Glioblastoma (GBM) is a highly malignant type of primary brain tumor with a high mortality rate. Although the current standard therapy consists of surgery followed by radiation and temozolomide (TMZ), chemotherapy can extend patient’s post-operative survival but most cases eventually demonstrate resistance to TMZ. O⁶-methylguanine-DNA methyltransferase (MGMT) repairs the main cytotoxic lesion, as O⁶-methylguanine, generated by TMZ, can be the main mechanism of the drug resistance. In addition, mismatch repair and BER also contribute to TMZ resistance. TMZ treatment can induce self-protective autophagy, a mechanism by which tumor cells resist TMZ treatment. Emerging evidence also demonstrated that a small population of cells expressing stem cell markers, also identified as GBM stem cells (GSCs), contributes to drug resistance and tumor recurrence owing to their ability for self-renewal and invasion into neighboring tissue. Some molecules maintain stem cell properties. Other molecules or signaling pathways regulate stemness and influence MGMT activity, making these GCSs attractive therapeutic targets. Treatments targeting these molecules and pathways result in suppression of GSCs stemness and, in highly resistant cases, a decrease in MGMT activity. Recently, some novel therapeutic strategies, targeted molecules, immunotherapies, and microRNAs have provided new potential treatments for highly resistant GBM cases. In this review, we summarize the current knowledge of different resistance mechanisms, novel strategies for enhancing the effect of TMZ, and emerging therapeutic approaches to eliminate GSCs, all with the aim to produce a successful GBM treatment and discuss future directions for basic and clinical research to achieve this end.

The long-term effects of motor cortex stimulation (MCS) and spinal cord stimulation (SCS) remain unknown. To identify the long-term effects after MCS or SCS and determine any associated predictive factors for the outcomes. Fifty patients underwent MCS (n = 15) or SCS (n = 35) for chronic neuropathic pain. The degree of pain was assessed preoperatively, at 1, 6, and 12 months after surgery, and during the time of the last follow-up using Visual Analog Scale (VAS). Percentage of pain relief (PPR) was calculated, with “long-term effect” defined as PPR ≥ 30% and the presence of continued pain relief over 12 months. Outcomes were classified into excellent (PPR ≥ 70%) and good (PPR 30–69%) sub-categories. Long-term effects of MCS and SCS were observed in 53.3% and 57.1% of the patients, respectively. There were no predictive factors of long-term effects identified for any of the various preoperative conditions. However, the VAS at 1 month after surgery was significantly associated with the long-term effects in both MCS and SCS. All patients with an excellent outcome at 1 month after the surgery continued to exhibit these effects. In contrast, patients with the good outcome at 1 month exhibited a significant decrease in the effects at 6 months after surgery. The long-term effects of MCS and SCS were approximately 50% during the more than 8.5 and 3.5 years of follow-up, respectively. The VAS at 1 month after surgery may be a postoperative predictor of the long-term effects for both MCS and SCS.

Stent-assisted coil embolization (SACE) is used to address wide-necked or complex aneurysms. However, periprocedural and/or late in-stent thrombosis (IST) elicit neurological events. We investigated the incidence and timed the development of acute IST during SACE with braided- or laser-cut stents in a retrospective study. Between May 2013 and April 2018, we evaluated 11 ISTs that occurred in the course of 185 SACE procedures (self-expandable laser-cut stent, n = 128; braided stent, n = 57). The onset of IST was measured from the time of stent placement. All 11 patients with IST were treated with anticoagulants and underwent hypertension induction. Post-procedural neurological events due to IST were also recorded. The implantation of a laser-cut stent elicited IST in 5 of 128 patients (3.9%); braided stent placements resulted in IST in 6 of 57 patients (10.5%) (P = 0.1). The mean stent diameter was significantly smaller in patients with-IST than without IST (3.0 ± 0.9 mm vs. 4.5 ± 0.7 mm, P = 0.007). The mean interval between stent placement and IST onset was 19 ± 7.7 min; it was significantly earlier for braided- than laser-cut stents (17.5 ± 4.1 min vs. 29.0 ± 4.8 min, P = 0.006). All ISTs were resolved during the procedure. Three patients experienced postoperative neurologic events. We recommend the meticulous and prolonged monitoring of images after stent placement because delayed intraoperative IST can occur especially when laser-cut stents are used.

Epilepsy surgery aims to control epilepsy by resecting the epileptogenic region while preserving function. In some patients with epileptogenic foci in and around functionally eloquent areas, awake surgery is implemented. We analyzed the surgical outcomes of such patients and discuss the clinical application of awake surgery for epilepsy. We examined five consecutive patients, in whom we performed lesionectomy for epilepsy with awake craniotomy, with postoperative follow-up > 2 years. All patients showed clear lesions on magnetic resonance imaging (MRI) in the right frontal (n = 1), left temporal (n = 1), and left parietal lobe (n = 3). Intraoperatively, under awake conditions, sensorimotor mapping was performed; primary motor and/or sensory areas were successfully identified in four cases, but not in one case of temporal craniotomy. Language mapping was performed in four cases, and language areas were identified in three cases. In one case with a left parietal arteriovenous malformation (AVM) scar, language centers were not identified, probably because of a functional shift. Electrocorticograms (ECoGs) were recorded in all cases, before and after resection. ECoG information changed surgical strategy during surgery in two of five cases. Postoperatively, no patient demonstrated neurological deterioration. Seizure disappeared in four of five cases (Engel class 1), but recurred after 2 years in the remaining patient due to tumor recurrence. Thus, for patients with epileptogenic foci in and around functionally eloquent areas, awake surgery allows maximal resection of the foci; intraoperative ECoG evaluation and functional mapping allow functional preservation. This leads to improved seizure control and functional outcomes.

We report a case of head injury with posterior reversible encephalopathy syndrome (PRES), followed by Guillain-Barré syndrome (GBS). A 74-year-old man was brought to our hospital after a fall. Computed tomography revealed intracranial hemorrhage. Magnetic resonance imaging showed bilateral reversible intensities with features of vasogenic edema in parietooccipital areas, suggesting PRES. After admission, weakness and areflexia of extremities and respiratory muscles developed gradually, which favored a diagnosis of GBS. Common etiologies of PRES were absent. Concurrent occurrence of PRES and GBS is rare. Given that PRES can be an initial manifestation of GBS, GBS must be considered in head trauma patients with PRES.