Inhibition of neuronal necroptosis mediated by RIP1/RIP3/MLKL provides neuroprotective effects on kaolin-induced hydrocephalus in mice.

OBJECTIVES: Necroptosis is widespread in neurodegenerative diseases. Here, we examined necroptosis in the hippocampus and cortex after hydrocephalus and found that a necroptosis pathway inhibitor alleviates necroptosis and provides neuroprotective effects. MATERIALS AND METHODS: Hydrocephalus was induced in C57BL/6 mice by kaolin. Haematoxylin and eosin (HE), Nissl, PI and Fluoro-Jade B (FJB) staining were used for general observations. Phosphorylated receptor-interacting protein kinase 3 (p-RIP3) and phosphorylated mixed lineage kinase domain-like (p-MLKL) were measured by Western blotting and immunohistochemistry. Scanning electron microscopy (SEM) was used to observe ependymal cilia. Magnetic resonance imaging (MRI) and the Morris water maze (MWM) test were used to assess neurobehavioral changes. Immunofluorescence was used to detect microglial and astrocyte activation. Inflammatory cytokines were measured by Western blotting and RT-PCR. RESULTS: Obvious pathological changes appeared in the hippocampus and cortex after hydrocephalus, and expression of the necroptosis markers p-RIP3, p-MLKL and inflammatory cytokines increased. Necrostatin-1 (Nec-1) and GSK872 reduced necrotic cell death, attenuated p-RIP3 and p-MLKL levels, slightly improved neurobehaviours and inhibited microglial and astrocyte activation and inflammation. CONCLUSIONS: RIP1/RIP3/MLKL mediates necroptosis in the cortex and hippocampus in a hydrocephalus mouse model, and Nec-1 and GSK872 have some neuroprotective effects.

Adult Sellar Region Atypical Teratoid/Rhabdoid Tumor: A Retrospective Study and Literature Review.

Background: Adult sellar region atypical teratoid/rhabdoid tumor (AT/RT) is a rare lesion. We aimed to elucidate clinical, radiologic, and pathological characteristics, treatment strategies, and outcomes of this disease. Methods: Five adult sellar AT/RT patients were retrospectively analyzed between January 2015 and December 2018. In addition, we performed a review of the reported data on adult sellar AT/RT. Results: Patients (n = 5) were female with a median age of 50 years. The mean duration of symptoms, of which headache was the most frequent, was 1.6 months (range, 2 weeks-8 months). The average tumor size was 2.82 cm (range, 1.9-4.5 cm). All lesions were irregularly shaped. MRI showed heterogeneous enhancement in three of five lesions. Four of five patients underwent subtotal resection (STR) and one gross total resection (GTR). Whereas, one patient received post-operative adjuvant radiotherapy, one patient received post-operative combination of radio- and chemotherapy. The review of the reported data showed that 39 cases of adult sellar AT/RT had been reported. The estimated median overall survival (OS) was 23 months with a 1-year survival estimate of 59.7%. The median OS for patients with GTR was 28 months and 17 months for patients with STR. Kaplan-Meier analysis showed that patients with high (≥35%) MIB-1/Ki67 index value had a significantly shorter OS compared with those with low (<35%) index value (p = 0.033), and that patients who received post-operative combination radio- and chemotherapy had longer OS than that of those who did not (p < 0.001). Conclusion: Adult sellar region AT/RT is a rapidly growing tumor with a poor prognosis. High levels of MIB1/Ki-67 on histology may indicate aggressive feature of the tumor. Maximal safe resection followed by adjuvant radiotherapy combined with chemotherapy may be the optimal therapeutic strategy for adult sellar region AT/RT.

The Effectiveness of Lumbar Drainage in the Management of Delayed or Recurrent Cerebrospinal Fluid Leaks: A Retrospective Case Series in a Single Center.

OBJECTIVE: Little is known about the effectiveness of lumbar drainage (LD) in the treatment of delayed or recurrent cerebrospinal fluid (CSF) leaks. We report our institutional experience and the effectiveness of LD in the management of delayed or recurrent CSF leaks. METHODS: Between January 2014 and December 2018, a total 21 patients with delayed or recurrent CSF leaks were enrolled in the research. All patients were treated conservatively for 48 hours, and LD was prescribed if CSF leaks still existed after 48 hours. If LD failed, endoscopic endonasal surgery (EES) was performed as soon as possible. Medical records were collected to analyze the effectiveness of LD. RESULTS: Among 21 patients, 4 patients experienced resolution with conservative treatment, and 17 patients were treated by CSF diversion by LD. The total cure rate of LD was 9/17 (52.9%). The cure rate was not statistically significantly different (relative risk = 3.33; Fisher exact test P = 0.131) between the traumatic group (8/12, 66.7%) and the transsphenoidal surgery group (1/5, 20.0%). During the follow-up time, no recurrence of CSF leaks was observed. CONCLUSIONS: The cure rate of LD in delayed or recurrent CSF leaks was lower than that of initial treatment with LD. The cure rate in the traumatic group tended to be higher than that in the transsphenoidal surgery group. EES can be used as a remedial treatment for patients in whom LD has failed.

Health-Related Quality of Life and Posttraumatic Growth in Low-Grade Gliomas in China: A Prospective Study.

OBJECTIVE: The present study aimed to describe the quality of life (QoL) changes of survivors of low-grade gliomas (LGGs) 1 year after surgery and to identify determinants of QoL with an emphasis on the role of perceived posttraumatic growth (PTG). We also tried to examine the linear and quadratic relationship between QoL and PTG. METHODS: Two hundred sixty participants were included in the final data analysis. The Chinese version of posttraumatic growth inventory and the Functional Assessment of Cancer Therapy-Brain scale were used to measure PTG and QoL. Hierarchical linear models were fitted to explore the individual time trajectories in change of QoL and examine the relationship between demographics, clinical features, PTG, and QoL. RESULTS: All dimensions of QoL and PTG increased over time except physical well-being, social well-being in QoL, and new possibilities in PTG. Time, PTG score, insurance, socioeconomic status, and right hemisphere tumor position were positive predictors of QoL. Seizure and depression negatively predicted QoL. The quadratic of PTG predicted QoL; however, the coefficient of quadratic PTG approached zero. CONCLUSIONS: In general, PTG and QoL increased over time. Perceived PTG could significantly predict QoL of LGGs survivors 1 year after surgery. A quadratic relation between PTG and QoL was not found. Although our data suggested that the growth of QoL may vary across different patients, there were only 2 time points in this study. Future studies should set more time points to examine this relationship.