Midline Shift Research Articles

Predicting Progression of Intracranial Hemorrhage in the Prehospital TXA for TBI Trial.

Progression of intracranial hemorrhage is a common, potentially devastating complication after moderate/severe traumatic brain injury (TBI). Clinicians have few tools to predict which patients with traumatic intracranial hemorrhage on their initial head computed tomographic scan (hCT) scan will progress. The objective of this investigation was to identify clinical, imaging, and/or protein biomarkers associated with progression of intracranial hemorrhage (PICH) after moderate/severe TBI and to create an accurate predictive model of PICH based on clinical features available at presentation. We analyzed a subset of subjects from the phase II double-blind, multi-center randomized "Prehospital Tranexamic Acid Use for TBI" trial. This subset was limited to the placebo arm of the parent trial with evidence of hemorrhage on the initial head CT and a follow-up CT 6 hours after. PICH was defined as an increase in hemorrhage size by 30% or more, or the development of new hemorrhage in the intra- and extra-axial intracranial vault between the initial and the follow-up head CT. Two independent radiologists evaluated each head CT, and conflicts were adjudicated by a third. Clinical and radiographic characteristics were collected, along with plasma protein biomarkers at admission. Principal component analysis (PCA) was performed, and each principal component (PC) was interrogated for its association with PICH. Finally, expert opinion and recursive feature extraction (RFE) were used to select input features for the construction of several super- vised classification models. Their ability to predict PICH were quantified and compared. In this subset of subjects (n=104), 46% (n=48) demonstrated PICH. Univariate analyses showed no association between PICH and age, sex, admission Glasgow Coma Scale (GCS), GCS motor subscore, presence of midline shift, admission platelet count or admission INR. Radiographic severity scores (Marshall score [P=0.007], Rotterdam score [P=0.004]) and initial hematoma volume [P=0.005] were associated with PICH. Higher levels of admission GFAP (P<0.001) and MAP (P=0.011) were also associated with PICH. Of the PCs, PC1 was significantly associated with PICH (P=0.0125). Using multimodal data input, machine learning classifiers successfully discriminated patients with or without PICH. Models composed of machine selected features performed better than models composed of expert selected variables (reaching an average of 77% accuracy, AUC = 0.78 versus AUC = 0.68 for the expert selected variables). Predictive models utilizing variables measured at admission can accurately predict PICH, confirmed by the 6-hour follow-up head CT. Our best performing models must now be externally validated in a separate cohort of TBI patients with low GCS and initial head CT positive for hemorrhage.

Endovascular Treatment for Cerebral Venous Sinus Thrombosis: Comparison among Different Endovascular Procedures

Abstract Background: Cerebral venous sinus thrombosis (CVST) is a rare, treatable cause of stroke. Even though CVST has an established medical treatment, 15% of patients remain refractory to treatment. These patients may be candidates for endovascular treatment (EVT), yet the selection of patients remains a challenge. The study aims to understand the profile and outcome of patients treated with EVT and the type of procedure associated with good outcomes. Methods: This is a single-center, retrospective analysis of CVST patients who underwent EVT from 2009 till 2022. Patients who received only medical management were excluded. Modified Rankin Scale (mRS) ≤2 at 3 months was taken as the primary outcome. Secondary outcomes assessed were hospital stay, death, recurrence, mRS ≤ 2 at discharge, and angiographic recanalization. Results: Fifty-two patients were included. Twenty-eight (53.8%) were males; the mean age was 33.3 ± 12.3 years. Headache (n = 44, 84.6%) predominated among the symptoms. The common risk factors were anemia (n = 13, 25.5%) and hyperhomocysteinemia (n = 13, 25.5%). Worsening of sensorium (n = 21, 40.3%) and non-improvement of symptoms (n = 15, 28.8%) were the common indications for the procedure. Twenty-five (48.1%) people underwent in situ thrombolysis (IST). Death occurred in eight (15.3%) patients. Thirty-six (73.5%; 36/49) patients had a good outcome at 3 months. IST had a significantly better outcome (mRS ≤ 2, n = 20, 80%) compared to other procedures (P = 0.04). Hospital stay was lesser in the IST subgroup, but without statistical significance. Midline shift &gt;5 mm (odds ratio [OR] 6.8 [1.5–30.9], P = 0.01) and Glasgow Coma Scale &lt;9 before the procedure (OR 27.2 [3.1–236.4], P = 0.002) predicted bad outcomes at 3 months. Female gender (OR 4.5 [1.07–8.8], P = 0.03), presence of altered sensorium (OR 10.2 [1.2–87.5], P = 0.01), encephalopathic syndrome (P = 0.02), presence of parenchymal bleed (OR 3.7 [0.9–4.5], P = 0.04), and midline shift (OR 4.8 [1.1–20.2], P = 0.03) were associated with poor outcome at discharge. Conclusion: EVT yielded good outcomes in carefully selected, medically refractory patients of CVST. IST performed well compared to other procedures.

Risk stratification and predictive modeling of postoperative delirium in chronic subdural hematoma.

Background- Postoperative delirium is a common complication associated with the elderly, causing increased morbidity and prolonged hospital stay. However, its risk factors in chronic subdural hematoma patients have not been well studied. Methods- A total of 202 consecutive patients with chronic subdural hematoma at Peking University Third Hospital between January 2018 and January 2023 were enrolled. Various clinical indicators were analyzed to identify independent risk factors for postoperative delirium using univariate and multivariate regression analyses. Delirium risk prediction models were developed as a nomogram and a Markov chain. Results- Out of the 202 patients (age, 71 (IQR, 18); female-to-male ratio, 1:2.7) studied, 63 (31.2%) experienced postoperative delirium. Univariate analysis identified age (p < 0.001), gender (p = 0.014), restraint belt use (p < 0.001), electrolyte imbalance (p < 0.001), visual analog scale score (p < 0.001), hematoma thickness (p < 0.001), midline shift (p < 0.001), hematoma side (p = 0.013), hematoma location (p = 0.018), and urinal catheterization (p = 0.028) as significant factors. Multivariate regression analysis confirmed the significance of restraint belt use (B = 7.657, p < 0.001), electrolyte imbalance (B = -3.993, p = 0.001), visual analog scale score (B = 2.331, p = 0.016), and midline shift (B = 0.335, p = 0.007). Hematoma thickness and age had no significant impact. Conclusion- Increased midline shift and visual analog scale scores, alongside restraint belt use and electrolyte imbalance elevate delirium risk in chronic subdural hematoma surgery. Our prediction models may offer reference value in this context.

Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17–44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

Middle meningeal artery patency after surgical evacuation for chronic subdural hematoma.

Chronic subdural hematoma (CSDH) often requires surgical evacuation, but recurrence rates remain high. Middle meningeal artery (MMA) embolization (MMAE) has been proposed as an alternative or adjunct treatment. There is concern that prior surgery might limit patency, access, penetration, and efficacy of MMAE, such that some recent trials excluded patients with prior craniotomy. However, the impact of prior open surgery on MMA patency has not been studied. A retrospective analysis was conducted on patients who underwent MMAE for cSDH (2019-2022), after prior surgical evacuation or not. MMA patency was assessed using a six-point grading scale. Of the 109 MMAEs (84 patients, median age 72 years, 20.2% females), 58.7% were upfront MMAEs, while 41.3% were after prior surgery (20 craniotomies, 25 burr holes). Median hematoma thickness was 14mm and midline shift 3mm. Hematoma thickness reduction, surgical rescue, and functional outcome did not differ between MMAE subgroups and were not affected by MMA patency or total area of craniotomy or burr-holes. MMA patency was reduced in the craniotomy group only, specifically in the distal portion of the anterior division (p = 0.005), and correlated with craniotomy area (p < 0.001). MMA remains relatively patent after burr-hole evacuation of cSDH, while craniotomy typically only affects the frontal-distal division. However, MMA patency, evacuation method, and total area do not affect outcomes. These findings support the use of MMAE regardless of prior surgery and may influence future trial inclusion/exclusion criteria. Further studies are needed to optimize the timing and techniques for MMAE in cSDH management.

432 Middle Meningeal Artery Embolization Reduces Recurrence Following Surgery for Septated Chronic Subdural Hematomas

INTRODUCTION: Chronic subdural hematoma (cSDH) causes a significant burden of disease and plagued by hematoma recurrence after surgical evacuation, particularly in septated cSDH. Middle meningeal artery embolization (MMAE) has emerged as a promising treatment both as an adjunct to surgery and as a primary treatment. METHODS: This a single center, retrospective cohort study of patients treated with surgery for septated cSDH. Patients in the surgery + MMAE cohort were identified from a prospectively collected MMAE registry and compared to a historical surgery cohort presenting over a 2-year period prior to the introduction of MMAE in our institution. Included patients had evacuation of septated cSDH with either burrholes or craniotomy. CT imaging was assessed hematoma width and midline shift perioperatively and at follow up. The primary outcome was reoperation and secondary outcome recurrence and change in hematoma depth and midline shift. RESULTS: A total of 34 cSDHs in 23 patients (MMAE + surgery) and 94 cSDHs in 76 patients (surgery) met the inclusion criteria. No significant differences of baseline characteristics was identified.The rate of reoperation was significantly higher in the surgery cohort (n = 16) compared with the surgery + MMAE cohort (n = 0) (p = 0.006). CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.

Association of Serum Macrophage Migration Inhibitory Factor with 3-Month Poor Outcome and Malignant Cerebral Edema in Patients with Large Hemispheric Infarction.

We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). Patients with LHI within 24h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144-6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841-10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236-6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534-9.637, p = 0.004). Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies.

869 Early Signs of Elevated Intracranial Pressure (ICP) on Computed Tomography Correlate With Measured ICP in the Intensive Care Unit and Six-month Outcome Following Moderate to Severe TBI

INTRODUCTION: Identifying patients at risk for increased intracranial pressure (ICP) followingTBI via baseline computed tomography (CT) has not previously been validated in a prospective dataset. METHODS: Data were obtained from the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECTIII) multicenter clinical trial. Baseline CT scans for 881 participants were individually reviewed by a blinded central neuroradiologist. Five signs of elevated ICP were measured (sulcal obliteration, lateral ventricle compression, 3rd ventricle compression, midline shift, and herniation). Associations between signs of increased ICP and outcomes (6-month functional outcome and mortality) were assessed. RESULTS: Sulcal obliteration (p = 0.029) and third ventricular compression (p = 0.039) were associated with elevated ICP. Univariate regression analyses indicated that increasing combinations of the five defined signs of elevated ICP were associated with mortality, poor functional outcome, and time to death. There was also an increased likelihood of mortality if patients required craniotomy (OR = 4.318, 95% Confidence Interval [1.330-16.030]) or hemicraniectomy (OR = 2.993 [1.109-8.482]). On multivariate regression analyses, hemorrhage location was associated with mortality (posterior fossa, OR = 3.208 [1.120-9.188] and basal ganglia, OR = 3.079 [1.178-8.077]). Volume of hemorrhage &gt;30cc was also associated with increased mortality, OR = 3.702 [1.575-8.956]). The proportion of patient hours with sustained ICP = 20 mmHg, and maximum ICP = 20 mmHg, were also directly correlated with increased mortality (OR = 64.99 [7.731-635.51]; and OR = 1.025 [1.004-1.047]). Poor functional outcome was predicted by concurrent presence of all five radiographic signs of elevated ICP (OR = 4.44 [1.514-14.183]) and presence of frontal lobe (OR = 2.951 [1.265-7.067]), subarachnoid (OR = 2.231 [1.067-4.717]), or intraventricular (OR = 2.249 [1.159-4.508]) hemorrhage. Time to death was modulated by total patient days of elevated ICP = 20 mmHg (Effect Size = 3.424 [1.500, 5.439]) in the first two weeks of hospitalization. CONCLUSIONS: ICP-related imaging variables can be prognosticate for moderate-severe TBI.

General surgeon performed emergency craniotomies in regional Queensland hospitals: a 20-year state-wide study on patient outcomes.

Traumatic brain injuries account for up to 50% of trauma related deaths and if surgical intervention is indicated, consensus suggests a maximum of 4 hours to surgical decompression. The occurrence and outcomes of craniotomies performed by non-neurosurgeons in regional Queensland hospitals have never been reported previously in the literature. A retrospective review was performed at all regional Queensland hospitals without an on-site neurosurgical service from January 2001 to December 2022 to identify patients undergoing emergency craniotomy. Data recorded included basic demographics, history of anti-coagulant use, mechanism of injury, type of haemorrhage, Glasgow Coma Score and Glasgow Outcome Scale (GOS) on discharge. Radiological parameters measured included midline shift and maximal coronal depth of haematoma. The primary aim of this study was to assess the clinical and radiological outcomes of patients who underwent a craniotomy performed by general surgeons. Over the past 20 years there have been 23 emergency decompressive procedures (one excluded) performed in regional Queensland. Preoperative imaging demonstrated 9 extradural haematomas and 13 subdural haematomas. Six of 17 transferred cases required reoperation after transfer to a neurosurgical centre. Survival was observed in 9 of 22 cases, with 'good' functional outcome (GOS ≥3) observed in 7 cases. In no cases were rurally performed burr holes effective. Qualitatively, a larger craniotomy may be associated with better clinical and radiological outcomes. Although rare occurrences, our results demonstrate that general surgeon performed craniotomies are frequently efficacious in producing radiological and/or clinical improvement and should be considered as a potentially lifesaving procedure.

NK1 tachykinin receptor antagonist treatment reduces cerebral edema and intracranial pressure in an ovine model of ischemic stroke.

Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo). Anesthetized sheep (n = 24) were subject to 2-hours tMCAo and randomized (n = 6/group) to receive early NK1-R treatment (days 1-3 post-stroke), delayed NK1-R treatment (day 5 post-stroke), or saline vehicle. At 6-days post-stroke animals were re-anaesthetized and ICP measured, followed by MRI to evaluate infarction, edema and BBB dysfunction. Following both early and delayed NK1-R antagonist administration, ICP was significantly reduced on day 6 compared to vehicle animals (p < 0.05), accompanied by a reduction in cerebral edema, midline shift and BBB dysfunction (p < 0.05). This study demonstrates that NK1-R antagonist treatment is an effective novel therapy for cerebral edema and elevated ICP following stroke in an ovine model, warranting future clinical evaluation.

Middle meningeal artery embolization for the treatment of unilateral large chronic subdural hematoma patients with significant midline shift: A single-center experience.

The amount of midline shift (MLS) considered safe for middle meningeal artery embolization (MMAE) in patients with chronic subdural hematoma (CSDH) has not been established. Whether MMAE could be used as upfront treatment for unilateral large CSDH patients with significant MLS (>1 cm) has not been reported. To investigate the efficacy and safety of MMAE in unilateral large CSDH patients with MLS > 1 cm. Eleven carefully selected CSDH patients with mild or moderate symptoms and significant MLS > 1 cm from 1 May 2021 to 31 August 2022 were included in the study. All patients were treated with MMAE using polyvinyl alcohol (PVA) particles. Outcomes were assessed clinically and with interval imaging studies at follow-up. All 19 MMAs (unilateral embolization in three patients and bilateral embolization in eight patients) were successfully embolized. All 11 patients were followed for subsequent months, and there was no recurrence and enlargement of CSDH. Procedural adverse events, mortality, or complications were not observed. The average time to achieve a 50% reduction in MLS was approximately four weeks, while it took approximately eight weeks to achieve a 50% reduction in maximal volume. All 11 patients showed improvement in their neurological symptoms at three days post-operation, including four hemiplegic patients. MMAE may demonstrate safety in carefully selected CSDH patients with significant midline shift (MLS > 1 cm), particularly in those who are not suitable for surgery, thus providing a potential alternative approach.

Middle meningeal artery embolization reduces recurrence following surgery for septated chronic subdural hematomas

BackgroundSeptated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. MethodsThis is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. ResultsA total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. ConclusionsMMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.

Prediction of functional outcome in supratentorial intracerebral hemorrhage patients treated with stereotactic computed tomographic-guided aspiration and recombinant tissue plasminogen activator (rt-PA)

Background and purposeMinimally invasive surgery for ICH has shown a significantly improved functional outcome for selected ICH patients. This study aimed to evaluate the factors influencing the outcome of supratentorial ICH patients treated with stereotactic computed tomographic (CT) guided recombinant tissue plasminogen activator (rt-PA). MethodsWe retrospectively evaluated data from 80 consecutive supratentorial ICH patients between December 2017 and July 2020, analyzing their 180-day outcomes, and identifying clinical, radiological factors for good prognosis within 180 days. ResultsThe mean age was 55.6 years (SD 11.4). The median preoperative Glasgow Coma Scale (GCS) score was 9 (interquartile range - IQR 6–12). The mean final ICH volume was 26.5 ml (SD 27.5), with ICH volume reduction by an average of 66.7 %. Six months after the procedure, 40 patients (50 %) had favorable outcomes (modified Rankin Scale [mRS]) score 0–3). In multivariate analysis, age (odds ratio [OR] = 0.939, 95 % confidence interval (CI) = 0.894 – 0.986; p = 0.012), the GCS score before operation (OR = 1.525, 95 % CI = 1.008 – 2.309; p = 0.046), the initial midline shift (OR = 0.808, 95 % CI = 0.661 – 0.988; p = 0.038), and the residual volume hematoma (OR = 0.949, 95 % CI = 0.908 – 0.992, p = 0.020) were the significant predictors of a favorable 180-day outcome. Receiver operating characteristic curve analysis confirmed that the best cut-off point for predicting the good functional 180-day outcome was a GCS score of 9 before the procedure [area under the curve: 0.721, 95 % CI = 0.608 – 0.833, p = 0.001]. ConclusionCT-guided thrombolysis and aspiration can be safe and effective in reducing ICH volume. A preoperation GCS score above or equal to 9 and younger age were associated with improved long-term outcomes in patients with supratentorial ICH.

Tumor-Induced Parkinsonism Due to a Large Meningioma Diagnosed by 99mTc-TRODAT-1 SPECT/CT.

A 67-year-old woman complained of rest and postural tremors in her left upper extremity, associated with bradykinesia and gait disorder since 2 years ago, with no significant response to antiparkinsonism drugs. Dopamine transporter SPECT/CT revealed a remarkable area of 99mTc-TRODAT-1 uptake in a huge tumoral lesion in the right frontotemporal region, compressing and dislocating the right striatum with evidence of significant midline shift. The patient underwent surgical resection with a diagnosis of meningioma on preoperative MRI and postoperative histology report, experiencing a marked recovery in symptoms after 1 month.

Dialysis disequilibrium syndrome in neurosurgery: literature review and illustrative case example.

The dialysis disequilibrium syndrome (DDS) is a complication in those undergoing dialysis for chronic kidney disease (CKD) or acute kidney injury (AKI), characterized by nonspecific symptoms that may progress to coma and death secondary to cerebral edema. This syndrome is associated with rapid change in electrolytes during dialysis with changes in intracranial pressure (ICP) and may have a higher incidence in the elderly neurosurgical patient population. Literature review and illustrative case example. A 62-year-old female presented with acute mental status change during hemodialysis (HD), with a history of a nonsurgical acute subdural hematoma (SDH) 10days prior. Imaging showed a conversion of the acute SDH to chronic SDH of 12.2mm in size with a 14.1 midline shift, for which she underwent a hemicraniectomy with SDH evacuation, with a gradual return to baseline. The literature review identified 5 publications meeting the inclusion criteria. Major theories of DDS include a reverse urea effect, intracerebral acidosis, idiogenic osmoles, and local inflammation. This complication may occur more frequently in the elderly neurosurgical patient population, likely due to age-related comorbidities, preexisting neurological insult, and increased permeability of the blood-brain barrier (BBB), leading to cerebral edema. DDS is a rare and potentially fatal complication of HD that may have a higher incidence in the elderly neurosurgical patient population, yet remains to be fully understood. Further study is recommended to characterize the pathophysiological mechanism and incidence of DDS in neurosurgical patients.

Spinal and cervical nodal metastases in apatient with glioblastoma.

This article presents the rare case of a54-year-old gentleman with primary glioblastoma developing multiple extracranial metastases 7months after diagnosis. Initially, the patient complained of progressive headaches, confusion, and weakness of the left arm. Magnetic resonance imaging of the brain showed aright temporoparietal tumor with substantial surrounding subcortical edema and midline shift to the left. Two consecutive craniotomies resulted in complete microsurgical resection of the lesion. Histology was consistent with aWorld Health Organization gradeIV, IDH-wildtype glioblastoma. Further treatment was standard chemoradiation including intensity-modulated radiotherapy with oral temozolomide chemotherapy. Seven months after diagnosis, the cranial lesion progressed, and the patient developed painful metastases in multiple bones and suspicious right-sided cervical lymph nodes. Immunohistochemistry and molecular signature supported the case of ametastatic glioblastoma. Further treatment was palliative radiotherapy of the spinal lesions along with symptomatic pain management. Extracranial metastasis of glioblastoma is arare complication of which only afew cases have been reported in the literature. Little is known about the precise mechanisms of tumor dissemination and the appropriate treatment.

Intratumoral histological and molecular heterogeneity in an adult diffuse glioma.

Adult-type diffuse gliomas are the most prevalent type of malignant adult brain tumors. Intratumoral heterogeneity can hinder accurate diagnosis and subsequent treatment. This case report documents a tumor with intratumoral heterogeneity, both histologically and by methylation analysis, located within the left cerebral hemisphere of a 29-year-old female. She presented after a witnessed generalized tonic clonic seizure at home. Two years prior she had a witnessed seizure; however, no brain imaging was done at the time. Magnetic resonance imaging (MRI), on this admission, showed a mass lesion in the left frontal operculum with poorly identified margins and right-sided midline shift. Sampling from the left temporal lobe showed an IDH-mutant, ATRX-mutant astrocytoma, which appeared grade 4 in the enhancing anterior portion and grade 2 in the left temporal lobe. Methylation analysis confirmed this heterogeneity. In summary, this is an excellent example of tumor heterogeneity both histologically and by molecular analysis. It is probable, given the clinical history of presentation 2 years prior, that this tumor originated as a low-grade glioma and subsequently evolved.

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

An unusual finding of an anaplastic meningioma in NF2-related schwannomatosis.

NF2-related schwannomatosis (NF2) is a rare autosomal-dominant genetic disorder characterized by bilateral vestibular schwannomas and multiple meningiomas. This case report presents the extremely rare occurrence of an anaplastic meningioma in a 12-year-old male with previously undiagnosed NF2. The patient presented with a history of abdominal pain and episodic emesis, gait unsteadiness, right upper and lower extremity weakness, and facial weakness. He had sensorineural hearing loss and wore bilateral hearing aids. MR imaging revealed a sizable left frontoparietal, dural-based meningioma with heterogeneous enhancement with mass effect on the brain and midline shift. Multiple additional CNS lesions were noted including a homogenous lesion at the level of T5 indicative of compression of the spinal cord. The patient underwent a frontotemporoparietal craniotomy for the removal of his large dural-based meningioma, utilizing neuronavigation and transdural ultrasonography for precise en bloc resection of the mass. Histopathology revealed an anaplastic meningioma, WHO grade 3, characterized by brisk mitotic activity, small-cell changes, high Ki-67 proliferation rate, and significant loss of P16. We report an anaplastic meningioma associated with an underlying diagnosis of NF2 for which we describe clinical and histopathological features.

Rare variant of large pediatric glioneuronal tumor with novel MYO5A::NTRK3 fusion: illustrative case.

Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group. A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as "glioneuronal tumor kinase-fused" (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib. This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.