Genetic testing in children enrolled in epilepsy surgery program. A real-life study.

OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.

Predictors of postoperative complications and functional outcomes in pediatric patients with surgically treated fourth ventricle tumors.

BACKGROUND: Tumors of the fourth ventricle are frequently treated pathologies in pediatric neurosurgery. Data regarding predictors for permanent neurological deficits, long-term functional outcomes, cerebellar mutism (CM), the extent of resection (EOR), and oncological outcomes are scarce. We attempt to contribute to this topic with an analysis of our institutional cohort. METHODS: A retrospective single-center study of patients aged ≤ 19 years who underwent primary surgical resection of a fourth ventricular tumor over a 15-year period (2006-2021). Predictors analyzed included age, gender, surgical approach, anatomical pattern, tumor grade, EOR, tumor volume, and others as appropriate. RESULTS: One hundred six patients were included (64 males, mean age 7.3 years). The rate of permanent neurological deficit was 24.2%; lateral tumor extension (p = 0.036) and tumor volume greater than 38 cm3 (p = 0.020) were significant predictors. The presence of a deficit was the only significant predictor of reduced (less than 90) Lansky score (p = 0.005). CM occurred in 20.8% of patients and was influenced by medulloblastoma histology (p = 0.011), lateral tumor extension (p = 0.017), and male gender (p = 0.021). No significant difference between the transvermian and telovelar approach in the development of CM was detected (p = 0.478). No significant predictor was found for the EOR. EOR was not found to be a significant predictor of overall survival for both low-grade and high-grade tumors; however, gross total resection (GTR) was protective against tumor recurrence compared to near-total or subtotal resection (p < 0.001). In addition, survival was found to be better in older patients (≥ 7.0 years, p = 0.019). CONCLUSION: The overall rate of postoperative complications remains high due to the eloquent localization. Older patients (> 7 years) have been found to have better outcomes and prognosis. Achieving GTR whenever feasible and safe has been shown to be critical for tumor recurrence. CM was more common in patients with medulloblastoma and in patients with tumors extending through the foramen of Luschka. The telovelar approach uses a safe and anatomically sparing corridor; however, it has not been associated with a lower incidence of CM and neurological sequelae in our series, showing that each case should be assessed on an individual basis.

Integrated genomic analysis reveals actionable targets in pediatric spinal cord low-grade gliomas.

Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients. Driver molecular alteration was found in 92% of patients (24/26). A novel variant of KIAA1549:BRAF fusion (ex10:ex9) was identified using RNA-seq in four cases. Importantly, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, and two-thirds of pediatric patients with sLGGs required extensive molecular examination. The majority (23/24) of detected alterations were potentially druggable targets. Four patients in our cohort received targeted therapy with MEK or NTRK inhibitors. Three of those exhibited clinical improvement (two with trametinib, one with larotrectinib), and two patients achieved partial response. Methylation profiling was implemented to further refine the diagnosis and revealed intertumoral heterogeneity in sLGGs. Although 55% of tumors clustered with pilocytic astrocytoma, other rare entities were identified in this patient population. In particular, diffuse leptomeningeal glioneuronal tumors (n = 3) and high-grade astrocytoma with piloid features (n = 1) and pleomorphic xanthoastrocytoma (n = 1) were present. A proportion of tumors (14%) had no match with the current version of the classifier. Complex molecular genetic sLGGs characterization was invaluable to refine diagnosis, which has proven to be essential in such a rare tumor entity. Moreover, identifying a high proportion of drugable targets in sLGGs opened an opportunity for new treatment modalities.

Survival and functional outcomes in paediatric thalamic and thalamopeduncular low grade gliomas.

BACKGROUND: Childhood thalamopeduncular gliomas arise at the interface of the thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological function. We present long-term clinical and oncological outcomes of maximal safe resection. METHODS: Retrospective review of prospectively collected data: demography, symptomatology, imaging, extent of resection, surgical complications, histology, functional and oncological outcome. RESULTS: During 16-year period (2005-2020), 21 patients were treated at our institution. These were 13 girls and 8 boys (mean age 7.6 years). Presentation included progressive hemiparesis in 9 patients, raised intracranial pressure in 9 patients and cerebellar symptomatology in 3 patients. The tumour was confined to the thalamus in 6 cases. Extent of resection was judged on postoperative imaging as total (6), near-total (6) and less extensive (9). Surgical complications included progression of baseline neurological status in 6 patients, and 5 of these gradually improved to preoperative status. All tumours were classified as low-grade gliomas. Disease progression was observed in 9 patients (median progression-free survival 7.3 years). At last follow-up (median 6.1 years), all patients were alive, median Lansky score of 90. Seven patients were without evidence of disease, 6 had stable disease, 7 stable following progression and 1 had progressive disease managed expectantly. CONCLUSION: Paediatric patients with low-grade thalamopeduncular gliomas have excellent long-term functional and oncological outcomes when gross total resection is not achievable. Surgery should aim at total resection; however, neurological function should not be endangered due to excellent chance for long-term survival.

May intraoperative detection of stereotactically inserted intracerebral electrodes increase precision of resective epilepsy surgery?

OBJECT: Epilepsy surgery is an effective treatment for selected patients with focal intractable epilepsy. Complete removal of the epileptogenic zone significantly increases the chances for postoperative seizure-freedom. In complex surgical candidates, delineation of the epileptogenic zone requires a long-term invasive video/EEG from intracranial electrodes. It is especially challenging to achieve a complete resection in deep brain structures such as opercular-insular cortex. We report a novel approach utilizing intraoperative visual detection of stereotactically implanted depth electrodes to inform and guide the extent of surgical resection. METHODS: We retrospectively reviewed data of pediatric patients operated in Motol Epilepsy Center between October 2010 and June 2020 who underwent resections guided by intraoperative visual detection of depth electrodes following SEEG. The outcome in terms of seizure- and AED-freedom was assessed individually in each patient. RESULTS: Nineteen patients (age at surgery 2.9-18.6 years, median 13 years) were included in the study. The epileptogenic zone involved opercular-insular cortex in eighteen patients. The intraoperative detection of the electrodes was successful in seventeen patients and the surgery was regarded complete in sixteen. Thirteen patients were seizure-free at final follow-up including six drug-free cases. The successful intraoperative detection of the electrodes was associated with favorable outcome in terms of achieving complete resection and seizure-freedom in most cases. On the contrary, the patients in whom the procedure failed had poor postsurgical outcome. CONCLUSION: The reported technique helps to achieve the complete resection in challenging patients with the epileptogenic zone in deep brain structures.

Methylation pattern in the diagnosis and prognosis of brain cancer.

Examination of changes in the methylation profile of DNA in cancer is currently used to determine the diagnosis or prognostic and predictive biomarkers. It complements histological or molecular biological examinations. At the same time, it helps to identify new diagnostic groups and subgroups. Currently, this diagnosis is most common in brain tumors, where it has become a routine examination. The established methylation profile may help even where the diagnosis or subgroup classification of the disease cannot be determined in any other way, as is the case with medulloblastoma.

An immunotherapy effect analysis in Rasmussen encephalitis.

BACKGROUND: Immune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy. METHODS: Immunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected. RESULTS: Sustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8+ T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients' CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8+ T cells in the brain tissue, as well as in the overall CD8+ T cell population and chemokine/cytokine production in the CSF. CONCLUSIONS: We provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.

The clinical utility of intraoperative electrocorticography in pediatric epilepsy surgical strategy and planning.

OBJECTIVE: In this study, the authors aimed to determine 1) whether the use of intraoperative electrocorticography (ECoG) affects outcomes and complication rates of children undergoing resective epilepsy surgery; 2) which patient- and epilepsy-related variables might influence ECoG-based surgical strategy; and 3) what the predictors of epilepsy surgery outcomes are. METHODS: Over a period of 12 years, data were collected on pediatric patients who underwent tailored brain resections in the Motol Epilepsy Center. In patients in whom an abnormal ECoG pattern (e.g., spiking, suppression burst, or recruiting rhythm) was not observed beyond presurgically planned resection margins, the authors did not modify the surgical plan (group A). In those with significant abnormal ECoG findings beyond resection margins, the authors either did (group B) or did not (group C) modify the surgical plan, depending on the proximity of the eloquent cortex or potential extent of resection. Using Fisher's exact test and the chi-square test, the 3 groups were compared in relation to epilepsy surgery outcomes and complication rate. Next, multivariate models were constructed to identify variables associated with each of the groups and with epilepsy surgery outcomes. RESULTS: Patients in group C achieved significantly lower rates of seizure freedom compared to groups A (OR 30.3, p < 0.001) and B (OR 35.2, p < 0.001); groups A and B did not significantly differ (p = 0.78). Patients in whom the surgical plan was modified suffered from more frequent complications (B vs A+C, OR 3.8, p = 0.01), but these were mostly minor (duration < 3 months; B vs A+C, p = 0.008). In all cases, tissue samples from extended resections were positive for the presence of the original pathology. Patients with intended modification of the surgical plan (groups B+C) suffered more often from daily seizures, had a higher age at first seizure, had intellectual disability, and were regarded as MR-negative (p < 0.001). Unfavorable surgical outcome (Engel class II-IV) was associated with focal cortical dysplasia, incomplete resection based on MRI and/or ECoG findings, negative MRI finding, and inability to modify the surgical plan when indicated. CONCLUSIONS: Intraoperative ECoG serves as a reliable tool to guide resection and may inform the prognosis for seizure freedom in pediatric patients undergoing epilepsy surgery. ECoG-based modification of the surgical plan is associated with a higher rate of minor complications. Children in whom ECoG-based modification of the surgical plan is indicated but not feasible achieve significantly worse surgical outcomes.

A novel effective paradigm of intraoperative electrical stimulation mapping in children.

OBJECTIVE: Resective epilepsy surgery is an established treatment method for children with focal intractable epilepsy, but the use of this method introduces the risk of postsurgical motor deficits. Electrical stimulation mapping (ESM), used to define motor areas and pathways, frequently fails in children. The authors developed and tested a novel ESM protocol in children of all age categories. METHODS: The ESM protocol utilizes high-frequency electric cortical stimulation combined with continuous intraoperative motor-evoked potential (MEP) monitoring. The relationships between stimulation current intensity and selected presurgical and surgery-associated variables were analyzed in 66 children (aged 7 months to 18 years) undergoing 70 resective epilepsy surgeries in proximity to the motor cortex or corticospinal tracts. RESULTS: ESM elicited MEP responses in all children. Stimulation current intensity was associated with patient age at surgery and date of surgery (F value = 6.81, p < 0.001). Increase in stimulation current intensity predicted postsurgical motor deficits (F value = 44.5, p < 0.001) without effects on patient postsurgical seizure freedom (p > 0.05). CONCLUSIONS: The proposed ESM paradigm developed in our center represents a reliable method for preventing and predicting postsurgical motor deficits in all age groups of children. This novel ESM protocol may increase the safety and possibly also the completeness of epilepsy surgery. It could be adopted in pediatric epilepsy surgery centers.

Torcular dural sinus malformations: a single-center case series and a review of literature.

INTRODUCTION: Torcular dural sinus malformations (tDSMs) are rare vascular pathologies with various anatomoclinical pictures and prognosis. We analyzed our case series and corroborated the complexity of this rare unit by a review of literature. CASE SERIES: From 2003 to 2018, we treated four tDSMs patients. The evolution of three postnatally diagnosed cases of similar angioarchitecture contrasted with a fourth antenatally diagnosed case with significant torcular thrombosis. All patients were examined by computed tomography, magnetic resonance imaging, CT angiography, and MRI angiography. Three patients underwent digital subtraction angiography with embolization of feeders. Unusual pathological images were depicted. CONCLUSIONS: Early diagnosis along with embolization of feeders and lake could improve the outcome for tDSM patients with dural arteriovenous shunts. Ventriculoperitoneal shunt implantation before endovascular treatment led to significant worsening of both clinical presentation and MRI picture. For patients who persist with hydrocephalus despite the endovascular approach, we suggest endoscopic third ventriculostomy as a first-line treatment option. Antenatally diagnosed patients with thrombosed lakes constitute a prognostically better group of patients. Spontaneous thrombosis and remodelation of the lake can, however, still leave neurological sequelae, as observed in our patient.

Cognitive performance in distinct groups of children undergoing epilepsy surgery-a single-centre experience.

BACKGROUND: We aimed first to describe trends in cognitive performance over time in a large patient cohort (n = 203) from a single tertiary centre for paediatric epilepsy surgery over the period of 16 years divided in two (developing-pre-2011 vs. established-post-2011). Secondly, we tried to identify subgroups of epilepsy surgery candidates with distinctive epilepsy-related characteristics that associate with their pre- and post-surgical cognitive performance. Thirdly, we analysed variables affecting pre-surgical and post-surgical IQ/DQ and their change (post- vs. pre-surgical). METHODS: We analysed IQ/DQ data obtained using standardized neuropsychological tests before epilepsy surgery and one year post-surgically, along with details of patient's epilepsy, epilepsy surgery and outcomes in terms of freedom from seizures. Using regression analysis, we described the trend in post-operative IQ/DQ. Cognitive outcomes and the associated epilepsy- and epilepsy surgery-related variables were compared between periods before and after 2011. Using multivariate analysis we analysed the effect of individual variables on pre- and post-operative IQ/DQ and its change. RESULTS: Epilepsy surgery tends to improve post-surgical IQ/DQ, most significantly in patients with lower pre-surgical IQ/DQ, and post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ (Rho = 0.888, p < 0.001). We found no significant difference in pre-, post-surgical IQ/DQ and IQ/DQ change between the periods of pre-2011 and post-2011 (p = 0.7, p = 0.469, p = 0.796, respectively). Patients with temporal or extratemporal epilepsy differed in their pre-surgical IQ/DQ (p = 0.001) and in IQ/DQ change (p = 0.002) from those with hemispheric epilepsy, with no significant difference in post-surgical IQ/DQ (p = 0.888). Groups of patients with different underlying histopathology showed significantly different pre- and post-surgical IQ/DQ (p < 0.001 and p < 0.001 respectively) but not IQ/DQ change (p = 0.345).Variables associated with severe epilepsy showed effect on cognitive performance in multivariate model. DISCUSSION: Post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ and greatest IQ/DQ gain occurs in patients with lower pre-surgical IQ/DQ scores. Cognitive performance was not affected by changes in paediatric epilepsy surgery practice. Pre- and post-operative cognitive performances, as well as patients' potential for cognitive recovery, are highly dependent on the underlying aetiology and epileptic syndrome.

Generalized quasiperiodic epileptiform activity in sleep is associated with cognitive impairment in children with drug-resistant focal lesional epilepsy.

OBJECTIVE: To evaluate the impact of generalized quasiperiodic epileptiform discharges ("hurdles") observed in non-rapid eye movement (NREM) sleep on cognitive function in children with intractable focal epilepsy. "Hurdles" pattern does not meet the criteria of the electrical status epilepticus in slow-wave sleep (ESES). METHODS: In a retrospective analysis, 24 patients with "hurdles" and their 24 peers matched for demographic and epilepsy-related variables were compared in terms of neuropsychological domains and electroencephalography (EEG)-derived quantifiers. Both "hurdles" and controls were children between 2 and 19 years of age who had intractable focal epilepsy evaluated as candidates of resective epilepsy surgery. RESULTS: Full-scale intelligence quotient/developmental quotient (FSIQ/DQ) (P = .002) and visuoconstructional skills (P = .004) were significantly lower in children with "hurdles" compared to controls. Patients with "hurdles" presented with higher interictal spike indexes in sleep (P < .001, median difference -0.9, 95% confidence interval [CI] -1.4, -0.6) and wakefulness (P < .001, median difference -0.3, 95% CI -0.5, -1). Relative time of sleep spindles in NREM sleep was significantly reduced (P < .001, median difference 0.1, 95% CI 0.0, 0.1) in the "hurdles" group. The time proportion of sleep spindles represented a significant positive (P = .008) and spike index of generalized spikes in sleep a significant negative explanatory variable (P = .004) of FSIQ/DQ scores. The proportion of seizure-free patients 2 years after epilepsy surgery did not differ significantly between the two groups (P = .19). SIGNIFICANCE: Although the "hurdles" pattern does not fulfill the criteria of ESES, it is associated with a pronounced cognitive dysfunction. Disturbed sleep structure marked by reduced sleep spindles and generalized spiking in sleep is associated with worse cognitive performance. Despite having a generalized nature, we did not find a lower probability of postsurgical seizure freedom in patients with "hurdles" pattern.

Jugular Bulb Dysmaturation in Torcular Dural Sinus Malformation: Clinical Images and Review of Literature.

We present unique clinical images of jugular bulb dysmaturation (JBD) in an infant with torcular dural sinus malformation (tDSM). Lasjaunias et al hypothesized that the former possess a pivoting role for development of the latter. However, reports about tDSM are extremely rare and lack focus on JBD presence. In this paper we focused on JBD depiction. The combination of magnetic resonance imaging angiography, computed tomography angiography, and digital subtraction angiography imaging of JBD is unique. Moreover, we reviewed current tDSM literature and showed that the presence of JBD in tDSMs correlates significantly with a higher mortality.

Evolution of pediatric epilepsy surgery program over 2000-2017: Improvement of care?

PURPOSE: We assessed trends in spectrum of candidates, diagnostic algorithm, therapeutic approach and outcome of a pediatric epilepsy surgery program between 2000 and 2017. METHODS: All pediatric patients who underwent curative epilepsy surgery in Motol Epilepsy Center during selected period (n = 233) were included in the study and divided into two groups according to time of the surgery (developing program 2000-2010: n = 86, established program 2011-2017: n = 147). Differences in presurgical, surgical and outcome variables between the groups were statistically analyzed. RESULTS: A total of 264 resections or hemispheric disconnections were performed (including 31 reoperations). In the later epoch median age of candidates decreased. Median duration of disease shortened in patients with temporal lobe epilepsy. Number of patients with non-localizing MRI findings (subtle or multiple lesions) rose, as well as those with epileptogenic zone adjacent to eloquent cortex. There was a trend towards one-step procedures guided by multimodal neuroimaging and intraoperative electrophysiology; long-term invasive EEG was performed in fewer patients. Subdural electrodes for long-term invasive monitoring were almost completely replaced by stereo-EEG. The number of focal resections and hemispherotomies rose over time. Surgeries were more often regarded complete. Histopathological findings of resected tissue documented developing spectrum of candidates. 82.0% of all children were seizure-free two years after surgery; major complications occurred in 4.6% procedures; both groups did not significantly differ in these parameters. CONCLUSION: In the established pediatric epilepsy surgery program, our patients underwent epilepsy surgery at younger age and suffered from more complex structural pathology. Outcomes and including complication rate remained stable.

Brain gliomas, hydrocephalus and idiopathic aqueduct stenosis in children with neurofibromatosis type 1.

PURPOSE: To evaluate the incidence and clinical importance of brain gliomas - optic pathway gliomas (OPGs) and especially gliomas outside the optic pathway (GOOP) for children with neurofibromatosis type 1 (NF1), additionally, to assess the causes of obstructive hydrocephalus in NF1 children with an emphasis on cases caused by idiopathic aqueduct stenosis. SUBJECTS AND METHODS: We analysed data from 285 NF1 children followed up on our department from 1990 to 2010 by the same examination battery. RESULTS: We have found OPGs in 77/285 (27%) children and GOOPs in 29/285 (10,2%) of NF1 children, of who 19 had OPG and GOOP together, so the total number of brain glioma was 87/285 (30,5%). GOOPs were significantly more often treated than OPGs (p > 0.01). OPGs contain clinically important subgroup of 14/285 (4.9%) spreading to hypothalamus. Spontaneous regression was documented in 4/285 (1.4%) gliomas and the same number of NF1 children died due to gliomas. Obstructive hydrocephalus was found in 22/285 (7.7%) patients and 14/22 cases were due to glioma. Idiopathic aqueduct stenosis caused hydrocephalus in 6/22 cases and was found in 2.1% of NF1 children. Two had other cause. CONCLUSIONS: The total brain glioma number (OPGs and only GOOPs together) better reflected the overall brain tumour risk for NF1 children. However, GOOPs occur less frequently than OPGs, they are more clinically relevant. The obstructive hydrocephalus was severe and featuring frequent complication, especially those with GOOP. Idiopathic aqueduct stenosis shows an unpredictable cause of hydrocephalus in comparison with glioma and is another reason for careful neurologic follow up.

Cytometric analysis of cell suspension generated by cavitron ultrasonic surgical aspirator in pediatric brain tumors.

PURPOSE: The aim of this study was to test the possibility of using specimens obtained by a cavitron ultrasonic surgical aspirator (CUSA) in flow and mass cytometry investigations of pediatric brain tumors. METHODS: CUSA specimens obtained from 19 pediatric patients with brain tumors were investigated. Flow and mass cytometry methods were applied to analyze the composition of material collected using the CUSA. Cell suspensions were prepared from CUSA aspirates. Then sample viability was assessed by conventional flow cytometry and subsequently stained with a panel of 31 metal-labeled antibodies. RESULTS: Viability assessment was performed using conventional flow cytometry. Viability of cells in the acquired samples was below 50% in 16 of 19 cases. A mass cytometry investigation and subsequent analysis enabled us to discriminate brain tumor cells from contaminating leukocytes, whose proportions varied across the specimens. The addition of the viability marker cisplatin directly into the mass cytometry panel gave the means to selecting viable cells only for subsequent analyses. The proportion of non-viable cells was higher among tumor cells compared leukocytes. CONCLUSIONS: When the analysis of the tumor cell immunophenotype is performed with markers for determining viability, the expression of the investigated markers can be evaluated. Suitable markers can be selected by high-throughput methods, such as mass cytometry, and those that are diagnostically relevant can be investigated using flow cytometry, which is more flexible in terms of time.

Sagittal craniosynostosis associated with midline cephalhematoma or vice versa, case report and a review of the literature.

INTRODUCTION: Sagittal craniosynostosis associated with midline cephalhematoma is a rare finding. Despite the controversy regarding its etiopathogenesis, this condition represents a clear indication for surgery. CASE REPORT: We present a case of a 10-week-old boy with an ossified midline vertex cephalhematoma and sagittal craniosynostosis. The child underwent a cephalhematoma excision and minimally invasive non-endoscopic narrow vertex craniectomy, with calvarial vault remodeling followed by 2 weeks use of a cranial orthosis. On 5-month follow-up, mesocephaly was achieved. CONCLUSION: Our case is well documented with native CT, 3D CT, intraoperative pictures, and 3D head scan imaging. We described our minimally invasive non-endoscopic technique that led to a rapid cranial vault remodeling with reduction of cranial orthosis need. A review of literature focused on surgical techniques is included.

Electromagnetic navigation-guided neuroendoscopic transfrontal transaqueductal fenestration of expansive posterior fossa arachnoid cyst with simultaneous endoscopic third ventriculostomy in an infant.

INTRODUCTION: We present an infant with an expansive posterior fossa arachnoid cyst and severe clinical deterioration due to decompensated obstructive hydrocephalus. Given the dilated Sylvius aqueduct, we favoured the endoscopic transfrontal transaqueductal route to approach the cyst. CASE REPORT: A 12-month-old boy was acutely admitted for severe symptoms of intracranial hypertension. Imaging revealed spacious cystic formation in the posterior fossa with expansive behaviour towards the brain stem, fourth ventricle and cerebellum associated with obstructive triventricular hydrocephalus. The patient underwent electromagnetically navigated transfrontal transaqueductal cyst fenestration with simultaneous ETV from two precoronal trajectories with a rigid endoscope. CONCLUSION: A transaqueductal approach with a rigid endoscope is rarely published, and we were amazed by the impact on the child's clinical improvement after this minimally invasive endoscopic procedure. The case is well documented with imaging and perioperative neuroendoscopic views.