Analysis of radiosurgical results in patients with brain metastases according to the number of brain lesions: is stereotactic radiosurgery effective for multiple brain metastases?

Chang, Won Seok,Kim, Hae Yu,Chang, Jin Woo,Park, Yong Gou,Chang, Jong Hee Journal of Neurosurgery Publishing Group 2010 Journal of Neurosurgery Vol.113 No.-

<B>Object</B><P>Whole-brain radiation therapy (WBRT), open resection, and stereotactic radiosurgery (SRS) are widely used for treatment of metastatic brain lesions, and many physicians recommend WBRT for multiple brain metastases. However, WBRT can be performed only once per patient, with rare exceptions. Some patients may require SRS for multiple metastatic brain lesions, particularly those patients harboring more than 10 lesions. In this paper, treatment results of SRS for brain metastasis were analyzed, and an attempt was made to determine whether SRS is effective, even in cases involving multiple metastatic brain lesions.</P><B>Methods</B><P>The authors evaluated the cases of 323 patients who underwent SRS between October 2005 and October 2008 for the treatment of metastatic brain lesions. Treatment was performed using the Gamma Knife model C or Perfexion. The patients were divided into 4 groups according to the number of lesions visible on MR images: Group 1, 1-5 lesions; Group 2, 6-10 lesions: Group 3, 11-15 lesions; and Group 4, > 15 lesions. Patient survival and progression-free survival times, taking into account both local and distant tumor recurrences, were analyzed.</P><B>Results</B><P>The patients consisted of 172 men and 151 women with a mean age at SRS of 59 years (range 30-89 years). The overall median survival time after SRS was 10 months (range 8.7-11.4 months). The median survival time of each group was as follows: Group 1, 10 months; Group 2, 10 months; Group 3, 13 months; and Group 4, 8 months. There was no statistical difference between survival times after SRS (log-rank test, p = 0.554), although the probability of development of new lesions in the brain was greater in Group 4 (p = 0.014). Local tumor control rates were not statistically different among the groups (log-rank test, p = 0.989); however, remote disease progression was more frequent in Group 4 (log-rank test, p = 0.014).</P><B>Conclusions</B><P>In this study, patients harboring more than 15 metastatic brain lesions were found to have faster development of new lesions in the brain. This may be due to the biological properties of the patients' primary lesions, for example, having a greater tendency to disseminate hematogenously, especially to the brain, or a higher probability of missed or invisible lesions (microscopic metastases) to treat on stereotactic MR images at the time of radiosurgery. However, the mean survival times after SRS were not statistically different between groups. According to the aforementioned results, SRS may be a good treatment option for local control of metastatic lesions and for improved survival in patients with multiple metastatic brain lesions, even those patients who harbor more than 15 metastatic brain lesions, who, after SRS, may have early and easily detectable new metastatic lesions.</P>

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on glial scar formation after spinal cord injury in rats

Chung, Joonho,Kim, Moon Hang,Yoon, Yong Je,Kim, Kil Hwan,Park, So Ra,Choi, Byung Hyune Journal of Neurosurgery Publishing Group 2014 Journal of Neurosurgery: Spine Vol.21 No.6

<B>Object</B><P>This study investigated the effects of granulocyte colony-stimulating factor (G-CSF) on glial scar formation after spinal cord injury (SCI) in rats and compared the therapeutic effects between G-CSF and granulocytemacrophage colony-stimulating factor (GM-CSF) to evaluate G-CSF as a potential substitute for GM-CSF in clinical application.</P><B>Methods</B><P>Rats were randomly assigned to 1 of 4 groups: a sham-operated group (Group 1), an SCI group without treatment (Group 2), an SCI group treated with G-CSF (Group 3), and an SCI group treated with GM-CSF (Group 4). G-CSF and GM-CSF were administered via intraperitoneal injection immediately after SCI. The effects of G-CSF and GM-CSF on functional recovery, glial scar formation, and axonal regeneration were evaluated and compared.</P><B>Results</B><P>The rats in Groups 3 and 4 showed better functional recovery and more decreased cavity sizes than those in Group 2 (p < 0.05). Both G-CSF and GM-CSF suppressed intensive expression of glial fibrillary acidic protein around the cavity at 4 weeks and reduced the expression of chondroitin sulfate proteoglycans (p < 0.05). Also, early administration of G-CSF and GM-CSF protected axon fibers from destructive injury and facilitated axonal regeneration. There were no significant differences in comparisons of functional recovery, glial scar formation, and axonal regeneration between G-CSF and GM-CSF.</P><B>Conclusions</B><P>G-CSF suppressed glial scar formation after SCI in rats, possibly by restricting the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans, which might facilitate functional recovery from SCI. GM-CSF and G-CSF had similar effects on glial scar formation and functional recovery after SCI, suggesting that G-CSF can potentially be substituted for GM-CSF in the treatment of SCI.</P>

Hypoxia-inducible expression of vascular endothelial growth factor for the treatment of spinal cord injury in a rat model

Choi, Byung Hyune,Ha, Yoon,Huang, Xian,Park, So Ra,Chung, Joonho,Hyun, Dong Keun,Park, Hyeonseon,Park, Hyung Chun,Kim, Sung Wan,Lee, Minhyung Journal of Neurosurgery Publishing Group 2007 Journal of Neurosurgery: Spine Vol.7 No.1

<B>Object</B><P>Vascular endothelial growth factor (VEGF) has been investigated as a therapy for many disorders and injuries involving ischemia. In this report, we constructed and evaluated a hypoxia-inducible VEGF expression system as a treatment for spinal cord injury (SCI).</P><B>Methods</B><P>The hypoxia-inducible VEGF plasmid was constructed using the erythropoietin (Epo) enhancer with the Simian virus 40 (SV40) promoter (pEpo-SV-VEGF) or the RTP801 promoter (pRTP801-VEGF). The expression of VEGF in vitro was evaluated after transfection into N2A cells. The plasmids were then injected into rat spinal cords with contusion injuries. The expression of VEGF in vivo was measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Locomotor recovery in the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale for locomotor analysis.</P><B>Results</B><P>In vitro transfection showed that pEpo-SV-VEGF or pRTP801-VEGF induced VEGF expression under hypoxic conditions, whereas pSV-VEGF did not. The VEGF level was higher in the pEpo-SV-VEGF and pRTP801-VEGF groups than in the control group. The VEGF expression was detected in neurons and astrocytes of the spinal cord. Locomotor recovery was improved in the pEpo-SV-VEGF and pRTP801-VEGF groups, and BBB scores were higher than in the control group. Staining using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling showed that the number of apoptotic cells decreased in the plasmid-injected groups compared with the control group, and significant differences were observed between the hypoxia-responsive groups and the pSV-VEGF group.</P><B>Conclusions</B><P>These results suggest that the hypoxia-inducible VEGF expression system may be useful for gene therapy of SCI.</P>

Cystic vestibular schwannomas: a possible role of matrix metalloproteinase-2 in cyst development and unfavorable surgical outcome

Moon, Kyung-Sub,Jung, Shin,Seo, Seung-Kwon,Jung, Tae-Young,Kim, In-Young,Ryu, Hyang-Hwa,Jin, Yong-Hao,Jin, Shu-Guang,Jeong, Young-Il,Kim, Kyung-Keun,Kang, Sam-Suk Journal of Neurosurgery Publishing Group 2007 Journal of Neurosurgery Vol.106 No.5

<B>Object</B><P>The authors evaluated the clinical manifestations and surgical results in patients with cystic vestibular schwannoma (VS), and investigated the matrix metalloproteinase (MMP) expression of the cyst fluid and wall in an attempt to elucidate the pathogenesis and characteristics of this disease.</P><B>Methods</B><P>The clinical and neuroimaging features, perioperative findings, and surgical outcomes in 24 cases of cystic VS and 82 cases of solid VS, all of which were treated using the suboccipital approach, were retrospectively compared. To evaluate the role of MMP in cystic VS, gelatin zymography and immunohistochemical studies of the cyst fluid, wall, and solid portion were performed in nine cases of this disease.</P><P>The mean duration of symptoms was shorter (14.0 months compared with 26.1 months; p = 0.04) and the mean size of the tumor was larger (43.8 mm compared with 34.2 mm; p = 0.048) in the cystic than the solid VS group. Although gross-total resection was easier to accomplish in this group (100% compared with 84.1%), adhesion to the facial nerve was more frequent (62.5% compared with 48.8%; p = 0.042). On gelatin zymography studies, MMP-2 expression was ubiquitously observed in all cyst fluids. Immunohistochemical analysis of the cyst wall showed that MMP-2 was apparently localized to the tumor cells on the luminal inner surface, adjacent to the cyst cavity.</P><B>Conclusions</B><P>Resection of cystic VS is complicated by severe adhesion of the tumor capsule to the facial nerve and the large size of the lesion. The authors believe that MMP-2 may be involved in the pathogenesis of cyst formation or in its enlargement and may aggravate adhesion to the facial nerve, either by promoting the enlargement of the tumor or engendering the degradation of the tumor-nerve barrier proteolytically.</P>

The biomechanical evaluation of calcium phosphate cements for use in vertebroplasty

Hong, Suk-Joo,Park, Youn-Kwan,Kim, Jung Hyuk,Lee, Soon Hyuck,Ryu, Kyung Nam,Park, Cheol Min,Kim, Yeon Soo Journal of Neurosurgery Publishing Group 2006 Journal of Neurosurgery: Spine Vol.4 No.2

<B>Object</B><P>The authors evaluate the biomechanical properties of vertebral bodies (VBs) stabilized with calcium phosphate (CaP) cements for use in vertebroplasty in comparison with polymethylmethacrylate (PMMA).</P><B>Methods</B><P>In the first phase of the study, 73 VBs (T3-L2; thoracic region [T3-8] and thoracolumbar region [T9-L2]) were collected from seven fresh human cadavers. Compression tests were performed before and after vertebroplasty using PMMA (compression strength 80 MPa) and three kinds of CaP cements-CaP1 (5 MPa), CaP2 (20 MPa), and CaP3 (50 MPa). The authors compared the maximal compression loads (MCLs) and stiffness before and after vertebroplasty in each of the four cement groups. In the second phase of the study, 18 paired spinal units (PSUs) were collected from three fresh human cadavers, and the authors injected two types of cement selected from the first phase of the study into the lower level of six PSUs. They compared the MCLs of the untreated and two treated groups (there were six PSUs in each type of group) to analyze the tendency of inducing compression fractures in the upper level of the PSUs.</P><P>The MCLs of the PMMA-injected vertebrae were significantly increased after vertebroplasty. The MCL levels of the CaP3-injected vertebrae and the CaP2-injected thoracolumbar vertebrae were decreased from those of untreated vertebrae without being significant. The MCLs of CaP1-injected vertebrae and CaP2-injected thoracic vertebrae were significantly decreased after vertebroplasty. The stiffness of all cement groups was decreased after vertebroplasty compared with initial stiffness, significantly so in all three thoracic CaP groups. In the second compression test with PSUs, the MCLs of the CaP2- and CaP3-injected PSUs were not significantly different from those of the untreated control PSUs.</P><B>Conclusions</B><P>The CaP3-injected vertebrae restored the MCLs of human vertebrae closer to their initial levels than the PMMA-injected vertebrae did. The CaP2- and CaP3-injected PSUs showed no tendency to induce compression fractures in adjacent VBs.</P>

Clinical analysis of spinal stereotactic radiosurgery in the treatment of neurogenic tumors

Shin, Dong-Won,Sohn, Moon-Jun,Kim, Han-Seong,Lee, Dong-Joon,Jeon, Sang Ryong,Hwang, Yoon Joon,Jho, Eek-Hoon Journal of Neurosurgery Publishing Group 2015 Journal of Neurosurgery: Spine Vol.23 No.4

<B>OBJECT</B><P>In this study the authors sought to evaluate clinical outcomes after using stereotactic radiosurgery (SRS) to treat benign and malignant spinal neurogenic tumors.</P><B>METHODS</B><P>The authors reviewed a total of 66 procedures of spinal SRS performed between 2001 and 2013 for 110 tumors in 58 patients with spinal neurogenic tumors, which included schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNSTs). The clinical and radiological findings were evaluated in patients with benign neurogenic tumors. For the 4 patients with MPNSTs, the authors reported overall survival and results of additional immunohistochemical staining to predict the survival difference among the patients.</P><B>RESULTS</B><P>Of the 92 benign neurogenic tumors, 65 tumors that were serially followed up using MRI after SRS showed significant change in mean tumor volume, from a mean of 12.0 ± 2.6 cm<SUP>3</SUP> pre-SRS to 10.8 ± 2.5 cm<SUP>3</SUP> post-SRS (p = 0.027), over an average of 44 months. The local control rate of benign neurogenic tumors was 95.4%. The 34 patients who presented with clinical symptoms of pain showed a significant symptomatic improvement. The initial mean visual analog scale (VAS) score was 6.0 and decreased dramatically to 1.0 after SRS during an average follow-up period of 10.9 months (median of 8.1 months). Although the proportions of transient swelling and loss of intramural enhancement were significantly different among the groups, there was no statistically significant correlation between those 2 factors and local tumor control (p = 0.253 and 0.067, respectively; Fisher’s exact text). Cross-table analysis also indicated that there was no statistically significant relationship between groups with loss of intramural enhancement and transient swelling. The median survival of neurofibromatosis Type 1 (NF1)-related and sporadic MPNSTs was 1.13 and 5.8 years, respectively. Immunohistochemical results showed that S100 was expressed in a sporadic MPNST or neurofibroma, whereas topoisomerase-IIa was expressed in NF1-related MPNSTs.</P><B>CONCLUSIONS</B><P>SRS is an effective treatment modality for benign neurogenic tumors, while MPNSTs showed heterogeneity in their responses to SRS.</P>

Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation

Cho, Hee Kyung,Cho, Yun Woo,Kim, Eun Hyuk,Sluijter, Menno E.,Hwang, Se Jin,Ahn, Sang Ho Journal of Neurosurgery Publishing Group 2013 Journal of neurosurgery. Spine Vol.19 No.2

<B>Object</B><P>Herniated discs can induce sciatica by mechanical compression and/or chemical irritation caused by proinflammatory cytokines. Using immunohistochemistry methods in the dorsal horn of a rat model of lumbar disc herniation, the authors investigated the effects of pulsed radiofrequency (PRF) current administration to the dorsal root ganglion (DRG) on pain-related behavior and activation of microglia, astrocytes, and mitogen-activated protein kinase.</P><B>Methods</B><P>A total of 33 Sprague-Dawley rats were randomly assigned to either a sham-operated group (n = 10) or a nucleus pulposus (NP)-exposed group (n = 23). Rats in the NP-exposed group were further subdivided into NP exposed with sham stimulation (NP+sham stimulation, n = 10), NP exposed with PRF (NP+PRF, n = 10), or euthanasia 10 days after NP exposure (n = 3). The DRGs in the NP+PRF rats were exposed to PRF waves (2 Hz) for 120 seconds at 45 V on postoperative Day 10. Rats were tested for mechanical allodynia 10 days after surgery and at 8 hours, 1 day, 3 days, 10 days, 20 days, and 40 days after PRF administration. Immunohistochemical staining of astrocytes (glial fibrillary acidic protein), microglia (OX-42), and phosphorylated extracellular signal-regulated kinases (pERKs) in the spinal dorsal horn was performed at 41 days after PRF administration.</P><B>Results</B><P>Starting at 8 hours after PRF administration, mechanical withdrawal thresholds dramatically increased; this response persisted for 40 days (p < 0.05). After PRF administration, immunohistochemical expressions of OX-42 and pERK in the spinal dorsal horn were quantitatively reduced (p < 0.05).</P><B>Conclusions</B><P>Pulsed radiofrequency administration to the DRG reduced mechanical allodynia and downregulated microglia activity and pERK expression in the spinal dorsal horn of a rat model of lumbar disc herniation.</P>

Relationship between cortical resection and visual function after occipital lobe epilepsy surgery

Heo, Won,Kim, June Sic,Chung, Chun Kee,Lee, Sang Kun Journal of Neurosurgery Publishing Group 2018 Journal of neurosurgery Vol.129 No.2

<B>OBJECTIVE</B><P>In this study, the authors investigated long-term clinical and visual outcomes of patients after occipital lobe epilepsy (OLE) surgery and analyzed the relationship between visual cortical resection and visual function after OLE surgery.</P><B>METHODS</B><P>A total of 42 consecutive patients who were diagnosed with OLE and underwent occipital lobe resection between June 1995 and November 2013 were included. Clinical, radiological, and histopathological data were reviewed retrospectively. Seizure outcomes were categorized according to the Engel classification. Visual function after surgery was assessed using the National Eye Institute Visual Functioning Questionnaire 25. The relationship between the resected area of the visual cortex and visual function was demonstrated by multivariate linear regression models.</P><B>RESULTS</B><P>After a mean follow-up period of 102.2 months, 27 (64.3%) patients were seizure free, and 6 (14.3%) patients had an Engel Class II outcome. Nineteen (57.6%) of 33 patients had a normal visual field or quadrantanopia after surgery (normal and quadrantanopia groups). Patients in the normal and quadrantanopia groups had better vision-related quality of life than those in the hemianopsia group. The resection of lateral occipital areas 1 and 2 of the occipital lobe was significantly associated with difficulties in general vision, peripheral vision, and vision-specific roles. In addition, the resection of intraparietal sulcus 3 or 4 was significantly associated with decreased social functioning.</P><B>CONCLUSIONS</B><P>The authors found a favorable seizure control rate (Engel Class I or II) of 78.6%, and 57.6% of the subjects had good visual function (normal vision or quadrantanopia) after OLE surgery. Lateral occipital cortical resection had a significant effect on visual function despite preservation of the visual field.</P>

Incidence of embolism associated with carotid artery stenting: open-cell versus closed-cell stents

Park, Keun Young,Kim, Dong Ik,Kim, Byung Moon,Nam, Hyo Suk,Kim, Young Dae,Heo, Ji Hoe,Kim, Dong Joon Journal of Neurosurgery Publishing Group 2013 Journal of neurosurgery Vol.119 No.3

<B>Object</B><P>Carotid artery stenting (CAS) can be an alternative option for carotid endarterectomy in the prevention of ischemic stroke caused by carotid artery stenosis. The purpose of this study was to evaluate the influence of stent design on the incidence of procedural and postprocedural embolism associated with CAS treatment.</P><B>Methods</B><P>Ninety-six symptomatic and asymptomatic patients, consisting of 79 males and 17 females, with moderate to severe carotid artery stenosis and a mean age of 69.0 years were treated with CAS. The stent type (48 closed-cell and 48 open-cell stents) was randomly allocated before the procedure. Imaging, procedural, and clinical outcomes were assessed and compared. The symptomatic subgroup (76 patients) was also analyzed to determine the influence of stent design on outcome.</P><B>Results</B><P>New lesions on postprocedural diffusion-weighted imaging (DWI) were significantly more frequent in the open-cell than in the closed-cell stent group (24 vs 12, respectively; p = 0.020). The 30-day clinical outcome was not different between the 2 stent groups. In the symptomatic patient group, stent design (p = 0.017, OR 4.173) and recent smoking history (p = 0.036, OR 4.755) were strong risk factors for new lesions on postprocedural DWI.</P><B>Conclusions</B><P>Stent design may have an influence on the risk of new embolism, and selecting the appropriate stent may improve outcome.</P>

Solitary fibrous tumor/hemangiopericytoma: treatment results based on the 2016 WHO classification

Sung, Kyoung Su,Moon, Ju Hyung,Kim, Eui Hyun,Kang, Seok-Gu,Kim, Se Hoon,Suh, Chang-Ok,Kim, Sun Ho,Lee, Kyu-Sung,Chang, Won Seok,Chang, Jong Hee Journal of Neurosurgery Publishing Group 2019 Journal of Neurosurgery Vol.130 No.2

<B>OBJECTIVE</B><P>Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a new combined entity for which a soft-tissue-type grading system, ranging from grades I to III, has been introduced in the 2016 WHO classification of tumors of the CNS. The results of the treatment of this new disease entity require evaluation.</P><B>METHODS</B><P>The authors retrospectively reevaluated the pathological findings and medical records of patients with SFT/HPC. This study included 60 patients (27 men and 33 women, median age 42.5 years, range 13-69 years) treated at Severance Hospital between February 1981 and February 2016. Four, 40, and 16 patients were categorized as having SFT/HPC grades I, II, and III, respectively. Among these patients, SFTs diagnosed in 7 patients were regraded as grades I (n = 4), II (n = 2), and III (n = 1).</P><B>RESULTS</B><P>The median overall survival (OS) was 73.2 months (range 1.4-275.7 months), and the progression-free survival (PFS) after the first operation was 53.8 months (range 1.4-217.7 months). Six patients (10%) showed extracranial metastasis during a median period of 103.7 months (range 31.9-182.3 months). Nineteen patients (31.7%) presented with tumor recurrences. The patients in the grade III group had shorter PFS and OS, as well as a shorter period to extracranial metastasis, compared with patients in the grade II group. In the grade II group, patients who underwent gross-total resection showed longer PFS than those who underwent subtotal resection; however, there was no difference in OS. Patients who underwent adjuvant radiation therapy (RT) after surgery had longer PFS compared with that of patients who did not undergo adjuvant RT.</P><B>CONCLUSIONS</B><P>The SFT/HPC grade I group showed a relatively benign course compared with those of the other groups. The grade III group presented a course with a more aggressive nature than that of the grade II group. In the grade II group, the extent of resection and adjuvant RT was significantly associated with longer PFS. The long-term follow-up and periodic systemic evaluation are mandatory to detect systemic metastasis.</P>