Clinical course and predictors of outcome following surgical treatment of benign peripheral nerve sheath tumors, a single center retrospective study.

INTRODUCTION: Peripheral nerve sheath tumors are the most common tumor of the peripheral nerves. In general, surgery has a favorable outcome and is the treatment of choice. However, postoperative neurologic deficits are not uncommon, and predictors of outcome are poorly defined. OBJECTIVE: To evaluate clinical outcomes after surgical treatment of benign peripheral nerve sheath tumors and identify outcome predictors that may affect preoperative decision making and improve surgical outcomes. METHOD: In this single center retrospective study, all patients surgically treated for a benign peripheral nerve sheath tumor between 2005 and 2020 were eligible for inclusion. Medical records and imaging data were reviewed. Studied outcomes were changes in neurological symptoms, pain, and tumor recurrence. Logistic regression was performed to identify possible outcome predictors. RESULTS: In total, 81 patients undergoing 85 separate surgeries for benign peripheral nerve sheath tumors were included. The most common preoperative symptoms were local pain (90%) followed by a noticeable mass (78%), radiating pain (72%), sensory deficit (18%), and motor deficit (16%). A postoperative improvement of symptoms was seen in 94% of those with pain, 48% of those with sensory deficits and 78% of those with motor deficits. However, 35% and 9% developed new postoperative sensory and motor deficits, respectively. Multivariable analysis showed complete tumor removal as a predictor of reduced pain (p = 0.033), and younger age and larger tumors were risk factors for persistent or increased sensory deficits (p = 0.002 and p = 0.005, respectively). There were no significant predictors of motor deficits. Neurocutaneous syndromes were associated with increased odds of tumor recurrence on univariable analysis (p = 0.008). CONCLUSION: Surgery of benign peripheral nerve sheath tumors is a safe procedure with a favorable outcome in most cases. Younger age and larger tumors were risk factors for persistent or increased sensory deficits, while complete tumor removal was associated with reduced pain. Patients with neurocutaneous syndromes had a higher rate of tumor recurrence. To further evaluate outcome predictors, we recommend future studies to focus on longer follow-up periods to assess the natural course of postoperative neurological deficits.

The negative impact of treatment delays on the long-term neurological outcomes of spinal dural arteriovenous fistulas: a longitudinal cohort study.

OBJECTIVE: Dural arteriovenous fistulas are rare vascular malformations that affect the brain and spinal cord. Spinal dural arteriovenous fistulas (sdAVFs) are the most frequently encountered vascular malformation affecting the spinal cord. The object of this study was to evaluate the impact of treatment delays on the long-term neurological outcomes of either open surgical or interventional treatment of sdAVFs. METHODS: In this retrospective, population-based cohort study, the authors examined consecutive patients with diagnosed sdAVFs at a tertiary care center between 2005 and 2020. Patients were assessed using the Aminoff-Logue disability scale (ALS) at various time points including symptom onset, primary care visit, first specialist outpatient visit, as well as both short and long-term follow-ups. The postoperative long-term ALS gait and bladder grades constituted the primary outcomes of the study. RESULTS: Among the 34 patients included in the study, the median age was 65 years, and there was a male predominance (71%). Most lesions were in the lumbar region (47%). Significant worsening in ALS gait and bladder grades was observed preoperatively, followed by postoperative improvements (p < 0.05). There was no difference in outcomes between surgical and endovascular treatments. Older age (OR 1.10, 95% CI 1.03-1.17, p = 0.007), worse preoperative ALS gait grades (OR 5.12, 95% CI 2.18-12.4, p < 0.001), and longer time from first specialist outpatient visit to first treatment (OR 1.00, 95% CI 1.00-1.01, p = 0.040) were independently associated with worse long-term gait outcomes. Only the preoperative ALS bladder score was a predictor of worse long-term bladder function (OR 92.7, 95% CI 28.0-306.7, p < 0.001). CONCLUSIONS: Both surgical and endovascular treatments for sdAVFs led to significant neurological improvements. However, treatment delays were associated with less favorable long-term outcomes. Prompt diagnosis and early intervention prior to symptom progression may enhance recovery and help to preserve neurological function.

Long-Term Functional Outcomes Following Surgical Treatment of Spinal Schwannomas: A Population-Based Cohort Study.

Spinal schwannomas are the second most common form of primary intradural spinal tumor. Despite being benign, they may cause spinal cord compression and subsequently acute or chronic neurological dysfunction. The primary treatment is surgical resection. The aim of this study was to identify pre- and postoperative predictors of favorable outcomes after surgical treatment for spinal schwannoma. All adult patients surgically treated for spinal schwannoma between 2006 and 2020 were eligible for inclusion. Medical records and imaging data were retrospectively reviewed. The primary outcome measures were neurological improvement according to the modified McCormick Scale (mMC) and changes in motor deficit, sensory deficit, gait disturbance, bladder dysfunction, and pain at long-term follow-up. In total, 180 patients with a median follow-up time of 4.4 years were included. Pain was the most common presenting symptom (87%). The median time between symptom presentation and surgery was 12 months, while the median time between diagnosis (first MRI) and surgery was 3 months. Gross total resection (GTR) was achieved in 150 (83%) patients and the nerve root could be preserved in 133 (74%) patients. A postoperative complication occurred in 10 patients (5.6%). There were significant postoperative improvements in terms of motor, sensory, gait, and bladder functions, as well as pain (p < 0.001). Of these symptoms, bladder dysfunction was the one most often improved, with complete symptom resolution in all cases. However, no other predictors of improvement could be identified. There were three cases of recurrence after GTR and nine cases of regrowth after STR. Reoperation was performed in six (3.3%) cases. GTR was associated with a significant improvement in neurological status at long-term follow-up and increased the chance of progression-free survival.

Dysphagia, health-related quality of life, and return to work after occipitocervical fixation.

PURPOSE: The purpose of this study was to evaluate patient-reported outcome measures (PROMS) on dysphagia, health-related quality of life (HRQoL) and return to work after occipitocervical fixation (OCF). Postoperative radiographic measurements were evaluated to identify possible predictors of dysphagia. METHODS: All individuals (≥ 18 years) who underwent an OCF at the study center or were registered in the Swedish spine registry (Swespine) between 2005 and 2019, and were still alive when the study was conducted, were eligible for inclusion. There was no overlap between the cohorts. Prospectively collected data on dysphagia (Dysphagia Short Questionnaire DSQ), HRQoL (EQ5D-3L) and return to work were used. Radiological and baseline patient data were retrospectively collected. In addition, HRQoL data of a matched sample of individuals was elicited from the Stockholm Public Health Survey 2006. RESULTS: In total, 54 individuals were included. At long-term follow-up, 26 individuals (51%) had no dysphagia, and 25 (49%) reported some degree of dysphagia: 11 (22%) had mild dysphagia, and 14 (27%) had moderate to severe dysphagia. On a group level, the OCF sample scored significantly lower EQVAS and EQ-5Dindex values compared to the general population (60.0 vs. 80.0, p = 0.016; 0.43 vs. 0.80, p < 0.001). Individuals working preoperatively returned to work after surgery. Of those responding, 88% stated that they would undergo the OCF operation if it was offered today. No predictors of dysphagia based on radiographic measurements were identified. CONCLUSION: Occipitocervical fixation results in a high frequency of long-term dysphagia. The HRQoL of OCF patients is significantly reduced compared to matched controls. However, most patients are satisfied with their surgery. No radiographic predictors of long-term dysphagia could be identified. Future prospective and systematic studies with larger samples and more objective outcome measures are needed to elucidate the causes of dysphagia in OCF.

Absolute Contusion Expansion Is Superior to Relative Expansion in Predicting Traumatic Brain Injury Outcomes: A Multi-Center Observational Cohort Study.

Contusion expansion (CE) is a potentially treatable outcome predictor in traumatic brain injury (TBI), and a suitable end-point for hemostatic therapy trials. However, there is no consensus on the definition of clinically relevant CE, both in terms of measurement criteria (absolute vs. relative volume increase) and cutoff values. In light of this, the aim of this study was to assess the predictive abilities of different CE definitions on outcome. We performed a multi-center observational cohort study of adults with moderate-to-severe TBI treated in an intensive care unit. The exposure of interest was CE, defined as the absolute and relative volume change between the first and second computed tomography scan. The primary outcome was the Glasgow Outcome Scale (GOS) at 6-12 months post-injury, dichotomized into unfavorable (GOS ≤3) or favorable (GOS ≥4). The secondary outcome was all-cause mortality. In total, 798 patients were included, with a median duration of 7.0 h between the first and second CT scan. The median absolute and relative CE was 1.5 mL (interquartile range [IQR] 0.1-8.3 mL) and 100% (IQR 10-530%), respectively. Both CE forms were independently associated with unfavorable GOS. Absolute CE outperformed relative CE in predicting both unfavorable GOS (area under the curve [AUC]: 0.65 vs. 0.60, p = 0.002) and all-cause mortality (AUC: 0.66 vs. 0.60, p = 0.003). For dichotomized CE, absolute cutoffs of 1-10 mL yielded the best results. We conclude that absolute CE demonstrates stronger outcome correlation than relative CE. In studies focusing on lesion progression in TBI, it may be advantageous to use absolute CE as the primary outcome metric. For dichotomized outcomes, cutoffs between 1 and 10 mL are suggested, depending on the desired sensitivity-specificity balance.

Predictors of intracranial hemorrhage in neonatal patients on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a life-supportive treatment in neonatal patients with refractory lung and/or heart failure. Intracranial hemorrhage (ICH) is a severe complication and reliable predictors are warranted. The aims of this study were to explore the incidence and possible predictors of ICH in ECMO-treated neonatal patients. We performed a single-center retrospective observational cohort study. Patients aged ≤ 28 days treated with ECMO between 2010 and 2018 were included. Exclusion criteria were ICH, ischemic stroke, cerebrovascular malformation before ECMO initiation or detected within 12 h of admission, ECMO treatment < 12 h, or prior treatment with ECMO at another facility > 12 h. The primary outcome was a CT-verified ICH. Logistic regression models were employed to identify possible predictors of the primary outcome. Of the 223 patients included, 29 (13%) developed an ICH during ECMO treatment. Thirty-day mortality was 59% in the ICH group and 16% in the non-ICH group (p < 0.0001). Lower gestational age (p < 0.01, odds ratio (OR) 0.96; 95%CI 0.94-0.98), and higher pre-ECMO lactate levels (p = 0.017, OR 1.1; 95%CI 1.01-1.18) were independently associated with increased risk of ICH-development. In the clinical setting, identification of risk factors and multimodal neuromonitoring could help initiate steps that lower the risk of ICH in these patients.

Molecular anatomy of adult mouse leptomeninges.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

Long-term outcomes following surgical treatment of spinal arachnoid cysts: a population-based consecutive cohort study.

BACKGROUND CONTEXT: Spinal arachnoid cysts (SACs) are rare, cerebrospinal fluid-filled sacs lined by an arachnoid membrane in the spinal canal. Symptoms can develop due to pressure on the spinal cord or adjacent spinal nerves by the cyst itself or by interrupted flow of cerebrospinal fluid. If noninvasive management fails or neurological deterioration occurs, surgical treatment is recommended. However, data is lacking on long-term outcomes after surgery. PURPOSE: To determine long-term outcomes in patients surgically treated for SACs. STUDY DESIGN: Population-based cohort-study. PATIENT SAMPLE: All consecutive patients treated for either intra- or extradural SACs with surgery between 2005 and 2020 at the author's institution were included. OUTCOME MEASURES: American Spinal Injury Association Impairment Scale (AIS) and modified Japanese Orthopedic Association score (mJOA). METHODS: Data was primarily extracted from electronic patient medical notes. Telephone interviews were performed to assess long-term postoperative outcomes. All analyses were conducted using the statistical software program R version 4.0.5. Statistical significance was set at p<.05. RESULTS: Thirty-four patients were included. Cyst excision was performed in 11 (32%) cases, and fenestration in the remaining 23 (68%). The median follow-up time was 8.0 years. Surgery resulted in a significant long-term improvement in both AIS (p=.012) and mJOA (p=.005). Sensory deficit was the symptom that most often improved (81%), followed by pain (74%) and motor function (64%). AIS deteriorated in two patients, of which one case was attributed to a surgical complication. Local cyst recurrence requiring reoperation was seen in 4 (12%) cases, all of them following cyst fenestration. One patient (3%) required reoperation for progression of the cyst progression at a different level. CONCLUSION: This study reports outcomes of surgically treated SACs with the longest follow-up time to date. Microsurgical cyst excision or fenestration were safe treatment options, and the neurological improvements seen in the immediate postoperative phase were maintained at long-term follow-up.

An unusual cause of chronic neuropathic pain: report of a case of multiple intradural spinal arachnoid cysts and review of the literature.

Spinal arachnoid cysts (SACs) arise either intra- or extradurally and are usually solitary, while cases of multiple SACs have been scarcely reported in the literature. Herein, we report on a rare case of multiple and recurring intradural spinal arachnoid cysts (SACs) causing severe spinal cord compression and neuropathic radicular pain, in a 35-year-old female with a 10-year follow-up. Two separate attempts at surgery were performed but only provided temporary relief since the cysts recurred and new ones formed along the entirety of the spinal cord. Finally, a conservative approach with physiotherapy and a combination of analgesic medications was pursued.

Long-term Outcomes After Periprocedural and Spontaneous Spinal Cord Infarctions: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Spinal cord infarction (SCInf) is a rare condition where consensus regarding diagnostic criteria is lacking, and misdiagnosis or delayed diagnosis can be detrimental. The aim of this study was to describe baseline findings and predictors of long-term functional outcome in a population-based cohort of patients with SCInf. METHODS: All adult patients (aged 18 years or older) treated at the spinal cord injury unit of the study center, between 2006 and 2019, and discharged with a G95 diagnosis (other and unspecified disease of the spinal cord) were screened for inclusion. The diagnostic criteria proposed by Zalewski et al. were retrospectively applied to evaluate the certainty of the SCInf diagnosis. RESULTS: A total of 270 patients were screened and 57 were included in the study, of whom 30 had a spontaneous SCInf and 27 had a periprocedural SCInf. The median American Spinal Cord Injury Association Impairment Scale (AIS) on admission was C, which at a median follow-up of 2.1 years had improved to D (p = 0.002). Compared with periprocedural cases, those with spontaneous SCInf showed significantly better admission AIS (median AIS D vs B, p < 0.001), fewer multilevel SCInf (27% vs 59%, p = 0.029), shorter hospital stay (median 22 vs 44 days, p < 0.001), and better AIS (median AIS D vs C, p < 0.001) and ambulatory status on long-term follow-up (66% vs 1%, p < 0.001). Regression analyses revealed that spontaneous SCInfs (odds ratio [OR] 5.91 [1.92-18.1], p = 0.002) and more favorable admission AIS (OR 33.6 [7.72-146], p < 0.001) were significant predictors of more favorable AIS at follow-up, with admission AIS demonstrating independent predictive ability (OR 35.9 [8.05-160], p < 0.001). DISCUSSION: SCInf is a rare neurologic emergency lacking specific management guidelines. While the presumptive diagnosis is based on the typical presentation and clinical findings, T2-weighted and diffusion-weighted MRI were the most useful diagnostic tools in establishing a definitive diagnosis. Our data show that spontaneous SCInf mostly affected a single spinal cord segment, whereas periprocedural cases were more extensive, had poorer AIS on admission, poorer ambulatory function, and longer hospital stays. Regardless of the etiology, significant neurologic improvements were seen at long-term follow-up, highlighting the importance of active rehabilitation.

Learning Curve Analysis and Adverse Events After Implementation of Neurosurgical Laser Ablation Treatment: A Population-Based Single-Institution Consecutive Series.

OBJECTIVE AND METHODS: We conducted a retrospective review of the first 30 patients treated with stereotactic laser ablation (SLA) at our institution since the introduction of the technique in September 2019. We aimed to analyze our initial results and potential learning curve by investigating precision and lesion coverage and assessing the frequency and nature of adverse events according to the Landriel-Ibanez classification for neurosurgical complications. RESULTS: Indications were de novo gliomas (23%), recurrent gliomas (57%), and epileptogenic foci (20%). There was a trend toward improvement of lesion coverage and target deviation, and a statistically significant improvement in entry point deviation, over time. Four patients (13.3%) experienced a new neurological deficit, where three patients had transient and one patient had permanent deficits, respectively. Our results show a learning curve on precision measures over the first 30 cases. Based on our results the technique can safely be implemented at centers with experience in stereotaxy.

Radiographic measurements for the prediction of dysphagia after occipitocervical fusion: a systematic review.

BACKGROUND: Occipitocervical fusion (OCF) is a procedure performed for multiple upper cervical pathologies. A common postprocedural complication of OCF is dysphagia, which has been linked to the narrowing of the pharyngeal space due to fixation in a hyper-flexed angle. Postoperative dysphagia is linked to reduced quality of life, prolonged hospital stay, aspiration pneumonia, and increased mortality. This has led to investigations of the association between sagittal radiographic angles and dysphagia following OCF. METHODS: A systematic review of the literature was performed to explore the current evidence regarding cervical sagittal radiographic measurements and dysphagia following OCF. A search strategy was carried out using the PubMed, Embase, and Web of Science databases from their dates of inception until August 2022. Only original English-language studies were considered. Moreover, studies had to include the correlation between dysphagia and at least one radiographic measurement in the sagittal plane. RESULTS: The search and subsequent selection process yielded eight studies that were included in the final review, totaling 329 patients in whom dysphagia had been assessed and graded. The dysphagia score by Bazaz et al. (Spine 27, 22:2453-2458, 2002) was used most often. The pooled incidence of dysphagia, in the early postoperative period, was estimated at 26.4%. At long-term follow-up (range: 17-72 months), about one-third of patients experienced resolution of symptoms, which resulted in a long-term post-OCF dysphagia incidence of 16.5%. Across the studies included, six different radiographic parameters were used to derive several measures which were repeatedly and significantly associated with the occurrence of dysphagia. CONCLUSIONS: The high incidence of postoperative dysphagia following OCF warrants close monitoring of patients, especially in the short-term postoperative period. These patients may be assessed through standardized tools where the one by Bazaz et al. was the most commonly used. Moreover, there are several radiographic measurements that can be used to predict the occurrence of dysphagia. These findings may serve as a basis for strategies to prevent the occurrence of dysphagia after OCF.

Time Course and Clinical Significance of Hematoma Expansion in Moderate-to-Severe Traumatic Brain Injury: An Observational Cohort Study.

BACKGROUND: Preventing intracranial hematoma expansion has been advertised as a possible treatment opportunity in traumatic brain injury (TBI). However, the time course of hematoma expansion, and whether the expansion affects outcome, remains poorly understood. In light of this, the aim of this study was to use 3D volume rendering to determine how traumatic intracranial hematomas expand over time and evaluate its impact on outcome. METHODS: Single-center, population-based, observational cohort study of adults with moderate-to-severe TBI. Hematoma expansion was defined as the change in hematoma volume from the baseline computed tomography scan until the lesion had stopped progressing. Volumes were calculated by using semiautomated volumetric segmentation. Functional outcome was measured by using the 12 month Glasgow outcome scale (GOS). RESULTS: In total, 643 patients were included. The mean baseline hematoma volume was 4.2 ml, and the subsequent mean hematoma expansion was 3.8 ml. Overall, 33% of hematomas had stopped progressing within 3 h, and 94% of hematomas had stopped progressing within 24 h of injury. Contusions expanded significantly more, and for a longer period of time, than extra-axial hematomas. There was a significant dose-response relationship between hematoma expansion and 12 month GOS, even after adjusting for known outcome predictors, with every 1-ml increase in hematoma volume associated with a 6% increased risk of 1-point GOS deduction. CONCLUSIONS: Hematoma expansion is a driver of unfavorable outcome in TBI, with small changes in hematoma volume also impacting functional outcome. This study also proposes a wider window of opportunity to prevent lesion progression than what has previously been suggested.

Current Knowledge on Spinal Meningiomas-Surgical Treatment, Complications, and Outcomes: A Systematic Review and Meta-Analysis (Part 2).

Background: Most of the knowledge on spinal meningiomas is extrapolated from their intracranial counterparts, even though they are considered separate entities. This review aimed to systematically summarize studies covering different aspects of spinal meningiomas and their management. Methods: Databases were searched for all studies concerning spinal meningiomas dating from 2000 and onwards. When possible, a meta-analysis was performed. Results: Neurological outcomes of surgery were consistently favorable across studies, with a complication rate of 7.9% and 78.9% of the patients demonstrating good postoperative neurological function (McCormick score 1−2). The most relevant predictors of unfavorable outcomes were poor preoperative status, longer time from diagnosis to surgery, and surgery of recurrent tumors. The recurrence rate after surgery was estimated at 6%. Meta-analysis and/or survival analysis revealed that higher WHO grade (p < 0.001), higher Simpson grade (p < 0.001), ventral tumor location (p = 0.02), and male sex (p = 0.014) were all associated with higher odds of recurrence. However, the meta-analysis did not show any difference between Simpson grade 1 and grade 2 with respect to the odds of recurrence (p = 0.94). Surgery provided immediate and durable health-related quality-of-life improvement, as well as a high frequency of return to work. Conclusion: Spinal meningioma surgery is a relatively safe procedure with a low risk of tumor recurrence and high likelihood of favorable postoperative outcomes.

Current Knowledge on Spinal Meningiomas Epidemiology, Tumor Characteristics and Non-Surgical Treatment Options: A Systematic Review and Pooled Analysis (Part 1).

BACKGROUND: Spinal meningiomas are the most common primary intradural spinal tumors. Although they are a separate entity, a large portion of the knowledge on spinal meningiomas is based on findings in intracranial meningiomas. Therefore, a comprehensive review of all the literature on spinal meningiomas was performed. METHODS: Electronic databases were searched for all studies on spinal meningiomas dating from 2000 and onward. Findings of matching studies were pooled to strengthen the current body of evidence. RESULTS: A total of 104 studies were included. The majority of patients were female (72.83%), elderly (peak decade: seventh), and had a world health organization (WHO) grade 1 tumor (95.7%). Interestingly, the minority of pediatric patients had a male overrepresentation (62.0% vs. 27.17%) and higher-grade tumors (33.3% vs. 4.3%). Sensory and motor dysfunction and pain were the most common presenting symptoms. Despite a handful of studies reporting promising findings associated with the use of non-surgical treatment options, the literature still suffers from contradictory results and limitations of study designs. CONCLUSIONS: Elderly females with WHO grade 1 tumors constituted the stereotypical type of patient. Compared to surgical alternatives, the evidence for the use of non-surgical treatments is still relatively weak.

Stockholm score of lesion detection on computed tomography following mild traumatic brain injury (SELECT-TBI): study protocol for a multicentre, retrospective, observational cohort study.

INTRODUCTION: Mild traumatic brain injury (mTBI) is one of the most common reasons for emergency department (ED) visits. A portion of patients with mTBI will develop an intracranial lesion that might require medical or surgical intervention. In these patients, swift diagnosis and management is paramount. Several guidelines have been developed to help direct patients with mTBI for head CT scanning, but they lack specificity, do not consider the interactions between risk factors and do not provide an individualised estimate of intracranial lesion risk. The aim of this study is to create a model that estimates individualised intracranial lesion risks in patients with mTBI who present to the ED. METHODS AND ANALYSIS: This will be a retrospective cohort study conducted at ED hospitals in Stockholm, Sweden. Eligible patients are adults (≥15 years) with mTBI who presented to the ED within 24 hours of injury and performed a CT scan. The primary outcome will be a traumatic lesion on head CT. The secondary outcomes will be any clinically significant lesion, defined as an intracranial finding that led to neurosurgical intervention, hospital admission ≥48 hours due to TBI or death due to TBI. Machine-learning models will be applied to create scores predicting the primary and secondary outcomes. An estimated 20 000 patients will be included. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority (Dnr: 2020-05728). The research findings will be disseminated through peer-reviewed scientific publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT04995068.

Unsuccessful external validation of the MAC-score for predicting increased MIB-1 index in patients with spinal meningiomas.

Objective: Recently, the MAC-spinal meningioma score (MAC-score) was proposed to preoperatively identify spinal meningioma patients with high MIB-1 indices. Risk factors were age ≥ 65 years, a modified McCormick score (mMCs) ≥ 2, and absence of tumor calcification. The aim of this study was to externally validate the MAC-score in an independent cohort. Methods: Using the same inclusion and exclusion criteria as in the original study, we performed a retrospective, single-center, population-based, cohort study that included patients who had undergone surgical treatment for spinal meningiomas between 2005 - 2017. Data was collected from patient charts and radiographic images. Validation was performed by applying the MAC-score to our cohort and evaluating the area under the receiver operating characteristic curve (AUC). Results: In total, 108 patients were included. Baseline and outcome data were comparable to the original development study. An increased MIB-1 index (≥5%) was observed in 56 (52%) patients. AUC of the MAC-score in our validation cohort was 0.61 (95% CI: 0.51 - 0.71), which corresponds to a poor discriminative ability. Conclusion: The MAC-score showed poor discriminative ability for MIB-1 index prediction in patients with spinal meningiomas. Moreover, the MAC-score rests on a weak theoretical and statistical foundation. Consequently, we argue against its clinical implementation.

Ventriculoperitoneal Shunt Treatment Increases 7 Alpha Hy-Droxy-3-Oxo-4-Cholestenoic Acid and 24-Hydroxycholesterol Concentrations in Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is the most common form of hydrocephalus in the adult population, and is often treated with cerebrospinal fluid (CSF) drainage using a ventriculoperitoneal (VP) shunt. Symptoms of iNPH include gait impairment, cognitive decline, and urinary incontinence. The pathophysiology behind the symptoms of iNPH is still unknown, and no reliable biomarkers have been established to date. The aim of this study was to investigate the possible use of the oxysterols as biomarkers in this disease. CSF levels of the oxysterols 24S- and 27-hydroxycholesterol, as well as the major metabolite of 27-hydroxycholesterol, 7 alpha hydroxy-3-oxo-4-cholestenoic acid (7HOCA), were measured in iNPH-patients before and after treatment with a VP-shunt. Corresponding measurements were also performed in healthy controls. VP-shunt treatment significantly increased the levels of 7HOCA and 24S-hydroxycholesterol in CSF (p = 0.014 and p = 0.037, respectively). The results are discussed in relation to the beneficial effects of VP-shunt treatment. Furthermore, the possibility that CSF drainage may reduce an inhibitory effect of transiently increased pressure on the metabolic capacity of neuronal cells in the brain is discussed. This capacity includes the elimination of cholesterol by the 24S-hydroxylase mechanisms.

Incidence and predictors of brain infarction in neonatal patients on extracorporeal membrane oxygenation: an observational cohort study.

To determine the incidence and identify predictors of brain infarctions (BI) in neonatal patients treated with extracorporeal membrane oxygenation (ECMO). We performed a retrospective cohort study at ECMO Centre Karolinska, Stockholm, Sweden. Logistic regression models were used to identify BI predictors. Neonates (age 0-28 days) treated with veno-arterial (VA) or veno-venous (VV) ECMO between 2010 and 2018. The primary outcome was a computed tomography (CT) verified BI diagnosed during ECMO treatment. In total, 223 patients were included, 102 patients (46%) underwent at least one brain CT and 27 patients (12%) were diagnosed with a BI. BI diagnosis was associated with increased 30-day mortality (48% vs. 18%). High pre-ECMO Pediatric Index of Mortality score, sepsis as the indication for ECMO treatment, VA ECMO, conversion between ECMO modes, use of continuous renal replacement therapy, and extracranial thrombosis were identified as independent predictors of BI development. The incidence of BI in neonatal ECMO patients may be higher than previously understood. Risk factor identification may help initiate steps to lower the risk or facilitate earlier diagnosis of BI in neonates undergoing ECMO treatment.

Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas.

Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1-2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and progressive diseases.