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
Chun-Wei Yu, Kuan-Ting Chen, Yu-Lan Liu, Yi-Chiao Hsieh, Dun-Wei Huang, Yi-Feng Lee, Tsui-Jung Chien, and Dueng-Yuan Hueng
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.
Fengping Zhu, Yi Qian, Bin Xu, Yuxiang Gu, Kaavya Karunanithi, Wei Zhu, Liang Chen, Ying Mao, and Michael K. Morgan
Although intracranial vessel remodeling has been observed in moyamoya disease, concerns remain regarding the effect of bypass surgery on hemodynamic changes within the internal carotid artery (ICA). The authors aimed to quantify the surgical effect of bypass surgery on bilateral ICAs in moyamoya disease and to estimate pressure drop (PD) along the length of the ICA to predict surgical outcomes.
Records of patients who underwent bypass surgery for treatment of moyamoya disease and in whom flow rates were obtained pre- and postsurgery by quantitative MR angiography were retrospectively reviewed. Quantitative MR angiography and computational fluid dynamics were applied to measure morphological and hemodynamic changes during pre- and postbypass procedures. The results for vessel diameter, volumetric flow, PD, and mean wall shear stress along the length of the ICA were analyzed. Subgroup analysis was performed for the circle of Willis (CoW) configurations.
Twenty-three patients were included. The PD in ICAs on the surgical side (surgical ICAs) decreased by 21.18% (SD ± 30.1%) and increased by 11.75% (SD ± 28.6%) in ICAs on the nonsurgical side (contralateral ICAs) (p = 0.001). When the PD in contralateral ICAs was compared between patients with a complete or incomplete CoW, the authors found that the PDI in the former group decreased by 2.45% and increased by 20.88% in the latter (p = 0.05). Regression tests revealed that a greater postoperative decrease in PD corresponded to shrinking of ICAs (R2 = 0.22, p = 0.02).
PD may be used as a reliable biomechanical indicator for the assessment of surgical treatment outcomes. The vessel remodeling characteristics of contralateral ICA were related to CoW configurations.
Chun-Lung Chou, Hsin-Hung Chen, Huai-Che Yang, Yi-Wei Chen, Ching-Jen Chen, Yu-Wei Chen, Hsiu-Mei Wu, Wan-Yuo Guo, David Hung-Chi Pan, Wen-Yuh Chung, Tai-Tong Wong, and Cheng-Chia Lee
Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival.
This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group.
The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0–16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1–56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409).
The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors’ results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.
Ching-Chang Chen, Shao-Wei Chen, Po-Hsun Tu, Yin-Cheng Huang, Zhuo-Hao Liu, Alvin Yi-Chou Wang, Shih-Tseng Lee, Tien-Hsing Chen, Chi-Tung Cheng, Shang-Yu Wang, and An-Hsun Chou
Burr hole craniostomy is an effective and simple procedure for treating chronic subdural hematoma (CSDH). However, the surgical outcomes and recurrence of CSDH in patients with liver cirrhosis (LC) remain unknown.
A nationwide population-based cohort study was retrospectively conducted using data from the Taiwan National Health Insurance Research Database. The study included 29,163 patients who underwent first-time craniostomy for CSDH removal between January 1, 2001, and December 31, 2013. In total, 1223 patients with LC and 2446 matched non-LC control patients were eligible for analysis. All-cause mortality, surgical complications, repeat craniostomy, extended craniotomy, and long-term medical costs were analyzed.
The in-hospital mortality rate (8.7% vs 3.1% for patients with LC and non-LC patients, respectively), frequency of hospital admission, length of ICU stay, number of blood transfusions, and medical expenditures of patients with LC who underwent craniostomy for CSDH were considerably higher than those of non-LC control patients. Patients with LC tended to require an extended craniotomy to remove subdural hematomas in the hospital or during long-term follow-up. The surgical outcome worsened with an increase in the severity of LC.
Even for simple procedures following minor head trauma, LC remains a serious comorbidity with a poor prognosis.
Po-Chuan Hsieh, Yi-Ming Wu, Alvin Yi-Chou Wang, Ching-Chang Chen, Chien-Hung Chang, Shy-Chyi Chin, Tai-Wei Erich Wu, Chieh-Tsai Wu, and Shih-Tseng Lee
Diverse treatment results are observed in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). Significant initial perfusion compromise is thought to predict a worse treatment outcome, but this has scant support in the literature. In this cohort study, the authors correlate the treatment outcomes with a novel poor-outcome imaging predictor representing impaired cerebral perfusion on initial CT angiography (CTA).
The authors reviewed the treatment results of 148 patients with poor-grade aSAH treated at a single tertiary referral center between 2007 and 2016. Patients with the “venous delay” phenomenon on initial CTA were identified. The outcome assessments used the modified Rankin Scale (mRS) at the 3rd month after aSAH. Factors that may have had an impact on outcome were retrospectively analyzed.
Compared with previously identified outcome predictors, the venous delay phenomenon on initial CTA was found to have the strongest correlation with posttreatment outcomes on both univariable (p < 0.0001) and multivariable analysis (OR 4.480, 95% CI 1.565–12.826; p = 0.0052). Older age and a higher Hunt and Hess grade at presentation were other factors that were associated with poor outcome, defined as an mRS score of 3 to 6.
The venous delay phenomenon on initial CTA can serve as an imaging predictor for worse functional outcome and may aid in decision making when treating patients with poor-grade aSAH.
Mun-Chun Yeap, Ching-Chang Chen, Zhuo-Hao Liu, Po-Chuan Hsieh, Cheng-Chi Lee, Yu-Tse Liu, Alvin Yi-Chou Wang, Yin-Cheng Huang, Kuo-Chen Wei, Chieh-Tsai Wu, and Po-Hsun Tu
Cranioplasty is a relatively simple and less invasive intervention, but it is associated with a high incidence of postoperative seizures. The incidence of, and the risk factors for, such seizures and the effect of prophylactic antiepileptic drugs (AEDs) have not been well studied. The authors’ aim was to evaluate the risk factors that predispose patients to postcranioplasty seizures and to examine the role of seizure prophylaxis in cranioplasty.
The records of patients who had undergone cranioplasty at the authors’ medical center between 2009 and 2014 with at last 2 years of follow-up were retrospectively reviewed. Demographic and clinical characteristics, the occurrence of postoperative seizures, and postoperative complications were analyzed.
Among the 583 patients eligible for inclusion in the study, 247 had preexisting seizures or used AEDs before the cranioplasty and 336 had no seizures prior to cranioplasty. Of these 336 patients, 89 (26.5%) had new-onset seizures following cranioplasty. Prophylactic AEDs were administered to 56 patients for 1 week after cranioplasty. No early seizures occurred in these patients, and this finding was statistically significant (p = 0.012). Liver cirrhosis, intraoperative blood loss, and shunt-dependent hydrocephalus were risk factors for postcranioplasty seizures in the multivariable analysis.
Cranioplasty is associated with a high incidence of postoperative seizures. The prophylactic use of AEDs can reduce the occurrence of early seizures.
Ichiro Nakano and E. Antonio Chiocca
Tzu-Ming Yang, Wei-Che Lin, Wen-Neng Chang, Jih-Tsun Ho, Hung-Chen Wang, Nai-Wen Tsai, Yi-Ting Shih, and Cheng-Hsien Lu
Seizures are an important neurological complication of spontaneous intracerebral hemorrhage (ICH). A better understanding of the risk factors of seizures following ICH is needed to predict which patients will require treatment.
Two hundred and forty-three adult patients were enrolled in this 1-year retrospective study. Multiple logistic regression was used to evaluate the relationship between baseline clinical factors and the presence or absence of seizure during the study period.
Seizures occurred in 20 patients with ICH, including acute symptomatic seizures in 9 and unprovoked seizures in 11. None progressed to status epilepticus during hospitalization. After a minimum 3-year follow-up period, the mean Glasgow Outcome Scale score was 3.8 ± 1.1 for patients who had had seizures and 3.5 ± 1.3 for those who had not. The multiple logistic regression model demonstrated that the mean ICH volume was independently associated with seizures, and any increase of 1 mm3 in ICH volume increased the seizure rate by 2.7%.
Higher mean ICH volumes at presentation were predictive of seizure, and the presence of late seizures was predictive of developing epilepsy. Most seizures occurred within 2 years of spontaneous ICH over a minimum of 3 years of follow-up.