Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms.

Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.

Ultrasound-Navigated Multiple Hippocampal Transections: An Anatomical Study.

BACKGROUND: Multiple hippocampal transection (MHT) is a surgical technique used for the treatment of drug-resistant mesial temporal lobe epilepsy in situations where standard procedures would pose a high risk for memory deterioration. During MHT, the longitudinal fibers of the hippocampus, implicated in epilepsy spreading, are interrupted, while the transverse memory circuits are spared. The extent of MHT is governed by intraoperative electrocorticography; abolition of epileptic discharges serves as an end point to terminate the transection. In other words, the aim of MHT is not the anatomical completeness of hippocampal transection. In contrast, we hypothesize that only the complete transection of hippocampal cross-section is needed to durably terminate epilepsy, avoiding possible postoperative reorganization of longitudinal pathways. Here, we report an anatomical study designed to evaluate the feasibility of complete transection of hippocampus with the aid of ultrasound neuronavigation and we propose new instruments to reach this goal. METHODS: Five cadaveric brains were analyzed in this study. MHT was performed on both sides of each brain either with or without ultrasound neuronavigation. The percentage of transected cross-section of the hippocampus was measured using magnetic resonance imaging (MRI) and both sides were compared. RESULTS: The ultrasound-guided MHTs were more likely to achieve complete hippocampal transection compared with the nonnavigated MHT transection (73 vs 58%; p < 0.01). Our study also allowed us to propose specialized transectors to minimize invasivity of this procedure. CONCLUSION: Completeness of MHT can be better reached with the aid of an ultrasound neuronavigation system; modified instruments for this procedure were also designed.

Immunoreactivity of HOXB13 in Neuroendocrine Neoplasms Is a Sensitive and Specific Marker of Rectal Well-Differentiated Neuroendocrine Tumors.

HoxB13 is a transcription factor involved in defining of posterior endodermal derivatives, including prostate and rectum. While it is used as a marker of prostatic adenocarcinoma, it has not been studied systematically in neuroendocrine neoplasms. Thus, we performed HoxB13 immunohistochemistry in tissue microarrays and the whole sections of 232 neuroendocrine neoplasms. These included 34 paragangliomas (PGs), 20 cauda equina neuroendocrine tumors (CENETs), 123 well-differentiated neuroendocrine tumors (WDNETs), and 55 neuroendocrine carcinomas (NECs). WDNETs were additionally analyzed with SATB2, and colorectal WDNETs with CDX2 and serotonin immunohistochemistry. In total, HoxB13 immunoreactivity was observed in 95% (19/20) CENETs, 10.6% (13/123) WDNETs, and 12.9% (7/54) NECs. No PGs were positive. Large intestine WDNETs expressed HoxB13 in 68.4% (13/19); five negative tumors originated in cecum and one in rectum. In rectum, 92.9% (13/14) WDNETs expressed HoxB13. HoxB13 was 92.9% sensitive and 100% specific, showing 100% positive predictive value for the rectal origin of WDNET. In NECs, HoxB13 was positive in 15.4% (2/13) GIT tumors and 80% (4/5) prostatic NECs, but in none of urinary bladder NECs (0/8). SATB2 was positive in 17.1% (21/123) WDNETs, including 78.9% (15/19) of colorectal WDNETs, 71.4% (5/7) appendiceal WDNETs, and 2.9% (1/34) small intestine WDNETs. All 4 SATB2-negative large bowel tumors originated in the cecum. When both markers combined, HoxB13+/SATB2+ immunoprofile was seen exclusively in rectal WDNETs (positive predictive value 100%), while HoxB13-/SATB2+ immunoprofile was highly suggestive of the appendiceal origin (positive predictive value 71.4%). Therefore, HoxB13 can be useful as an immunohistochemical marker of rectal WDNETs and prostatic NECs.

Expression of neuroendocrine markers in meningeal and extrameningeal solitary fibrous tumors: a potential diagnostic pitfall.

Solitary fibrous tumors (SFTs) may show unusual morphologies, and in such circumstances, an unexpected immunoprofile can be misleading. Following an index case of myxoid meningeal SFT with a neuroendocrine immunoprofile, we decided to assess a neuroendocrine profile in SFTs from various locations. The cohort of 9 meningeal and 28 extrameningeal SFTs was evaluated for CNS WHO grade (G1-G3) and 4-tiered Demicco risk stratification. Immunohistochemical detection of synaptophysin, chromogranin, INSM1, CD56, and CD57 was performed in each case and semiquantitatively assessed (0: no expression; 1+: <10% positive; 2+: 11-50%; and 3+: >51%); whole sections (meningeal SFTs) or tissue microarray (extrameningeal SFTs) were used for immunohistochemistry. The cohort included 13 men and 24 women. Meningeal SFTs included 5 WHO G1, 3 WHO G2, and 1 WHO G3 tumors. Extrameningeal SFTs included 21 low-risk, 4 intermediate-risk, and 2 high-risk tumors. INSM1 immunoreactivity was observed in 12 of 37 cases (32%; 8 cases 1+, 3 cases 2+, and 1 case 3+); synaptophysin was positive in 6 of 35 cases (19%; 5 cases 1+ and 1 case 2+); CD56 was positive in 20 of 37 cases (54%; 16 cases 1+, 3 cases 2+, and 1 case 3+); and CD57 was expressed in 14 of 36 cases (39%; 5 cases 1+, 4 cases 2+, and 5 cases 3+). Chromogranin positivity was not observed. No significant association was observed between expression of neuroendocrine markers and tumor grade, Demicco risk group or meningeal and extrameningeal location. Extrapleural SFTs showed a tendency for positivity of INSM1 (P = .014, χ2) and CD57 (P = .017, χ2) compared to pleural SFTs.

Efficiency of interlaminar uniportal endoscopic lumbar discectomy.

AIM: Prospective evaluation of the results of endoscopic lumbar discectomy. METHODS: 95 patients were consecutively enrolled in the study between 2017 and 2021. We monitored low back pain and sciatica according to the Visual Analogue Scale (VAS), the limitations in daily activities (Oswestry Disability Index, ODI), overall satisfaction according to a 0-100 % scale, and the rate of surgical complications and reoperations. RESULTS: Postoperatively, the VAS values of low back pain and sciatica decreased significantly from 5 to 1 point and from 6 to 1 point, respectively, and the pain remained in the tolerable range (VAS 1-2) throughout the follow-up period. The ODI score improved significantly from severe disability (46 %), preoperatively, to moderate disability at discharge and one month after surgery (29 % and 22 %, respectively), down to minimal disability at 3 and 12 months after surgery (12 % and 14 %, respectively). Overall patient satisfaction improved significantly at all follow-up time points (46 %, 70 %, 77 %, 80 %, and 78 %, respectively). Reoperation rate was 6.3 %. Cerebrospinal fluid leakage was observed in one case only (1.1 %). Transient postoperative perianogenital sensory impairment occurred in two patients (2.1 %). There was no evidence of surgical site infection or haematoma. CONCLUSION: Endoscopic discectomy provides significant pain relief and improves the patient's ability to perform activities of daily living, contributing to greater satisfaction. It is a safe method with a low risk of surgical and neurological complications (Tab. 3, Fig. 3, Ref. 27).

Speed and quality of interbody fusion in porous bioceramic Al2O3 and polyetheretherketone cages for anterior cervical discectomy and fusion: a comparative study.

BACKGROUND: The objective of this prospective randomized monocentric study is to compare the speed and quality of interbody fusion of implanted porous Al2O3 (aluminium oxide) cages with PEEK (polyetheretherketone) cages in ACDF (anterior cervical discectomy and fusion). MATERIALS AND METHODS: A total of 111 patients were enrolled in the study, which was carried out between 2015 and 2021. The 18-month follow-up (FU) was completed in 68 patients with an Al2O3 cage and 35 patients with a PEEK cage in one-level ACDF. Initially, the first evidence (initialization) of fusion was evaluated on computed tomography. Subsequently, interbody fusion was evaluated according to the fusion quality scale, fusion rate and incidence of subsidence. RESULTS: Signs of incipient fusion at 3 months were detected in 22% of cases with the Al2O3 cage and 37.1% with the PEEK cage. At 12-month FU, the fusion rate was 88.2% for Al2O3 and 97.1% for PEEK cages, and at the final FU at 18 months, 92.6% and 100%, respectively. The incidence of subsidence was observed to be 11.8% and 22.9% of cases with Al2O3 and PEEK cages, respectively. CONCLUSIONS: Porous Al2O3 cages demonstrated a lower speed and quality of fusion in comparison with PEEK cages. However, the fusion rate of Al2O3 cages was within the range of published results for various cages. The incidence of subsidence of Al2O3 cages was lower compared to published results. We consider the porous Al2O3 cage as safe for a stand-alone disc replacement in ACDF.

The Need for Emphasis on Intracranial Hypertension Management in Spontaneous Skull Base Meningoencephaloceles.

OBJECTIVE: To provide an analysis of patients with spontaneous skull base meningoencephaloceles (MECs) to determine whether definitive surgical treatment requires management of elevated intracranial pressure (ICP). METHODS: Data of 10 subjects with spontaneous MECs were collected and retrospectively evaluated. Measurement of ICP, prior interventions, treatment with acetazolamide, and characteristics of long-term elevated ICP, among others, were analyzed. Our own indications for cerebrospinal fluid (CSF) diversion and use of postoperative external lumbar drain were analyzed as well. RESULTS: The sphenoid region was the most common location of MECs. CSF leak was diagnosed in all subjects. The most common graphical signs of elevated ICP were empty sella and arachnoid pits, both of which were present in 90% of cases. Lumbar puncture with opening pressure measurement was performed in 7 patients. Ventriculoperitoneal shunt insertion was indicated in 4 cases before skull base repair and in 2 cases after skull base repair. Two postoperative CSF leaks were managed with external lumbar drain and subsequent shunt installation. CONCLUSIONS: Spontaneous MECs are often associated with CSF leak. ICP assessment should be a standard of care to ensure successful operative repair of MECs. Insertion of a CSF diversion device must be considered where direct or indirect signs of intracranial hypertension are present.

Cauda equina neuroendocrine tumors show biological features distinct from other paragangliomas and visceral neuroendocrine tumors.

Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.

Pitx2 is a useful marker of midgut-derived neuroendocrine tumours - an immunohistochemical study of 224 cases.

Pitx2 is a transcription factor responsible for establishment of the right-left axis and development of the gut and pituitary. In mouse embryos, Pitx2 is expressed in the greater curvature of the stomach and midgut. Previously, Pitx2 was studied in pituitary neuroendocrine tumours but not in other NETs. Pitx2 expression was immunohistochemically assessed in whole sections and tissue microarrays in a cohort of 224 neuroendocrine neoplasms, and was analysed in 29 cases. The cohort included 18 cauda equina NETs, 38 paragangliomas, 98 cases of primary visceral NETs from different organs, 23 metastases of visceral NETs and 47 neuroendocrine carcinomas (NECs). Pitx2 expression was observed in 29.5% (29 of 98) NETs and 14.9% (7 of 47) NECs, but was not observed in any paraganglioma or cauda equina NET. Pitx2 was observed only in tumours of midgut-derived organs, including the small intestine (100%, 20 of 20), appendix (88.9%, eight of nine) and large intestine (9.1%, one of 11 - only caecal NET). The NETs of remaining locations were negative. Pitx2 was 96.7% sensitive and 100% specific for NETs of midgut origin. In NECs, Pitx2 positivity was observed in goblet cell adenocarcinoma (75%, three of four), medullary thyroid carcinoma (42.9, three of seven) and one Merkel cell carcinoma (25%, one of four). In metastatic NETs, Pitx2 was observed in all the tumours originating in the small intestine (n = 17) or caecum (n = 1). No positivity was observed in tumours from other locations (four pancreas, one lung). We observed no correlation between immunoreactivity and mRNA expression. Thus, Pitx2 immunohistochemistry can be helpful in assessing the midgut origin of NETs.

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017-2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017-2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

One-year neuropsychological outcome after temporal lobe epilepsy surgery in large Czech sample: Search for factors contributing to memory decline.

Background: Assessment of cognitive functions is an integral part of the evaluation the efficacy of temporal resections. We studied postoperative neuropsychological changes and factors contributing to worse memory outcomes in patients who experienced a significant decline using reliable change indices. Methods: We prospectively studied 110 patients in whom we indicated anteromesial temporal resection (AMTR) and 46 patients who underwent selective amygdalohippocampectomy (SAHE). We administrated Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and the Verbal Fluency Test before and 1 year after the operation. Results: At a group level, we did not observe any statistically significant changes in global, verbal, and visual MQ in either the AMTR or the SAHE group. At an individual level, we found a mean decrease of verbal MQ after left-sided AMTR by -4.43 points (P = 0.01). We detected no significant differences between the left and right side of surgery in the SAHE group. In patients with significant postoperative memory decline, we found either pre-existing extrahippocampal deficits/postoperative complications or incomplete hippocampal resection or a combination of these factors. Conclusion: In addition to the side of surgery, structural integrity and functional adequacy of resected hippocampus and volume of resected tissue and preoperative extrahippocampal lesions/postoperative complications also contribute to postoperative memory decline after temporal lobe epilepsy surgery.

Flow Preserving Endovascular Treatment of Traumatic Pseudoaneurysms of the Distal Anterior Cerebral Artery-Case Reports and Review of Literature.

Traumatic intracranial pseudoaneurysms (tIPAs) are a very rare pathology caused by blunt or penetrating head trauma. Diagnostic and therapeutic challenges of tIPAs are due to their unpredictable onset during the initial injury, or in a delayed manner, their unclear traumatic mechanism. Moreover, the presence of subarachnoid, subdural, or intraventricular hematoma may often cause them to be overlooked, which can potentially be followed by lethal rebleeding. Treatment of these lesions is controversial and on a case-by-case basis with regard to endovascular therapy or open surgery. We report two cases of three tIPAs of the distal anterior cerebral artery (dACA) with immediate and delayed onset after the trauma. Endovascular therapy resulted in complete obliteration of lesions with flow preservation in the parent artery using the flow diverter-assisted coiling strategy. The aim of this manuscript is to discuss the mechanism, angioanatomical characteristics, and current treatment options for these exceptional lesions.

Optical coherence tomography and visual evoked potentials in evaluation of optic chiasm decompression.

Chiasmal compression is a known cause of visual impairment, often leading to surgical decompression of the optic chiasm (OC). A prospective study was held at University Hospital in Hradec Králové to explore sensitivity of optical coherence tomography (OCT) and visual evoked potentials (VEPs) to OC compression and eventual changes after a decompression. 16 patients with OC compression, caused by different sellar pathologies, were included. The main inclusion criterion was the indication for decompressive surgery. Visual acuity (VA), visual field (VF), retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness, and peak time and amplitude of pattern-reversal (P-VEPs) and motion-onset VEPs (M-VEPs) were measured pre- and postoperatively. The degree of OC compression was determined on preoperative magnetic resonance imaging. For M-VEPs, there was a significant postoperative shortening of the peak time (N160) (p < 0.05). P100 peak time and its amplitude did not change significantly. The M-VEPs N160 amplitude showed a close relationship to the VF improvement. Thinner preoperative RNFL does not present a statistically important limiting factor for better functional outcomes. The morphological status of the sellar region should be taken into consideration when one evaluates the chiasmal syndrome. M-VEPs enable detection of functional changes in the visual pathway better than P-VEPs.

Calcifying pseudoneoplasm of neuroaxis (CAPNON): a comprehensive immunohistochemical and morphological characterization of five cases.

Calcifying pseudoneoplasm of neuroaxis (CAPNON) is a rare lesion of the central nervous system with uncertain histogenesis. We further explored phenotypic spectrum of the entity with respect to possible histogenesis. We collected 5 cases of CAPNONs, performed a detailed morphological assessment, and performed an extensive immunohistochemical analysis (EMA, progesterone receptors, MUC4, SSTR2A, cytokeratin AE1/3, cytokeratin 18, GFAP, neurofilaments, desmin, nestin, synaptophysin, S100 protein, SOX10, CD56, Podoplanin, SATB2, ERG, CD45, and CD163) to elucidate the histogenesis. Furthermore, we performed NGS analysis of one case. The clinical course was benign in all cases. All lesions showed extensively calcified matrix in multilobular arrangement, with a palisade of osteoblast-like cells. Characteristic fibrohyaline matrix was notable in 4/5 cases, while one case was myxoid with rod-like calcifications. Metaplastic lamellar bone was present in 4/5 cases and psammoma bodies were present in 2/5 cases. In 4/5 cases, areas of entrapped glial tissue were present. Expression of EMA was focally present in 3/5 cases, SSTR2A and nestin in 2/5 cases, and progesterone receptor in 2/5 cases in rare cells. We did not observe concomitant expression of EMA, SSTR2A, and progesterone receptor in the same cellular subsets. In one case, NGS showed multiple chromosomal alterations and missense mutation in PIK3CA, attributable to the admixed meningothelial population compatible with meningioma. In another case, biphasic proliferation with myoepithelial phenotype was present. The lesions showed no lineage-specific immunoprofile. Additional pathology was identified in two cases, furthermore suggestive of a possible reactive origin of the lesion.

Small RNA Sequencing Identifies PIWI-Interacting RNAs Deregulated in Glioblastoma-piR-9491 and piR-12488 Reduce Tumor Cell Colonies In Vitro.

Glioblastoma (GBM) is the most frequently occurring primary malignant brain tumor of astrocytic origin. To change poor prognosis, it is necessary to deeply understand the molecular mechanisms of gliomagenesis and identify new potential biomarkers and therapeutic targets. PIWI-interacting RNAs (piRNAs) help in maintaining genome stability, and their deregulation has already been observed in many tumors. Recent studies suggest that these molecules could also play an important role in the glioma biology. To determine GBM-associated piRNAs, we performed small RNA sequencing analysis in the discovery set of 19 GBM and 11 non-tumor brain samples followed by TaqMan qRT-PCR analyses in the independent set of 77 GBM and 23 non-tumor patients. Obtained data were subsequently bioinformatically analyzed. Small RNA sequencing revealed 58 significantly deregulated piRNA molecules in GBM samples in comparison with non-tumor brain tissues. Deregulation of piR-1849, piR-9491, piR-12487, and piR-12488 was successfully confirmed in the independent groups of patients and controls (all p < 0.0001), and piR-9491 and piR-12488 reduced GBM cells' ability to form colonies in vitro. In addition, piR-23231 was significantly associated with the overall survival of the GBM patients treated with Stupp regimen (p = 0.007). Our results suggest that piRNAs could be a novel promising diagnostic and prognostic biomarker in GBM potentially playing important roles in gliomagenesis.

A rare case of non-traumatic spinal epidural hematoma in lumbar region associated with apixaban therapy.

Spontaneous spinal epidural hematoma (SSEH) is a very rare clinical entity with potential diagnostic difficulties and which can result in severe neurological deficit. The etiology of this rare condition is largely not known, but with potential predisposition in patients on anticoagulation medication. This includes the novel anticoagulants with direct inhibition of the factor Xa mechanism (DOACs). These medications are supposed to have more predictable pharmacokinetics with fewer severe haemorrhagic adverse events in comparison with standard warfarin therapy. However, in the last few years, an increasing number of case reports have been published of haemorrhage into the central nervous system. We present a case of non-traumatic spinal epidural hematoma in the lumbar region in a patient on chronic apixaban therapy. To the best of our knowledge, it is the first described SSEH in the lumbar region associated with apixaban therapy.

Mechanical thrombectomy performed in thrombosed fusiform aneurysm after surgery for craniopharyngioma in adult.

INTRODUCTION: Fusiform dilatation of the internal carotid artery (ICA) is reported as a possible complication of craniopharyngioma resection in childhood. Here, the authors describe such a complication in an adult patient who presented with acute symptomatic thrombosis 7 months after surgery. MATERIALS AND METHODS: A 45-year-old woman presented with left hemispheric stroke due to a thrombotic supraclinoid occlusion of the terminal ICA (so called "T" occlusion). Successful revascularisation was achieved with mechanical thrombectomy. Beside recanalization of the M1 middle cerebral artery segment and ICA, an irregular filling of the fusiform aneurysm of the communicating segment of the left ICA was observed. The patient recovered after mechanical thrombectomy with no clinical sequelae. Due to the persistent filling of the aneurysm sac, a flow diverter stent was deployed across the diseased vessel segment two weeks later. The patient underwent resection of the craniopharyngioma from ipsilateral pterional craniotomy 7 months ago. Five years later the patient works full time as a nurse with no regrowth of the craniopharyngioma and no aneurysm reperfusion. RESULTS: This case, together with four other previously reported cases, documents that fusiform aneurysm as a complication of the craniopharygioma resection is not restricted to the childhood population but may also rarely occur in adults. As the patient suffered from acute symptomatic thrombosis which required treatment under the protocol for acute large vessel occlusions, we decided to treat the aneurysm with the flow diverter stent.

Trends and outcomes for non-elective neurosurgical procedures in Central Europe during the COVID-19 pandemic.

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th-April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017-2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

Cytokeratin 8/18-negative somatotroph pituitary neuroendocrine tumours (PitNETs, adenomas) show variable morphological features and do not represent a clinicopathologically distinct entity.

AIMS: In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically. METHODS AND RESULTS: Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin-like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E-cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1/3, CK 8/18, vimentin, neurofilament light chain, internexin-α) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8/18 antibody, while the remainder expressed only internexin-α intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK-negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E-cadherin compared to the non-sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co-expression of prolactin and morphology of either mammosomatotroph or somatotroph-lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1-positive tumours. CONCLUSIONS: CK-negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.

Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.