MedNexus
Volume 40 · Issue 06 · 2024
MedNexus
Glioma is the most common primary intracranial malignant tumor in adults, among which glioblastoma (GBM) is highly malignant and the prognosis of patients is extremely poor. At present, the standard treatment plan for GBM is the maximum range of safe resection, complemented by temozolomide concurrent radiotherapy and adjuvant chemotherapy, and the newly emerging tumor electric field therapy, but the overall efficacy is limited. In recent years, immunotherapy has shown great potential in other tumor fields and is expected to improve the clinical prognosis of glioma patients. This paper focuses on the current situation and development trend of immunotherapy for glioma.
To explore the clinical characteristics and prognostic factors of patients with solitary fibrous tumor (SFT) of the central nervous system.
The clinical data of 102 SFT patients who underwent surgical treatment at the Neurosurgery Center of Beijing Tiantan Hospital, Capital Medical University from January 2016 to December 2020 were retrospectively analyzed. The patients′ clinical data, perioperative and postoperative brain MRI examination results, survival status and disease progression during the follow-up period, as well as the extent of tumor surgical resection and pathological examination results were collected. The life table method was used to calculate the progression-free survival rate and overall survival rate at 1, 3, and 5 years. The log-rank test was used to compare the survival distribution of patients with different age, World Health Organization (WHO) tumor grade, surgical resection degree, maximum tumor diameter, and tumor location grouping, and to compare whether there was peritumoral edema before surgery and whether the tumor was unevenly enhanced after contrast administration, whether the tumor involved the venous sinus, whether the tumor invaded extracranially, and the survival distribution of patients with or without postoperative radiotherapy (PORT). Furthermore, a multivariate Cox proportional hazards model was used to conduct influencing factor analysis to determine the influencing factors of progression-free survival and overall survival. The log-rank test was used to compare the impact of different treatment strategies on the survival of SFT patients.
The age of the 102 patients was 45.9±13.4 years old, and the male-to-female ratio was approximately 1.22 ∶1.00. Among the 102 patients, 67 (65.7%) had tumors located on the supratentorial cerebellum, 35 (34.3%) located at the skull base; 67 cases(65.7%) had peritumoral edema, 62 cases (60.8%) had heterogeneous tumor contrast enhancement, 53 cases (52.0%) involved venous sinuses, and 9 cases (8.8%) had extracranial invasion. After pathological examination, 8 cases were WHO grade 1, 49 cases were grade 2, and 45 cases were grade 3. Among the 102 patients, 74 underwent total tumor resection (GTR), 28 underwent subtotal resection (STR), and 57 underwent PORT. The median follow-up time of 102 patients was 48 (35, 66) months; by the last follow-up, 30.4% (31/102) of patients had tumor recurrence; 9.8% (10/102) died due to tumor progression, and 1.0% (1/102) died of postoperative complications; 4.9% (5/102) patients developed distant metastasis. The progression-free survival rates of 102 patients at 1, 3, and 5 years were 80%, 67%, and 67% respectively; the overall survival rates at 1, 3, and 5 years were 97%, 91%, and 89%, respectively. The results of univariate analysis showed that patients with lower WHO grade, GTR, and tumors not involving venous sinuses had a higher progression-free survival rate (all P<0.05); patients aged <60 years and GTR had a higher overall survival rate (all P<0.05). Multivariate Cox proportional hazards model analysis results showed that the tumor WHO grade 3 (HR=4.45, 95%CI: 1.80-10.99, P<0.001), STR (HR=9.82, 95%CI: 3.68-26.16, P<0.001) were all risk factors for short progression-free survival in SFT patients; and STR was also a risk factor for short overall survival in SFT patients (HR=8.73, 95%CI: 1.70-44.90, P=0.010). Survival analysis of patients grouped by different treatment strategies showed that in the overall cohort, compared with the STR group (n=11), the progression-free survival rate of patients in the STR+ PORT group (n=17) was higher (P=0.026). Among patients with tumors of WHO grade 3, compared with the GTR group (n=5), the progression-free survival rate of patients in the GTR+ PORT group (n=23) was higher (P=0.029).
SFT of the central nervous system is more common in the supratentorial cerebellum, and is more common in WHO grades 2 and 3. Extracranial metastasis can occur, and the overall prognosis within 5 years after surgery is good. Patients whose tumors are WHO grade 3 and STR have shorter progression-free survival, and patients with STR have shorter overall survival.
To explore the clinical characteristics of supratentorial asymptomatic meningiomas.
A total of 163 patients with asymptomatic meningiomas diagnosed in the Neurosurgery Center of Beijing Tiantan Hospital, Capital Medical University from January 2019 to August 2023 were retrospectively collected, of which 122 were surgically treated and 41 were outpatients undergoing follow-up. We documented the patient′s gender, age distribution, tumor location, size, histopathological type, World Health Organization (WHO) grade, etc.
Among the 163 patients, there were 51 males and 112 females, with a male-to-female ratio of 1.0 ∶2.2; the age of onset was 53.25±10.75 years old (22-80 years old), and patients aged 50-59 accounted for the highest proportion (68 cases, 41.72%), followed by 60 to 69 years old (36 cases, 22.09%); the age difference between male and female patients was not statistically significant (P=0.127). Tumors located on the convex surface of the brain were most common, accounting for 73.62% (120 cases), followed by the parasagittal sinus, accounting for 16.56% (27 cases). Tumors adjacent to the falx cerebri, within the ventricular system, and supra-tentorium cerebelli were less frequently observed. The M(Q1, Q3) of the tumor volume was 6.08 (1.87, 15.78) cm3. Among the 122 patients who underwent surgical resection, 97 cases (79.51%) were WHO grade 1, 21 cases (17.21%) were grade 2, and 4 cases (3.28%) were grade 3. The predominant histopathological types were transitional (44 cases, 36.07%), fibroblastic (31 cases, 25.41%), and meningothelial (21 cases, 17.21%), with fibroblastic meningiomas presenting the most widespread distribution across different locations, followed by transitional and meningothelial types. Postoperative complications occurred in 21 cases (17.20%), distributed as 10 cases (8.20%) in WHO grade 1, 8 cases (6.56%) in grade 2, and 3 cases (2.46%) in grade 3.
Initial findings indicate that supratentorial asymptomatic meningiomas may exhibit distinct clinical features compared with the general profile of meningiomas.
To explore the influencing factors of hypopituitarism after surgery for non-functioning pituitary neuroendocrine tumors.
A retrospective analysis was conducted on the clinical data of non-functioning pituitary neuroendocrine tumors registered by the Department of Neurosurgery of the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022 in China′s National Brain Tumor Registration Platform. A total of 1 210 patients were included. The patient′s age, gender, clinical symptoms, preoperative and postoperative hormone levels, surgical method, surgical duration and follow-up time were collected. The patient′s tumor volume, preoperative tumor apoplexy, Knosp grade, texture and extent of resection were collected. Univariate and multivariate logistic regression analyses (backward elimination method) were used to determine the influencing factors of postoperative hypopituitarism.
Among 1 210 patients, 617 (51.0%) had hypopituitarism after surgery. The follow-up time [M(Q1, Q3)] of 1 210 patients was 6.5 (3.0-11.2) months. The results of univariate logistic regression analysis showed that preoperative tumor apoplexy, preoperative hypopituitarism, tumor volume and operation duration were all influencing factors of postoperative hypopituitarism (all P<0.05). The results of multivariate logistic regression analysis showed that preoperative tumor apoplexy (OR=1.96, 95%CI: 1.20-3.26, P=0.008) and preoperative hypopituitarism (OR=2.89, 95%CI: 2.09-4.05, P<0.001) and larger tumor size (OR=1.02, 95%CI: 1.00-1.03, P=0.015) were risk factors for postoperative hypopituitarism.
Patients with non-functioning pituitary neuroendocrine tumors who have preoperative hypopituitarism, large tumor size, and tumor apoplexy have a higher risk of postoperative hypopituitarism.
To investigate the clinical efficacy and adverse event (AE) of tumor-treating fields (TTFields) therapy in the treatment of glioblastoma (GBM).
A retrospective analysis was conducted on the clinical data of 12 patients with GBM treated at the Department of Neurosurgery of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2019 to December 2023. Among the 8 newly-diagnosed patients, treatment involved radiotherapy combined with concomitant temozolomide (TMZ) at 2 to 6 weeks after tumor resection, followed by adjuvant TMZ and TTFields. For the 4 recurrent GBM patients, TTFields therapy was applied starting 2 to 6 weeks after redo surgery either as the sole treatment (1 patient) or alongside bevacizumab (3 patients). Regular follow-up was conducted every 2 to 4 months, measuring overall survival (OS), progression-free survival (PFS), and AEs. The severity of AEs was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE).
TTFields were administered for a median daily duration of 23.0 hours (8.0-23.5 hours), with a median total usage duration of 6.5 months (1-47 months). AEs were reported in 9 patients, including 6 cases of dermatitis and 3 cases of heat sensation. In terms of severity, 5 were categorized as class-1 AE, 3 as class-2 AE, and 1 as class-3 AE. The median follow-up duration was 14 months (range: 7-51 months), with 8 patients followed for more than 12 months. At the last follow-up, 10 patients were alive, and 2 deceased at 15 and 33 months postoperatively. Eight patients experienced disease progression with a PFS ranging from 2 to 26 months. Four patients had a PFS ≥12 months.
In both newly-diagnosed and recurrent GBMs TTFields therapy causes mild to moderate localized AEs while it could potentially contribute to enhanced patient survival.
To summarize the clinical characteristics and prognosis of intracranial germ cell tumors (IGCTs) in children.
The clinical data of 38 pediatric patients with IGCTs admitted to the Neurosurgery Department of Beijing Children′s Hospital, Capital Medical University from May 2015 to April 2022 were retrospectively analyzed. Among the 38 children, 8 had germinoma and 30 had non-germinomatous germ cell tumors (NGGCTs). Among them, 34 cases were confirmed by craniotomy, 2 cases were confirmed by lesion biopsy, 1 case was diagnosed as germinoma by diagnostic chemotherapy, and 1 case was diagnosed as NGGCT by combining tumor markers and imaging examinations. The Kaplan-Meier method and log-rank analysis were used to explore the influencing factors on the outcomes of children with IGCTs.
Among the 38 children, the male to female ratio was 4.4 ∶1.0; the age [M(range)] was 9.3 (0.9-14.0) years old, and the ages were concentrated in 2 to 4 years old and 8 to 14 years old. The most common locations of tumors were the pineal region (65.8%, 25/38) and sellar region (10.5%, 4/38). The most common manifestation of IGCTs in the pineal region was intracranial hypertension (80.0%, 20/25), and the most common manifestation of IGCTs in the sellar region was polydipsia and polyuria (3/4). The median follow-up time (range) of 38 children was 40.3 months (0.6-86.7 months). As of the last follow-up, 31 cases were alive, 5 cases had died, and 2 cases were lost to follow-up. The overall 5-year survival rate was 90.2% (excluding death from non-tumor factors), the 5-year progression-free survival rate and overall survival rate of children with germinoma were 83.3%, and the 5-year progression-free survival rate and overall survival rate of children with NGGCTs were 83.8% and 91.9% respectively. Compared with children aged >6 years, NGGCTs were more common in children aged ≤6 years (12/12 vs. 18/26, P=0.039).
The age of onset of IGCTs in children shows a bimodal distribution, and lesions are more common in the pineal and sellar regions. The clinical manifestations of children are related to the site of lesion, and the survival prognosis is good.
To explore the clinical characteristics and risk factors of cerebral hyperperfusion syndrome (CHS) after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery in adults with moyamoya disease.
A retrospective analysis was performed on the clinical data of 213 adult patients with moyamoya disease treated by STA-MCA bypass combined with temporalis muscle taping or multi-point drilling in the skull at the Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University from August 2019 to September 2022. According to whether patients developed CHS 14 days after surgery, they were divided into CHS group and non-CHS group. The clinical outcome of the patients was evaluated based on the modified Rankin Scale score (mRS) 3 months after surgery. Univariate analysis and multivariate logistic regression model analysis methods were used to explore the risk factors for CHS after STA-MCA bypass surgery in patients with moyamoya disease.
Among 213 patients, 35 cases (16.4%) developed CHS after surgery, including 5 cases (14.3%) of cerebral hemorrhage, 6 cases (17.1%) of focal epileptic seizures, and 24 cases (68.6%) of transient neurological dysfunction. Three months after surgery, 202 cases had mRS scores of 0 to 2 points, and 11 cases had mRS scores of 3 to 6 points. Three months after surgery, the mRS of the CHS group was 1 (0, 1), of which 94.3% (33/35) were 0 to 2; the mRS of the non-CHS group was 1 (0, 1), of which 94.9% (169/178) scored 0 to 2 points, and the difference between the two groups was not statistically significant (χ2=0.59, P=0.441). The results of univariate analysis showed that there were statistically significant differences between the CHS group and the non-CHS group in terms of history of hypertension, cerebral hemorrhage as the first symptom, advanced Suzuki stage on the surgical side (stages Ⅳ to Ⅵ), or preoperative serum hematocrit (all P<0.05). Multivariate logistic regression analysis showed that patient′s history of hypertension (OR=3.69, 95%CI: 1.52-9.00, P=0.004), cerebral hemorrhage as the first symptom (OR=3.21, 95%CI: 1.08-9.54; P=0.036) and higher preoperative hematocrit level (OR=1.17, 95%CI: 1.06-1.29, P=0.002) were all risk factors for CHS in patients with moyamoya disease after STA-MCA bypass surgery.
CHS in adult patients with moyamoya disease after STA-MCA bypass surgery mostly manifests as transient neurological dysfunction, and the prognosis of the patients 3 months after surgery is not significantly different from that of patients without CHS. Adult patients with moyamoya disease who have a history of hypertension, whose first symptom is cerebral hemorrhage, and who have a high preoperative hematocrit level are more likely to develop CHS after STA-MCA bypass surgery.
To explore the role of intracranial pressure (ICP) monitoring in the treatment of traumatic brain injury (TBI) with decompressive craniectomy (DC).
The clinical data of 218 patients with moderate and severe TBI treated with DC in the Department of Neurosurgery, Henan Provincial People′s Hospital from January 2018 to December 2022 were retrospectively analyzed. Based on the Glasgow Coma Score (GCS) within 24 h after admission, the patients with 9 to 12 points were classified as moderate TBI (mTBI, 117 cases), and those with 3 to 8 points were classified as severe TBI (sTBI, 101 cases). According to whether ICP monitoring was used during surgery, the patients were divided into mTBI monitoring group (57 cases), mTBI non-monitoring group (60 cases), sTBI monitoring group (50 cases), and sTBI non-monitoring group (51 cases). We then analyzed the inter-group differences in the surgical duration, intensive care unit (ICU) stay length and total hospital stay length, mannitol dosage, mechanical ventilation duration, discharge GCS, extended Glasgow Outcome Scale (GOS-E) and surgery-related complications. GOS-E was followed up 6 months after surgery, and the outcomes of GOS-E 4 to 8 points were considered as good, 2 to 3 points as poor, and 1 point as death.
Compared with the mTBI unmonitored group, patients in the mTBI monitored group had higher GCS and GOS-E at discharge, shorter ICU stay, and less mannitol usage, and the differences were statistically significant (all P<0.05). Compared with sTBI unmonitored, the GCS and GOS-E of patients in the sTBI monitoring group were both higher at discharge, and the differences were statistically significant (both P<0.05), while the differences in length of stay in the ICU or mannitol usage was not statistically significant (both P> 0.05). Compared with the non-monitored groups in mTBI and sTBI, the monitored groups had no statistically significant differences in operation duration, mechanical ventilation duration, or postoperative related complications (all P>0.05). After 6 months of follow-up, the proportions of favorable outcomes in the mTBI unmonitored group and the mTBI monitored group were 50.9% (29/57) and 43.3% (26/60) respectively, and those of poor outcomes were 26.3% (15/57) and 23.3% (14/60) respectively, and the mortality rates were 22.8% (13/57) and 33.3% (20/60) respectively. The proportions of favorable outcomes in the sTBI monitored group and the sTBI unmonitored group were 50.0% (25/50) and 41.2% (21/51) respectively, those of poor outcomes were 4.0% (2/50) and 7.8% (4/51) respectively, the mortality rates were 46.0% (23/50) and 51.0% (26/51) respectively, and the differences were all statistically significant (all P<0.05).
ICP monitoring in DC would not increase the duration of surgery or the incidence of surgery-related complications; it will help improve the prognosis of patients.
To observe the efficacy of precisely controlled hematoma drainage mode in the treatment of hypertensive cerebral hemorrhage during and after catheter drainage and its impact on cerebral perfusion.
Patients with basal ganglia-thalamic area hemorrhage admitted to the Neurosurgery Department of Hunan Brain Hospital of Hunan Province from January 2021 to January 2023 were prospectively included, and they were randomly divided into a precision-controlled hematoma drainage group (experimental group) and a conventional hematoma drainage group (control group) using the random number table method. The preoperative clinical data, operation duration, residual hematoma volume 24 hours after operation, and hematoma re-expansion within 72 hours after operation were compared between the two groups of patients. Magnetic resonance perfusion-weighted imaging (PWI) examination was performed on the 5th day after operation in the two groups to analyzed their differences in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) in the hematoma area and penumbra zone of the patients. At 6 months after surgery, the daily life of the two groups of patients was evaluated based on the ADL (Activities of Daily Living) scores.
There were no statistically significant differences in age, gender, preoperative Glasgow Coma Score (GCS), hematoma side, intraparenchymal hematoma volume, or Graeb score between the two groups (all P>0.05). The operation duration of the experimental group and the control group were 108.8±9.1 min and 92.0±5.6 min respectively, the residual hematoma volume at 24 hours after operation was 18.1±2.2 ml and 25.1±2.8 ml, the ADL scores at 6 months after operation were 72.5±22.2 and 61.5±23.9 respectively, and the differences in the above indicators were statistically significant (all P<0.05). The number of patients with hematoma enlargement at 72 hours after surgery was 0 and 5 in the experimental and control groups respectively (P=0.065). The PWI results on the 5th day after surgery showed that compared with the control group, the CBF and CBV values in the hematoma area and penumbra area of the experimental group were increased, the MTT and TTP values were shortened, and the differences were statistically significant (all P<0.01).
Application of precise control of the hematoma drainage mode in the whole process of catheterization and drainage surgery for hypertensive cerebral hemorrhage may prolong the operation time, while it may facilitate the drainage of the hematoma, enhance the blood perfusion of the hematoma and its surrounding areas, and improve the patient′s prognosis.
To explore the efficacy of single versus double burr hole drainage in treating the chronic subdural hematoma (CSDH).
A retrospective analysis was performed on the clinical data of 118 patients with unilateral CSDH treated with burr hole drainage in the Department of Neurosurgery of Second People′s Hospital of Shenzhen from February 2017 to October 2020. The patients were divided into single burr hole drainage group (n=83, referred to as the single-hole group) and the double burr hole drainage group (n=35, referred to as the double-hole group) according to the surgical method. There were no statistically significant differences in preoperative baseline data such as gender distribution, age, trauma history, etc. between the two groups of patients (all P>0.05). The two groups of patients were compared in terms of operation duration, intraoperative blood loss, postoperative complications, improvement in symptoms and muscle strength, Glasgow Coma Score at discharge, length of hospitalization, hospitalization costs, and recurrence rate of CSDH 3 months after surgery.
The operations of both groups of patients were successfully completed. Between the two groups, there was no significant difference in the symptom improvement rate of patients [96.1% (73/76) vs. 97.0% (32/33)], muscle strength improvement rate (27/41 vs. 12/18), Glasgow Coma Score at discharge (14.84±0.75 points vs. 14.97±0.17 points) and CSDH recurrence rate 3 months after surgery[3.6% (3/83) vs. 0] (all P>0.05). Compared with the single-hole group, the operation time of patients (87.7±26.9 min vs. 48.1±14.9 min], intraoperative blood loss [M(Q1, Q3): 30 (20, 50) ml vs. 20 (10, 20) ml], postoperative intracranial gas volume [15 (12, 30) ml vs. 5 (3, 5) ml], length of hospitalization [10 (7, 15) d vs. 7 (4, 12) d] and hospitalization expenses [33 791 (29 476, 37 923) yuan vs. 22 026 (15 682, 30 800) yuan] in the double-hole group all increased, and the differences were statistically significant (all P < 0.05).
The symptom improvement rate and recurrence rate of patients with unilateral CSDH treated with single-hole and double-hole drilling drainage seem similar. Patients treated with single-hole drilling and drainage have less intraoperative bleeding, less postoperative intracranial pneumatosis, shorter hospital stay and less expenses.
To investigate the surgical method and efficacy of decompression of the internal jugular vein (IJV) by partially removing the transverse process of the atlas in the treatment of cranial tinnitus caused by compression and stenosis of the IJV.
A retrospective analysis was conducted on the clinical data of 32 patients with stenosis of the upper segment of the IJV admitted to the Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University from September 2020 to September 2022. Before operation, the stenosis of IJV caused by the compression of transverse process of atlas was confirmed by using color Doppler ultrasound imaging and CT venography. Based on the characteristics of clinical symptoms, 32 patients were divided into patients in the progressive stage (including early and middle stage of cranial tinnitus) (23 cases) and those in the continuous stage (9 cases). A total of 27 patients underwent unilateral partial grinding decompression of transverse process of atlas, and the other 5 patients underwent bilateral partial grinding decompression of transverse process of atlas. Surgery-related complications were documented. Postoperative clinical and imaging follow-up was performed, and the evaluation indicators included the symptom improvement, restoration of IJV morphology and improvement of blood flow at 1 week and 3 months post operation.
Among the 32 patients, surgical complications included 1 case of intraoperative IJV injury, 1 case of weakness of shrug and neck rotation, 1 case of neck and shoulder discomfort, and 1 case of incision infection. Three months after surgery, the total improvement rate of postoperative tinnitus and accompanying symptoms, tinnitus only, IJV morphology, blood flow was 62.5%(20/32), 28.1%(9/32), 84.3%(27/32) and 75.0%(24/32), respectively. Improvement of the IJV blood flow after surgery was more significant in patients with tinnitus in the progressive stage (early and middle stage) than in those with sustained tinnitus (Ζ=2.06, P=0.039).
Decompression of IJV by partial grinding of transverse process of atlas can effectively relieve the compression stenosis of upper part of IJV, improve the IJV morphology and blood flow, alleviate the early symptoms and accompanying symptoms of patients with cranial tinnitus. The surgical complications are relatively mild.
To explore the color Doppler ultrasound manifestations of internal jugular vein stenosis caused by atlas compression in patients with cranial tinnitus and/or tinnitus.
A retrospective analysis was performed on the clinical data of 25 patients with tinnitus and internal jugular vein stenosis caused by compression of the transverse process of the atlas who underwent internal jugular vein color Doppler ultrasound in the Ultrasonography Department of Beijing Shijitan Hospital, Capital Medical University from September 2020 to March 2023. All 25 patients were confirmed to have unilateral compression of the internal jugular vein by the transverse process of the atlas through head and neck CT venography (CTV) and surgery. The diameter, cross section area, the maximum velocity, the maximum pressure gradient and mean flow volume of three segments of the bilateral internal jugular vein were compared and analyzed.
Compared with the healthy side, the diameter and cross section area of J1, J2, J3 segment of the internal jugular vein on the affected side were smaller, and the differences were statistically significant (all P<0.05). There was no significant difference in the maximum velocity or maximum pressure gradient of J1 segment between the affected and healthy sides (both P>0.05). Compared with the healthy side, the maximum velocity and maximum pressure gradient of J2 and J3 segments of the internal jugular vein on the affected side were smaller, and mean flow volume of each segment was smaller, and the differences were statistically significant (all P<0.05).
The internal jugular vein stenosis caused by atlas compression show that the diameter, cross section area and mean flow volume of the whole segments of the affected internal jugular vein are decreased on color Doppler ultrasound. The maximum velocity and the maximum pressure gradient of J2 and J3 segments are decreased. Color Doppler ultrasound can indirectly reflect the patency of the internal jugular vein reflux.
To explore the risk factors for postoperative hematoma enlargement in patients with craniocerebral trauma in plateau areas and to analyze their outcomes.
A retrospective analysis was performed on the clinical data of 353 patients of craniocerebral trauma in plateau areas who were admitted to the Department of Neurosurgery of Southern Central Hospital of Yunnan Province (331 cases) and the Department of Neurosurgery of the PLA 956th Hospital (22 cases) and underwent surgical treatment from May 2019 to January 2023. According to the changes in hematoma volume shown in the CT examination results within 3 days after surgery, the patients were divided into a hematoma enlargement group and a hematoma non-enlargement group. The clinical data of the patients were collected, including whether there were multiple intracranial hematomas, Sylvian hemorrhage, skull fractures, midline shifts, serum hemoglobin levels, admission blood pressure, admission Glasgow Coma Scale (GCS), serum platelet count, combined underlying diseases, and blood glucose level and other conditions. Univariate analysis and multivariate logistic regression model were used to explore the factors that may affect the expansion of postoperative hematoma in patients with craniocerebral trauma. The modified Glasgow Outcome Score (GOS) was used to evaluate the patient′s outcome at discharge, and the rate of good recovery (GOS ≥ 4 points) between the two groups was compared. Kaplan-Meier survival curves were drawn, and the outcome at discharge between the two groups was compared using the log-rank test.
Among the 353 patients, 34 (9.63%) were in the hematoma enlargement group and 319 (90.37%) were in the hematoma non-enlargement group. Compared with the hematoma non-enlargement group, the hematoma enlargement group had a higher proportion of patients with Sylvian hemorrhage and multiple intracranial hematomas, lower GCS on admission, greater midline shift distance, and higher systolic blood pressure (all P<0.05). However, there were no statistically significant differences in gender, age, nationality, whether there were underlying diseases, skull fracture, epidural hematoma, serum platelet count, blood glucose level, hemoglobin, or diastolic blood pressure (all P>0.05). The results of multivariate logistic regression model analysis showed that there was significant midline shift (OR=0.34, 95%CI: 0.17-0.68, P=0.002) and the presence of Sylvian hemorrhage (OR=2.16, 95%CI: 1.06-4.41, P= 0.035), multiple intracranial hematomas (OR=4.72, 95%CI: 2.21-10.05, P<0.001), lower admission GCS (OR=1.20, 95%CI: 1.09-1.33, P<0.001) and high systolic blood pressure at admission (OR=0.99, 95%CI: 0.98-1.00, P=0.030) were risk factors for postoperative hematoma enlargement in patients with craniocerebral trauma in plateau areas. The rate of good recovery in the hematoma enlargement group was significantly lower than that in the hematoma non-enlargement group [32.35% (11/34) vs. 71.16% (227/319), χ2=21.07, P<0.001]. The length of hospitalization [M (Q1, Q3)] was 17 (10, 24) days. Log-rank analysis results showed that the difference in survival rates between the two groups was not statistically significant (P>0.05).
Patients with craniocerebral trauma in plateau areas who have Sylvian hemorrhage or multiple intracranial hematomas, significant midline shift, low admission GCS, and high admission systolic blood pressure are more likely to have hematoma enlargement after surgery. The short-term prognosis of patients with hematoma enlargement is poor.
To establish a mouse model of cognitive impairment following repetitive mild traumatic brain injury (rmTBI) and to investigate its intracranial early pathological changes.
Forty-five C57BL/6 mice were randomly divided into a healthy control group (n=15, referred to as the control group) and an rmTBI modeling group (n=30, referred to as the rmTBI group). The rmTBI group underwent repetitive closed head impacts using a weight-drop device once a day for seven consecutive days. At 3 and 30 days post injury, head MRS scans were performed (n=6). At 30 days post injury, motor coordination and cognitive function of the two groups of mice were evaluated using the rotarod and Morris water maze experiments. Transmission electron microscopy was used to analyze the axonal outer diameter and myelin sheath thickness in the medial prefrontal cortex and hippocampal CA2 region of mice in the rmTBI group at 3 days post injury (n=3), the rmTBI group at 30 days post injury (n=3) and the control group (n=3), with the calculation of the G-ratio [axonal outer diameter / (axonal outer diameter-2 × myelin sheath thickness)]. Spearman′s correlation analysis was conducted for axonal outer diameter and myelin sheath thickness.
MRS (magnetic resonance spectroscopy) results showed that there were no statistically significant differences in cortical NAA/Cr values or hippocampal NAA/Cr values between the control group and the rmTBI group at 3 and 30 days post-injury (all P>0.05). The results of the rotarod and Morris water maze experiments indicated that the motor coordination and cognitive function of mice in the rmTBI group were impaired compared to the control group (all P<0.05). Electron microscopic examination revealed that in the medial prefrontal cortex, there were no statistically significant differences in the neuronal axonal outer diameter between the rmTBI group at 3 days post-injury, the rmTBI group at 30 days post-injury, and the control group (H=2.11, P=0.347). However, there was a significant difference in myelin sheath thickness among the three groups (H=-2.52, P=0.035), with the 30 days post-injury rmTBI group exhibiting smaller myelin sheath thickness compared to the control group [median(Q1, Q3): 0.11 (0.09, 0.13) μm and 0.12 (0.11, 0.14)μm, respectively]. In the hippocampal CA2 region, both the 3 days post-injury and 30 days post-injury rmTBI groups exhibited vacuolar changes in the myelin sheath layers, along with axonal wrapping and myelin sheath detachment. There were statistically significant differences in axonal outer diameter and myelin sheath thickness among the three groups (all P<0.05), with the 30 days post-injury rmTBI group showing the smallest axonal outer diameter compared to the 3 days post-injury rmTBI group [0.67 (0.59, 0.84)μm vs. 0.82 (0.72, 0.99)μm], and the myelin sheath thickness of the 3 days post-injury rmTBI group [0.12 (0.11, 0.14)μm] was greater than that of the control group [0.11 (0.09, 0.12)μm] and the 30 days post-injury rmTBI group [0.08 (0.06, 0.11)μm]. The G-ratio in the hippocampal CA2 region was significantly different between the control group and both the 3 days post-injury and 30 days post-injury rmTBI groups (Z=4.25, P<0.001), with the highest value observed in the 30 days post-injury rmTBI group; whereas, there was no statistically significant difference in the medial prefrontal cortex region among the three groups (Z=1.55, P=0.267). The correlation analysis results indicated a positive correlation between axonal outer diameter and myelin sheath thickness in the medial prefrontal cortex and hippocampal CA2 region of mice in the control group, and the 3 days and 30 days post-injury rmTBI groups (all P<0.05), with the strongest correlation observed in the medial prefrontal cortex region of the control group (R=0.66) and the weakest correlation seen in the hippocampal CA2 region of the 3 days post-injury rmTBI group (R=0.33).
At 30 days following rmTBI, mice exhibit significantly decreased motor coordination and cognitive function. The pathological findings in the animal model suggest mild damage to the myelin sheath in the medial prefrontal cortex, with relatively intact axonal structures, while the hippocampal CA2 region exhibits unstable axon-myelin sheath structures, demyelination, and myelin regeneration, indicating a causal relationship with the aforementioned functional impairments.
To investigate the expression of phosphoinositide 3 kinase regulatory subunit 3 (PIK3R3) in growth hormone pituitary neuroendocrine tumors (GH-PitNETs) and its relationship with PitNET cell proliferation, migration and invasion.
The expression of PIK3R3 in GH-PitNETs was analyzed using the PitNETs dataset in Gene Expression Omnibus (GEO). Using cell lines derived from different PitNETs, the expression of PIK3R3 in GH3, MMQ and AtT-20 cells was detected by Western blot. Lentiviral infection was used to knockdown the PIK3R3 gene in the GH3 cells, and the cells were divided into PIK3R3 knocked down 2 group (Sh-PIK3R3-2), PIK3R3 knocked down 3 group (Sh-PIK3R3-2) and untransfected control group (Sh-NC). Cell proliferation was detected by CCK-8, EdU and colony formation assay. Apoptosis was detected by flow cytometry. Cell migration and invasion were detected by Transwell assay. The expression of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), Vimentin, matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), AKT and phosphory-lated AKT (P-AKT) were detected by Western blot.
GEO database analysis showed that PIK3R3 expression was upregulated in GH-PitNETs compared to normal pituitary or paraneoplastic tissues (all P<0.05), whereas there was no statistically significant difference in prolactin-type PitNETs, adrenocorticotropic hormone-type PitNETs, and gonadotropin PitNETs (all P > 0.05). Western blot showed that PIK3R3 was highly expressed in GH3 cells compared to MMQ and AtT-20 cells (both P < 0.05). CCK-8 assay showed that the absorbance of the cells in the Sh-PIK3R3-2 and Sh-PIK3R3-3 groups were 0.19±0.02, 0.46±0.03, 1.25±0.06 and 0.17±0.02, 0.37±0.02, 1.03±0.05 at 24 h, 48 h and 72 h, respectively, which were all lower than the control group′s 0.24±0.02, 0.64±0.04, 1.67±0.09 (all P <0.05). EdU assay showed that the rates of EdU-positive cells in the Sh-PIK3R3-2 and Sh-PIK3R3-3 groups were (16.87±1.63)% and (13.45±1.33)%, respectively, which were all lower than the control group′s (34.51±2.76)% (all P < 0.05). Colony formation assay showed that the number of cell colonies in the Sh-PIK3R3-2 and Sh-PIK3R3-3 groups were 84±10 and 75±8 respectively, which were lower than that in the control group (173±19) (all P < 0.05). Flow cytometry assay showed that the apoptosis rates of the Sh-PIK3R3-2 and Sh-PIK3R3-3 groups were (25.62±2.14)% and (27.40±2.51)% respectively, which were all higher than the control group’s (14.12±1.48)% (all P < 0.05). Transwell migration assay showed that the numbers of migrating cells in the Sh-PIK3R3-2 and Sh-PIK3R3-3 groups were 182±15 and 166±13 respectively, both lower than the control group′s (428±27) (all P < 0.05). Transwell invasion assay showed that the numbers of invading cells in the Sh-PIK3R3-2 and Sh-PIK3R3-3 groups were 31±5 and 22±3 respectively, both lower than the control group′s (64±9) (all P < 0.05). Western blot assay showed that compared with the control group, both PIK3R3 knockdown groups showed decreased expression of N-cadherin, Vimentin, MMP2, MMP9, and P-AKT (all P < 0.05), increased expression of E-cadherin (all P < 0.05), and no significant change in AKT expression (all P > 0.05).
PIK3R3 is highly expressed in GH-PitNETs and promotes cell proliferation, migration, and invasion by activating AKT signaling transduction.
To investigate the cerebroprotective effect of verbascoside (VB) in mice with intracerebral hemorrhage (ICH) and whether it is related to the inhibition of Toll-like receptor 4 (TLR4)-mediated acute inflammatory response.
Eight-week-old C57BL/6 male mice were used for the study, including 40 wild-type and 20 TLR4 knockout (TLR4-/-) mice. The wild-type mice were divided into sham group, ICH group, and post-ICH VB treatment group (ICH+ VB 15 mg/kg or 30 mg/kg) according to the complete randomization method, and the TLR4-/- group mice were divided into TLR4-/-+ ICH group and TLR4-/-+ ICH+ VB (30 mg/kg) group, with 10 mice in each group. The ICH model was constructed using the method of type Ⅶ collagenase injection in the right striatum. After the model was successfully established (modified Garcia score ≤10), the mice were injected intraperitoneally with VB (15, 30 mg/kg) or an equal volume of saline once a day for 3 consecutive days. The modified Garcia score was used to evaluate the damage of brain function, and the area of cerebral hematomas was calculated to assess the hemorrhage volume after slicing, the water content of brain tissues was calculated by the wet/dry method, and the rate of neuronal apoptosis was detected by TUNEL staining. Immunofluorescence staining (IF) was used to detect the relative expression of Iba-1 in brain tissues. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) assay and Western blot (WB) assay were used to detect the expression of TLR4 and its downstream inflammatory mediators, including nuclear factor-κB, tumor necrosis factor alpha (TNF-α), interleukin (IL) 1β and IL-6. Differences in the above indexes between groups of wild-type mice and between groups of TLR4-/- were compared. Cortical tissues of TLR4-/- mice within 2 hours of birth were removed to culture primary neurons, and the neurons were co-cultured with mouse microglia cell lines (BV2 cells) using Transwell chambers, and were treated with red blood cell (RBC) lysates or RBC lysates + VB (50 μmol/L) respectively for 24 h. Then, the expression of NeuN protein in neurons was observed using IF.
Compared with the ICH group, the modified Garcia scores of mice in the VB-treated groups (particularly in the ICH+ VB 30 mg/kg group) were significantly higher (P<0.05). Brain hemorrhage volume in the sham group, ICH group, ICH+ VB 15 mg/kg group, and ICH+ VB 30 mg/kg group were 0 mm3, 7.33±1.99 mm3, 3.19±0.47 mm3, 1.66±0.26 mm3, the water content of brain tissue was 79.00±0.50%, 85.00±0.75%, 81.50±0.50%, 80.25±0.25%, the apoptosis rate of neurons was 4.8±2.0%, 38.7±6.8%, 21.5±6.9%, 9.8±4.2%, and the differences were statistically significant (P<0.05). IF results showed that the relative expression of Iba-1 in brain tissues of the ICH group was significantly higher than that of the VB-treated group (P<0.05). The qRT-PCR and WB results showed that, compared with those in the the ICH group, the mRNA, NF-κB, TNF-α, IL-1β, and IL-6 mRNA and protein expression levels in the VB-treated group were reduced (P<0.05). The differences in Garcia score, brain tissue water content, and neuronal apoptosis rate were not significantly different between TLR4-/-+ ICH+ VB group and TLR4-/-+ ICH group (all P>0.05). Meanwhile, in the in vitro experiments, there was no statistically significant difference in the survival of neurons co-cultured with BV2 cells after treatment with RBC lysate or RBC lysate + VB (50 μmol/L) (P=0.872).
VB can improve the neural function deficit in mice after ICH, reduce the volume of hemorrhage, degree of brain edema and apoptosis of neurons, which might be related to the mechanism of inhibiting TLR4 signaling pathway, reducing the activation of microglia and release of pro-inflammatory cytokines.
Patients with subdural effusion combined with meningeal metastatic cancer are relatively rare, with difficult early diagnosis and poor prognosis, and clinicians lack experience in diagnosis and treatment. In March 2022, a patient with meningeal metastatic cancer with subdural effusion onset and no previous history of malignant tumor was admitted to the Department of Neurosurgery, Gulou Hospital affiliated to Nanjing University School of Medicine. Now, the relevant diagnosis and treatment experience is summarized and analyzed, in order to provide ideas for the timely diagnosis of this disease.
Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin's lymphoma. Because the disease grows diffusely and infiltratively, its location is deep, and it often spreads widely in the early stage. In the past, the incidence of complications after lesion resection is high, and it can't prolong the survival of patients. Therefore, at present, stereotactic biopsy is only used clinically to obtain pathological diagnosis. Its clinical treatment is a comprehensive chemotherapy regimen based on high-dose methotrexate. However, in recent years, with the advancement of neurosurgical technology and the improvement of intraoperative neuroelectrophysiological monitoring, neuronavigation and other equipment, the safety and effectiveness of surgery have been improved, and surgical resection of lesions combined with chemotherapy may benefit PCNSL patients. Therefore, this article mainly reviews the research progress of neurosurgery combined with chemotherapy for PCNSL, in order to provide reference for the clinical treatment of PCNSL.
At present, there is a lack of systematic understanding of extracranial venous return disorder in the industry. The main reason is that there is no consensus on its etiology and pathogenesis, among which venous outflow tract obstruction is considered to be an important etiology. Previous anatomical studies have shown that the internal jugular vein, located at the base of the skull, is susceptible to compression by adjacent bone, muscular structures. Various reasons such as stenosis inside the internal jugular vein and stenosis caused by exogenous compression may cause venous return disorder, and patients may have corresponding symptoms such as headache, dizziness, tinnitus, neck discomfort and sleep disorder. This article reviews the diagnosis and treatment methods of internal jugular venous return disorder tinnitus caused by exogenous compression at home and abroad, aiming to improve clinicians' awareness of this kind of disease.
For critically ill patients with refractory intracranial hypertension, decompressive craniectomy is the treatment of choice, which can not only effectively reduce intracranial pressure, but also save the patient's life. The traditional preauricular inverse question mark incision has always been a common incision in decompressive craniectomy. Although some scholars have used different incisions during this period, all of them will damage the adjacent blood vessels to varying degrees, resulting in a series of postoperative complications. In order to protect the blood supply of skin flap to the greatest extent and reduce the occurrence of postoperative complications, some scholars have proposed the use of "C"-shaped incision behind the ear for decompressive craniectomy to treat intracranial hypertension, which has been clinically confirmed to have good decompression effect and can also reduce the infection rate of skin flap. This article reviews the application progress of "C"-shaped incision behind the ear, in order to provide theoretical basis for the clinical application of decompressive craniectomy with this incision.
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