Long-term follow up of patients with WHO grade 2 oligodendroglioma.

PURPOSE: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. METHODS: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. RESULTS: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival. CONCLUSION: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.

Dynamics in cognition and health-related quality of life in grade 2 and 3 gliomas after surgery.

BACKGROUND: The focus of clinical management and research in gliomas has been on survival, but the interest in the treatment effects on cognition and health-related quality of life (HRQoL) is emerging. The primary aim of this study was to investigate the dynamics in cognition after brain tumor surgery for astrocytomas and oligodendrogliomas grade 2 and 3. The secondary aim was to investigate the association of postoperative changes in cognition with changes HRQoL. METHODS: In this observational study, 48 patients operated for an astrocytoma or oligodendrogliomas, grade 2 or 3, at the Department of Neurosurgery, Uppsala, Sweden, 2016-2021, were included. Cognitive and language skills were assessed with a selected test battery and HRQoL was patient-reported as assessed with RAND-36 pre- and approximately 3 months postoperatively. RESULTS: There was a significant postoperative decrease in attention span and verbal learning, but the patients improved in the test for visual memory. There was no change in visual attention, executive function, verbal memory, visual organization and construction, verbal fluency, and confrontation naming. The RAND-36 variables physical function, role physical, general health, vitality, and social functioning decreased significantly after surgery. Patients operated for tumor recurrence exhibited greater deterioration in attention and a greater extent of resection correlated with a less pronounced decrease in verbal memory, but there were otherwise weak associations between the dynamics in cognition and patient-, tumor-, and treatment-variables. A decline in cognitive variables was not associated with worse HRQoL. CONCLUSIONS: Although both several cognitive and HRQoL domains deteriorated postoperatively, these changes did not correlate with each other. This highlights the complexity of cognitive and HRQoL dynamics in the early postoperative phase.

Time course of neurological deficits after surgery for primary brain tumours.

BACKGROUND: The postoperative course after surgery for primary brain tumours can be difficult to predict. We examined the time course of postoperative neurological deficits and analysed possible predisposing factors. METHOD: Hundred adults with a radiological suspicion of low- or high-grade glioma were prospectively included and the postoperative course analysed. Possible predictors of postoperative neurological deterioration were evaluated. RESULTS: New postoperative neurologic deficits occurred in 37% of the patients, and in 4%, there were worsening of a preoperative deficit. In 78%, the deficits occurred directly after surgery. The probable cause of deterioration was EEG-verified seizures in 7, ischemic lesion in 5 and both in 1, resection of eloquent tissue in 6, resection close to eloquent tissue including SMA in 11 and postoperative haematoma in 1 patient. Seizures were the main cause of delayed neurological deterioration. Two-thirds of patients with postoperative deterioration showed complete regression of the deficits, and in 6% of all patients, there was a slight disturbance of the function after 3 months. Remaining deficits were found in 6% and only in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of postoperative neurological deterioration and preoperative neurological deficits of remaining deficits. CONCLUSIONS: Postoperative neurological deficits occurred in 41% and remained in 6% of patients. Remaining deficits were found in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of neurological deterioration and preoperative neurological deficits of remaining deficits.

Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.

PURPOSE: Oligodendrogliomas are heterogeneous tumors in terms of imaging appearance, and a deeper understanding of the histopathological tumor characteristics in correlation to imaging parameters is needed. We used PET-to-MRI-to-histology co-registration with the aim of studying intra-tumoral 11C-methionine (MET) uptake in relation to tumor perfusion and the protein expression of histological cell markers in corresponding areas. METHODS: Consecutive histological sections of four tumors covering the entire en bloc-removed tumor were immunostained with antibodies against IDH1-mutated protein (tumor cells), Ki67 (proliferating cells), and CD34 (blood vessels). Software was developed for anatomical landmarks-based co-registration of subsequent histological images, which were overlaid on corresponding MET PET scans and MRI perfusion maps. Regions of interest (ROIs) on PET were selected throughout the entire tumor volume, covering hot spot areas, areas adjacent to hot spots, and tumor borders with infiltrating zone. Tumor-to-normal tissue (T/N) ratios of MET uptake and mean relative cerebral blood volume (rCBV) were measured in the ROIs and protein expression of histological cell markers was quantified in corresponding regions. Statistical correlations were calculated between MET uptake, rCBV, and quantified protein expression. RESULTS: A total of 84 ROIs were selected in four oligodendrogliomas. A significant correlation (p < 0.05) between MET uptake and tumor cell density was demonstrated in all tumors separately. In two tumors, MET correlated with the density of proliferating cells and vessel cell density. There were no significant correlations between MET uptake and rCBV, and between rCBV and histological cell markers. CONCLUSIONS: The MET uptake in hot spots, outside hotspots, and in infiltrating tumor edges unanimously reflects tumor cell density. The correlation between MET uptake and vessel density and density of proliferating cells is less stringent in infiltrating tumor edges and is probably more susceptible to artifacts caused by larger blood vessels surrounding the tumor. Although based on a limited number of samples, this study provides histological proof for MET as an indicator of tumor cell density and for the lack of statistically significant correlations between rCBV and histological cell markers in oligodendrogliomas.

Continuous EEG monitoring after brain tumor surgery.

BACKGROUND: Prolonged seizures generate cerebral hypoxia and increased intracranial pressure, resulting in an increased risk of neurological deterioration, increased long-term morbidity, and shorter survival. Seizures should be recognized early and treated promptly. The aim of the study was to investigate the occurrence of postoperative seizures in patients undergoing craniotomy for primary brain tumors and to determine if non-convulsive seizures could explain some of the postoperative neurological deterioration that may occur after surgery. METHODS: A single-center prospective study of 100 patients with suspected glioma. Participants were studied with EEG and video recording for at least 24 h after surgery. RESULTS: Seven patients (7%) displayed seizure activity on EEG recording within 24 h after surgery and another two patients (2%) developed late seizures. One of the patients with early seizures also developed late seizures. In five patients (5%), there were non-convulsive seizures. Four of these patients had a combination of clinically overt and non-convulsive seizures and in one patient, all seizures were non-convulsive. The non-convulsive seizures accounted for the majority of total seizure time in those patients. Non-convulsive seizures could not explain six cases of unexpected postoperative neurological deterioration. Postoperative ischemic lesions were more common in patients with early postoperative seizures. CONCLUSIONS: Early seizures, including non-convulsive, occurred in 7% of our patients. Within this group, non-convulsive seizure activity had longer durations than clinically overt seizures, but only 1% of patients had exclusively non-convulsive seizures. Seizures were not associated with unexpected neurological deterioration.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

BACKGROUND: The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years. METHOD: A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments. RESULTS: More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed. CONCLUSIONS: There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.

Diffusion Kurtosis Imaging of Gliomas Grades II and III - A Study of Perilesional Tumor Infiltration, Tumor Grades and Subtypes at Clinical Presentation.

BACKGROUND: Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas). PATIENTS AND METHODS: Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves. RESULTS: There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=<0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815. CONCLUSIONS: Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging: a histogram analysis approach.

INTRODUCTION: Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas. METHODS: MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated. RESULTS: In DCE, the skewness of transfer constant (k(trans)) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80). CONCLUSIONS: Histogram parameters from k(trans) (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.

Qualitative and Visual Along-Tract Analysis of Diffusion-Based Parameters in Patients with Diffuse Gliomas.

BACKGROUND: Grade 2-3 diffuse gliomas (DGs) show extensive infiltration through white matter (WM) tracts. Along-tract analysis of WM tracts based on diffusion tensor tractography (DTI) can been performed to assess the microstructural integrity of WM tracts. The clinical implication of these DTI-related findings is still under debate, especially in tumor patients. The aim of this study was to analyze and compare diffusion-based parameters along WM tracts and variables specific to WM -tumor interactions in DGs and correlate them with preoperative neuropsychological assessment. METHODS: Fourteen patients with IDH-mutated grade 2-3 DGs were included. Tumor volumes were manually segmented on 3D-FLAIR images after spatial normalisation to MNI space. DTI was acquired using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data were reconstructed within the MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM tracts were reconstructed based on the HCP-1065 template. All WM tracts were stretched to the same length of 100 indices, and for each index diffusion-based parameters fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and quantitative anisotropy (QA) were sampled. Tumor-related parameters (TRP); tumor volume (Tv), maximum tumor presence (MTP) and the number of sequential indices in which a tumor is present (Te) were derived based on the along-tract analysis. Normal data were constructed by calculating the average and standard deviations of contralateral and not-affected WM tracts for each diffusion-based parameter, respectively. Affected WM tracts were individually compared to normal data using a z-test. Preoperative neuropsychological assessment was performed in all subjects and correlated to results from the along-tract analysis using correlation and logistic regression models. RESULTS: Abnormalities in diffusion-based parameters were detected in WM tracts. Topographical and quantitative information were presented within the same graph. AD and MD displayed the highest linear correlation with the TRPs. Abnormal QA showed a linear correlation with Tv per WM tract. Neuropsychological impairment was correlated with all the TRPs and with abnormal FA (p < 0.05) and abnormal QA (p < 0.01). Abnormal QA was the only independent variable able to predict the presence of neuropsychological impairment in the patients based on the linear regression analysis. CONCLUSIONS: Graphical presentation of the along-tract analysis presented in this study shows that it may be a sensitive and robust method to acquire and display topographical and qualitative information regarding WM tracts in close proximity to DGs. Further studies and refinements to the methods presented herein may advance current clinical methods for evaluating displacement and infiltrations and further aid the efforts of pre-planning surgical interventions with the goal to maximise EOR and tailor oncological treatment.

Perfusion and diffusion MRI combined with ¹¹C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas.

Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with ¹¹C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBV(max)) and the minimum mean diffusivity (MD(min)) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBV(max) corresponded with hotspot regions in all tumors, regions with MD(min) corresponded with hotspot regions in 20/23 tumors. The correlation between rCBV(max) (r = 0.19, P = 0.38) and MD(min) (r = -0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBV(max). Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBV(max) suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.

Somatotropic and thyroid hormones in the acute phase of subarachnoid haemorrhage.

BACKGROUND: Somatotropic and thyroid hormones are probably important for the recovery after acute brain injury. Still, the dynamics of these hormones after spontaneous subarachnoid haemorrhage (SAH) is not well described. The purpose of this study was to investigate the relation between somatotropic and thyroid hormones and clinical factors after SAH. METHODS: Twenty patients with spontaneous SAH were included prospectively. Serum concentrations of TSH, fT4, T3, IGF-1 and GH were measured once a day for 7 days after SAH. Hormone patterns and serum concentrations were compared to the severity of SAH, neurological condition at admission, clinical course and outcome of the patients. RESULTS: During the first week after SAH, all patients showed increased GH and IGF-1 concentrations. In the whole group, concentrations of TSH increased, whereas T3 and fT4 decreased. There were no relations of serum concentrations of IGF-1 or GH to clinical condition at admission, clinical course or outcome of the patients. Half of the patients showed low T3 serum concentrations. A complicated course was associated with a deeper fall in TSH and T3 concentrations. There were negative correlations for mean concentrations of TSH and T3 versus WFNS grade and a positive correlation for T3 versus GOS after 6 months, indicating that low concentrations of TSH and T3 were connected to worse SAH grade and poor outcome. CONCLUSIONS: All patients showed increased GH and IGF-1 concentrations irrespective of the grade of SAH or clinical course. Patients with a complicated clinical course showed a more pronounced fall in TSH and T3 concentrations and low serum T3 concentrations were related to a more serious SAH and poor patient outcome. These results need to be studied further and they may contribute to the accumulated knowledge needed to understand the complex mechanisms influencing the unpredictable clinical course after SAH.

Sleep in neurointensive care patients, and patients after brain tumor surgery.

BACKGROUND: Severely brain injured patients treated in the neuro intensive care unit (NICU) are usually sedated. Sedation may affect not only the ability to sleep, but also the EEG rhythms used to identify sleep. AIM: The aims were: To study if sleep patterns could be identified in the severely brain injured and sedated patients in the NICUTo study if sleep patterns could be identified in patients the night after brain tumor surgery in the neurointermediate care unit (NIMCU)To search for risk factors for not being able to sleep after brain tumor surgery. STUDY DESIGN: Two populations were included; one with patients affected by severe brain injury and one with patients who had undergone planned brain tumor surgery. This was a quantitative observational study using EEG. Eligible neurointensive care patients for this study had to be suffering from a neurosurgical condition (for example subarachnoid haemorrhage, acute subdural hematoma, intracerebral haemorrhage and meningitis), have affected consciousness and age over 18 years. Thirty-seven patients were included from NICU. Ninety-eight patients, with a suspected glioma (WHO grade II-IV) planned for surgery were also included. RESULTS: Neuro intensive care patients, sedated and treated in ventilator, showed no EEG sleep patterns at all. After brain tumor surgery, sleep occurred in 74% of the patients, despite frequent wake-up tests. The patients with sleep patterns were on average 8 years younger, p = 0.03. CONCLUSIONS: Patients with severe brain injury are at risk of having no sleep when treated at the NICU, whereas after brain tumor surgery, sleep occurs in three-fourths of the patients. Further studies and new methods are warranted to identify sleep and investigate how the loss of sleep affects these patients and how sleep disturbances can be managed.

Patient-reported quality of life in grade 2 and 3 gliomas after surgery, can we do more?

OBJECTIVE: To study the effects of surgery and the explanatory variables for patient-reported health-related quality of life (HRQoL) after brain tumor surgery for astrocytomas and oligodendrogliomas grade 2 and 3. METHODS: Patients operated for an astrocytoma or an oligodendrogliomas, grade 2 or 3, at the Department of Neurosurgery, Uppsala, Sweden, 2016-2021, were included. HRQoL was assessed with RAND-36 preoperatively and 4 months postoperatively. Demographic, tumor, and treatment data were prospectively collected. RESULTS: Sixty-two patients were included, 34 with an astrocytoma and 28 with an oligodendroglioma. Physical function, role physical, general health, vitality, and social functioning decreased significantly (p-values < 0.01) 4 months after surgery, whereas bodily pain, role emotional, and mental health remained unchanged. In Spearman analyses, younger patients deteriorated more in role physical, females worsened less often in general health but more often in social functioning than males, a higher level of education correlated with a more pronounced drop in social functioning, and a greater extent of resection corresponded to a worsening in physical function postoperatively (p-values < 0.05). CONCLUSIONS: Several HRQoL domains deteriorated after glioma surgery in specific groups of patients, particularly general health, vitality, physical, and social functions. This was only weakly explained by surgical variables. Specific groups of patients may need closer follow-ups and tailored support/rehabilitation to detect and address these HRQoL deteriorations.

Continuous subcortical language mapping in awake glioma surgery.

Repetitive monopolar short-train stimulation (STS) delivered from a suction probe enables continuous mapping and distance assessment of corticospinal tracts during asleep glioma resection. In this study, we explored this stimulation technique in awake glioma surgery. Fourteen patients with glioma involving language-related tracts were prospectively included. Continuous (3-Hz) cathodal monopolar STS (five pulses, 250 Hz) was delivered via the tip of a suction probe throughout tumor resection while testing language performance. At 70 subcortical locations, surgery was paused to deliver STS in a steady suction probe position. Monopolar STS influence on language performance at different subcortical locations was separated into three groups. Group 1 represented locations where STS did not produce language disturbance. Groups 2 and 3 represented subcortical locations where STS produced language interference at different threshold intensities (≥7.5 and ≤5 mA, respectively). For validation, bipolar Penfield stimulation (PS; 60 Hz for 3 s) was used as a "gold standard" comparison method to detect close proximity to language-related tracts and classified as positive or negative regarding language interference. There was no language interference from STS in 28 locations (Group 1), and PS was negative for all sites. In Group 2 (STS threshold ≥ 7.5 mA; median, 10 mA), there was language interference at 18 locations, and PS (median, 4 mA) was positive in only one location. In Group 3 (STS threshold ≤ 5 mA; median, 5 mA), there was language interference at 24 locations, and positive PS (median 4 mA) was significantly (p < 0.01) more common (15 out of 24 locations) compared with Groups 1 and 2. Despite the continuous stimulation throughout tumor resection, there were no seizures in any of the patients. In five patients, temporary current spread to the facial nerve was observed. We conclude that continuous subcortical STS is feasibly also in awake glioma surgery and that no language interference from STS or interference at ≥7.5 mA seems to indicate safe distance to language tracts as judged by PS comparisons. STS language interference at STS ≤ 5 mA was not consistently confirmed by PS, which needs to be addressed.

Depression and post-traumatic stress disorder after aneurysmal subarachnoid haemorrhage in relation to lifetime psychiatric morbidity.

INTRODUCTION: Little is known about the roles that lifetime psychiatric disorders play in psychiatric and vocational outcomes of aneurysmal subarachnoid haemorrhage (SAH). MATERIALS AND METHODS: Eighty-three SAH patients without apparent cognitive dysfunction were assessed using the Structured Clinical Interview for DSM-IV axis I disorders (SCID-I) after their SAH. Diagnoses were assessed for three time periods, 'lifetime before SAH', '12 months before SAH' and '7 months after SAH'. RESULTS: Forty-five percentage of patients with SAH reported at least one lifetime psychiatric disorder. After SAH, symptoms of depression and/or post-traumatic stress disorder (PTSD) were seen in 41%, more often in those with a psychiatric history prior to SAH (p = 0.001). In logistic regressions, depression after SAH was associated with a lifetime history of major depression, or of anxiety or substance use disorder, as well as with lifetime psychiatric comorbidity. Subsyndromal or full PTSD was predicted by a lifetime history of major depression. After the SAH, 18 patients (22%) had received psychotropic medication and/or psychological treatment, 13 of whom had a disorder. Those with a lifetime history of major depression or treatment with antidepressants before SAH had lower return to work rates than others (p = 0.019 and p = 0.031, respectively). This was also true for those with symptoms of depression and/or PTSD, or with antidepressant treatment after SAH (p = 0.001 and p = 0.031, respectively). CONCLUSIONS: Depression and PTSD are present in a substantial proportion of patients 7 months after SAH. Those with a history of psychiatric morbidity, any time before the SAH, are more at risk and also constitute a risk group for difficulties in returning to work.

Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage.

OBJECTIVE: An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH. PATIENTS: Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed. RESULTS: S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia. CONCLUSION: There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.

Role of Preoperative Assessment in Predicting Tumor-Induced Plasticity in Patients with Diffuse Gliomas.

When diffuse gliomas (DG) affect the brain's potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor-brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganization in these patients. FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG) was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language assessments were performed in all patients. The distance between eloquent spots and tumor margins was measured. All variables were used for correlation and logistic regression analyses. Eloquent tumors were detected in 75% of the patients with no single variable able to predict this finding. Impaired NPS functions correlated with invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2/A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. Preoperative NPS impairment is linked with high risk of eloquent tumors. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.

Erratum to "Ecstatic and gelastic seizures related to the hypothalamus" [Epilepsy Behav. Rep. 14 (2020) 100358].

[This corrects the article DOI: 10.1016/j.ebr.2020.100358.].

Ecstatic and gelastic seizures related to the hypothalamus.

Ecstatic seizures constitute a rare form of epilepsy, and the semiology is diverse. Previously, brain areas including the temporal lobe and the insula have been identified to be involved in clinical expression. The aim of this report is to review changes in ecstatic seizures in a patient before and after operation for a hypothalamic hamartoma, and to scrutinize the relation to gelastic seizures. In this case, the ecstatic seizures disappeared after surgery of the hamartoma but reappeared eleven years later. Clinical information was retrospectively obtained from medical records, interviews, and a questionnaire covering seizure semiology that pertained to ecstatic and gelastic seizures. Our findings imply a possible connection between gelastic and ecstatic seizures, originating from a hypothalamic hamartoma. To our knowledge, this location has not previously been described in ecstatic seizures. Gelastic seizures may in this case be associated with ecstatic seizures. We speculate that patients with ecstatic seizures may have an ictal activation of neuronal networks that involve the insula. Our case may add information to the knowledge concerning ecstatic seizures.