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Clinical results of Gamma Knife surgery for cavernous sinus hemangiomas

Clinical article

Peng Li, Haibo Ren, Shizhen Zhang, and Wei Wang

Object

The purpose of this study was to gain an understanding of the efficacy and safety of Gamma Knife surgery (GKS) for the treatment of cavernous sinus hemangiomas (CSHs). The authors report on 16 patients who underwent GKS as a primary or adjuvant treatment for CSH.

Methods

Sixteen patients harboring CSHs (14 women and 2 men ranging in age from 21 to 65 years [mean 41.3 years]) underwent GKS at West China Hospital. In 4 patients the diagnosis was based on histological findings; in the other 12 patients it was based on findings on MR images. After patients were given a local anesthetic agent, the treatments were performed using a Leksell Gamma Knife model C. Gadolinium-enhanced MR images of T1-weighted, T2-weighted, and FLAIR sequences were obtained to determine the pretreatment location of the lesion. A mean peripheral dose of 13.3 Gy (range 11–14 Gy) was directed to the 40%–50% isodose line.

Results

The mean follow-up time in this study was 21.5 months (range 12–36 months). In 11 of 12 patients with symptoms, clinical improvement was reported at an average of 3.3 months (range 1–8 months) after GKS. Significant or partial tumor shrinkage was observed in 14 patients (87.5%) at the last follow-up. No new neurological impairments were reported after GKS.

Conclusions

Magnetic resonance imaging may play an important role in the preoperative diagnosis of CSHs. Gamma Knife surgery may be a safe and effective primary or adjuvant treatment option for CSHs; however, long-term follow-up with more cases is needed to verify the benefits of this treatment.

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Improved functional outcome in NTOS patients following resection of the subclavius muscle with radiological signs of nerve impingement: indication of participation of the subclavius in brachial plexus compression

Yanxi Liu, Zhan Zhang, Jiangbo Wang, Guangzhi Wu, Wei Yu, and Shusen Cui

OBJECTIVE

Both clinical and radiological reports have suggested that the subclavius, a muscle in the costoclavicular space of the thoracic outlet, participates in neurogenic thoracic outlet syndrome (NTOS) in some instances, especially during movements narrowing the costoclavicular space. Magnetic resonance imaging can identify subclavius muscles with signs of nerve impingement, yet the impact of the subclavius in such situations remains unclear. Therefore, the authors investigated whether dividing or sparing the subclavius characterized by nerve impingement on MRI would affect surgical outcomes.

METHODS

In this retrospective nonrandomized study, authors analyzed all NTOS patients with a subclavius muscle characterized by nerve impingement on MRI (loss of normal fat planes surrounding the brachial plexus) in the period between March 2010 and November 2016. Patients were divided into two groups: the sparing group, in which patients had undergone conventional supraclavicular scalenectomy and first rib resection (FRR), and the dividing group, in which patients had undergone scalenectomy, FRR, and subclavius dividing using a modified supraclavicular incision. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, a shoulder range of motion subscale (DASH items 6, 12–15, and 19) concerning overhead activities that can significantly narrow the costoclavicular space, postoperative MRI studies, and patient self-assessments were used to assess surgical outcomes. Univariate and multivariate analyses were conducted to identify independent factors associated with subscale scores.

RESULTS

From a total of 261 patients screened, 71 were eligible for study inclusion. Compared with the sparing group (33 patients), the dividing group (38 patients) had similar postoperative DASH scores and self-assessments but better subscale scores (9.50 ± 2.76 vs 11.94 ± 2.87, p = 0.0005). Postoperative MRI on hyperabduction showed that the brachial plexus became surrounded by normal fat tissue in the costoclavicular space in the diving group but still had signs of impingement from the untreated subclavius muscle in the sparing group. This observation agreed with a better functional recovery in terms of overhead activities in the dividing group, which was reflected by better subscale scores. Multivariate analyses indicated that the type of treatment and symptom duration prior to surgery influenced the subscale scores independently.

CONCLUSIONS

This study revealed that an untreated radiological nerve-compressing subclavius muscle could lead to a relatively lower degree of recovery in the ability to perform overhead activities for NTOS patients postoperatively, suggesting that such subclavius muscles may participate in positional brachial plexus compression during movements narrowing the costoclavicular space. Dividing the muscles could decompress the costoclavicular space more effectively and may lead to better functional recovery.

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Letter to the Editor. Stimulating cholinergic neurons causes urinary incontinence after DBS of the Gpi

Wei Liu and Jian-Guo Zhang

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Communication between malignant glioma cells and vascular endothelial cells through gap junctions

Wei Zhang, Joseph A. DeMattia, Hua Song, and William T. Couldwell

Object. Extensive invasion and angiogenesis are hallmark features of malignant gliomas. Communication between malignant glioma cells and surrounding astrocytes occurs, resulting in transformation of the astrocytic phenotype. In the present study, the authors examined whether malignant glioma cells and vascular endothelial cells (VECs) communicate through the formation of gap junctions and whether this communication influences angiogenesis.

Methods. Connexin43 (Cx43), a gap junction protein expressed in glioma cells, was identified in human umbilical VECs (HUVECs). Immunocytochemical staining for Cx43 demonstrated immunoreactive plaques at areas of cell—cell contact among HUVECs as well as between HUVECs and Cx43-expressing malignant glioma cells. Dye transfer, performed using the gap junction—permeable dye dicarboxy-dichlorofluorescein diacetate (CDCF), among these cocultures indicated that these were functional communications. Calcium signaling also occurred from malignant glioma cells to HUVECs. Tube formation by HUVECs cocultured with Cx43-transfected T98G malignant glioma cells (T98G-Cx43 cells) or with U87MG malignant glioma cells, which naturally express Cx43, was significantly increased compared with tube formation by HUVECs alone. The difference in tube formation by HUVECs cocultured with empty vector—transfected T98G glioma cells (T98G-mock cells) or with Cx43-deficient U373MG malignant glioma cells and tube formation by HUVECs alone was not statistically significant. Furthermore, the concentration of vascular endothelial growth factor (VEGF), an angiogenic factor important for the induction of angiogenesis and blood vessel formation, was significantly higher in medium harvested from cultures of T98G-Cx43 cells than in that harvested from cultures of control T98G-mock cells. Human malignant glioma U87MG cells also secreted increased concentrations of VEGF as compared with HUVECs alone. Nevertheless, there was no statistically significant difference in tube formation by HUVECs cultured in medium conditioned by either Cx43-expressing or Cx43-deficient glioma cells, suggesting that the direct gap junction communication between glioma cells and HUVECs may play a much more significant role than the increased VEGF secretion in vascular tube formation in this assay.

Conclusions. These results indicate that functional gap junction formation between human malignant glioma cells and VECs occurs. This communication appears to influence tumor angiogenesis. Targeting gap junction signaling may offer a potential mechanism for therapy in patients with these tumors.

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Paravertebral glomangiomatosis

Case report

Ping Zhou, Hongying Zhang, Hong Bu, Xiangli Yin, Rui Zhang, Jing Fu, Zhang Zhang, Huijiao Chen, Bing Wei, and Xi Liu

Glomangiomatosis is benign but may manifest as diffusely, locally infiltrating lesions and recur after simple excision. However, conservative treatment should be advocated. The authors report a recent case in which the lesion occurred in the paravertebral area. The patient was a 39-year-old Chinese man who complained of chronic lumbago for 20 years. The clinicopathological features, in conjunction with the immunostaining pattern and ultrastructural features, confirmed the diagnosis. Glomangiomatosis is an extremely rare soft-tissue lesion. To the best of authors' knowledge, only 10 cases have been reported in the English-language literature worldwide, and the current case is the first to represent a lesion arising from the paravertebral area. The authors review the English-language literature in glomangiomatosis.

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Primary medulla oblongata teratomas

Report of 2 cases

Da Li, Shu-Yu Hao, Zhen Wu, Li-Wei Zhang, and Jun-Ting Zhang

Medulla oblongata teratomas are rare. The authors report 2 new cases of teratomas that occurred exclusively in the medulla oblongata. The first case was in a 9-year-old boy who presented with a 6-month history of neck pain and repeated paroxysmal vomiting. Based on preoperative radiographic findings, the initial diagnosis was of an intraaxial medulla oblongata hemangioblastoma. Intraoperatively, the cystic component of the tumor was gray, gelatinous, and soft in consistency. The solid component was light pink, rubbery, and nodular in appearance, with an identifiable boundary. The lesion was completely removed. Histopathological investigation revealed a mature teratoma. Postoperatively, the patient was supported with ventilator assistance and received a tracheotomy, but died of intracranial infection. The second case was in a 10-year-old boy with intermittent headache for 1 month. Radiographs revealed an exophytic cystic and solid lesion with dorsal involvement of the medulla oblongata. The lesion was predominantly solid, pinkish gray, tenacious, and moderately vascularized, with clearly delineated surgical dissection planes. The histopathological examination confirmed a diagnosis of immature teratoma. Total resection was achieved, followed by postoperative chemotherapy. He was alive without recurrence of the lesion or symptoms at 59 months after surgery.

Resection of medulla oblongata teratoma is challenging, with inherent surgical risks that are contingent on the tumor growth pattern. Teratomas should be considered in the differential diagnosis of brainstem lesions. Chemotherapy has been suggested for immature teratomas. Long-term follow-up and larger studies of teratomas in unusual locations are required to improve practitioners' understanding of this disease's treatment and outcomes.

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Destructive pathological changes in the rat spinal cord due to chronic mechanical compression

Laboratory investigation

Peng Xu, Wei-Ming Gong, Yao Li, Tao Zhang, Kai Zhang, De-Zhen Yin, and Tang-Hong Jia

Object

Chronic mechanical compression of the spinal cord, which is commonly caused by degeneration of the spine, impairs motor and sensory functions insidiously and progressively. Yet the exact mechanisms of chronic spinal cord compression (SCC) remain to be elucidated. To study the pathophysiology of this condition, the authors developed a simple animal experimental model that reproduced the clinical course of mechanical compression of the spinal cord.

Methods

A custom-designed compression device was implanted on the exposed spinal cord of female Wistar rats between the T-7 and T-9 vertebrae. A root canal screw attached to a plastic plate was tightened 1 complete turn (1 pitch) every 7 days for 6 weeks. The placement of the compression device and the degree of compression were validated every week using radiography. Furthermore, a motor sensory deficit index was also calculated every week. After 3, 6, 9, or 12 weeks, the compressed T7–9 spinal cords were harvested and examined histologically.

Results

Lateral projection of the thoracic spine showed a progressively increasing rate of mean spinal cord narrowing in the compression group. Motor and sensory deficiencies were observed from Week 3 onward; paralysis was observed in 2 rats at Week 12. Motor deficiency appeared earlier than sensory deficiency. Obvious pathological changes were observed starting at Week 6. The number of neurons in the gray matter of rats with chronic compression of the spinal cord decreased progressively in the 6- and 9-week compression groups. In the white matter, myelin destruction and loss of axons and glia were noted. The number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL)–positive neurons increased in the ventral-to-dorsal direction. The number of TUNEL-positive cells increased from Week 6 onward and peaked at Week 9.

Conclusions

This practical model accurately reproduces characteristic features of clinical chronic SCC, including progressive motor and sensory disturbances after a latency and insidious neuronal loss.

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Hemorrhage risks and functional outcomes of untreated brainstem cavernous malformations

Clinical article

Da Li, Shu-Yu Hao, Gui-Jun Jia, Zhen Wu, Li-Wei Zhang, and Jun-Ting Zhang

Object

Cerebral cavernous malformations have been studied widely, but the natural history of brainstem cavernous malformations (CMs) is not well defined, and hemorrhages caused by brainstem CMs are devastating. The goal of this study was to quantify the hemorrhage risks and functional outcomes of patients with brainstem CMs.

Methods

This prospective, longitudinal, cohort study included patients with brainstem CMs diagnosed between 1985 and 2012. The clinical courses of all patients were recorded. Predictors of hemorrhage and the overall untreated outcomes were evaluated.

Results

A total of 331 patients (46.5% female) were included, with a mean follow-up duration of 6.5 years. The annual hemorrhage rates in patients initially presenting with hemorrhage with (n = 215) or without (n = 34) focal neurological deficits were 15.9% and 12.4%, respectively. However, the annual hemorrhage rate was 8.7% in patients initially presenting without hemorrhage (n = 82). The risk factors for hemorrhage were female sex (hazard ratio [HR] 1.445, p = 0.041), prior hemorrhage (HR 1.277, p = 0.029), and perilesional edema (HR 1.830, p = 0.002). Overall, neurological function at the most recent assessment was improved compared with neurological function at diagnosis. Additionally, 307 patients (92.7%) improved or stabilized, 268 (81.0%) lived independently, and 95 (28.7%) completely recovered. Predictors favoring complete recovery were no prospective hemorrhage (HR 1.958, p = 0.001), younger age (HR 1.268, p = 0.001), and small lesion size (HR 1.578, p = 0.004).

Conclusions

Patients' initial presentation predicts their prospective annual hemorrhage rate. This study suggests that several strong risk factors for hemorrhage and predictors of brainstem CM outcomes may enable clinicians to evaluate the potential hemorrhage risks of their patients and design personalized treatments.

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A study of cognitive function in treatment-refractory obsessive-compulsive disorder treated with capsulotomy

Feilong Gong, Peng Li, Bin Li, Shizhen Zhang, Xinjie Zhang, Sen Yang, Hongbin Liu, and Wei Wang

OBJECTIVE

Anterior capsulotomy (AC) is sometimes used as a last resort for treatment-refractory obsessive-compulsive disorder (OCD). Previous studies assessing neuropsychological outcomes in patients with OCD have identified several forms of cognitive dysfunction that are associated with the disease, but few have focused on changes in cognitive function in OCD patients who have undergone surgery. In the present study, the authors investigated the effects of AC on the cognitive function of patients with treatment-refractory OCD.

METHODS

The authors selected 14 patients with treatment-refractory OCD who had undergone bilateral AC between 2007 and 2013, 14 nonsurgically treated OCD patients, and 14 healthy control subjects for this study. The 3 groups were matched for sex, age, and education. Several neuropsychological tests, including Similarities and Block Design, which are subsets of the Wechsler Abbreviated Scale of Intelligence; Immediate and Delayed Logical Memory and Immediate and Delayed Visual Reproduction, which are subsets of the Wechsler Memory Scale–Revised; and Corrects, Categories, Perseverative Errors, Nonperseverative Errors, and Errors, subtests of the Wisconsin Card Sorting Test, were conducted in all 42 subjects at baseline and after AC, after nonsurgical treatment, or at 6-month intervals, as appropriate. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to measure OCD symptoms in all 28 OCD patients.

RESULTS

The Y-BOCS scores decreased significantly in both OCD groups during the 12-month follow-up period. Surgical patients showed higher levels of improvement in verbal memory, visual memory, visuospatial skills, and executive function than the nonsurgically treated OCD patients.

CONCLUSIONS

The findings of this study suggest that AC not only reduces OCD symptoms but also attenuates moderate cognitive deficits.

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Primary intracranial malignant melanoma: proposed treatment protocol and overall survival in a single-institution series of 15 cases combined with 100 cases from the literature

Cheng-Bei Li, Lai-Rong Song, Da Li, Jian-Cong Weng, Li-Wei Zhang, Jun-Ting Zhang, and Zhen Wu

OBJECTIVE

The overall survival and pertinent adverse factors for primary intracranial malignant melanoma (PIMM) have not been previously determined. This aim of this study was to determine the rates of progression-free survival (PFS) and overall survival (OS) and identify the adverse factors for PIMM.

METHODS

This study included 15 cases from the authors’ own series and 100 cases with detailed clinical data that were obtained from the literature from 1914 to 2018 using the Ovid Medline, EMBASE, PubMed, Cochrane, and EBSCO databases. Patient demographics, treatment (surgery, chemotherapy, and radiotherapy [RT]), PFS, and OS were reviewed. Data from prior publications were processed and used according to PRISMA guidelines.

RESULTS

Diffuse lesions were identified in 24 (20.9%) patients, who had a younger age (p < 0.001). The mean follow-up time was 16.6 months, and 76 (66.1%) deaths occurred. The 6-month, 1-year, 3-year, and 5-year OS rates of the whole cohort were 62.8%, 49.9%, 28.9%, and 17.2%, respectively, with an estimated median survival time (EMST) of 12.0 months. The multivariate analysis revealed that gross-total resection (GTR) (HR 0.299, 95% CI 0.180–0.497, p < 0.001), radiotherapy (HR 0.577, 95% CI 0.359–0.929, p = 0.024), and chemotherapy (HR 0.420, 95% CI 0.240–0.735, p = 0.002) predicted a better OS. The EMST was 5.0 months in patients with diffuse-type PIMM and 13.0 months in patients with the solitary type. Patients receiving GTR with adjuvant RT and/or chemotherapy (GTR + [RT and/or chemo]) had significantly higher 1-year and 5-year OS rates (73.0% and 40.1%, respectively) and a longer EMST (53 months) than patients who underwent GTR alone (20.5 months) or RT and/or chemotherapy without GTR (13.0 months).

CONCLUSIONS

Optimal outcomes could be achieved by radical resection plus postoperative radiotherapy and/or chemotherapy. Patients with diffuse PIMM have a more severe clinical spectrum and poorer survival than patients with solitary PIMM. Immunotherapy and targeted therapy show promise as treatment options for PIMM based on results in patients with brain metastases from extracranial melanoma.