Enrichment of superoxide dismutase 2 in glioblastoma confers to acquisition of temozolomide resistance that is associated with tumor-initiating cell subsets.

BACKGROUND: Intratumor subsets with tumor-initiating features in glioblastoma are likely to survive treatment. Our goal is to identify the key factor in the process by which cells develop temozolomide (TMZ) resistance. METHODS: Resistant cell lines derived from U87MG and A172 were established through long-term co-incubation of TMZ. Primary tumors obtained from patients were maintained as patient-derived xenograft for studies of tumor-initating cell (TIC) features. The cell manifestations were assessed in the gene modulated cells for relevance to drug resistance. RESULTS: Among the mitochondria-related genes in the gene expression databases, superoxide dismutase 2 (SOD2) was a significant factor in resistance and patient survival. SOD2 in the resistant cells functionally determined the cell fate by limiting TMZ-stimulated superoxide reaction and cleavage of caspase-3. Genetic inhibition of the protein led to retrieval of drug effect in mouse study. SOD2 was also associated with the TIC features, which enriched in the resistant cells. The CD133+ specific subsets in the resistant cells exhibited superior superoxide regulation and the SOD2-related caspase-3 reaction. Experiments applying SOD2 modulation showed a positive correlation between the TIC features and the protein expression. Finally, co-treatment with TMZ and the SOD inhibitor sodium diethyldithiocarbamate trihydrate in xenograft mouse models with the TMZ-resistant primary tumor resulted in lower tumor proliferation, longer survival, and less CD133, Bmi-1, and SOD2 expression. CONCLUSION: SOD2 plays crucial roles in the tumor-initiating features that are related to TMZ resistance. Inhibition of the protein is a potential therapeutic strategy that can be used to enhance the effects of chemotherapy.

Demographics and Short-Term Outcomes of Spontaneous Subarachnoid Hemorrhage in Young Adults.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH) is a catastrophic disease with a high mortality. Although it is associated with poor prognosis in older patients, the socioeconomic consequences in younger patients with stroke may be more severe. We aimed to focus on the demographics and short-term outcomes of SAH in a population younger than 50 years. METHODS: We retrospectively enrolled 1689 patients with a primary diagnosis of SAH from 1993 to 2010. We identified intergroup differences in clinical variables between the patients aged 18-49 years (n = 531) and those aged ≥50 years (n = 1158). RESULTS: The patients with SAH included 688 men and 1001 women (an overall male/female ratio of 1:1.45), of whom 31.4% were aged 18-49 years. Men comprised 53.5% of the younger patients and 34.9% of the older patients (P < 0.01). The post-SAH sequela of hemiplegia was more common in the younger patients (P < 0.01), whereas the incidences of in-hospital mortality in the younger and older groups were 25.4% and 32.4%, respectively (P < 0.01). CONCLUSIONS: Adults younger than 50 years account for a significant portion of the population with SAH. There is a male predominance in this age group, probably related to early and substantial risk exposure. Although younger age imparts a higher probability of survival, it is also accompanied by a greater incidence of resultant sequelae. A better understanding of the age-related variability of SAH will assist in guidance for public health and adjustment of clinical management.

Experience with Novalis stereotactic radiosurgery for vestibular schwannomas.

BACKGROUND: The Novalis linear accelerator system, a well developed modality, can be used for stereotactic radiosurgery (SRS). The aim of this study was to clarify the efficiency and safety of Novalis SRS in treating vestibular schwannomas. MATERIALS AND METHODS: This 4-year retrospective study enrolled 23 patients with 26 vestibular schwannomas (3 patients suffered from neurofibromatosis Type II). Five patients had undergone tumor resection. All 26 tumors were treated using Novalis SRS, with a prescription dose that varied between 10 and 16Gy (mean, 11.8±1.7Gy). The average follow-up period was 56.5±22.1 months (range, 17-87 months). RESULTS: There were 9 men and 14 women. Their mean age at the time of treatment was 54.0±14.6 years (range, 27-84 years). On average, the original size of the tumor was 19.0±7.2mm in maximal diameter (range, 4.6-39.9mm). At the last follow-up, 20 tumors had regressed (76.9%), and there was no observed change in the size of 3 tumors (11.5%). Three of 26 tumors (11.5%) enlarged more than 2mm in one direction. Thus the ultimate radiological tumor control rate was 88.5% (23/26). In addition, 20 (87.0%) patients retained their pre-irradiation hearing function. Facial and trigeminal nerve function were both preserved in all patients. No death occurred during the follow-up, and no patient was treated with a second SRS or converted to tumor resection. CONCLUSION: Novalis SRS is a reliable treatment option for vestibular schwannomas. With an optimal radiation dose, satisfactory tumor control can be achieved while preserving cranial nerve function.

Is timing of cranioplasty following posttraumatic craniectomy related to neurological outcome?

BACKGROUND: With the use of decompressive craniectomy for traumatic brain injury (TBI) come a corresponding number of cranioplasties. TBI causes dynamic processes to commence or change during the period from injury to recovery; hence, the role of the timing of surgical intervention should be emphasized. AIMS: We attempt to identify the relationship between the timing of cranioplasty and neurological outcomes following posttraumatic craniectomy. METHODS: In this 3-year retrospective study, 105 patients undergoing decompressive craniectomies and subsequent cranioplasties for TBI were enrolled. We documented the patients' demographic information, including Glasgow Coma Scale (GCS) at admission for trauma. The follow-up period was terminated by death or a minimum of 6 months after TBI. Glasgow Outcome Scale (GOS) at the end of follow-up was used as an outcome measure. Unfavorable outcome was defined as a GOS score of 1-3. RESULTS: The 105 patients included 71 male and 34 female subjects. The mean age was 41.94 ± 19.73 years. Neurological assessment showed that admission GCS was 8.50 ± 3.15, on average. The mean time interval between cranioplasty and craniectomy was 78.84 ± 49.04 days (range, 13-245 days). Univariate logistic regression analysis showed that the association between the timing of cranioplasty and unfavorable outcomes was not statistically significant (odds ratio = 1.005, confidence interval 0.997-1.013; p = 0.195). CONCLUSION: The timing of cranioplasty following posttraumatic craniectomy was not related to the neurological outcomes of TBI. Despite the limitations of the retrospective design, the analyses provide preliminary information to elucidate the question.

Bilateral chronic subdural hematoma: what is the clinical significance?

BACKGROUND: Bilateral chronic subdural hematoma (CSDH) is not uncommon, although information on this condition is limited. AIMS: We aim to identify the differences in clinical characteristics between patients with bilateral or unilateral CSDH. METHODS: Ninety-eight patients with CSDH were enrolled in the two-year retrospective study. We investigated neurological outcome, morbidity, mortality, and recurrences after burr hole craniostomy for CSDH. RESULTS: Bilateral convexity hematomas were identified in 25 of 98 CSDH (25.51%). The patients with bilateral lesions had a lower incidence of hemiparesis than those having unilateral lesions (p = 0.004). Analysis of the neuro-images revealed significant differences in the presence of a midline shift (p = 0.001) and thickness of the hematoma (p < 0.001). The mean Markwalder subdural hematoma grade at admission was 1.89 ± 0.66 and 1.64 ± 0.49 in the unilateral and bilateral hematoma groups, respectively (p = 0.010). After a minimum follow-up period of 6 months, the mean Glasgow Outcome Scale was not significantly different (p = 0.060). The recurrence rate of up to 28.00% observed for the bilateral disease was found to be higher than 9.59% observed for the unilateral disease (p = 0.042). CONCLUSION: The frequency of focal neurological deficits was found to be lesser in patients with bilateral CSDH, and it may confound the diagnosis and delay treatment. To prevent neurological deterioration resulting from the thicker hematomas, early surgical decompression for bilateral CSDH should be implemented. Additionally, clinicians must be aware of the higher recurrent rate of bilateral CSDH after burr hole craniostomy.

Remote epidural hemorrhage after unilateral decompressive hemicraniectomy in brain-injured patients.

Epidural hemorrhage (EDH) that develops remote from the decompressed hemisphere can be associated with devastating morbidity after hemicraniectomy for traumatic brain injury (TBI). In this study, we investigated the incidence, risk factors, and outcome influence of post-craniectomy remote EDH. For this retrospective study, we enrolled 139 patients undergoing unilateral hemicraniectomy for TBI. The patients were subdivided into two groups based on whether EDH remote from the site of bone decompression was present (n=11) or not (n=128). We identified the intergroup differences in clinical parameters and outcomes. Multivariate odds regression was used to adjust for independent risk factors of the development of EDH. The incidence of remote EDH following decompressive hemicraniectomy for TBI was 7.9%. There were two independent risk factors for remote EDH, including absence of contusional hemorrhage (odds ratio, 95% confidence interval=6.158, 1.090-34.802; p=0.040) and presence of remote skull fracture (odds ratio, 95% confidence interval=19.770, 2.194-178.152; p=0.008) in preoperative computed tomography scans. The mean Glasgow Outcome Scale did not differ between the patients with and without EDH. In conclusion, remote EDH in patients undergoing unilateral decompressive hemicraniectomy for TBI is not uncommon. The absence of contusional hemorrhage and presence of remote skull fracture are independent risk factors. Although postcraniectomy remote EDH is devastating, timely computed tomography scanning and immediate hematoma evacuation are efficient and crucial for patient outcomes.

Acute autologous bone flap infection after cranioplasty for postinjury decompressive craniectomy.

BACKGROUND: Acute bone flap infection is a devastating complication after cranioplasty for postinjury decompressive craniectomy. We aim to identify the risk factors of autologous bone flap infection. METHODS: We enrolled 151 patients undergoing 153 cranioplasties in the 4-year retrospective study. Autologous bones stored at -75°C were used in the cranioplasties. Acute bone flap infection was defined as the onset of infection ≤14 days after cranioplasty. The epidemiological data of patients and details of the cranioplasty procedure were recorded. RESULTS: Acute bone flap infection was identified in five of the 153 cranioplasties, accounting for 3.3% of all episodes. Three of the 5 infected patients and five of 143 uninfected patients presented with dysfunction of subgaleal drainage comparatively, which was significantly different (p=0.001). Statistical analysis of the cranioplasty procedures and subsequent results of the two patient groups revealed the following significant findings: the duration of operation (p=0.03) and the length of hospital stay after cranioplasty (p<0.001). CONCLUSIONS: Dysfunction of subgaleal drainage and long operative duration of cranioplasty are risk factors of acute autologous bone flap infection. Regarding the prolonged hospital stay in complicated patients, better surgical techniques should be implemented in order to eliminate the risks of infection.

Multiple cerebral aneurysms and brain metastasis from primary cardiac myxosarcoma: a case report and literature review.

Primary neoplasms of the heart are rare. Malignant cardiac myxoma, or so-called myxosarcoma, accounts for about 6% of primary malignant cardiac tumors. Cerebral metastasis of malignant cardiac myxoma is extremely rare; only three cases have been reported and two of them included an autopsy study. The case described herein is the first reported brain metastasis combined with multiple cerebral aneurysms originating from primary cardiac myxosarcoma. The true incidence of cerebral myxomatous aneurysm is unknown and the pathogenesis of myxomatous aneurysm formation has not been fully defined. The current hypothesis favors that tumor materials from cardiac myxomas embolize into the vasa vasorum of the peripheral arteries and subsequently prolifere in the vessel wall. This then leads to a weakening of subintimal tissue, such as the internal elastic lamina, with subsequent aneurysm formation. The prognosis of cardiac myxosarcoma is very poor. Although malignancies most likely develop from the mesenchymal cells, they are difficult to treat with any modality (operation, chemotherapy, radiotherapy or transplantation) because these tumors have usually undergone extensive spread by the time the diagnosis is made.

Nocardial brain abscess.

Nocardial infections, although rare, are challenging for clinicians to treat. The associated mortality rate remains high; such infections usually occur in immunocompromised patients who have predisposing factors such as malignancy, diabetes mellitus, malnutrition and uremia. However, there have been increasing reports of nocardial infections being observed in immunocompetent patients. Nocardial organisms are mostly isolated from plants and soil, and infection occurs most often as a result of inhalation or direct skin inoculation. Nocardial infections disseminate hematogenously from the primary location to distant end organs, including the brain, kidneys, joints and eyes. Sulfonamides are the drug of choice, based on empirical data. Given the high rate of relapse and the characteristic resistance pattern, treatment should be aggressive and continued for months, with antibiotic treatment being adjusted according to the drug sensitivity test. In our institution, there have been three documented patients with a nocardial brain abscess. All patients were treated with surgical evacuation followed by antibiotics. Here, we report on one patient and review the literature.

Concurrent chemoradiotherapy for primary cervical spinal cord germinoma.

We report a rare case of primary intramedullary germinoma in the cervical spine of a 39-year-old woman without evidence of intracranial or disseminated disease. The germinoma was treated by a biopsy and follow-up concurrent chemoradiotherapy. This is the only reported case of primary spinal cord germinoma for which concurrent chemoradiotherapy was given. Furthermore, this is only the second reported case of histologically documented primary intramedullary cervical spinal cord germinoma. The patient was disease-free and there was near-complete resolution of the pre-operative neurological deficits at the 20-month follow-up examination.