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Gerhard M. Friehs, Joseph Legat, Zhen Zheng, Gerhard Pendl and Georg C. Noren

In order to determine the effectiveness of gamma knife (GK) radiosurgery in patients with malignant melanoma metastases, the authors conducted a prospective multicenter study. :Forty-five patients with a total of 96 lesions were treated and followed to measure survival time, tumor control rate, and Karnofsky Performance Scale (KPS) score. The mean survival time was 8.7 months (median 4.2 months), and tumor control was achieved in 86% of lesions. When obtained, the median preoperative KPS of 80 was maintained at a median of 80 post-GK treatment.

The authors found GK treatment for metastases of malignant melanoma to be highly effective in controlling tumor growth. Survival rates obtained after GK treatment were found to be superior to historically obtained data concerning external beam radiotherapy follow up. Radiosurgery with the GK can therefore be considered a good primary treatment option for metastatic brain disease of malignant melanoma.

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Zhen Zheng, Douglas Shearer, Georg Norén, Prakash Chougule and Gerhard Friehs

✓ This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program.

A 12 × 12 × 12—cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references.

The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm.

The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

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Steven T. Cobery, Georg Noren, Gerhard M. Friehs, Prakash Chougule, Zhen Zheng, Mel H. Epstein and William Taylor

✓ The authors investigated the use of gamma knife surgery (GKS) in the treatment of central neurocytoma, a usually benign primary brain tumor of the lateral and third ventricles. Four patients with subtotally resected or recurrent central neurocytomas were retrospectively studied. The prescription isodose was 9 to 13 Gy to the 30 to 50% peripheral isodose line. Pre- and postoperative magnetic resonance (MR) images were compared to determine the volume reduction following GKS. Follow-up review included annual MR imaging and clinical evaluation by a neurosurgeon. Follow-up periods ranged from 12 to 99 months.

Marked reduction in tumor size was seen in all four patients; the decrease in tumor volume for each was 48%, 72%, 81%, and 77%, respectively, at the last follow-up review. None of the four patients required additional treatment and none experienced a decline in neurological function during the follow-up period. No complications have been noted in any of these patients to date. Even though there have been few observations and follow-up time has been limited, because of the consistency of the response and the lack of observed side effects, GKS may be the treatment of choice for subtotally resected and recurrent central neurocytomas.

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Zachary N. Litvack, Georg Norén, Prakash B. Chougule and Zhen Zheng

Object

The goal of this retrospective study was to define the rates of preservation of functional hearing and growth control of vestibular schwannomas (VS) treated by gamma knife surgery (GKS) involving a consistent 12-Gy prescription dose.

Methods

One hundred thirty-four patients with unilateral VS underwent GKS between 1994 and 2000. The mean magnetic resonance (MR) imaging follow-up period was 31.7 months (maximum 72 months), and the mean audiometry follow-up interval was 26.3 months (maximum 60 months). The mean marginal dose was 12 ± 0.6 Gy. The mean maximum dose delivered to the tumor center was 25.4 Gy (range 17.4–34.3 Gy). The tumor control rate, defined as no change or a reduction in size at last follow up, was 96.7%. Of the patients studied, 97.7% remained free from the need to undergo tumor resection. Overall functional hearing preservation was 61.7%; the preservation rate for intra-canalicular tumors was 63.6%, for those with an intracranial diameter less than 1.5 cm it was 54.5%, for those between 1.5 and 3 cm it was 68.2%, and for those larger than 3 cm it was 33.3%. Early in the series, three patients (2.2%) developed temporary facial weakness (House–Brackmann Grade II–III) in the posttreatment period, but this resolved within a few weeks. No case of facial weakness occurred after 1996.

Conclusions

The authors demonstrated the efficacy, safety, and in many ways, the advantage of GKS over microsurgery for VS. Patients harboring tumors 3 cm or smaller in intracranial diameter, regardless of their age and medical condition, should be given the option of undergoing GKS as primary treatment.

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Peng-Fan Yang, Hui-Jian Zhang, Jia-Sheng Pei, Qiao Lin, Zhen Mei, Zi-Qian Chen, Yan-Zeng Jia, Zhong-Hui Zhong and Zhi-Yong Zheng

OBJECT

The objectives of this study were to describe a novel minimal-access subtemporal approach for selective resection of the amygdala and hippocampus in patients with medically refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis, and to analyze the related outcomes.

METHODS

The authors analyzed data from all cases involving patients with unilateral MTLE due to hippocampal sclerosis who were treated with selective amygdalohippocampectomy via the posterior subtemporal approach through a relatively small craniotomy, without a neuronavigation system, at their institution during the period from September 2010 to September 2012. Data were obtained on baseline characteristics, preoperative evaluations of unilateral mesial temporal sclerosis, surgical complications, and Engel class seizure outcomes. All patients underwent memory testing, IQ testing, and language testing.

RESULTS

The mean duration of follow-up was 33.6 months (range 24–48 months). There were no deaths and no cases of significant postoperative morbidity. One patient had a mild complication. At 2-year follow-up, 19 patients were seizure free (Engel Class I outcome). Verbal memory scores obtained at 3 months and at 2 years after surgery were significantly lower than preoperative scores for patients who underwent surgery on the left side of the brain (p < 0.05). Pictorial memory scores were higher following surgery compared with before surgery regardless of whether patients underwent left- or right-sided brain surgery. There was also improvement in performance IQ and total IQ following surgery in both groups. For patients who underwent right-sided brain surgery, verbal comprehension and semantic fluency testing scores were significantly higher at both 3 months and 2 years after surgery than before surgery. For patients who underwent left-sided brain surgery, scores on all language tests were significantly lower at 3 months after surgery than before surgery. Verbal comprehension testing scores returned to the preoperative level at 2 years after surgery.

CONCLUSIONS

The posterior subtemporal approach through a relatively small craniotomy allows adequate exposure and safe resection of mesial temporal structures and effectively reduces medically intractable MTLE. It preserves IQ but may have a detrimental effect on verbal memory and language ability.

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Jian Zheng, Zhen Liu, Weishan Li, Jiaxin Tang, Dongwei Zhang and Xiaobo Tang

OBJECTIVE

Inflammation and apoptosis are two key factors contributing to secondary brain injury after intracerebral hemorrhage (ICH). The objective of this study was to evaluate the effects of lithium posttreatment on behavior, brain atrophy, inflammation, and perihematomal cell death. Furthermore, the authors aimed to determine the role of the pro-apoptotic glycogen synthase kinase-3β (GSK-3β) after experimental ICH.

METHODS

Male Sprague-Dawley rats (n = 108) were subjected to intracerebral infusion of semicoagulated autologous blood. Window of opportunity and dose optimization studies of lithium on ICH-induced injury were performed by measuring neurological deficits. Animals with ICH received vehicle administration or lithium posttreatment (60 mg/kg) for up to 21 days. Hemispheric atrophy was evaluated. Perihematomal cell death was quantified through terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The number of myeloperoxidase (MPO)-positive neutrophils and OX42-positive microglia in the perihematomal areas were calculated. Western blotting was used for the quantification of GSK-3β, heat shock protein 70 (HSP70), nuclear factor-κB p65 (NF-κB p65), and cy-clooxygenase-2 (COX-2).

RESULTS

Lithium, at a dose of 60 mg/kg initiated from 2 hours after injury, exhibited the best effects of improving neurological outcomes 3, 5, 7, 14, 21, and 28 days after ICH, reduced the hemispheric atrophy at 42 days after surgery, and reduced the number of TUNEL-positive cells, MPO-positive neutrophils, and OX42-positive microglia in the perihematomal areas. Furthermore, lithium posttreatment modulated GSK-3β, increased HSP70, and decreased NF-κB p65 and COX-2 expression in the ipsilateral hemisphere.

CONCLUSIONS

Lithium posttreatment at a dose of 60 mg/kg, initiated beginning 2 hours after injury, improves functional and morphological outcomes, and inhibits inflammation and perihematomal cell death in a rat model of semicoagulated autologous blood ICH through inactivation of GSK-3β.

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Kai-Bing Tian, Jing-Jie Zheng, Jun-Peng Ma, Shu-Yu Hao, Liang Wang, Li-Wei Zhang, Zhen Wu, Jun-Ting Zhang and Da Li

OBJECTIVE

The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs.

METHODS

This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed.

RESULTS

A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (χ2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336–5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275–4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic pres entation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272–9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815–6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023–15.855, p < 0.001) had a greater chance of worsened neurological status.

CONCLUSIONS

This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

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Jing-Jie Zheng, Gui-Jun Zhang, Xu-Lei Huo, Liang Wang, Shu-Yu Hao, Li-Wei Zhang, Zhen Wu, Yu-Mei Wu, Jun-Ting Zhang and Da Li

OBJECTIVE

Primary intracranial rhabdomyosarcoma (PIRMS) is rare, and the effects of the treatment strategy on overall survival (OS) are unclear. This study aimed to evaluate risk factors pertinent to OS and to propose an optimal treatment strategy.

METHODS

Clinical data of patients with PIRMS treated at Beijing Tiantan Hospital and from the English-language literature between 1946 and 2018 were reviewed. A literature review was performed via Ovid, MEDLINE, Embase, PubMed, Web of Science, and Cochrane databases using the terms “rhabdomyosarcoma,” “intracranial,” “cerebral,” and “brain.” Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS

There were 8 males (66.7%) and 4 females with PIRMS at our institution, with a mean age of 24.3 years. Gross-total resection was achieved in 4 patients (33.3%), and adjuvant radiation and chemotherapy were administered in 5 (45.5%) and 3 (27.3%) patients, respectively. After a mean follow-up period of 13.7 months, all patients developed local-regional recurrence and died of the disease. Twenty-nine cases (14 female and 15 male) were reported in the literature with a median age of 9.0 years. After a mean follow-up duration of 18.6 months, 13 patients (44.8%) developed recurrences, 7 patients (24.1%) had extracranial metastasis, and 14 patients (48.3%) died. In the pooled cases, adjuvant radiation (hazard ratio [HR] 0.089, 95% confidence interval [CI] 0.027–0.288, p < 0.001) and age < 10 years (HR 0.227, 95% CI 0.077–0.666, p = 0.007) were independent predictors of good local-regional progression-free survival (LR-PFS). Adjuvant radiation therapy (HR 0.301, 95% CI 0.110–0.828, p = 0.020) and age < 10 years (HR 0.359, 95% CI 0.131–0.983, p = 0.046) were significant predictors for favorable OS in the multivariate model.

CONCLUSIONS

Due to the rarity of the disease, a poor outcome of PIRMS was demonstrated based on the pooled cohort. Use of radiation was associated with improved outcomes and should be considered to improve OS/LR-PFS. Further study is required to identify the optimal treatment regimen.

Systematic review no.: CRD42019121249 (crd.york.ac.uk/PROSPERO/)