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Kyohei Itamura, Ki-Eun Chang, Joshua Lucas, Daniel A. Donoho, Steven Giannotta and Gabriel Zada

OBJECTIVE

The present study aims to assess the clinical utility of a previously validated intraoperative meningioma consistency grading scale and its association with extent of resection (EOR) and various surgical outcomes.

METHODS

The previously validated grading system was prospectively assessed in 127 consecutive patients undergoing open craniotomy for meningioma by multiple neurosurgeons at two high-volume academic hospitals from 2013 to 2016. Consistency grading scores ranging from 1 (soft) to 5 (firm/calcified) were retrospectively analyzed to test for association with surgical outcomes and EOR, categorized as gross-total resection (GTR) or subtotal resection, defined by postoperative MRI.

RESULTS

One hundred twenty-seven patients were included in the analysis with a tumor consistency distribution as follows: grade 1, 3.1%; grade 2, 14.2%; grade 3, 44.1%; grade 4, 32.3%; and grade 5, 6.3%. The mean tumor diameter was 3.6 ± 1.7 cm. Tumor consistency grades were grouped into soft (grades 1 and 2), average (grade 3), and firm (grades 4 and 5) groups for statistical analysis with distributions of 17.3%, 44.1%, and 38.6%, respectively. There was no association between meningioma consistency and maximal tumor diameter, or location. Mean duration of surgery was longer for tumors with higher consistency: grades 1 and 2, 186 minutes; grade 3, 219 minutes; and grades 4 and 5, 299 minutes (p = 0.000028). There was a trend toward higher perioperative complication rates for tumors of increased consistency: grades 1 and 2, 4.5%; grade 3, 7.0%; and grades 4 and 5, 20.8% (p = 0.047). The proportion of GTR for each consistency group was as follows: grades 1 and 2, 77%; grade 3, 68%; and grades 4 and 5, 43% (p = 0.0062).

CONCLUSIONS

In addition to other important meningioma characteristics such as invasiveness, tumor consistency is a key determinant of surgical outcomes, including operative duration and EOR. Future studies predicting tumor consistency based on preoperative neuroimaging will help considerably with preoperative planning for meningiomas.

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So-Hyang Im, Chang Wan Oh, O-Ki Kwon, Jung Eun Kim and Dae Hee Han

Object. In moyamoya disease (MMD), ischemic events are usually precipitated by activities associated with hyperventilation or physical strain. The authors report on four patients with a rare combination of Graves disease—associated thyrotoxicosis and MMD, whose cerebrovascular ischemic events occurred while in a thyrotoxic state. The clinical correlation between MMD and Graves' thyrotoxicosis, and outcome after surgical intervention are described.

Methods. Four young women, ages 22 to 25 years, presented with profound cerebrovascular ischemic accidents. They had clinical and radiological features consistent with the diagnosis of MMD and were in the active thyrotoxic state of Graves disease. To prevent a future ischemic event, patients underwent superficial temporal artery—middle cerebral artery anastomosis combined with encephalomyosynangiosis or encephaloduroarteriosynangiosis after normalization of their hormonal conditions. All patients have been neurologically stable since revascularization procedures and lead a normal daily life.

In patients with MMD, cerebrovascular ischemic events may be precipitated by thyrotoxicosis. One possible pathomechanism of cerebrovascular ischemic aggravation in the thyrotoxic state may be a hemodynamic compromise induced by an excessive increase in the cerebral metabolism and oxygen demand over the compensation of the cerebral blood flow deficit through collateral supply in MMD.

Conclusions. Surgical revascularization after optimal control of thyrotoxicosis is thought to be an appropriate treatment in patients with MMD concurrent with Graves disease for the prevention of further ischemic events, especially in those with impaired cerebral perfusion and cerebral ischemic symptoms.

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Eun Ji Kim, Kyu-Chang Wang, Ji Yeoun Lee, Ji Hoon Phi, Sung-Hye Park, Jung-Eun Cheon, Young Eun Jang and Seung-Ki Kim

Infantile myofibromatosis, a rare mesenchymal disorder that develops in early childhood, is classified by the number of lesions that occur: solitary or multicentric. Involvement of the CNS is unusual in either type. Infantile myofibromatosis in the spine is exceptional, and most published cases represent a secondary invasion. Here, the authors report on an 8-month-old girl presenting with weakness below the ankle and an intraspinal mass extending from T-6 to the conus. The patient underwent only partial surgical removal of the lesion, and the pathology was confirmed as infantile myofibromatosis. After the operation, weakness in the lower extremities gradually improved; however, she could not walk at the time of the final follow-up. On follow-up MRI performed 19 months after the operation, the residual lesion remained unchanged with decreased enhancement.

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Ilya Lekht, Noah Brauner, Joshua Bakhsheshian, Ki-Eun Chang, Mittul Gulati, Mark S. Shiroishi, Edward G. Grant, Eisha Christian and Gabriel Zada

OBJECTIVE

Intraoperative contrast-enhanced ultrasound (iCEUS) offers dynamic imaging and provides functional data in real time. However, no standardized protocols or validated quantitative data exist to guide its routine use in neurosurgery. The authors aimed to provide further clinical data on the versatile application of iCEUS through a technical note and illustrative case series.

METHODS

Five patients undergoing craniotomies for suspected tumors were included. iCEUS was performed using a contrast agent composed of lipid shell microspheres enclosing perflutren (octafluoropropane) gas. Perfusion data were acquired through a time-intensity curve analysis protocol obtained using iCEUS prior to biopsy and/or resection of all lesions.

RESULTS

Three primary tumors (gemistocytic astrocytoma, glioblastoma multiforme, and meningioma), 1 metastatic lesion (melanoma), and 1 tumefactive demyelinating lesion (multiple sclerosis) were assessed using real-time iCEUS. No intraoperative complications occurred following multiple administrations of contrast agent in all cases. In all neoplastic cases, iCEUS replicated enhancement patterns observed on preoperative Gd-enhanced MRI, facilitated safe tumor debulking by differentiating neoplastic tissue from normal brain parenchyma, and helped identify arterial feeders and draining veins in and around the surgical cavity. Intraoperative CEUS was also useful in guiding a successful intraoperative needle biopsy of a cerebellar tumefactive demyelinating lesion obtained during real-time perfusion analysis.

CONCLUSIONS

Intraoperative CEUS has potential for safe, real-time, dynamic contrast-based imaging for routine use in neurooncological surgery and image-guided biopsy. Intraoperative CEUS eliminates the effect of anatomical distortions associated with standard neuronavigation and provides quantitative perfusion data in real time, which may hold major implications for intraoperative diagnosis, tissue differentiation, and quantification of extent of resection. Further prospective studies will help standardize the role of iCEUS in neurosurgery.

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Eun Jung Koh, Ji Hoon Phi, Sung-Hye Park, In-One Kim, Jung-Eun Cheon, Kyu-Chang Wang, Byung-Kyu Cho and Seung-Ki Kim

This 14-year-old boy presented with left hemiparesis, gait disturbance, and multiple cranial nerve palsies. Magnetic resonance imaging revealed a multicystic mass with hemorrhagic fluid–fluid levels in the right midbrain, suggesting the presence of a cavernous malformation. Diffusion tensor imaging showed the mass to be close to the right corticospinal tract and ipsilateral medial lemniscus. Subtotal removal of the mass was performed via a right subtemporal approach. The histopathological diagnosis was of a mixed germ cell tumor (GCT) comprising mature teratoma and germinoma cells with syncytiotrophoblastic giant cells. The patient underwent postoperative chemotherapy and radiotherapy, and no tumor progression was found during 1 year of follow-up.

Intracranial GCTs arise mainly in the pineal and the suprasellar area. Germ cell tumors in the brainstem are rare, with only 12 reported cases. Among these, 4 were in the midbrain and histologically were pure germinomas. To the authors' knowledge, this is the first reported case of a mixed GCT in the midbrain combining mature teratoma and germinoma cells.

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Ji Hoon Phi, Jung Won Choi, Moon-Woo Seong, Tackeun Kim, Youn Joo Moon, Joongyub Lee, Eun Jung Koh, Seul Ki Ryu, Tae Hee Kang, Jae Seung Bang, Chang Wan Oh, Sung Sup Park, Ji Yeoun Lee, Kyu-Chang Wang and Seung-Ki Kim

OBJECTIVE

In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not.

METHODS

The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing.

RESULTS

In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57–1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement.

CONCLUSIONS

The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1–moyamoya connection.

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Ji Hoon Phi, Jin Hyun Kim, Kyoung Mi Eun, Kyu-Chang Wang, Ki Ho Park, Seung Ah Choi, Young Yim Kim, Sung-Hye Park, Byung-Kyu Cho and Seung-Ki Kim

Object

Supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma are highly malignant embryonal brain tumors. They share morphological similarities, but differ in their differentiation patterns and global gene expression. The authors compared the expression of specific genes involved in neuroglial differentiation in supratentorial PNETs and medulloblastomas to define the distinct characters of these tumors.

Methods

The mRNA expression of 8 genes (SOX2, NOTCH1, ID1, ASCL-1, NEUROD1, NEUROG1, NEUROG2, and NRG1) was evaluated in 25 embryonal tumors (12 supratentorial PNETs and 13 medulloblastomas) by quantitative real-time polymerase chain reaction. The expression levels of the transcripts of these genes were compared between the tumor groups. Activation of the JAK/STAT3 pathway was assessed by immunoblotting. Relative expression levels of STAT3 and phosphorylated STAT3 proteins were compared.

Results

Supratentorial PNETs expressed significantly higher levels of SOX2, NOTCH1, ID1, and ASCL-1 transcripts, whereas the transcription of proneural basic helix-loop-helix factors, NEUROD1, NEUROG1 (significantly), and NEUROG2 (not significantly) was upregulated in medulloblastomas. The proportion of phosphorylated STAT3α relative to STAT3α was significantly greater in supratentorial PNETs than in medulloblastomas, indicating activation of the JAK/STAT3 pathway in supratentorial PNETs.

Conclusions

These results indicate that supratentorial PNET predominantly has glial features and medulloblastoma largely follows a neuronal differentiation pattern. These divergent differentiation patterns may be related to the location and origin of each tumor.

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Joshua Bakhsheshian, Diana L. Jin, Ki-Eun Chang, Ben A. Strickland, Dan A. Donoho, Steven Cen, William J. Mack, Frank Attenello, Eisha A. Christian and Gabriel Zada

OBJECTIVE

Patient demographic characteristics, hospital volume, and admission status have been shown to impact surgical outcomes of sellar region tumors in adults; however, the data available following the resection of craniopharyngiomas in the pediatric population remain limited. The authors sought to identify potential risk factors associated with outcomes following surgical management of pediatric craniopharyngiomas.

METHODS

The Nationwide Inpatient Sample database and Kids' Inpatient Database were analyzed to include admissions for pediatric patients (≤ 18 years) who underwent a transcranial or transsphenoidal craniotomy for resection of a craniopharyngioma. Patient-level factors, including age, race, comorbidities, and insurance type, as well as hospital factors were collected. Outcomes analyzed included mortality rate, endocrine and nonendocrine complications, hospital charges, and length of stay. A multivariate model controlling for variables analyzed was constructed to examine significant independent risk factors.

RESULTS

Between 2000 and 2011, 1961 pediatric patients were identified who underwent a transcranial (71.2%) or a transsphenoidal (28.8%) craniotomy for resection of a craniopharyngioma. A major predilection for age was observed with the selection of a transcranial (23.4% in < 7-year-olds, 28.1% in 7- to 12-year-olds, and 19.7% in 13- to 18-year-olds) versus transphenoidal (2.9% in < 7-year-olds, 7.4% in 7- to 12-year-olds, and 18.4% in 13- to 18-year-olds) approach. No significant outcomes were associated with a particular surgical approach, except that 7- to 12-year-old patients had a higher risk of nonendocrine complications (relative risk [RR] 2.42, 95% CI 1.04–5.65, p = 0.04) with the transsphenoidal approach when compared with 13- to 18-year-old patients. The overall inpatient mortality rate was 0.5% and the most common postoperative complication was diabetes insipidus (64.2%). There were no independent factors associated with inpatient mortality rates and no significant differences in outcomes among groups based on sex and race. The average length of stay was 11.8 days, and the mean hospital charge was $116,5 22. Hospitals with medium and large bed capacity were protective against nonendocrine complications (RR 0.53, 95% CI 0.3–0.93, p = 0.03 [medium]; RR 0.45, 95% CI 0.25–0.8, p < 0.01 [large]) and total complications (RR 0.73, 95% CI 0.55–0.97, p = 0.03 [medium]; RR 0.68, 95% CI 0.51–0.9, p < 0.01 [large]) when compared with hospitals with small bed capacity (< 200 beds). Patients admitted to rural hospitals had an increased risk for nonendocrine complications (RR 2.56, 95% CI 1.11–5.9, p = 0.03). The presence of one or more medical comorbidities increased the risk of higher total complications (RR 1.38, 95% CI 1.14–1.68), p < 0.01 [1 comorbidity]; RR 2.37, 95% CI 1.98–2.84, p < 0.01 [≥ 2 comorbidities]) and higher total hospital charges (RR 2.9, 95% CI 1.08–7.81, p = 0.04 [1 comorbidity]; RR 9.1, 95% CI 3.74–22.12, p < 0.01 [≥ 2 comorbidities]).

CONCLUSIONS

This analysis identified patient age, comorbidities, insurance type, hospital bed capacity, and rural or nonteaching hospital status as independent risk factors for postoperative complications and/or increased hospital charges in pediatric patients with craniopharyngioma. Transsphenoidal surgery in younger patients with craniopharyngioma was a risk factor for nonendocrine complications.

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Jung Won Choi, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Jung-Eun Cheon and Ji Hoon Phi

Object

Ventriculoperitoneal (VP) shunt surgery is the most common treatment for hydrocephalus. In certain situations, uncommon complications can occur after shunting procedures. The authors undertook this study to analyze the clinical characteristics of pediatric patients who developed multifocal intraparenchymal hemorrhages (MIPHs) as a complication of shunt surgery. The authors also analyzed the risk factors for MIPH in a large cohort of patients with hydrocephalus.

Methods

This study included all pediatric patients (age < 18 years) who underwent VP shunt surgery at the authors' institution between January 2001 and December 2012. During this period, 507 VP shunt operations were performed in 330 patients. Four of these patients were subsequently diagnosed as having MIPH. The authors analyzed the clinical characteristics of these patients in comparison with those of the entire group of shunt-treated patients.

Results

The incidence of MIPH was 1.2% (4 of 330 cases) for all pediatric patients who underwent VP shunt placement but 2.9% (4 of 140 cases) for infants less than 1 year old. When the analysis was limited to patients whose corrected age was less than 3 months, the incidence was 5.3% (4 of 76 cases). Of the 4 patients with MIPH, 2 were male and 2 were female. Their median age at surgery was 54 days (range 25–127 days), and in all 4 cases, the patients' corrected age was less than 1 month. Three patients were preterm infants, whereas one patient was full-term. None of these patients had a prior history of intracranial surgery (including CSF diversion procedures). All showed severe hydrocephalus during the preoperative period. Their clinical courses as patients with MIPH were comparatively favorable, despite the radiological findings.

Conclusions

MIPH is a rare but not negligible complication of VP shunt surgery. This complication might be a unique phenomenon in infants, especially young, preterm infants with severe hydrocephalus. Moreover, the absence of previous intracranial procedures might be one of the risk factors for this complication. The rapid alteration of brain conditions in the setting of immaturity might cause MIPH. To prevent this complication, the authors recommend that pressure settings of programmable valves should be gradually adapted to the target pressure.

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Ji Yeoun Lee, Sangjoon Chong, Young Hun Choi, Ji Hoon Phi, Jung-Eun Cheon, Seung-Ki Kim, Sung Hye Park, In-One Kim and Kyu-Chang Wang

OBJECTIVE

Since the entity limited dorsal myeloschisis (LDM) was proposed, numerous confusing clinical cases have been renamed according to the embryopathogenesis. However, clinical application of this label appears to require some clarification with regard to pathology. There have been cases in which all criteria for the diagnosis of LDM were met except for the presence of a neural component in the stalk, an entity the authors call “probable” LDM. The present study was performed to meticulously review these cases and suggest that a modified surgical strategy using limited laminectomy is sufficient to achieve the surgical goal of untethering.

METHODS

The authors retrospectively reviewed the imaging findings, operative notes, and pathology reports of spinal dysraphism patients with subcutaneous stalk lesions who had presented to their institution between 2010 and 2014.

RESULTS

Among 33 patients with LDM, 13 had the typical nonsaccular lesions with simple subcutaneous stalks connecting the skin opening to the spinal cord. Four cases had “true” LDM meeting all criteria for diagnosis, including pathological confirmation of CNS tissue by immunohistochemical staining with glial fibrillary acidic protein. There were also 9 cases in which all clinical, imaging, and surgical findings were compatible with LDM, but the “neural” component in the resected stalk was not confirmed. For all the cases, limited exposure of the stalk was done and satisfactory untethering was achieved.

CONCLUSIONS

One can speculate based on the initial error of embryogenesis that if the entire stalk were traced to the point of insertion on the cord, the neural component would be proven. However, this would require an extended level of laminectomy/laminotomy, which may be unnecessary, at least with regard to the completeness of untethering. Therefore, the authors propose that for some selected cases of LDM, a minimal extent of laminectomy may suffice for untethering, although it may be insufficient for diagnosing a true LDM.