Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration.

The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in nontumoral brain (NB) and grade I-IV gliomas. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (GBMs) that excluded long-survivor cases expressed higher levels of RSK1 (RSK1hi ). No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in GBM (RSK2hi ) were associated with worse survival. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBM demonstrating the lowest RSK3 protein levels. RSK1hi and, to a lesser extent, RSK2hi GBMs showed higher levels of phosphorylated RSK, which reveals RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker lysosomal protein transmembrane 5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration suggest RSK1 as a potential progression marker and therapeutic target for gliomas.

Subarachnoid neurocysticercosis and an intracranial infectious aneurysm: case report.

Infectious intracranial aneurysms (IIAs) represent 2%-6% of all intracranial aneurysms and, classically, have been associated with bacterial or fungal agents. The authors report the case of a 42-year-old woman who presented with a typical history of subarachnoid hemorrhage. Digital subtraction angiography (DSA) showed an aneurysmal dilatation on the frontal M2 segment of the left middle cerebral artery (MCA). The patient was treated surgically, and multiple cysts were found in the left carotid and sylvian cisterns, associated with a dense inflammatory exudate that involved the MCA. The cysts were removed, and a fusiform aneurysmal dilatation was identified. The lesion was not amenable to direct clipping, so the authors wrapped it. Histopathological analysis of the removed cysts revealed the typical pattern of subarachnoid neurocysticercosis. The patient received cysticidal therapy with albendazole and corticosteroids, and she recovered uneventfully. Follow-up DSA performed 6 months after surgery showed complete resolution of the aneurysm. The authors performed a review of the literature and believe that there is sufficient evidence to affirm that the subarachnoid form of neurocysticercosis may lead to the development of an IIA and that Taenia solium should be listed among the possible etiological agents of IIAs, along with bacterial and fungal agents.

Randomized controlled study comparing 2 surgical techniques for decompressive craniectomy: with watertight duraplasty and without watertight duraplasty.

OBJECTIVE: Decompressive craniectomy (DC) is a widely used procedure in neurosurgery; however, few studies focus on the best surgical technique for the procedure. The authors' objective was to conduct a prospective randomized controlled trial comparing 2 techniques for performing DC: with watertight duraplasty and without watertight duraplasty (rapid-closure DC). METHODS: The study population comprised patients ranging in age from 18 to 60 years who were admitted to the Neurotrauma Service of the Hospital da Restauração with a clinical indication for unilateral decompressive craniectomy. Patients were randomized by numbered envelopes into 2 groups: with watertight duraplasty (control group) and without watertight duraplasty (test group). After unilateral DC was completed, watertight duraplasty was performed in the control group, while in the test group, no watertight duraplasty was performed and the exposed parenchyma was covered with Surgicel and the remaining dura mater. Patients were then monitored daily from the date of surgery until hospital discharge or death. The primary end point was the incidence of surgical complications (CSF leak, wound infection, brain abscess, or subgaleal fluid collections). The following were analyzed as secondary end points: clinical outcome (analyzed using the Glasgow Outcome Scale [GOS]), surgical time, and hospital costs. RESULTS: Fifty-eight patients were enrolled, 29 in each group. Three patients were excluded, leaving 27 in the test group and 28 in the control group. There were no significant differences between groups regarding age, Glasgow Coma Scale score at the time of surgery, GOS score, and number of postoperative follow-up days. There were 9 surgical complications (5 in the control group and 4 in the test group), with no significant differences between the groups. The mean surgical time in the control group was 132 minutes, while in the test group the average surgical time was 101 minutes, a difference of 31 minutes (p = 0.001). The mean reduction in total cost was $420.00 USD (a 23.4% reduction) per procedure in the test group. CONCLUSIONS: Rapid-closure DC without watertight duraplasty is a safe procedure. It is not associated with a higher incidence of surgical complications (CSF leak, wound infection, brain abscess, or subgaleal fluid collections), and it decreased surgical time by 31 minutes on average. There was also a hospital cost reduction of $420.00 USD (23.4% reduction) per procedure. Clinical trial registration no.: NCT02594137 (clinicaltrials.gov).

Craniopharyngiomas: intratumoral chemotherapy with interferon-alpha: a multicenter preliminary study with 60 cases.

OBJECT: The authors assessed the efficacy of intratumoral interferon-alpha (IFNalpha)-based chemotherapy in pediatric patients with cystic craniopharyngiomas. METHODS: In a prospective multicenter study of 60 pediatric patients, the authors assessed the efficacy of intratumoral INFalpha2A-based chemotherapy. The study was conducted between 2000 and 2009 at 3 locations: the Medical School of the Federal University of São Paulo, Catholic University of Rome, and the Neurosurgery Institute of Santiago, Chile. The assessment included clinical and radiological control examinations, side effects observed, and total dose used. RESULTS: Sixty cases of cystic craniopharyngioma were analyzed. The cohort consisted of 35 male and 25 female children (mean age 11 years). Clinical and radiological improvement was achieved in 76% of the cases. New endocrinological deficits were observed in 13% of the cases. In approximately 30% of the patients, the evolution included some light side effects, the most common being headache (33%) and eyelid edema (28%). The number of cycles varied from 1 to 9 (mean 5 cycles), and the total dose applied per cycle was 36,000,000 IU. CONCLUSIONS: This has been the largest documented series of intratumoral chemotherapy using INFalpha for the control of cystic craniopharyngiomas. The treatment has proved efficacious; there was no mortality, and morbidity rates were low.