA aneurysms as well as aneurysms on the MCA with a long M1 segment were operated through a temporal keyhole, and aneurysms of the distal PCA (P2-P3) segment subtemporally. The frontoparietal parasagittal keyhole approach was used only for pericallosal artery aneurysms. Infratentorial aneurysms of the VA/PICA complex were operated via a retrosigmoid approach. On comparing the surgery results in patients with a keyhole craniotomy and those with standard craniotomy, similar outcomes were found for both groups, with excellent or very good outcomes (GOS 5 and 4) in 398 (82.57%) patients from the keyhole craniotomy group, and in 116 (79.45%) patients from the standard craniotomy group. The mortality rate in the keyhole group was 0.83% (4 patients) and 2.05% (3 patients) in the standard craniotomy group., Conclusion: Parallel treatment results in using two options--keyhole craniotomy and standard larger craniotomy--were analysed in the past eight years. Two experienced neurosurgical teams in performing both surgical approaches have reached almost similar morbidity and mortality rates, and overall surgical results. The type of craniotomy is selected according to the experience of the surgical team, and familiarity with certain approach. The authors have good experience with the minimally invasive approach for different intracranial pathology and recommend it especially in neurovascular surgery.

Cerebrospinal fluid (CSF) fistula as a consequence of brain missile injury and following infectious complications has been recognized for years. Different methods of treatment have been advocated. Missiles used in war cause extensive destruction of the skull and brain as a result of their high kinetic energy. On its transfer through the skull, such high kinetic energy causes fractures called "discontinuous fractures," which are distant from the entry wound and not related to the fracture of the vault. The role of the timely diagnosis of CSF fistulas and their early repair in the management of these wounds is emphasized. Data on 312 patients with missile injuries of the brain inflicted during the war in Croatia were retrieved and analyzed, with special reference to the complications of CSF fistulas and infection. Forty-five patients developed CSF fistula, 15 (33%) of them at the wound site, 23 (51%) as CSF rhinorrhea, and seven (15%) as CSF otorrhea. Six patients developed infectious complications. The presented strategy and operative approach resulted in a low incidence of infectious complications in the study series.