Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.
Hao-Li Liu, Hung-Wei Yang, Mu-Yi Hua and Kuo-Chen Wei
Frank Heller, Chia-Ming Hsu, Chi-Cheng Chuang, Kuo-Chen Wei and Fu-Chan Wei
✓ Infected full-thickness defects of the calvaria including the scalp, cranial bone, and dura mater, are often refractory to treatment and pose a difficult and urgent therapeutic problem for reconstructive surgeons. The authors report two cases in which successful reconstruction was achieved in one stage by using an anterolateral thigh fasciocutaneous flap. The well-vascularized fascia components were used to repair the infected dural defects. The skin flaps were used for coverage reconstruction.
Reng-Jye Lee, Chih-Feng Chen, Shih-Wei Hsu, Chun-Chung Lui and Yeh-Lin Kuo
✓ Endovascular therapy for dural carotid cavernous fistulas (CCFs) is generally accepted to be safe and effective. The authors report a rare complication of hemorrhage and subsequent venous infarcts of the pons and cerebellum after transvenous embolization.
This 41-year-old man presented with a severe left frontal headache, congestion of the left conjunctiva, blurred vision, and photophobia. Cerebral angiography demonstrated a right dural CCF. The patient underwent transvenous embolization of the cavernous sinus but had the initial complication of cerebellar hemorrhage. One month later, he developed progressive dizziness, ataxia, and right-sided weakness. Magnetic resonance imaging revealed severe cerebellar and pontine edema. The cause was a residual fistula combined with delayed occlusion of the inferior petrosal sinus. The fistula was obliterated after repeated embolizations. The patient's symptoms gradually resolved, and there was no evidence of recurrence during the 4-year follow-up period.
Incomplete transvenous embolization of a dural CCF can result in life-threatening vascular complications due to redistribution of shunt flow. Early recognition of redistributed drainage and preventive placement of coils at the origin of draining veins during the procedure could avert this rare complication.
Cheng-Loong Liang, Meng-Wei Ho, Kang Lu, Yu-Duan Tsai, Po-Chou Liliang, Kuo-Wei Wang and Han-Jung Chen
The authors conducted a study to assess the eye lens dosimetry in trigeminal neuralgia (TN) treatment when using the Leksell Gamma Knife model C.
Phantom studies were used to measure the maximal dose reaching the eye lens with and without eye shielding. Six consecutive patients with TN were evaluated for Gamma Knife surgery (GKS). The maximum prescribed dose of 80 Gy was delivered with a single shot using the 4-mm collimator helmet. High-sensitivity thermoluminescence dosimeter chips (TLDCs) were used to measure the dosimetry.
In vitro, the Leksell GammaPlan (LGP) system predicted the mean maximal doses of 1.08 ± 0.08 and 0.15 ± 0.01 Gy (mean ± standard deviation) to the lens ipsilateral to the treated trigeminal nerve without and with eye shielding, respectively. The TLDCs-measured dosimetry indicated the mean maximal doses of 1.12 ± 0.09 and 0.17 ± 0.01 Gy without and with eye shielding, respectively. The maximal doses to the lens contralateral to the nerve were similar.
In vivo, the LGP predicted the mean maximal doses to the lens ipsilateral to the treated nerve as 1.1 ± 0.07 and 0.16 ± 0.02 Gy, respectively, without and with eye shielding. The dosimetry measured by TLDCs indicated the mean maximal dose to the lens ipsilateral to the treated nerve as 0.17 ± 0.02 Gy with eye shielding. The mean maximal doses to the lens contralateral to the nerve were similar. Using the 110 and 125˚ gamma angles, the LGP predicted the mean maximal doses of 0.32 ± 0.04 and 0.12 ± 0.04 Gy to the lens without and with eye shielding, respectively.
Patients with TN undergoing GKS without eye shielding may develop cataracts due to the high radiation dose to the eye lenses. The authors suggest the routine use of bilateral eye shielding for the patients.
Sheng-Tzung Tsai, Wei-Yi Chuang, Chung-Chih Kuo, Paul C. P. Chao, Tsung-Ying Chen, Hsiang-Yi Hung and Shin-Yuan Chen
Deep brain stimulation (DBS) surgery under general anesthesia is an alternative option for patients with Parkinson’s disease (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored.
Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated mated using standard neurophysiological procedures.
The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05).
Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.
Report of two cases
Cheng-Hong Toh, Yao-Liang Chen, Ho-Fai Wong, Kuo-Chen Wei, Shu-Hang Ng and Yung-Liang Wan
✓ Rosai—Dorfman disease (RDD) is an idiopathic proliferation of histiocytes that affects the lymph nodes. Central nervous system involvement in the absence of nodal disease is extremely rare. On neuroimaging studies, intracranial RDD appears as solitary or multiple well-circumscribed, dura-based lesions. The authors report on two cases of RDD with locally aggressive features including dural sinus invasion, which to their knowledge has never before been described.
A 60-year-old woman presented with progressive dizziness and vertigo that had lasted for 1 week. Cranial computerized tomography and magnetic resonance imaging revealed an extraaxial homogeneous lobulated enhancing mass involving the right occipital lobe and the right cerebellar hemisphere. Invasion of the right transverse sinus was identified on a cerebral digital subtraction angiogram. A 59-year-old man with no prior medical illness experienced progressive weakness of both upper extremities and a partial complex seizure. Magnetic resonance imaging of his brain revealed a well-circumscribed enhancing mass in the left frontal lobe with extension to the right frontal lobe and invasion of the superior sagittal sinus. Both patients underwent resection of their brain masses. Pathological studies identified the disease as RDD in both patients.
Ching-Chung Ko, Tai-Yuan Chen, Sher-Wei Lim, Yu-Ting Kuo, Te-Chang Wu and Jeon-Hor Chen
A subset of benign, nonfunctioning pituitary macroadenomas (NFMAs) has been shown to undergo early progression/recurrence (P/R) during the first years after surgical resection. The aim of this study was to determine preoperative MR imaging features for the prediction of P/R in benign solid NFMAs, with emphasis on apparent diffusion coefficient (ADC) values.
We retrospectively investigated the preoperative MR imaging features for the prediction of P/R in benign solid NFMAs. Only the patients who had undergone preoperative MRI and postoperative MRI follow-ups for more than 1 year (at least every 6–12 months) were included. From November 2010 to December 2016, a total of 30 patients diagnosed with benign solid NFMAs were included (median follow-up time 45 months), and 19 (63.3%) patients had P/R (median time to P/R 24 months).
Benign solid NFMAs with cavernous sinus invasion, failed chiasmatic decompression, large tumor height and tumor volume, high diffusion-weighted imaging (DWI) signal, and lower ADC values/ratios were significantly associated with P/R (p < 0.05). The cutoff points of ADC value and ADC ratio for prediction of P/R are 0.77 × 10−3 mm2/sec and 1.01, respectively, with area under the curve (AUC) values (0.9 and 0.91) (p < 0.01). In multivariate Cox proportional hazards analysis, low ADC value (< 0.77 × 10−3 mm2/sec) is a high-risk factor of P/R (p < 0.05) with a hazard ratio of 14.07.
Benign solid NFMAs with low ADC values/ratios are at a significantly increased risk of P/R, and aggressive treatments accompanied by close follow-up with imaging studies should be considered.
Chia-Hua Chen, Pin-Yuan Chen, You-Yu Lin, Li-Ying Feng, Shin-Han Chen, Chia-Yuan Chen, Yin-Cheng Huang, Chiung-Yin Huang, Shih-Ming Jung, Leslie Y. Chen and Kuo-Chen Wei
Despite intensive medical treatment, patients with glioblastoma (grade IV glioma [GBM]) have a low 5-year survival rate of 5.5%. In this study, the authors tried to improve currently used therapies by identification of a therapeutic target, IGFBP3, for glioma treatment.
IGFBP3 RNA expression in 135 patients newly diagnosed with glioma was correlated with clinicopathological factors. Immunohistochemical analysis was performed to determine IGFBP3 protein expression in glioma specimens. The effect of IGFBP3 depletion on cell proliferation was examined using IGFBP3 knockdown glioma cells. Intracranial infusion of IGFBP3 siRNAs was performed to evaluate the effect of IGFBP3 depletion in mouse intracranial xenograft models.
We demonstrated higher IGFBP3 expression in GBM than in tumor margin and grade II glioma. IGFBP3 expression was not only positively correlated with tumor grades but also associated with tumor histology and IDH1/2 mutation status. Additionally, higher IGFBP3 expression predicted shorter overall survival in glioma and GBM proneural subgroup patients. In vitro cell culture studies suggested IGFBP3 knockdown suppressed cell proliferation and induced cell cycle G2/M arrest as well as apoptosis in glioma cells. Also, accumulation of DNA double-strand breaks and γH2AX was observed in IGFBP3 knockdown cells. IGFBP3 knockdown delayed in vivo tumor growth in mouse subcutaneous xenograft models. Furthermore, convection-enhanced delivery of IGFBP3 siRNA to mouse brain suppressed intracranial tumor growth and prolonged survival of tumor-bearing mice.
Our findings suggest IGFBP3 predicts poor outcome of glioma patients and is a potential therapeutic target for which depletion of its expression suppresses tumor growth through inducing apoptosis and accumulation of DNA damage in glioma cells.
Ching-Chang Chen, Peng-Wei Hsu, Shih-Tseng Lee, Chen-Nen Chang, Kuo-Chen Wei, Chieh-Tsai Wu, Yung-Hsin Hsu, Tzu-Kang Lin, Sai-Cheung Lee and Yin-Cheng Huang
Liver cirrhosis was identified as an independent predictor of poor outcomes in patients suffering trauma and in those undergoing major surgeries. The aim of this study was to report the authors' experiences treating patients with cirrhosis who undergo brain surgeries.
Between 2004 and 2009, 121 consecutive patients with cirrhosis underwent 144 brain procedures. Patients were categorized as Child-Turcotte-Pugh (referred to as “Child”) Class A, B, or C. The patient profiles, including the severity of cirrhosis, reason for surgery, complications, and prognosis factors, were analyzed.
In this retrospective study, the overall surgical complication rate for patients with cirrhosis was 52.1% and the mortality rate was 24.3%. For patients with acute traumatic brain injury (TBI), the complication, rebleeding, and mortality rates reached 84.4%, 68.8%, and 37.5%, respectively. Surgery for TBI was a significant risk factor for postoperative complications (p = 0.0002) and postoperative hemorrhage (p < 0.0001). Otherwise, according to the Child classification, the complication rate increased in a stepwise fashion from 38.7% to 60% to 84.2%, the rebleeding rate from 29.3% to 48.0% to 63.2%, and the mortality rate from 5.3% to 38% to 63.2% for Child A, B, and C, respectively. The Child classification was associated with higher risk of complications—Child B vs A OR 2.84 (95% CI 1.28–6.29), Child C vs A OR 5.39 (95% CI 1.32–22.02). It was also associated with risk of death—Child C vs A OR 30.43 (95% CI 7.71–120.02), Child B vs A OR 10.88 (95% CI 3.42–34.63).
Liver cirrhosis is a poor comorbidity factor for brain surgery. The authors' results suggest that the Child classification used independently is a poor prognostic factor; in addition, grave outcomes were observed in patients with TBI.