Awake Craniotomy in Conscious Sedation: The Role of A2 Agonists.

BACKGROUND: In Awake Craniotomy (AC), α2-agonists and remifentanil (clonidine and dexmedetomidine) are used in the preoperative phase and throughout the procedure to combine monitored anesthesia care and local anesthesia. The study aims were to specify the key role of α2-agonists administered and to evaluate complication presence/absence in anesthesiologic management. METHODS: 42 patients undergoing AC in 3 different centers in the south of Italy (Foggia, San Giovanni Rotondo, and Bari) were recruited. Our protocol involves analgo-sedation by administering Dexmedetomidine and Remifentanil in continuous intravenous infusion, allowing the patient to be sedated and in comfort but contactable and spontaneously breathing. During pre-surgery, the patient is premedicated with intramuscular clonidine (2 µg/kg). In the operating setting, Dexmedetomidine in infusion and Remifentanil in Target Controlled Infusion for effect are started. At the end of the surgical procedure, the infusion of drugs was suspended. RESULTS: There were no intraoperative side effects. The mean duration of interventions was 240 ± 62 min. The average quantity of Remifentanil and Dexmedetomidine infused during interventions were 4.2 ± 1.3 mg and 1.0 ± 0.3 mg, respectively. No significant side effects were described in the post-operative phase. A total of 86% of patients and 93% of surgeons were totally satisfied. CONCLUSIONS: Synergy between opioid drugs and α2 agonists plays a fundamental role in ensuring procedure success.

Real-Time Neuropsychological Testing (RTNT) and Music Listening during Glioblastoma Excision in Awake Surgery: A Case Report.

In this case report, real-time neuropsychological testing (RTNT) and music listening were applied for resections in the left temporal-parietal lobe during awake surgery (AS). The case is based on a 66-year-old with glioblastoma and alterations in expressive language and memory deficit. Neuropsychological assessment was run at baseline (2-3 days before surgery), discharge from hospital (2-3 days after surgery), and follow-up (1 month and 3 months). RTNT was started before beginning the anesthetic approach (T0) and during tumor excision (T1 and T2). At T0, T1, and T2 (before performing neuropsychological tests), music listening was applied. Before AS and after music listening, the patient reported a decrease in depression and anxiety. During AS, an improvement was shown in all cognitive parameters collected at T0, T1, and T2. After the excision and music listening, the patient reported a further decrease in depression and anxiety. Three days post surgery, and at follow-ups of one month and three months, the patient reported a further improvement in cognitive aspects, the absence of depression, and a reduction in anxiety symptoms. In conclusion, RTNT has been useful in detecting cognitive function levels during tumor excision. Music listening during AS decreased the patient's anxiety and depression symptoms.

Anesthetic Management for Awake Craniotomy Applied to Neurosurgery.

Our anesthetic technique proposed for awake craniotomy is the monitored anesthesia care (MAC) technique, with the patient in sedation throughout the intervention. Our protocol involves analgo-sedation through the administration of dexmedetomidine and remifentanil in a continuous intravenous infusion, allowing the patient to be sedated and in comfort, but contactable and spontaneously breathing. Pre-surgery, the patient is pre-medicated with intramuscular clonidine (2 µg/kg); it acts both as an anxiolytic and as an adjuvant in pain management and improves hemodynamic stability. In the operating setting, dexmedetomidine in infusion and remifentanil in target controlled infusion (TCI) for effect are started. The purpose of the association is to exploit the pharmacodynamics of dexmedetomidine which guarantees the control of respiratory drive, and the pharmacokinetics of remifentanil characterized by insensitivity to the drug. Post-operative management: at the end of the surgical procedure, the infusion of drugs was suspended. Wake-up craniotomy is associated with reduced hospital costs compared to craniotomy performed in general anesthesia, mainly due to reduced costs in the operating room and shorter hospital stays. Greater patient satisfaction and the benefits of avoiding hospital stay have led to the evolution of outpatient intracranial neurosurgery.

A miRNA signature for defining aggressive phenotype and prognosis in gliomas.

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA (miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours (2 WHO grade III and 22 glioblastomas) by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method (RT-qPCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas (TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, p = 0.04, and HR 1.18, p = 0.029 respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.

Regulation of KEAP1 expression by promoter methylation in malignant gliomas and association with patient's outcome.

In light with the view that KEAP1 loss of function may impact tumour behavior and modify response to chemotherapeutical agents, we sought to determine whether KEAP1 gene is epigenetically regulated in malignant gliomas. We developed a Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant gliomas and 20 normal brain tissues. The discriminatory power of the assay was assessed by Receiving Operating Characteristics (ROC) curve analysis. The AUC value of the curve was 0.823 (95%CI: 0.764-0.883) with an optimal cut off value of 0.133 yielding a 74% sensitivity (95%CI: 63%-82%) and an 85% specificity (95%CI: 64%-95%). Bisulfite sequencing analysis confirmed QMSP results and demonstrated a direct correlation between percentage of methylated CpGs and methylation levels (Spearman's Rho 0.929, P=0.003). Remarkably, a strong inverse correlation was observed between methylation levels and KEAP1 mRNA transcript in tumour tissue (Spearman's Rho -0.656 P=0.0001) and in a cell line before and after treatment with 5-azacytidine (P=0.003). RECPAM multivariate statistical analysis studying the interaction between MGMT and KEAP1 methylation in subjects treated with radiotherapy and temozolomide (n=70), identified three prognostic classes of glioma patients at different risk to progress. While simultaneous methylation of MGMT and KEAP1 promoters was associated with the lowest risk to progress, patients showing only MGMT methylation were the subgroup at the higher risk (HR 5.54, 95% CI 1.35-22.74). Our results further suggest that KEAP1 expression is epigenetically regulated. In addition we demonstrated that KEAP1 is frequently methylated in malignant gliomas and a predictor of patient's outcome.

Role of trait anxiety in persistent radicular pain after surgery for lumbar disc herniation: a 1-year longitudinal study.

OBJECTIVE: To evaluate anxiety and depression as prognostic factors for radicular and back pain after surgery in patients with lumbar disc herniation in a 1-year follow-up study. METHODS: A total of 108 patients with lumbar disc herniation were enrolled in the study. Anxiety was assessed by State and Trait Anxiety Inventory; current depression was assessed by Zung Self-Rating Depression Scale. Severity of pain was scored on the visual analog scale (VAS). The State and Trait Anxiety Inventory, Zung Self-Rating Depression Scale, and VAS were administered before surgery and 1, 3, 6, and 12 months after surgery. RESULTS: Before surgery, 72.2% of patients showed state anxiety, 54.6% of patients showed trait anxiety, and 11.1% of patients showed current depression. During the follow-up period, there was a significant decrease in the prevalence of state anxiety (P < .0001), no variation in the prevalence of trait anxiety (P = .115), and a significant increase in the prevalence of current depression (P = .002). Linear regression analysis showed that the presence of trait anxiety before surgery was the main determinant of the presence of pain after surgery (P < .0001). VAS scores were evaluated by dividing patients into 2 groups based on the presence or absence of trait anxiety before surgery. The subgroup affected by trait anxiety before surgery had significantly higher VAS scores at each follow-up assessment compared with patients without trait anxiety (P < .0001). CONCLUSION: The presence of trait anxiety before surgery is a prognostic factor for the persistence of pain after surgery.

State and trait anxiety and depression in patients with primary brain tumors before and after surgery: 1-year longitudinal study.

OBJECT: The aim in this study was to assess the state and trait types of anxiety as well as current depression before and after surgery in patients affected by brain tumors. The relationships between these affective disorders and the patient's sex, tumor histology, and laterality of the tumor were also evaluated. METHODS: A total of 72 patients affected by a primary brain tumor were enrolled in the study. Histological grades were assigned according to the World Health Organization classification. State and trait anxiety were assessed using the State and Trait Anxiety Inventory; current depression was assessed using the Zung Self-Rating Depression Scale. Cognitive impairment was assessed using the 10-item Short Portable Mental Status Questionnaire. Psychometric evaluation was assessed before surgery and at 1, 3, 6, and 12 months after surgery. RESULTS: Before brain surgery, 62.5% of patients showed state anxiety, 50% of patients showed trait anxiety, and 9.7% of patients showed current depression. During the follow-up period there was no significant variation in the percentage of patients with state anxiety (p=0.416) and trait anxiety (p=0.7), whereas a significant increase in the percentage of those with current depression was found (p<0.0001), in particular at 1 month (p=0.002) and 3 months (p=0.039) after surgical treatment. The tumor's laterality and histology showed no correlation with psychometric variables, whereas a relationship between the presence of trait anxiety at the enrollment and current depression after surgery (p<0.0001) was found. CONCLUSIONS: Patients affected by brain tumors frequently experience affective disorders. After brain surgery, a depressive state can develop. The psychometric assessment could be useful in these patients for quick recognition of psychological disorders.