Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to ‘Self’ tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive Tregs and to gain immune privilege. We analyzed four GBM transcriptome databases representing ≈900 tumors for hypoxia-responsive Tregs, steroidogenic pathways, and sperm/testicular and placenta-specific genes, stratifying tumors by expression. In silico analysis suggested that the presence of reproductive-associated Tregs in GBM tumors was associated with worse patient outcomes. These tumors have an androgenic signature, express male-specific antigens, and attract reproductive-associated Related Orphan Receptor C (RORC)-Treg immunosuppressive cells. GBM patient sera were interrogated for the presence of anti-sperm/testicular antibodies, along with age-matched controls, utilizing monkey testicle sections. GBM patient serum contained anti-sperm/testicular antibodies at levels > six-fold that of controls. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are associated with estrogenic tumors which appear to mimic placental tissue. We demonstrate that RORC-Tregs drive poor patient outcome, and Treg infiltration correlates strongly with androgen levels. Androgens support GBM expression of sperm/testicular proteins allowing Tregs from the patient’s reproductive system to infiltrate the tumor. In contrast, estrogen appears responsible for MDSC/TAM immunosuppression.
Background: Overdrainage after cerebrospinal fluid diversion remains a significant morbidity. The hydrostatic, gravitational force in the upright position can aggravate this. Siphon control (SC) mechanisms, as well as programmable and flow regulating devices, were developed to counteract this. However, limited studies have evaluated their safety and efficacy. In this study, direct comparisons of the complication rates between siphon control (SC) and non-SC (NSC), fixed versus programmable, and flow- versus pressure regulating valves are undertaken. Methods: A retrospective chart review was performed over all shunt implantations from January 2011 to December 2016 within the Houston Methodist Hospital system. Complication rates within 6 months of the operative date, including infection, subdural hematoma, malfunction, and any other shunt-related complication, were analyzed via Fisher’s exact test, with P < 0.05 regarded as significant. Subgroup analyses based on diagnoses – normal pressure hydrocephalus (HCP), pseudotumor cerebri, or other HCP – were also performed. Results: The overall shunt-related complication rate in this study was 19%. Overall rates of infection, shunt failure, and readmission within 180 days were 3%, 11%, and 34%, respectively. No difference was seen between SC and NSC groups in any complication rate overall or on subgroup analyses. When comparing fixed versus programmable and flow- versus pressure-regulating valves, the latter in each analysis had significantly lower malfunction and total complication rates. Conclusions: Programmable and pressure regulating devices may lead to lower shunt malfunction and total complication rates. Proper patient selection should guide valve choice. Future prospective studies may further elucidate the difference in complication rates between these various shunt designs.
Purpose Subependymal giant cell astrocytomas (SEGAs) are rare tumors typically found in tuberous sclerosis patients. They typically grow in the region of the foramen of Monro and can occlude it, leading to hydrocephalus. Currently, gross total resection is the standard of care, with low rates of recurrence but high rates of complication, especially with larger lesions. Laser interstitial thermal therapy (LITT) is a newly emerging treatment modality for a variety of pathologies. Here, we present a case series of SEGAs managed via LITT and endoscopic, stereotactic septostomy. Methods A retrospective chart review was performed to identify three cases in which SEGAs were treated via LITT and septostomy. Stereotactic ablation was performed via magnetic resonance (MR) thermometry with laser output set to 69% for 2.5 min, with post-ablation scans for visualization of treatment area.Results Average age at surgery was 8.2 years. Pre-operative tumor volumes were 0.43, 1.51, and 3.88 cm 3 . Post-operative tumor volumes were 0.25, 0.21, and 0.68 cm 3 . Mean tumor volume reduction was 70%. No complications occurred. Conclusion LITT with septostomy should be considered a viable primary or adjunct treatment modality for SEGAs.
Background and Importance : Intracranial artery fenestrations are very rare, however, when found, there is a high association with cerebral aneurysms. Clinical Presentation : This report describes a patient with multiple anterior and posterior circulation intracranial artery fenestrations and an anterior communicating artery aneurysm presenting with a thunderclap headache found to have a subarachnoid hemorrhage (SAH). The patient was treated with open surgery via clipping after a diagnostic angiography and did very well. Conclusion : There is an association between cerebral fenestrations and aneurysms, but it has not been studied in a prospective manner. This case is unusual in that the patient had both anterior and posterior circulation fenestrations, which is uncommon. Clinicians should have a high index of suspicion in patients being evaluated for SAH who have a cerebral artery fenestration with no aneurysm found.
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Aneurysms of the posterior inferior cerebellar artery (PICA) are rare, with limited consensus on appropriate management. These aneurysms have been noted to have a faster growth rate and are more prone to rupture. Accessing these aneurysms for microsurgical clipping is challenging, and has traditionally required significant removal of the occipital condyle, putting the patient at risk for future complications. Therefore, some have opted to utilize minimally invasive techniques such as a pipeline stent, though these methods can fail to cause complete occlusion of the aneurysm. The current case describes a patient who was found to have a PICA aneurysm that was initially managed with a pipeline stent. However, upon further follow up, the aneurysm showed continued filling, leading to the decision to clip the aneurysm. In this case, we describe the use of a far lateral approach for accessing and clipping a PICA aneurysm with minimal removal of the occipital condyle. The patient successfully tolerated the surgery and was discharged home.
BACKGROUND AND IMPORTANCE Superior cerebellar artery (SCA) perforator aneurysms are extremely rare, with only one other case published in the literature. There is no conclusive management strategy for these aneurysms, although endovascular treatment, open surgical treatment with clipping, and antifibrinolytic administration with spontaneous thrombosis have all been discussed. CLINICAL PRESENTATION A 61-yr-old male presented with intraventricular hemorrhage (IVH) primarily in the posterior fossa. He was found to have a dissecting left SCA perforator aneurysm lying on the floor of the fourth ventricle. The aneurysm was not amenable to endovascular treatment, and antifibrinolytic therapy failed to spontaneously thrombose the aneurysm. We performed a suboccipital craniotomy and used a supracerebellar transvermian approach to resect the aneurysm. There was total obliteration of the aneurysm on postoperative cerebral angiogram. CONCLUSION SCA perforator aneurysms represent an extremely uncommon subset of intracranial aneurysms. The best therapeutic strategy has yet to be definitively proven. When pursuing surgical treatment, the supracerebellar transvermian navigated approach can be a useful and safe option, as described and illustrated in this video.
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