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Jeffrey C. Allen, Jae Ho Kim, and Roger J. Packer

✓ A neoadjuvant (preradiotherapy) chemotherapy regimen consisting of either cyclophosphamide alone (60 to 80 mg/kg) or a modified multidrug regimen (vinblastine, bleomycin, cyclophosphamide, and cisplatin) was administered to 15 newly diagnosed patients with histologically confirmed, fully staged, primary germ-cell tumors (GCT's) of the central nervous system (CNS). There were 11 patients with germinomas and four with non-germinoma malignant GCT's. There were six females and nine males, whose median age was 13 years (range 4 months to 24 years). Seven germinoma patients (64%) had disseminated disease. For the germinoma patients, the subsequent radiotherapy dose was modified based on the response to the neoadjuvant chemotherapy, and craniospinal radiotherapy was given only to those with disseminated CNS disease at diagnosis. Ten of the 11 germinoma patients had complete disappearance of all evaluable disease after two courses of chemotherapy (cyclophosphamide in eight and multidrug in three) and one had a partial response. The planned dose of radiotherapy to the primary tumor was reduced from 5500 to 3000 rads, and the craniospinal dose was lowered from 3600 to 2000 rads. Ten patients remain in continuous disease-free remission 20+ to 89+ months after diagnosis (median follow-up period 47 months). All four patients with non-germinoma GCT's received the multidrug regimen, and two of three patients with evaluable disease had a partial response. High-dose regional and craniospinal radiotherapy was administered thereafter, but only two patients remain in their first remission.

Previously untreated germinoma is a highly chemosensitive disease and the neoadjuvant treatment strategy permits the identification of active chemotherapy regimens in newly diagnosed patients. Patients who have complete responses to neoadjuvant chemotherapy tolerate a significant radiotherapy dose reduction without compromising long-term survival, thereby allowing a reduction of some of the late effects of therapeutic radiation. Germinomas tend to disseminate early in the course of the disease and a pre-therapy staging evaluation permits individualized radiotherapy treatment planning.

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Samuel Ryu, Jack Rock, Mark Rosenblum, and Jae Ho Kim

Object. Single-dose radiosurgery for solitary spinal metastases can achieve rapid and durable pain control. This study was conducted to determine the patterns of failure after spinal radiosurgery.

Methods. Forty-nine patients with 61 solitary spinal metastases underwent radiosurgery between May 2001 and May 2003. Single-dose radiosurgery (10–16 Gy) was delivered only to the involved spinal segments. The authors undertook a retrospective review of clinical notes, including patient questionnaires and radiological studies (computerized tomography or magnetic resonance imaging), to analyze patterns of failure following radiosurgery with regard to the pain and tumor control.

Complete and partial pain relief was achieved in 85% of the lesions treated. Relapse of pain at the treated site was noted in 7%. Radiologically, lesions progressively metastasized to the immediately adjacent spines in 5%. These patients also had progressive primary and/or other systemic metastatic diseases.

Conclusions. Spine-related pain control/reduction was excellent. Tumor recurrence at the treated segment and progression to the immediately adjacent region were rare. The results support the use of spinal radiosurgery as an effective treatment option for solitary spinal metastasis.

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Jae Taek Hong, Tae Hyung Kim, Il Sup Kim, Seung Ho Yang, Jae Hoon Sung, Byung Chul Son, and Sang Won Lee

Object

The aim of this study was to analyze the exact location of the internal carotid artery (ICA) relative to the C-1 lateral mass and describe the effect of age on the tortuosity of the ICA.

Methods

The authors analyzed 641 patients who had undergone CT angiography to evaluate the location of the ICA in relation to the C-1 lateral mass. Each patient was assigned to 1 of 3 age groups (< 41 years, 41–60 years, and > 60 years of age). The degree of lateral positioning of the ICA was classified into 4 groups: Group 1 (lateral to the C-1 lateral mass), Group 2 (lateral half of the lateral mass), Group 3 (medial half of the lateral mass), or Group 4 (medial to the lateral mass). The anteroposterior relationship of the ICA was classified into Group A (posterior to the anterior tubercle) or Group B (anterior to the anterior tubercle). Distances from the ICA to the midline, anterior tubercle, and anterior cortex of the lateral mass were measured. Distances between the lateral margin of the lateral mass and the longus capitis muscle were also evaluated.

Results

The prevalence of the ICA located in front of the lateral mass (Groups 2 and 3) was 47.4% overall. The position of the ICA changes with age due to vessel tortuosity. Only 18.3% of patients in the youngest age group (< 41 years of age) had an ICA in front of the lateral mass (Group 2 or 3 area). However, this percentage increased in the older 2 groups (43.5% in the 41–60 year old group, and 57% in the > 60-year-old age group). The mean distance from the midline to the ICA was 22.6 mm, and the mean distance from the ICA to the C-1 anterior tubercle and the ventral cortex of the lateral mass was 4.7 and 4.5 mm, respectively. Moreover, the ICA is more prone to injury during bicortical C-1 screw placement when the longus capitis muscle is hypotrophic and does not cover the entire ventral surface of the lateral mass.

Conclusions

Elderly patients have a higher incidence of a medially located ICA that may contribute to the risk of injury to the ICA during bicortical C-1 screw or C1–2 transarticular screw placement. Although the small number of reported cases of ICA injury does not allow for determination of a direct relationship with specific anatomical characteristics, the presence of unfavorable anatomy does warrant serious consideration during evaluation for C-1 screw placement in elderly patients.

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Young-Seop Park, Seung-Jae Hyun, Ho Yong Choi, Ki-Jeong Kim, and Tae-Ahn Jahng

OBJECTIVE

The aim of this study was to investigate the risk of upper instrumented vertebra (UIV) fractures associated with UIV screw fixation (unicortical vs bicortical) and polymethylmethacrylate (PMMA) augmentation after adult spinal deformity surgery.

METHODS

A single-center, single-surgeon consecutive series of adult patients who underwent lumbar fusion for ≥ 4 levels (that is, the lower instrumented vertebra at the sacrum or pelvis and the UIV of the thoracolumbar spine [T9–L2]) were retrospectively reviewed. Age, sex, follow-up duration, sagittal UIV angle immediately postoperatively including several balance-related parameters (lumbar lordosis [LL], pelvic incidence, and sagittal vertical axis), bone mineral density, UIV screw fixation type, UIV PMMA augmentation, and UIV fracture were evaluated. Patients were divided into 3 groups: Group U, 15 patients with unicortical screw fixation at the UIV; Group P, 16 with bicortical screw fixation and PMMA augmentation at the UIV; and Group B, 21 with bicortical screw fixation without PMMA augmentation at the UIV.

RESULTS

The mean number of levels fused was 6.5 ± 2.5, 7.5 ± 2.5, and 6.5 ± 2.5; the median age was 50 ± 29, 72 ± 6, and 59 ± 24 years; and the mean follow-up was 31.5 ± 23.5, 13 ± 6, and 24 ± 17.5 months in Groups U, P, and B, respectively (p > 0.05). There were no significant differences in balance-related parameters (LL, sagittal vertical axis, pelvic incidence–LL, and so on) among the groups. UIV fracture rates in Groups U (0%), P (31.3%), and B (42.9%) increased in sequence by group (p = 0.006). UIV bicortical screw fixation increased the risk for UIV fracture (OR 5.39; p = 0.02).

CONCLUSIONS

Bicortical screw fixation at the UIV is a major risk factor for early UIV compression fracture, regardless of whether a thoracolumbosacral orthosis is used. To reduce the proximal junctional failure, unicortical screw fixation at the UIV is essential in adult spinal deformity correction surgery.

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Yukitaka Ushio, Roslyn Posner, Jae-Ho Kim, William R. Shapiro, and Jerome B. Posner

✓ Epidural spinal cord compression was produced in rats by injection of Walker 256 carcinoma cell suspension anterior to the T-12 or T-13 vertebral body. The tumor grows through the intervertebral foramina to compress the spinal cord and produce paraplegia in 3 to 4 weeks. The effect of several treatments upon clinical signs was assessed. Dexamethasone caused a significant but transient improvement in neurological function. Radiation therapy likewise improved neurological function, and was more effective when given by a high-dose protracted course than when given either in a single dose or a low-dose protracted course. Laminectomy was not helpful in relieving neurological symptoms. Dimethyl sulfoxide did not relieve neurological symptoms. Cyclophosphamide was most effective in relieving neurological symptoms, and most of the animals that were treated with that drug when they were severely weak but still able to move their hind limbs recovered fully. Some animals that were totally paraplegic when treatment began recovered function after radiation therapy or cyclophosphamide treatment, but recovery was better if treatment was started when animals could still move their hind limbs. This animal model appears to be a useful way of studying the treatment of human spinal cord compression produced by epidural neoplasms.

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Jae Ho Kim, Sung Jun Ahn, Mina Park, Yong Bae Kim, Bio Joo, Woosung Lee, and Sang Hyun Suh

OBJECTIVE

Metallic susceptibility artifact due to implanted clips is a major limitation of using 3D time-of-flight magnetic resonance angiography (TOF-MRA) for follow-up imaging of clipped aneurysms (CAs). The purpose of this study was to compare pointwise encoding time reduction with radial acquisition (PETRA) subtraction-based MRA with TOF-MRA in terms of imaging quality and visibility of clip-adjacent arteries for use in follow-up imaging of CAs.

METHODS

Sixty-two patients with 73 CAs were included retrospectively in this comparative study. All patients underwent PETRA-MRA after TOF-MRA performed simultaneously with 3-T MRI between September 2019 and March 2020. Two neuroradiologists independently compared images obtained with both MRA modalities to evaluate overall image quality using a 4-point scale and visibility of the parent artery and branching vessels near the clips using a 3-point scale. Subgroup analysis was performed according to the number of clips (less-clipped [1–2 clips] vs more-clipped [≥ 3 clips] aneurysms). The ability to detect aneurysm recurrence was also assessed.

RESULTS

Compared with TOF-MRA, PETRA-MRA showed acceptable image quality (score of 3.97 ± 0.18 for TOF-MRA vs 3.73 ± 0.53 for PETRA-MRA) and had greater visibility of the adjacent vessels near the CAs (score of 1.25 ± 0.59 for TOF-MRA vs 2.27 ± 0.75 for PETRA-MRA, p < 0.0001). PETRA-MRA had greater visibility of vessels adjacent to less-clipped aneurysms (score of 2.39 ± 0.75 for less-clipped aneurysms vs 2.09 ± 0.72 for more-clipped aneurysms, p = 0.014). Of 73 CAs, aneurysm recurrence in 4 cases was detected using PETRA-MRA.

CONCLUSIONS

This study demonstrated that PETRA-MRA is superior to TOF-MRA for visualizing adjacent vessels near clips and can be an advantageous alternative to TOF-MRA for follow-up imaging of CAs.

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Young-Hoon Kim, Young Jin Lee, Jung Ho Han, Soyeon Ahn, Jaebong Lee, Jae Hyoung Kim, Byung Se Choi, Jae Seung Bang, Chae-Yong Kim, Gyojun Hwang, O-Ki Kwon, and Chang Wan Oh

OBJECT

The authors aimed to assess whether the prevalence of intracranial aneurysms in patients with intracranial meningiomas was higher than that in a healthy population.

METHODS

The authors performed a hospital-based case-control study of 300 patients with newly diagnosed intracranial meningiomas and 900 age- and sex-matched controls without a history of brain tumors to evaluate any associations between intracranial aneurysms and intracranial meningiomas. Unconditional multivariate logistic regression models were used for case-control comparisons.

RESULTS

Intracranial aneurysms were identified in 23 patients (7.7%) and 24 controls (2.7%; p < 0.001). There was a significant association between intracranial aneurysms and intracranial meningiomas (OR 2.913, 95% CI 1.613–5.261) and hypertension (OR 1.905, 95% CI 1.053–3.446). In a subgroup analysis of the patients with newly diagnosed intracranial meningiomas, there was a significant association between intracranial aneurysms and hypertension (OR 2.876, 95% CI 1.125–7.352) and tumor volume (OR 1.012, 95% CI 1.001–1.024). These patients were also more likely than controls to have other intracranial vascular diseases (p < 0.001), such as isolated occlusion of the intracranial vessels, excluding intracranial aneurysms.

CONCLUSIONS

The prevalence of intracranial aneurysms was higher in patients with intracranial meningiomas. Hypertension and tumor volume appear to be associated with the formation of intracranial aneurysms in these patients.

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Hyoung-Sub Kim, Jong Beom Lee, Jong Hyeok Park, Ho Jin Lee, Jung Jae Lee, Shumayou Dutta, Il Sup Kim, and Jae Taek Hong

OBJECTIVE

Little is known about the risk factors for postoperative subaxial cervical kyphosis following craniovertebral junction (CVJ) fixation. The object of this study was to evaluate postoperative changes in cervical alignment and to identify the risk factors for postoperative kyphotic change in the subaxial cervical spine after CVJ fixation.

METHODS

One hundred fifteen patients were retrospectively analyzed for postoperative subaxial kyphosis after CVJ fixation. Relations between subaxial kyphosis and radiological risk factors, including segmental angles and ranges of motion (ROMs) at C0–1, C1–2, and C2–7, and clinical factors, such as age, sex, etiology, occipital fixation, extensor muscle resection at C2, additional C1–2 posterior wiring, and subaxial laminoplasty, were investigated. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for postoperative kyphotic changes in the subaxial cervical spine.

RESULTS

The C2–7 angle change was more than −10° in 30 (26.1%) of the 115 patients. Risk factor analysis showed CVJ fixation combined with subaxial laminoplasty (OR 9.336, 95% CI 1.484–58.734, p = 0.017) and a small ROM at the C0–1 segment (OR 0.836, 95% CI 0.757–0.923, p < 0.01) were related to postoperative subaxial kyphotic change. On the other hand, age, sex, resection of the C2 extensor muscle, rheumatoid arthritis, additional C1–2 posterior wiring, and postoperative segmental angles were not risk factors for postoperative subaxial kyphosis

CONCLUSIONS

Subaxial alignment change is not uncommon after CVJ fixation. Muscle detachment at the C2 spinous process was not a risk factor of kyphotic change. The study findings suggest that a small ROM at the C0–1 segment with or without occipital fixation and combined subaxial laminoplasty are risk factors for subaxial kyphotic change.

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Ho Jun Yi, Jung Eun Lee, Dong Hoon Lee, Young Il Kim, Chul Bum Cho, Il Sup Kim, Jae Hoon Sung, and Seung Ho Yang

OBJECTIVE

Perilesional edema is a predominant mechanism underlying secondary brain injury after traumatic brain injury (TBI). Perilesional edema is characterized by inflammation, production of proinflammatory cytokines, and migration of peripheral immune cells into the brain. The nucleotide-binding domain and leucine-rich repeat (NLR) family pyrin domain–containing 3 protein (NLRP3) is a key component of secondary injury. Pioglitazone regulates NLRP3 and other inflammatory cytokines. In the present study, the role of NLRP3 and the pharmacological effects of pioglitazone were investigated in animal TBI models.

METHODS

Brain contusion was induced in a weight drop model involving 3 groups of mice: C57 BL/6 (sham group), NLRP3 knockout (K/O group), and pioglitazone-treated mice (treatment group). The percentage of brain water content of the 3 groups of mice was compared over a period of time. Western blot, immunohistochemistry, and immunofluorescence analyses were conducted to investigate NLRP3-related inflammasomes and the effects of pioglitazone in the TBI models.

RESULTS

Brain edema was the highest on day 3 after TBI in the sham group. Brain edema in both the K/O and the treatment groups was lower than in the sham group. In Western blot, the expression of inflammasomes was higher after TBI in the sham group, but the expression of interleukin-1β, caspase-1, and NLRP3 was decreased significantly following treatment with pioglitazone. The expression of GFAP (glial fibrillary acidic protein) and Iba1 was decreased in both the K/O and treatment groups. In addition, confocal microscopy revealed a decrease in microglial cell and astrocyte activation following pioglitazone therapy.

CONCLUSIONS

The inflammasome NLRP3 plays a pivotal role in regulating cerebral edema and secondary inflammation. Interestingly, pioglitazone reduced cerebral edema and immune response after TBI by downregulating the effects of NLRP3. These results suggest that the clinical application of pioglitazone may be a neuroprotective strategy in TBI.

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Eun Jung Lee, Jeong Hoon Kim, Eun Suk Park, Young-Hoon Kim, Jae Koo Lee, Seok Ho Hong, Young Hyun Cho, and Chang Jin Kim

OBJECTIVE

Advances in neuroimaging techniques have led to the increased detection of asymptomatic intracranial meningiomas (IMs). Despite several studies on the natural history of IMs, a comprehensive evaluation method for estimating the growth potential of these tumors, based on the relative weight of each risk factor, has not been developed. The aim of this study was to develop a weighted scoring system that estimates the risk of rapid tumor growth to aid treatment decision making.

METHODS

The authors performed a retrospective analysis of 232 patients with presumed IM who had been prospectively followed up in the absence of treatment from 1997 to 2013. Tumor volume was measured by imaging at each follow-up visit, and the growth rate was determined by regression analysis. Predictors of rapid tumor growth (defined as ≥ 2 cm3/year) were identified using a logistic regression model; each factor was awarded a score based on its own coefficient value. The probability (P) of rapid tumor growth was estimated using the following formula:
FD1

RESULTS

Fifty-nine tumors (25.4%) showed rapid growth. Tumor size (OR per cm3 1.07, p = 0.000), absence of calcification (OR 3.87, p = 0.004), peritumoral edema (OR 2.74, p = 0.025), and hyperintense or isointense signal on T2-weighted MRI (OR 3.76, p = 0.049) were predictors of tumor growth rate. In the Asan Intracranial Meningioma Scoring System (AIMSS), tumor size was categorized into 3 groups of < 2.5 cm, ≥ 2.5 to < 4.0 cm, and ≥ 4.0 cm in diameter and awarded a score of 0, 3, and 6, respectively; the parameters of calcification and peritumoral edema were categorized into 2 groups based on their presence or absence and given a score of 0 or 2 and 1 or 0, respectively; and the signal on T2-weighted MRI was categorized into 2 groups of hypointense and hyperintense/isointense and given a score of 0 or 2, respectively. The risk of rapid tumor growth was estimated to be < 10% when the total score was 0–2, 10%–50% when the total score was 3–6, and ≥ 50% when the total score was 7–11 (Hosmer-Lemeshow goodness-of-fit test, p = 0.9958). The area under the receiver operating characteristic curve was 0.86.

CONCLUSIONS

The authors suggest a weighted scoring system (AIMSS) that predicts the specific probability of rapid tumor growth for patients with untreated IM. This scoring system will aid treatment decision making in clinical settings by screening out patients at high risk for rapid tumor growth.