Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage.

BACKGROUND: The objective of this document is to provide recommendations on the formal reliability of major clinical predictors often associated with intracerebral hemorrhage (ICH) neuroprognostication. METHODS: A narrative systematic review was completed using the Grading of Recommendations Assessment, Development, and Evaluation methodology and the Population, Intervention, Comparator, Outcome, Timing, Setting questions. Predictors, which included both individual clinical variables and prediction models, were selected based on clinical relevance and attention in the literature. Following construction of the evidence profile and summary of findings, recommendations were based on Grading of Recommendations Assessment, Development, and Evaluation criteria. Good practice statements addressed essential principles of neuroprognostication that could not be framed in the Population, Intervention, Comparator, Outcome, Timing, Setting format. RESULTS: Six candidate clinical variables and two clinical grading scales (the original ICH score and maximally treated ICH score) were selected for recommendation creation. A total of 347 articles out of 10,751 articles screened met our eligibility criteria. Consensus statements of good practice included deferring neuroprognostication-aside from the most clinically devastated patients-for at least the first 48-72 h of intensive care unit admission; understanding what outcomes would have been most valued by the patient; and counseling of patients and surrogates whose ultimate neurological recovery may occur over a variable period of time. Although many clinical variables and grading scales are associated with ICH poor outcome, no clinical variable alone or sole clinical grading scale was suggested by the panel as currently being reliable by itself for use in counseling patients with ICH and their surrogates, regarding functional outcome at 3 months and beyond or 30-day mortality. CONCLUSIONS: These guidelines provide recommendations on the formal reliability of predictors of poor outcome in the context of counseling patients with ICH and surrogates and suggest broad principles of neuroprognostication. Clinicians formulating their judgments of prognosis for patients with ICH should avoid anchoring bias based solely on any one clinical variable or published clinical grading scale.

Venous thromboembolism and intracranial hemorrhage in patients undergoing glioblastoma surgery.

In the perioperative management of patients with glioblastoma (GBM), physicians face the question of whether and when to administer prophylactic or therapeutic anticoagulation (AC). In this study, we investigate the effects of the timing of postoperative heparinization on thromboembolic events (TE) and postoperative hemorrhage (bleeding, PH) as well as the interactions between the two in the context of an underlying intracerebral malignancy. For this retrospective data analysis, 222 patients who underwent surgery for grade IV glioblastoma, IDH-wildtype (2016 CNS WHO) between 01/01/2014 and 31/12/2019 were included. We followed up for 12 months. We assessed various biographical and clinical data for risk factors and focused on the connection between timepoint of AC and adverse events. Subgroup analyses were performed for pulmonary artery embolism (PE), deep vein thrombosis, and postoperative intracranial hemorrhage (PH) that either required surgical intervention or was controlled radiologically only. Statistical analysis was performed using Mann-Whitney U-Test, Chi-square test, Fisher's exact test and univariate binomial logistic regression. p values below 0.05 were considered statistically significant. There was no significant association between prophylactic AC within 24 h and more frequent major bleeding (p = 0.350). AC in patients who developed major bleeding was regularly postponed by the physician/surgeon upon detection of the re-bleeding; therefore, patients with PH were anticoagulated significantly later (p = 0.034). The timing of anticoagulant administration did not differ significantly between patients who experienced a thromboembolic event and those who did not (p = 0.634). There was considerable overlap between the groups. Three of the six patients (50%) with PE had to be lysed or therapeutically anticoagulated and thereafter developed major bleeding (p < 0.001). Patients who experienced TE were more likely to die during hospitalization than those with major bleeding (p = 0.022 vs. p = 1.00). Prophylactic AC within 24 h after surgery does not result in more frequent bleeding. Our data suggests that postoperative intracranial hemorrhage is not caused by prophylactic AC but rather is a surgical complication or the result of antithrombotic therapy. However, thromboembolic events worsen patient outcomes far more than postoperative bleeding. The fact that bleeding may occur as a complication of life-saving lysis therapy in the setting of a thromboembolic event should be included in this cost-benefit consideration.

A new concept for expansion screws on the cervical spine using shape memory alloy - a feasibility study.

BACKGROUND: In general, sufficient anchoring of screws in the bone material ensures the intended primary stability. METHODS: Shape memory materials offers the option of using temperature-associated deformation energy in a targeted manner in order to do justice to the special situation of osteoporotic bones or the potential lack of anchoring. An expansion screw was developed that takes this possibility and these requirements into account. Using finite element analysis, the variability of screw configuration and actuator was assessed from shape memory. In particular, the dimensioning of the screw slot, the actuator length and the actuator diameter as well as the angle of attack in relation to the intended force development were considered. RESULTS: As a result of the finite element analysis, a special configuration of expansion screw and shape memory element could be found. Accordingly, with an optimal screw diameter of 4 mm, an actuator diameter of 0.8 mm, a screw slot of 7.8 mm in length and an angle of attack of 25 degrees, the best compromise between individual components and high efficiency in favor of maximum strength can be predicted. CONCLUSION: Shape memory material offers the possibility of using completely new forms of power development. By skillfully modifying the mechanical and shape memory elements, their interaction results in a calculated development of force in favor of a high primary stability of the screw material used. Activation by means of body temperature is a very elegant way of initializing the intended locking and screw strength.

Preserved White Matter Integrity and Recovery After Brain Tumor Surgery: A Prospective Pilot Study on the Frontal Aslant Tract.

Introduction: Damage to white matter tracts can cause severe neurological deficits, which are often hardly predictable before brain tumor surgery. To explore the possibility of assessing white matter integrity and its preservation, we chose the frontal aslant tract (FAT) due to its involvement in multiple neurological functions such as speech and movement initiation. Methods: Right-handed patients with left hemispheric intracerebral tumors underwent FAT tractography within 7 days before and 3 days after surgery. Neurological performance score and aphasia score were assessed within 7 days before and after surgery, as well as at follow-up 3 months postoperatively. Results: Fifteen patients were prospectively analyzed. After multivariate analysis and receiver operating characteristic analysis, we found that preoperative fractional anisotropy (FA) of the left FAT indicated the preoperative aphasia score (cutoff 0.40, p = 0.015). Aphasia scores 3 months postoperatively were predicted by both postoperative FA of the left FAT (cutoff 0.35, p = 0.005) and postoperatively preserved FA of the left FAT (cutoff 95.8%, p = 0.017). Postoperatively preserved right FAT FA inversely predicted postoperative aphasia score (cutoff 95.1%, p = 0.016). Discussion: Assessment of white matter integrity preservation is possible and correlates with outcome after brain tumor surgery. It may be useful for patient counseling and assessment of rehabilitation potential, as well as to investigate relevant brain networks in the future. Clinical Trial Registration: The trial was prospectively registered at ClinicalTrials.gov (NCT04302857).

Cerebrospinal Fluid Protein Concentrations in Hydrocephalus.

CSF protein levels are altered in neurological disorders, such as hydrocephalus of different etiologies. In this retrospective observational study, we analyzed cerebrospinal fluid (CSF) samples in hydrocephalic diseases such as aqueductal stenosis (AQS, n = 27), normal pressure hydrocephalus (NPH, n = 24), hydrocephalus communicans (commHC, n = 25) and idiopathic intracranial hypertension (IIH)/pseudotumor cerebri (PC, n = 7) in comparison with neurological patients without hydrocephalic configuration (control, n = 95). CSF was obtained through CSF diversion procedures and lumbar punction and analyzed for protein concentrations according to the institution's laboratory standards. We found significantly decreased CSF protein levels in patients suffering from AQS (0.13 mg/dL [0.1-0.16 mg/dL] p = 2.28 × 10-8) and from PC (0.18 mg/dL [0.12-0.24 mg/dL] p = 0.01) compared with controls (0.34 mg/dL [0.33-0.35 mg/dL]). Protein levels were not altered in patients suffering from commHC and NPH compared with neurologically healthy individuals. We propose that a decrease in CSF protein levels is part of an active counterregulatory mechanism to lower CSF volume and, subsequently, intracranial pressure in specific diseases. Research regarding said mechanism and more specific proteomic research on a cellular level must still be performed to prove this hypothesis. Differences in protein levels between different diseases point to different etiologies and mechanisms in different hydrocephalic pathologies.

Development and first results of a national databank on care and treatment outcome after traumatic brain injury.

PURPOSE: In absence of comprehensive data collection on traumatic brain injury (TBI), the German Society for Neurosurgery (DGNC) and the German Society for Trauma Surgery (DGU) developed a TBI databank for German-speaking countries. METHODS: From 2016 to 2020, the TBI databank DGNC/DGU was implemented as a module of the TraumaRegister (TR) DGU and tested in a 15-month pilot phase. Since its official launch in 2021, patients from the TR-DGU (intermediate or intensive care unit admission via shock room) with TBI (AIS head ≥ 1) can be enrolled. A data set of > 300 clinical, imaging, and laboratory variables, harmonized with other international TBI data collection structures is documented, and the treatment outcome is evaluated after 6- and 12 months. RESULTS: For this analysis, 318 patients in the TBI databank could be included (median age 58 years; 71% men). Falls were the most common cause of injury (55%), and antithrombotic medication was frequent (28%). Severe or moderate TBI were only present in 55% of patients, while 45% suffered a mild injury. Nevertheless, intracranial pathologies were present in 95% of brain imaging with traumatic subarachnoid hemorrhages (76%) being the most common. Intracranial surgeries were performed in 42% of cases. In-hospital mortality after TBI was 21% and surviving patients could be discharged after a median hospital stay of 11 days. At the 6-and 12 months follow-up, a favorable outcome was achieved by 70% and 90% of the participating TBI patients, respectively. Compared to a European cohort of 2138 TBI patients treated in the ICU between 2014 and 2017, patients in the TBI databank were already older, frailer, fell more commonly at home. CONCLUSION: Within five years, the TBI databank DGNC/DGU of the TR-DGU could be established and is since then prospectively enrolling TBI patients in German-speaking countries. With its large and harmonized data set and a 12-month follow-up, the TBI databank is a unique project in Europe, already allowing comparisons to other data collection structures and indicating a demographic change towards older and frailer TBI patients in Germany.

Perioperative external ventricular drainage vs. no-EVD strategy in pediatric posterior fossa tumors-pilot study results.

INTRODUCTION: Pediatric brain tumors of the posterior fossa often present with occlusive hydrocephalus. Endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS) has been established for definite hydrocephalus treatment. The aim of the study was to analyze the impact and safety of perioperative temporary external ventricular CSF drainage (EVD) placement on postoperative hydrocephalus outcome compared to a no-EVD strategy. PATIENTS AND METHODS: In a prospective database, 36 posterior fossa tumor patients of 2-18 years were included with a follow-up of 1 year. Fifty-eight percent presented with preoperative hydrocephalus. Patients were assigned to non-hydrocephalus group: group I (n = 15) and to preoperative hydrocephalus, group IIa with EVD placement (n = 9), and group IIb without EVD (n = 12). RESULTS: Median age of patients was 8.1 years (range 3.17 to 16.58 years). One-third of 21 hydrocephalus patients required ETV or VPS (n = 7). Occurrence of de novo hydrocephalus in group I after surgery was not observed in our cohort. Age and histology were no confounding factor for EVD placement between group IIa and IIb (p = 0.34). The use of EVD did not result in better control of hydrocephalus compared to no-EVD patients considering pre- and postoperative MRI ventricular indices (p = 0.4). Perioperative placement of an EVD resulted in a threefold risk for subsequent VPS or ETV (group IIa 55.5% vs group IIb 16.6%): relative risk for EVD patients compared to no-EVD patients with hydrocephalus was 3.3 (CI = 1.06-13.43, p = 0.09). CONCLUSION: Perioperative EVD placement appears to harbor a threefold relative risk of requiring subsequent permanent CSF diversion in children above 2 years. EVD was not more effective to control ventricular enlargement compared to tumor removal alone. The no-EVD strategy was safe and did not result in postoperative complications. Thus, to evaluate potential adverse effects on hydrocephalus outcome by EVD placement, a prospective study is warranted to falsify the results.

Trimethylamine N-oxide (TMAO) in patients with subarachnoid hemorrhage: a prospective observational study.

BACKGROUND: It is suspected that microbiome-derived trimethylamine N-oxide (TMAO) may enhance platelet responsiveness and accordingly be thrombophilic. The purpose of this prospective observational study is to evaluate TMAO in patients with subarachnoid hemorrhage (SAH) and compare it with a control group. A secondary aim was to investigate TMAO in the cerebrospinal fluid (CSF) from SAH patients. This should provide a better understanding of the role of TMAO in the pathogenesis of SAH and its thrombotic complications. METHODS: The study included patients with diagnosed spontaneous SAH recruited after initial treatment on admission and patients with nerve, nerve root, or plexus disorders serving as controls. Blood samples were gathered from all patients at recruitment. Additionally, sampling of SAH patients in the intensive care unit continued daily for 14 days. The CSF was collected out of existing external ventricular drains whenever possible. RESULTS: Thirty-four patients diagnosed with SAH, and 108 control patients participated in this study. Plasma TMAO levels at baseline were significantly lower in the SAH group (1.7 µmol/L) compared to the control group (2.9 µmol/L). TMAO was detectable in the CSF (0.4 µmol/L) and significantly lower than in plasma samples of the SAH group at baseline. Plasma and CSF TMAO levels correlated positively. The TMAO levels did not differ significantly during the observation period of 15 days. CONCLUSIONS: Although we assumed that patients with higher TMAO levels were at higher risk for SAH a priori, plasma TMAO levels were lower in patients with SAH compared with control subjects with nerve, nerve root, or plexus disorders on admission to the hospital. A characteristic pattern of plasma TMAO levels in patients with SAH was not found.

Preoperative language tract integrity is a limiting factor in recovery from aphasia after glioma surgery.

Aphasia can occur in a broad range of pathological conditions that affect cortical or subcortical structures. Here we test the hypothesis that white matter integrity of language pathways assessed by preoperative diffusion tensor imaging (DTI) is associated with language performance and its recovery after glioma resection. 27 patients with preoperative DTI were included. Segmentation of the arcuate fascicle (AF), the inferior fronto-occipital fascicle (IFOF), the inferior longitudinal fascicle (ILF), the superior longitudinal fascicle (SLF), and the uncinate fascicle (UF) was performed with a fully-connected neural network (FCNN, TractSeg). Median fractional anisotropy (FA) was extracted from the resulting volumes as surrogate marker for white matter integrity and tested for correlation with clinical parameters. After correction for demographic data and multiple testing, preoperative white matter integrity of the IFOF, the ILF, and the UF in the left hemisphere were independently and significantly associated with aphasia three months after surgery. Comparison between patients with and without aphasia three months after surgery revealed significant differences in preoperative white matter integrity of the left AF (p = 0.021), left IFOF (p = 0.015), left ILF (p = 0.003), left SLF (p = 0.001, p = 0.021, p = 0.043 for respective sub-bundles 1-3), left UF (p = 0.041) and the right AF (p = 0.027). Preoperative assessment of white matter integrity of the language network by time-efficient MRI protocols and FCNN-driven segmentation may assist in the evaluation of postoperative rehabilitation potential in glioma patients.

Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial.

RATIONALE: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. AIM: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. METHODS AND DESIGN: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. SAMPLE SIZE ESTIMATES: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21. STUDY OUTCOME: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6). DISCUSSION: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.

White Matter Integrity of the Corticospinal Tract for Estimation of Individual Patient Risk for Postoperative Neurological Deterioration after Glioma Surgery.

BACKGROUND: Tractography has become a standard tool for planning neurosurgical operations and has been proven to be useful for risk stratification. In various conditions, tractography-derived white matter integrity has been shown to be associated with neurological outcome. Postoperative performance has been shown to be a prognostic marker in glioma. We aimed to assess the relation of preoperative corticospinal tract (CST) integrity with postoperative neurological deterioration in patients with malignant glioma. METHODS: We retrospectively analyzed a cohort of 24 right-handed patients (41.7% female) for perioperative neurological performance score (NPS) and applied our anatomical tractography workflow to extract the median fractional anisotropy (FA) of the CST in preoperative magnetic resonance imaging (MRI). RESULTS: Median FA of the CST ipsilateral to the tumor correlated significantly with preoperative NPS (p = 0.025). After rank order correlation and multivariate linear regression, we found that the preoperative median FA of the right CST correlates with preoperative NPS, independently from epidemiological data (p = 0.019). In patients with lesions of the right hemisphere, median FA of the right CST was associated with a declining NPS in multivariate linear regression (p = 0.024). Receiver operating characteristic (ROC) analysis revealed an optimal FA cutoff at 0.3946 in this subgroup (area under the curve 0.83). Patients below that cutoff suffered from a decline in neurological performance significantly more often (p = 0.020). CONCLUSIONS: Assessment of preoperative white matter integrity may be a promising biomarker for risk estimation of patients undergoing craniotomy for resection of malignant glioma.

Feasibility of ApoC1 serum levels as tumor biomarker in glioblastoma patients: a pilot study.

Apolipoprotein C1 (ApoC1) has been detected immunohistochemically in glioblastoma tissue, probably expressed by activated monocytes and microglia. The present study was conceived to determine whether the amount of intratumoral ApoC1 expression leads to measurable changes of serum levels after glioblastoma resection or during recurrence. 176 blood samples from 70 glioblastoma patients were collected perioperatively and during subsequent therapy. ApoC1 serum levels were determined using an enzyme linked immunosorbent assay (ELISA). High absorption values due to lipemic or hemolytic serum were removed from the final dataset using a stem and leaf plot. Samples were grouped according to the treatment stage to compare mean ApoC1 serum levels. The number of patients with falling or increasing perioperative values was assessed. 167 ApoC1 serum values from 68 glioblastoma patients were amenable to statistical evaluation. Mean ApoC1 serum level was 91.9 µg/ml (n = 167, sd = 36.0). In samples from patients undergoing first glioblastoma resection, the mean preoperative value was significantly higher (94.8 µg/ml, n = 37, sd = 29.5) than after surgery (77.4 µg/ml, n = 41, sd = 23.2, p = 0.009). Individually, falling ApoC1 levels were detected in 25 and rising levels in 9 patients (p = 0.0061). Single absolute serum levels of ApoC1 do not allow an estimation of glioblastoma activity or tumor response. Although pathophysiologically of interest, ApoC1 serum levels did not qualify as a potential biomarker in glioblastoma management. Our results do not seem to encourage larger, multicenter studies.

Cervical intradural extramedullary cavernous malformation as a rare cause of subarachnoid hemorrhage without spinal dysfunction: illustrative case.

BACKGROUND: Intradural extramedullary cavernoma is a very rare lesion of the spinal cord, especially of the cervical spine. Its clinical presentation can vary with symptoms of sensory or motor deficits and even with symptoms of subarachnoid hemorrhage (SAH). OBSERVATIONS: The authors present a case of a 45-year-old man with SAH with prolonged neck pain and increasing headache confirmed by lumbar puncture. Head computed tomography revealed only discrete blood deposits in the right frontal and biparietal lobes. The finding of pan-cerebral angiography was negative for the cause of bleeding. Spinal magnetic resonance imaging revealed an intradural extramedullary mass lesion at cervical level C5-6. The finding of subsequent cervical angiography was negative. The diagnosis of a cavernous malformation was confirmed histopathologically after surgery. The cavernoma was completely removed, and full recovery of the initial symptoms was achieved. LESSONS: Spinal lesions should be considered in the diagnostic work-up for SAH with excluded origin of bleeding in cranial neuroimaging. An intradural extramedullary cavernous malformation is an extremely rare entity in the differential diagnosis of SAH, and surgical resection is the treatment of choice to prevent further bleeding and neurological deficits.

Influence of Trimethylamine N-Oxide on Platelet Activation.

Microbiome-derived trimethylamine N-oxide (TMAO) has been associated with platelet hyperreactivity and subsequent atherogenesis. Whether physiological TMAO-levels influence platelet-derived lipid mediators remains unknown. Little is known about pre-analytic factors potentially influencing TMAO concentrations. We aimed at developing a quantitative LC-MS/MS method to investigate in-vivo and in-vitro pre-analytical factors in TMAO analysis to properly assess the proposed activating effect of TMAO on platelets. TMAO, betaine, carnitine, and choline were analyzed by HILIC-ESI-MS/MS within 6 min total run time. Method validation included investigation of reproducibility, recovery, sensitivity, and in-vitro pre-analytical factors. A 24-h monitoring experiment was performed, evaluating in-vivo pre-analytical factors like daytime or diet. Finally, the effects of different TMAO concentrations on platelet activation and corresponding alterations of platelet-derived eicosanoid release were analyzed. The method showed high reproducibility (CVs ≤ 5.3%), good recovery rates (96-98%), and negligible in-vitro pre-analytical effects. The influence of in-vivo pre-analytical factors on TMAO levels was not observable within the applied experimental conditions. We did not find any correlation between TMAO levels and platelet activation at physiological TMAO concentrations, whereas platelet-derived eicosanoids presented activation of the cyclooxygenase and lipoxygenase pathways. In contrast to previously published results, we did not find any indications regarding diet dependency or circadian rhythmicity of TMAO levels. Our results do not support the hypothesis that TMAO increases platelet responsiveness via the release of lipid-mediators.

Facial Nerve Function After Microsurgical Resection in Vestibular Schwannoma Under Neurophysiological Monitoring.

Background: The use of intraoperative neurophysiological monitoring, including direct nerve stimulation (especially the facial nerve), acoustic evoked potentials (AEP) and somatosensory evoked potentials (SSEP), is a helpful tool in the microsurgery of vestibular schwannoma to prevent nerve injury. Patient characteristics and intraoperative and postoperative variables might also influence the postoperative facial nerve function. The study was performed to investigate these variables and the intraoperative neurophysiological monitoring values. Methods: Seventy-nine patients with vestibular schwannoma were included consecutively into this study. Intraoperative neurophysiological monitoring, including SSEP, AEP, and direct nerve stimulation for facial and trigeminal nerve electromyography, was performed utilizing digital data storage in all cases. The intensity (in volts) of the direct stimulation and the latency (in ms) for the orbicularis oculi and the orbicularis oris muscle and the amplitude (in mV) was measured. Univariate and multivariate statistical analyses concerning the different parameters was performed directly after the operation and in the subsequent follow-ups 3 and 6 months after the operation. Results: The mean intensity was 0.79 V (SD.29). The latency and amplitude for the oris muscle was 5.2 ms (SD 2.07) and 0.68 mV (SD.57), respectively. The mean latency for the occuli muscle was 5.58 ms (SD 2.2) and the amplitude was 0.58 mV (SD 1.04). The univariate and multivariate statistical analyses showed significance concerning the postoperative facial nerve function and the amplitude of the direct stimulation of the facial nerve in the orbicularis oris muscle (p = 0.03), so repeated direct nerve stimulation might show FN function deterioration. The mean diameter of the tumors was 24 mm (range 10-57 mm). Cross total resection and near total was achieved in 76 patients (96%) and subtotal in three patients (4%). The preoperative House-Brakeman score (HBS) 1 was constant in 65 (82%) cases. The mortality in our series was 0%; the overall morbidity was 10%. The HBS was not influenced concerning the extent of resection. The mean follow-up was 28 months (range 6 to 60 months). The limitations of the study might be a low number of patients and the retrospective character of the study. Conclusion: Intraoperative neurophysiological monitoring is crucial in vestibular schwannoma surgery. Repeated direct nerve stimulation and a detected decreased amplitude might show facial nerve function deterioration.

Viability of Glioblastoma Cells and Fibroblasts in the Presence of Imidazole-Containing Compounds.

The naturally occurring dipeptide carnosine (ß-alanyl-L-histidine) specifically attenuates tumor growth. Here, we ask whether other small imidazole-containing compounds also affect the viability of tumor cells without affecting non-malignant cells and whether the formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L-alanyl-L-histidine (LA-LH), ß-alanyl-L-alanine, L-histidine, histamine, imidazole, ß-alanine, and L-alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L-histidine and formation of histamine was investigated by high-performance liquid chromatography coupled to mass spectrometry. Carnosine and LA-LH inhibited tumor cell growth with minor effects on fibroblasts, and L-histidine, histamine, and imidazole affected viability in both cell types. Compounds without the imidazole moiety did not diminish viability. In the presence of LA-LH but not in the presence of carnosine, a significant rise in intracellular amounts of histidine was detected in all cells. The formation of histamine was not detectable in the presence of carnosine, LA-LH, or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA-LH. Despite the fact that histamine has a strong effect on cell viability, the formation of histamine is not responsible for the effects on the cell viability of carnosine, LA-LH, and histidine.

Usefulness and Limits of Tractography for Surgery in the Precentral Gyrus-A Case Report.

The resection of tumors within the primary motor cortex is a constant challenge. Although tractography may help in preoperative planning, it has limited application. While it can give valuable information on subcortical fibers, it is less accurate in the cortical layer of the brain. A 38-year-old patient presented with paresis of the right hand and focal epileptic seizures due to a tumor in the left precentral gyrus. Transcranial magnetic stimulation was not applicable due to seizures, so microsurgical resection was performed with preoperative tractography and intraoperative direct electrical stimulation. A histopathological assessment revealed a diagnosis of glioblastoma. Postoperative magnetic resonance imaging (MRI) showed complete resection. The paresis dissolved completely during follow-up. Surgery within the precentral gyrus is of high risk and requires multimodal functional planning. If interpreted with vigilance and consciousness of the underlying physical premises, tractography can provide helpful information within its limitations, which is especially subcortically. However, it may also help in the identification of functional cortex columns of the brain in the presence of a tumor.