The neurovascular unit (NVU), composed of endothelial cells, pericytes, juxtaposed astrocytes and microglia together with neurons, is essential for proper central nervous system functioning. The NVU ...critically regulates blood-brain barrier (BBB) function, which is impaired in several neurological diseases and is therefore a key therapeutic target. To understand the extent and cellular source of BBB dysfunction, simultaneous isolation and analysis of NVU cells is needed. Here, we describe a protocol for the EPAM-ia method, which is based on flow cytometry for simultaneous isolation and analysis of endothelial cells, pericytes, astrocytes and microglia. This method is based on differential processing of NVU cell types using enzymes, mechanical homogenization and filtration specific for each cell type followed by combining them for immunostaining and fluorescence-activated cell sorting. The gating strategy encompasses cell-type-specific and exclusion markers for contaminating cells to isolate the major NVU cell types. This protocol takes ~6 h for two sets of one or two animals. The isolation part requires experience in animal handling, fresh tissue processing and immunolabeling for flow cytometry. Sorted NVU cells can be used for downstream applications including transcriptomics, proteomics and cell culture. Multiple cell-type analyses using UpSet can then be applied to obtain robust targets from single or multiple NVU cell types in neurological diseases associated with BBB dysfunction. The EPAM-ia method is also amenable to isolation of several other cell types, including cancer cells and immune cells. This protocol is applicable to healthy and pathological tissue from mouse and human sources and to several cell types compared with similar protocols.
: Air-pouch balloon-assisted probes have proven to be both simple and reliable tools for intracranial pressure (ICP) monitoring. However, we experienced reproducible falsely high ICP measurements ...when the ICP probe was inserted into the intracerebral hematoma cavity. Thus, the aim of the experimental and translational study was to analyze the influence of ICP probe placement with regard to measured ICP values.
: Two Spiegelberg 3PN sensors were simultaneously inserted into a closed drain system and were connected to two separate ICP monitors thereby allowing for simultaneous ICP measurements. This closed system was also engineered to allow for pressure to be gradually increased in a controlled fashion. Once the pressure was verified using two identical ICP probes, one of the probes was coated with blood in an effort to replicate placement within an intraparenchymal hematoma. Pressures recorded using the coated probe and control probe were then recorded and compared across a range of 0-60 mmHg. In an effort to further the translational relevance of our results, two ICP probes were inserted in a patient that presented with a large basal ganglia hemorrhage that met criteria for ICP monitoring. One probe was inserted into the hematoma and the other into brain parenchyma; ICP values were recorded from both probes and the results compared.
: The experimental set-up demonstrated a reliable correlation between both control ICP probes. Interestingly, the ICP probe covered with clot displayed a significantly higher average ICP value when compared to the control probe between 0 mmHg and 50 mmHg (
< 0.001); at 60 mmHg, there was no significant difference noted. Critically, this trend in discordance was even more pronounced in the clinical setting with the ICP probe placed within the hematoma cavity having reported significantly higher ICP values as compared to the probe within brain parenchyma.
: Our experimental study and clinical pilot highlight a potential pitfall in ICP measurement that may result secondary to probe placement within hematoma. Such aberrant results may lead to inappropriate interventions in an effort to address falsely elevated ICPs.
Robotic guidance might be an alternative to classic stereotaxy for biopsies of intracranial lesions. Both methods were compared regarding time efficacy, histopathological results and complications.
A ...retrospective analysis enrolling all patients undergoing robotic- or stereotactic biopsies between 01/2015 and 12/2018 was conducted. Trajectory planning was performed on magnetic resonance imaging (MRI). With the Robotic Surgery Assistant (ROSA), patient registration was accomplished using a facial laser scan in the operating room (OR), immediately followed by biopsy. In stereotaxy, patients were transported to the CT for Leksell Frame registration, followed by biopsy in the OR.
The average overall procedure time amounted in robotics to 169 min and in stereotaxy to 179 min (p = 0.005). The difference was greatest for temporal targets, amounting in robotics to 161 min and in stereotaxy to 188 min (p = 0,0007). However, the average time spent purely in the OR amounted in robotics to 140 min and in stereotaxy to 113 min (p < 0.001). In 150 robotic biopsies, diagnostic yield amounted to 98%, in 266 stereotactic biopsies to 91%. Symptomatic postoperative hemorrhages were observed in 3 patients (2%) in robotic biopsy and 7 patients (2,7%) in stereotactic biopsy.
Robotics showed a shorter overall procedure time as there is no need for a transport to the CT whereas the pure OR time was shorter in stereotaxy due to skipping the laser registration process. Diagnostic yield was higher in robotics, most likely due to case selection, complication rates were equal.
IMPORTANCE: According to the current American Heart Association/American Stroke Association guidelines, decompressive surgery is indicated in patients with cerebellar infarcts that demonstrate severe ...cerebellar swelling. However, there is no universal definition of swelling and/or infarct volume(s) available to support a decision for surgery. OBJECTIVE: To evaluate functional outcomes in surgically compared with conservatively managed patients with cerebellar infarcts. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective multicenter cohort study, patients with cerebellar infarcts treated at 5 tertiary referral hospitals or stroke centers within Germany between 2008 and 2021 were included. Data were analyzed from November 2020 to November 2023. EXPOSURES: Surgical treatment (ie, posterior fossa decompression plus standard of care) vs conservative management (ie, medical standard of care). MAIN OUTCOMES AND MEASURES: The primary outcome examined was functional status evaluated by the modified Rankin Scale (mRS) at discharge and 1-year follow-up. Secondary outcomes included the predicted probabilities for favorable outcome (mRS score of 0 to 3) stratified by infarct volumes or Glasgow Coma Scale score at admission and treatment modality. Analyses included propensity score matching, with adjustments for age, sex, Glasgow Coma Scale score at admission, brainstem involvement, and infarct volume. RESULTS: Of 531 included patients with cerebellar infarcts, 301 (57%) were male, and the mean (SD) age was 68 (14.4) years. After propensity score matching, a total of 71 patients received surgical treatment and 71 patients conservative treatment. There was no significant difference in favorable outcomes (ie, mRS score of 0 to 3) at discharge for those treated surgically vs conservatively (47 66% vs 45 65%; odds ratio, 1.1; 95% CI, 0.5-2.2; P > .99) or at follow-up (35 73% vs 33 61%; odds ratio, 1.8; 95% CI, 0.7-4.2; P > .99). In patients with cerebellar infarct volumes of 35 mL or greater, surgical treatment was associated with a significant improvement in favorable outcomes at 1-year follow-up (38 61% vs 3 25%; odds ratio, 4.8; 95% CI, 1.2-19.3; P = .03), while conservative treatment was associated with favorable outcomes at 1-year follow-up in patients with infarct volumes of less than 25 mL (2 34% vs 218 74%; odds ratio, 0.2; 95% CI, 0-1.0; P = .047). CONCLUSIONS AND RELEVANCE: Overall, surgery was not associated with improved outcomes compared with conservative management in patients with cerebellar infarcts. However, when stratifying based on infarct volume, surgical treatment appeared to be beneficial in patients with larger infarct volumes, while conservative management appeared favorable in patients with smaller infarct volumes.
Seizures are among the most common symptoms of meningioma. This retrospective study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified ...STAMPE2 score. In 556 patients who underwent meningioma surgery, we correlated different risk factors with the occurrence of postoperative seizures. A modified STAMPE2 score was applied. Risk factors for preoperative seizures were edema (
= 0.039) and temporal location (
= 0.038). For postoperative seizures preoperative tumor size (
< 0.001), sensomotory deficit (
= 0.004) and sphenoid wing location (
= 0.032) were independent risk factors. In terms of postoperative status epilepticus; sphenoid wing location (
= 0.022), tumor volume (
= 0.045) and preoperative seizures (
< 0.001) were independent risk factors. Postoperative seizures lead to a KPS deterioration and thus an impaired quality of life (
< 0.001). Late seizures occurred in 43% of patients with postoperative seizures. The small sub-cohort of patients (2.7%) with a STAMPE2 score of more than six points had a significantly increased risk for seizures (
< 0.001, total risk 70%). We concluded that besides distinct risk factors, high scores of the modified STAMPE2 score could estimate the risk of postoperative seizures. However, it seems not transferable to our cohort.
Despite the high incidence and multitudes of operative techniques, the risk factors for chronic subdural hematoma (CSDH) recurrence are still under debate and a universal consensus on the ...pathophysiology is lacking. We hypothesized that clinically inapparent, a low-grade infection could be responsible for CSDH recurrence. This investigation is a single-center prospective observational study including patients with recurrent CSDH. In total, 44 patients with CSDH recurrence received an intraoperative swab-based microbiological test. The intraoperative swab revealed an inapparent low-grade hematoma infection in 29% of the recurrent CSDH cases. The majority (69%) of the identified germs belonged to the
staphylococcus
genus. We therefore, propose a novel potential pathophysiology for CSDH recurrence.
Space-occupying cerebellar stroke (SOCS) when coupled with neurological deterioration represents a neurosurgical emergency. Although current evidence supports surgical intervention in such patients ...with SOCS and rapid neurological deterioration, the optimal surgical methods/techniques to be applied remain a matter of debate.
We conducted a retrospective, multicenter study of patients undergoing surgery for SOCS. Patients were stratified according to the type of surgery as (1) suboccipital decompressive craniectomy (SDC) or (2) suboccipital craniotomy with concurrent necrosectomy. The primary end point examined was functional outcome using the modified Rankin Scale (mRS) at discharge and at 3 months (mRS 0-3 defined as favorable and mRS 4-6 as unfavorable outcome). Secondary end points included the analysis of in-house postoperative complications, mortality, and length of hospitalization.
Ninety-two patients were included in the final analysis: 49 underwent necrosectomy and 43 underwent SDC. Those with necrosectomy displayed significantly higher rate of favorable outcome at discharge as compared with those who underwent SDC alone: 65.3% vs 27.9%, respectively ( P < .001, odds ratios 4.9, 95% CI 2.0-11.8). This difference was also observed at 3 months: 65.3% vs 41.7% ( P = .030, odds ratios 2.7, 95% CI 1.1-6.7). No significant differences were observed in mortality and/or postoperative complications, such as hemorrhagic transformation, infection, and/or the development of cerebrospinal fluid leaks/fistulas.
In the setting of SOCS, patients treated with necrosectomy displayed better functional outcomes than those patients who underwent SDC alone. Ultimately, prospective, randomized studies will be needed to confirm this finding.
The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, ...we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.
A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.
The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups.
In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
Several individual predictors for outcomes in patients with cerebellar stroke (CS) have been previously identified. There is, however, no established clinical score for CS. Therefore, the aim of this ...study was to develop simple and accurate grading scales for patients with CS in an effort to better estimate mortality and outcomes.
This multicentric retrospective study included 531 patients with ischemic CS presenting to 5 different academic neurosurgical and neurological departments throughout Germany between 2008 and 2021. Logistic regression analysis was performed to determine independent predictors related to 30-day mortality and unfavorable outcome (modified Rankin Scale score of 4-6). By weighing each parameter via calculation of regression coefficients, an ischemic CS-score and CS-grading scale (CS-GS) were developed and internally validated.
Independent predictors for 30-day mortality were aged ≥70 years (odds ratio, 5.2), Glasgow Coma Scale score 3 to 4 at admission (odds ratio, 2.6), stroke volume ≥25 cm
(odds ratio, 2.7), and involvement of the brain stem (odds ratio, 3.9). When integrating each parameter into the CS-score, age≥70 years and brain stem stroke were assigned 2 points, Glasgow Coma Scale score 3 to 4, and stroke volume≥25 cm
1 point resulting in a score ranging from 0 to 6. CS-score of 0, 1, 2, 3, 4, 5, and 6 points resulted in 30-day mortality of 1%, 6%, 6%, 17%, 21%, 55%, and 67%, respectively. Independent predictors for 30-day unfavorable outcomes consisted of all components of the CS-score with an additional variable focused on comorbidities (CS-GS). Except for Glasgow Coma Scale score 3 to 4 at admission, which was assigned 3 points, all other parameters were assigned 1 point resulting in an overall score ranging from 0 to 7. CS-GS of 0, 1, 2, 3, 4, 5, 6, and 7 points resulted in 30-day unfavorable outcome of 1%, 17%, 33%, 40%, 50%, 80%, 77%, and 100%, respectively. Both 30-day mortality and unfavorable outcomes increased with increasing CS-score and CS-GS (
<0.001).
The CS-score and CS-GS are simple and accurate grading scales for the prediction of 30-day mortality and unfavorable outcome in patients with CS. While the score systems proposed here may not directly impact treatment decisions, it may help discuss mortality and outcome with patients and caregivers.
Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date, only limited data on anticoagulation ...management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label. A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT scan confirmed PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data. Out of 584 GBM patients, 8% suffered from postoperative PE. Out of these, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis, or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6 and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS. In our analysis, DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis, and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.
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