The glymphatic system for neurosurgeons: a scoping review.

The discovery of the glymphatic system has revolutionized our understanding of cerebrospinal fluid (CSF) circulation and interstitial waste clearance in the brain. This scoping review aims to synthesize the current literature on the glymphatic system's role in neurosurgical conditions and its potential as a therapeutic target. We conducted a comprehensive search in PubMed and Scopus databases for studies published between January 1, 2012, and October 31, 2023. Studies were selected based on their relevance to neurosurgical conditions and glymphatic function, with both animal and human studies included. Data extraction focused on the methods for quantifying glymphatic function and the main results. A total of 67 articles were included, covering conditions such as idiopathic normal pressure hydrocephalus (iNPH), idiopathic intracranial hypertension (IIH), subarachnoid hemorrhage (SAH), stroke, intracranial tumors, and traumatic brain injury (TBI). Significant glymphatic dysregulation was noted in iNPH and IIH, with evidence of impaired CSF dynamics and delayed clearance. SAH studies indicated glymphatic dysfunction with the potential therapeutic effects of nimodipine and tissue plasminogen activator. In stroke, alterations in glymphatic activity correlated with the extent of edema and neurological recovery. TBI studies highlighted the role of the glymphatic system in post-injury cognitive outcomes. Results indicate that the regulation of aquaporin-4 (AQP4) channels is a critical target for therapeutic intervention. The glymphatic system plays a critical role in the pathophysiology of various neurosurgical conditions, influencing brain edema and CSF dynamics. Targeting the regulation of AQP4 channels presents as a significant therapeutic strategy. Although promising, the translation of these findings into clinical practice requires further human studies. Future research should focus on establishing non-invasive biomarkers for glymphatic function and exploring the long-term effects of glymphatic dysfunction.

Successful adaptation of twinning concept for global neurosurgery collaborations-a validation study.

INTRODUCTION: Globally, many regions have an urgent, unmet need of neurosurgical care. A multi-step neurosurgical twinning technique, International Neurosurgical Twinning Modeled for Africa (INTIMA), was proved to be successful during a previous mission to Neurosurgical Unit, Enugu, Nigeria. The Swedish African Neurosurgical Collaboration (SANC) performed a developmental mission together with the local neurosurgical unit in The Gambia, adopting the INTIMA model. METHODS: A multidisciplinary team visited for a 2-week collaborative mission at the Neurosurgical Department of the Edward Francis Small Teaching Hospital in Banjul, The Gambia. The mission followed the data of neurosurgical operations during and after the mission as well as about the operations 3 months prior to and after the mission was collected. RESULTS: During the mission, a total of 22 operations was carried out, the most common being degenerative spinal conditions (n = 9). In the 3 months following the mission, 43 operations were performed compared to 24 during the 3 months leading up to the mission. The complexity of the performed procedures increased after the mission. An operating microscope (Möller-Wedel) was donated and installed and the neurosurgeons on site underwent training in microneurosurgery. The surgical nurses, nurses at the postoperative ward, and the physiotherapists underwent training. A biomedical engineer serviced multiple appliances and devices improving the patient care on site while training local technicians. CONCLUSION: This study validated the use of the INTIMA model previously described in a mission by Swedish African Neurosurgical Collaboration (SANC). The model is sustainable and produces notable results. The core strength of the model is in the multidisciplinary team securing all the aspects and steps of the neurosurgical care. Installation of an operating microscope opened for further microsurgical possibilities, improving the neurosurgical care in The Gambia.

Observations from the first 100 cases of intraoperative MRI - experiences, trends and short-term outcomes.

BACKGROUND: We sought to analyze, in well-defined clinical setting, the first 100 patients treated at the intraoperative MRI (iMRI) hybrid surgical theatre at our facility in a population-based setting to evaluate which pathologies are best approached with iMRI assisted surgeries, as this is not yet clearly defined. METHODS: Patients undergoing surgery in the 3T iMRI hybrid surgical theatre at our neurosurgical department between December 2017 to May 2021 were included after informed consent. Demographic, clinical, surgical, histological, radiological and outcome parameters, as well as variables related to iMRI, were retrospectively collected and analyzed. Patients were subdivided into adult and pediatric cohorts. RESULTS: Various neurosurgical procedures were performed; resection of tumors and epileptic foci, endoscopic skull base procedures including pituitary lesions, deep brain stimulation (DBS) and laser interstitial thermal therapy (LITT). In total, 41 patients were pediatric. An iMRI scan was carried out in 96% of cases and led to continuation of surgery in 50% of cases, mainly due to visualized remaining pathological tissue (95.2%). Median time to iMRI from intubation was 280 min and median total duration of surgery was 445 min. The majority of patients experienced no postoperative complications (70%), 13 patients suffered permanent postoperative deficits, predominantly visual. CONCLUSION: Herein, we demonstrate the first 100 patients undergoing neurosurgery aided by iMRI at our facility since introduction. Indications for surgery differed between pediatric and adult patients. The iMRI was utilized for tumor surgeries, particularly adult low-grade gliomas and pediatric tumors, as well as for epilepsy surgery and DBS. In this heterogenous population, iMRI led to continuation of surgery in 50%. To establish the benefit in maximizing the extent of resection in these brain pathologies future studies are recommended. CLINICAL TRIAL NUMBER: Not applicable.

Changes in clinical management of diffuse IDH-mutated lower-grade gliomas: patterns of care in a 15-year period.

BACKGROUND: Isocitrate dehydrogenase (IDH) mutated diffuse lower-grade gliomas (dLGG) are infiltrating brain tumors and increasing evidence is in favor of early multimodal treatment. In a Scandinavian population-based setting, we wanted to study treatment patterns over the last 15 years, focusing on the short-term postoperative course to better understand the potential negative consequences of treatment. METHODS: Patients ≥ 18 years with primary IDH-mutated dLGG grade 2 and 3, operated between January 2007-June 2021 were identified. Patients were divided into subgroups (2007-2011, 2012-2016, and 2017-2021) and comparisons regarding tumor- and disease characteristics, treatment, and postoperative outcome were performed. RESULTS: We identified 202 patients (n = 61, 2007-2011; n = 72, 2012-2016; n = 69, 2017-2021), where of 193 underwent resection without change in proportion of resections over time. More patients underwent complete resections in recent times (6.1%; 15.7%; 26.1%, respectively; p = 0.016). Forty-two patients had any neurological deficit postoperatively (14.8%; 23.6%; 23.2%; p = 0.379), mostly minor and transient. Differences in oncological therapy were seen between the investigated subgroups. Early radiotherapy alone (32.8%; 7%; 2.9%; p < 0.001), concomitant chemoradiotherapy (23%; 37.5%; 17.4%; p = 0.022), sequential chemoradiotherapy (0%; 18%; 49.3%; p < 0.001), and no adjuvant treatment (42.6%; 23.6%; 18.8%; p = 0.009) shifted during the studied period. Increasingly more patients received proton radiotherapy compared to photon radiotherapy during the later time periods (p < 0.001). CONCLUSION: Complete resections were performed more often in later time periods without an apparent increase in surgical morbidity. Early adjuvant oncological treatment shifted towards providing chemotherapy and combined chemoradiotherapy more often in later time periods. Protons replaced photons as the radiation modality of choice.

Is intracranial volume a risk factor for IDH-mutant low-grade glioma? A case-control study.

PURPOSE: Risk of cancer has been associated with body or organ size in several studies. We sought to investigate the relationship between intracranial volume (ICV) (as a proxy for lifetime maximum brain size) and risk of IDH-mutant low-grade glioma. METHODS: In a multicenter case-control study based on population-based data, we included 154 patients with IDH-mutant WHO grade 2 glioma and 995 healthy controls. ICV in both groups was calculated from 3D MRI brain scans using an automated reverse brain mask method, and then compared using a binomial logistic regression model. RESULTS: We found a non-linear association between ICV and risk of glioma with increasing risk above and below a threshold of 1394 ml (p < 0.001). After adjusting for ICV, sex was not a risk factor for glioma. CONCLUSION: Intracranial volume may be a risk factor for IDH-mutant low-grade glioma, but the relationship seems to be non-linear with increased risk both above and below a threshold in intracranial volume.

Shared decision-making in neurosurgery: a scoping review.

BACKGROUND: In modern neurosurgery, there are often several treatment alternatives, with different risks and benefits. Shared decision-making (SDM) has gained interest during the last decade, although SDM in the neurosurgical field is not widely studied. Therefore, the aim of this scoping review was to present the current landscape of SDM in neurosurgery. METHODS: A literature review was carried out in PubMed and Scopus. We used a search strategy based on keywords used in existing literature on SDM in neurosurgery. Full-text, peer-reviewed articles published from 2000 up to the search date February 16, 2021, with patients 18 years and older were included if articles evaluated SDM in neurosurgery from the patient's perspective. RESULTS: We identified 22 articles whereof 7 covered vestibular schwannomas, 7 covered spinal surgery, and 4 covered gliomas. The other topics were brain metastases, benign brain lesions, Parkinson's disease and evaluation of neurosurgical care. Different methods were used, with majority using forms, questionnaires, or interviews. Effects of SDM interventions were studied in 6 articles; the remaining articles explored factors influencing patients' decisions or discussed SDM aids. CONCLUSION: SDM is a tool to involve patients in the decision-making process and considers patients' preferences and what the patients find important. This scoping review illustrates the relative lack of SDM in the neurosurgical literature. Even though results indicate potential benefit of SDM, the extent of influence on treatment, outcome, and patient's satisfaction is still unknown. Finally, the use of decision aids may be a meaningful contribution to the SDM process.

The clinical significance of the T2-FLAIR mismatch sign in grade II and III gliomas: a population-based study.

BACKGROUND: The T2-FLAIR mismatch sign is an imaging finding highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted (non-codel) gliomas (astrocytomas). In previous studies, it has shown excellent specificity but limited sensitivity for IDH-mut astrocytomas. Whether the mismatch sign is a marker of a clinically relevant subtype of IDH-mut astrocytomas is unknown. METHODS: We included histopathologically verified supratentorial lower-grade gliomas (LGG) WHO grade II-III retrospectively during the period 2010-2016. In the period 2017-2018, patients with suspected LGG radiologically were prospectively included, and in this cohort other diagnoses than glioma could occur. Clinical, radiological and molecular data were collected. For clinical evaluation we included all patients with IDH-mut astrocytomas. In the 2010-2016 cohort DNA methylation analysis with Infinium MethylationEPIC BeadChip (Illumina) was performed for patients with an IDH-mut astrocytoma with available tissue. We aimed to examine the association of the T2-FLAIR mismatch sign with clinical factors and outcomes. Additionally, we evaluated the diagnostic reliability of the mismatch sign and its relation to methylation profiles. RESULTS: Out of 215 patients with LGG, 135 had known IDH-mutation and 1p19q codeletion status. Fifty patients had an IDH-mut astrocytoma and 12 of these (24.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut detection were 26.4 and 97.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without mismatch sign when grouped according to T2-FLAIR mismatch sign with respect to baseline characteristics, clinical outcomes and methylation profiles. The overall interrater agreement between neuroradiologist and clinical neurosurgeons for the T2-FLAIR mismatch sign was significant when all 215 MRI examination assessed (κ = 0.77, p < 0.001, N = 215). CONCLUSION: The T2-FLAIR mismatch sign in patients with an IDH-mut astrocytoma is not associated with clinical presentation or outcome. It seems unlikely that the IDH-mut astrocytomas with mismatch sign represent a specific subentity. Finally, we have validated that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.

Neurosurgical treatment and outcome patterns of meningioma in Sweden: a nationwide registry-based study.

BACKGROUND: Surgery is the main treatment modality for intracranial meningiomas, but data on short-term surgical outcome are limited. The aim of this Swedish nationwide registry-based study was to benchmark the 30-day complication rate in a cohort of meningioma patients using data from the Swedish brain tumor registry (SBTR). Furthermore, we investigated outcomes for asymptomatic patients. METHODS: Data were collected from the SBTR for all adults with histopathologically verified intracranial meningioma between 2009 and 2015. Patient symptoms, tumor characteristics, and complications within 30 days postoperatively were analyzed. RESULTS: In total, 2324 patients, with a mean age of 58.7 years (SD 13.5), underwent surgery for intracranial meningioma and 14.1% of the patients were asymptomatic before the intervention. The most common symptom prior to treatment was focal deficit, which occurred in 1450 patients (62.4%). Moreover, within 30 days after surgery, 344 patients (14.8%) developed new neurological deficits and new-onset seizures occurred in 105 patients (4.5%), while 8.3% of asymptomatic patients developed neurological deficit and 3.7% new-onset seizures. Due to complications, reoperations were performed in 120 patients (5.2%). The postoperative 30-day mortality in the whole cohort was 1.5%. CONCLUSION: This study benchmarks the 30-day complication rate after meningioma surgery and provides outcome data in the highly relevant group of asymptomatic patients using data from the Swedish brain tumor registry. Since surgical decision-making is a careful consideration of short-term risk versus long-term benefit, this information may be useful for both caregivers and patients.

Clinical experiences and learning curves from robot-assisted neurosurgical biopsies with Stealth Autoguide™.

Background: Biopsies of intracranial lesions are a cornerstone in the diagnosis of unresectable tumors to guide neurooncological treatment; however, the procedure is also associated with risks. The results from the cranial robot guidance system Stealth Autoguide™ were studied after introduction at a neurosurgical department. Primary aims include the presentation of clinical and radiological data, accuracy of radiological diagnosis, learning curves of the new technology, diagnostic yield, and precision. The secondary aim was to study complications. Methods: Retrospective data inclusion was performed on patients ≥ 18 years undergoing biopsy with Stealth Autoguide™ due to suspected brain tumors in the first 3 years after the introduction of the technique. Data regarding clinical characteristics, intraoperative variables, pathological diagnosis, and complications were recorded. Analyses of learning curves were performed. Results: A total of 79 procedures were performed on 78 patients with a mean age of 62 years (SD 12.7, range 23-82), 30.8% were female. Tumors were often multifocal (63.3%) and supratentorial (89.9%). The diagnostic yield was 87.3%. The first-hand radiological diagnosis was correct in 62.0%. A slight decrease in operation time was observed, although not significant. The surgeon contributed to 12% of the variability. Conclusions: Robot-assisted biopsies with Stealth Autoguide™ seem to be comparable, with regards to complications, to frame-based and other frameless neurosurgical biopsies. Learning curves demonstrated no statistical differences in time of surgery and only 12% surgeon-related variation (ie, variation caused by the change of performing surgeon), suggesting a successful implementation of this technical adjunct.

Functional outcome after introduction of hemilaminectomy in management of spinal schwannomas and meningiomas.

Background: Schwannomas and meningiomas are intradural extramedullary spinal tumors which are regularly encountered in the neurosurgical clinic. These tumors cause neurological deficit by compression on the spinal cord and commonly pain when affecting the cauda equina. The traditional treatment with standard laminectomy (SL) can cause instability to the dorsal segments of the spinal column, and the less invasive option of hemilaminectomy (HL) has therefore been developed. We aim in this study to investigate transition from SL to HL in a population-based cohort. Methods: Adult patients (18 years and older) undergoing primary surgery due to spinal meningioma or schwannoma between 2007 and 2022 at the neurosurgical clinic were included. Data related to clinical, surgical and outcome variables were retrospectively collected. Results: A total of 187 patients were identified: 155 in the SL group, 26 in the HL group and in 6 patients a combination of SL and HL. The mean age of the SL group was 62.7 years (SD14.2) compared to 58.0 (SD15.7) in the HL group (p = 0.16). Preoperative motor deficit was more common in SL group compared to HL group (76.8 % and 61.5 %, respectively, p = 0.14). Thoracal location was most common for both groups (SL 65.8 % and HL 61.5 %). Postoperative change in McCormick grades and early complications were similar between groups. Conclusion: Outcome after hemilaminectomy due to intradural extramedullary schwannoma or meningioma is comparable to standard laminectomy with regards to postoperative complications and neurological improvement. Our findings support the transition to hemilaminectomy in selected cases.

The T1/T2 Ratio is Associated With Resectability in Patients With Isocitrate Dehydrogenase-Mutant Astrocytomas Central Nervous System World Health Organization Grades 2 and 3.

BACKGROUND AND OBJECTIVES: Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas. METHODS: Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS. RESULTS: The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 vs 4.6 cm3, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01). CONCLUSION: The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.

[The glymphatic system - an overview]. / Glymfatiska systemet ­ renar hjärnan från slaggprodukter.

The glymphatic system as a concept was introduced a decade ago and the knowledge regarding the circulation of the cerebrospinal fluid has since been revised. The research of the glymphatic system is extensive today, but there are many knowledge gaps. The glymphatic system was first investigated in animal experiments, but with the MR techniques available today the glymphatic system has also been shown to exist in humans. Studies suggest that the glymphatic system may be involved in the pathophysiological processes of neurological pathologies, such as degenerative brain disorders and normal pressure hydrocephalus (NPH), but also in the aftermath of ischemic stroke, subarachnoidal hemorrhage and traumatic brain injury. It is believed that the glymphatic system with its cleansing capabilities is upregulated during sleep, and interestingly studies show association between lack of sleep and neurodegenerative diseases. In this article, we present an overview of the glymphatic system and its possible role in intracranial pathologies.

[Spinal neurosurgery: radiculopathy and myelopathy]. / Spinal neurokirurgi på grund av radikulopati och myelopati.

The field of spinal neurosurgery covers degenerative conditions and trauma as well as tumors, malformations and vascular disorders of spine and spinal cord. This article focuses on the Swedish spinal neurosurgical care regarding radiculopathy and myelopathy. Disc herniation, foraminal stenosis, spinal stenosis and spinal cord compression due to degenerative disorders or tumors are discussed. Treatment options such as anterior cervical decompression and fusion, posterior forami-notomy, laminectomy and approaches to spinal intradural tumors are briefly presented. The aim is to present symptoms, diagnostics and treatment options of common conditions to facilitate early detection and referral to neurosurgical centers to avoid delayed dia-gnosis and neurological impairment.

Meningioma classification by immunohistochemistry: A replicability study.

Introduction: Meningiomas account for nearly 40% of intracranial tumors. Recently, the immunohistochemistry (IHC) markers S100B, SCGN, ACADL and MCM2 have been shown to be associated with underlying biological subtypes of meningioma (MG1-MG4). We aimed to evaluate these IHC markers in a clinical setting. Research question: Are the new proposed IHC markers clinically useful? Methods: In total, 244 patients with meningiomas with tissue in TMAs were included and the IHC markers S100B, SCGN, ACADL and MCM2 were analyzed. Two sets of analyses were performed; the first included all samples with any staining considered positive, the second only samples with >10% immunopositivity. PFS and OS were analyzed in correlation to immunopositivity in the second analysis set. Results: In the first set of analyses only 26.2% of samples could be to allocate to one group. No further analyses were performed with this selection. In the second set of analyses 52.0% could be allocated to a group. There was an enrichment of WHO grade 2 and 3 tumors in MG3 and MG4 as compared to MG1 (24.1% and 25.7% vs. 12.1%). Both the molecular group (p â€‹= â€‹0.032) and WHO grade (p â€‹= â€‹0.005) had significant impact on PFS, but only WHO grade predicted OS (p â€‹= â€‹0.033). Conclusion: We studied the proposed new method of classifying meningiomas into groups MG1, MG2, MG3 and MG4 using IHC markers, but found difficulties applying the classification system in our material mainly due to lack of exclusivity of markers. Thus, in its present form the classification method lacks clinical applicability.

Differences in Presentation, Radiological Features, and Outcomes in Traumatic Versus Spontaneous Acute Subdural Hematomas-A Single-Institution Population-Based Study.

BACKGROUND: Spontaneous acute subdural hematoma (sASDH) is a rare neurosurgical condition, with the literature mainly consisting of case reports. In the present study, we compared sASDH with traumatic ASDH (tASDH) to determine the differences in presentation, radiological features, and outcomes in a population-based setting. METHODS: All adult patients (age ≥18 years) who had undergone surgery for ASDH (n = 266), either spontaneous or traumatic, from 2010 to 2020 were included retrospectively. The cohort was divided into 2 groups for comparative analysis: sASDH group (n = 24) versus tASDH group (n = 242). RESULTS: Of the 266 patients, 24 (9.0%) had presented with sASDH. The sASDH group had a mean age of 66.2 years, and sudden headache was the most common presenting symptom (83.3%). The sASDH group had a higher Glasgow coma scale score at presentation compared with the tASDH group (Glasgow coma scale scores, 10 and 8, respectively; P < 0.01). The outcomes, assessed using the Glasgow outcome scale (GOS), revealed a greater incidence of more favorable outcomes (GOS score 4-5) for the sASDH group (72.7%) than for the tASDH group (41.5%). CONCLUSIONS: In the present population-based study of surgically evacuated ASDH cases, 9% were spontaneous without previous trauma. The outcomes (GOS scores) were significantly more favorable for those with sASDH than for those with tASDH. In one half of the patients with sASDH, arterial bleeding was noted perioperatively, although the preoperative radiological examinations revealed no abnormalities for most patients. However, the lack of sufficient examinations such as computed tomography angiography made it difficult to establish the most common etiology of bleeding in those with sASDH. Further research is warranted to determine the reference standard method for the investigation of sASDH.

Stemness and clinical features in relation to the subventricular zone in diffuse lower-grade glioma: an exploratory study.

Background: The subventricular zone (SVZ) of the human brain is a site of adult stem cell proliferation and a microenvironment for neural stem cells (NSCs). It has been suggested that NSCs in the SVZ are potential cells of origin containing driver mutations of glioblastoma, but their role in the origin of diffuse lower-grade gliomas (dLGGs) is not much studied. Methods: We included 188 patients ≥18 years with IDH-mutated dLGG (WHO grades 2-3) histologically diagnosed between 2007 and 2020. Tissue microarrays of tumor samples for patients between 2007 and 2016 were used for immunodetection of Nestin, SOX2, SOX9, KLF4, NANOG, CD133 cMYC, and Ki67. DNA methylation profile was used for stemness index (mDNAsi). Tumor contact with the SVZ was assessed and the distance was computed. Results: Overall, 70.2% of the dLGG had SVZ contact. Tumors with SVZ contact were larger (102.4 vs 30.9 mL, P < .01), the patients were older (44.3 vs 40.4 years, P = .04) and more often had symptoms related to increased intracranial pressure (31.8% vs 7.1%, P < .01). The expression of SOX2, SOX9, Nestin, and Ki67 showed intersample variability, but no difference was found between tumors with or without SVZ contact, nor with the actual distance to the SVZ. mDNAsi was similar between groups (P = .42). Conclusions: We found no statistical relationship between proximity with the SVZ and mDNAsi or expression of SOX2, SOX9, Nestin, and Ki67 in IDH-mutated dLGG. Our data suggest that the potential impact of SVZ on IDH-mutated dLGG is probably not associated with a more stemness-like tumor profile.

Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV).

INTRODUCTION: Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. METHODS AND ANALYSIS: The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. ETHICS AND DISSEMINATION: The study is approved by appropriate ethics or patient safety boards in all participating countries. TRIAL REGISTRATION NUMBER: NCT04773938; Pre-results.

[Paroxysmal sympathetic hyperactivity]. / ABC om Paroxysmal sympatisk hyperaktivitet.

Paroxysmal sympathetic hyperactivity (PSH) is a condition mainly described in patients after traumatic brain injury and it is also known under the terms "autonomic storm" and "dysautonomia". It affects between 8-10% of patients after traumatic brain injury and can also affect patients after other neurological diseases, such as anoxic brain injury, stroke, tumors or infections. PSH manifests with six main symptoms: tachycardia, tachypnea, hypertension, hyperthermia, hyperhidrosis and increased muscle tonus. It is of outmost importance to exclude other causes for the symptoms and there are diagnostic criteria established to identify and diagnose PSH. The treatment is pharmacological and non-pharmacological and often multimodal. PSH is probably underdiagnosed and increased awareness is needed.

Selection of CT variables and prognostic models for outcome prediction in patients with traumatic brain injury.

BACKGROUND: Traumatic brain injuries (TBI) are associated with high risk of morbidity and mortality. Early outcome prediction in patients with TBI require reliable data input and stable prognostic models. The aim of this investigation was to analyze different CT classification systems and prognostic calculators in a representative population of TBI-patients, with known outcomes, in a neurointensive care unit (NICU), to identify the most suitable CT scoring system for continued research. MATERIALS AND METHODS: We retrospectively included 158 consecutive patients with TBI admitted to the NICU at a level 1 trauma center in Sweden from 2012 to 2016. Baseline data on admission was recorded, CT scans were reviewed, and patient outcome one year after trauma was assessed according to Glasgow Outcome Scale (GOS). The Marshall classification, Rotterdam scoring system, Helsinki CT score and Stockholm CT score were tested, in addition to the IMPACT and CRASH prognostic calculators. The results were then compared with the actual outcomes. RESULTS: Glasgow Coma Scale score on admission was 3-8 in 38%, 9-13 in 27.2%, and 14-15 in 34.8% of the patients. GOS after one year showed good recovery in 15.8%, moderate disability in 27.2%, severe disability in 24.7%, vegetative state in 1.3% and death in 29.7%. When adding the variables from the IMPACT base model to the CT scoring systems, the Stockholm CT score yielded the strongest relationship to actual outcome. The results from the prognostic calculators IMPACT and CRASH were divided into two subgroups of mortality (percentages); ≤50% (favorable outcome) and > 50% (unfavorable outcome). This yielded favorable IMPACT and CRASH scores in 54.4 and 38.0% respectively. CONCLUSION: The Stockholm CT score and the Helsinki score yielded the closest relationship between the models and the actual outcomes in this consecutive patient series, representative of a NICU TBI-population. Furthermore, the Stockholm CT score yielded the strongest overall relationship when adding variables from the IMPACT base model and would be our method of choice for continued research when using any of the current available CT score models.

DNA methylation profiling for molecular classification of adult diffuse lower-grade gliomas.

BACKGROUND: DNA methylation profiling has facilitated and improved the classification of a wide variety of tumors of the central nervous system. In this study, we investigated the potential utility of DNA methylation profiling to achieve molecular diagnosis in adult primary diffuse lower-grade glioma (dLGG) according to WHO 2016 classification system. We also evaluated whether methylation profiling could provide improved molecular characterization and identify prognostic differences beyond the classical histological WHO grade together with IDH mutation status and 1p/19q codeletion status. All patients diagnosed with dLGG in the period 2007-2016 from the Västra Götaland region in Sweden were assessed for inclusion in the study. RESULTS: A total of 166 dLGG cases were subjected for genome-wide DNA methylation analysis. Of these, 126 (76%) were assigned a defined diagnostic methylation class with a class prediction score ≥ 0.84 and subclass score ≥ 0.50. The assigned methylation classes were highly associated with their IDH mutation status and 1p/19q codeletion status. IDH-wildtype gliomas were further divided into subgroups with distinct molecular features. CONCLUSION: The stratification of the patients by methylation profiling was as effective as the integrated WHO 2016 molecular reclassification at predicting the clinical outcome of the patients. Our study shows that DNA methylation profiling is a reliable and robust approach for the classification of dLGG into molecular defined subgroups, providing accurate detection of molecular markers according to WHO 2016 classification.