Hypopituitarism after Gamma Knife surgery for postoperative nonfunctioning pituitary adenoma

Oh, Ji Woong,Sung, Kyoung Su,Moon, Ju Hyung,Kim, Eui Hyun,Chang, Won Seok,Jung, Hyun Ho,Chang, Jin Woo,Park, Yong Gou,Kim, Sun Ho,Chang, Jong Hee American Association of Neurological Surgeons 2018 Journal of Neurosurgery Vol.129 No.suppl1

<B>OBJECTIVE</B><P>This study investigated long-term follow-up data on the combined pituitary function test (CPFT) in patients who had undergone transsphenoidal surgery (TSS) for nonfunctioning pituitary adenoma (NFPA) to determine the clinical parameters indicative of hypopituitarism following postoperative Gamma Knife surgery (GKS).</P><B>METHODS</B><P>Between 2001 and 2015, a total of 971 NFPA patients underwent TSS, and 76 of them (7.8%) underwent postoperative GKS. All 76 patients were evaluated with a CPFT before and after GKS. The hormonal states were analyzed based on the following parameters: relevant factors before GKS (age, sex, extent of resection, pre-GKS hormonal states, time interval between TSS and GKS), GKS-related factors (tumor volume; radiation dose to tumor, pituitary stalk, and normal gland; distance between tumor and stalk), and clinical outcomes (tumor control rate, changes in hormonal states, need for hormone-related medication due to hormonal changes).</P><B>RESULTS</B><P>Of the 971 NFPA patients, 797 had gross-total resection (GTR) and 174 had subtotal resection (STR). Twenty-five GTR patients (3.1%) and 51 STR patients (29.3%) underwent GKS. The average follow-up period after GKS was 53.5 ± 35.5 months, and the tumor control rate was 96%. Of the 76 patients who underwent GKS, 23 were excluded due to pre-GKS panhypopituitarism (22) or loss to follow-up (1). Hypopituitarism developed in 13 (24.5%) of the remaining 53 patients after GKS. A higher incidence of post-GKS hypopituitarism occurred in the patients with normal pre-GKS hormonal states (41.7%, 10/24) than in the patients with abnormal pre-GKS hormonal states (10.3%, 3/29; p = 0.024). Target tumor volume (4.7 ± 3.9 cm<SUP>3</SUP>), distance between tumor and pituitary stalk (2.0 ± 2.2 mm), stalk dose (cutoffs: mean dose 7.56 Gy, maximal dose 12.3 Gy), and normal gland dose (cutoffs: maximal dose 13.9 Gy, minimal dose 5.25 Gy) were factors predictive of post-GKS hypopituitarism (p < 0.05).</P><B>CONCLUSIONS</B><P>This study analyzed the long-term follow-up CPFT data on hormonal changes in NFPA patients who underwent GKS after TSS. The authors propose a cutoff value for the radiation dose to the pituitary stalk and normal gland for the prevention of post-GKS hypopituitarism.</P>

The natural clinical course of hemodynamically stable adult moyamoya disease

Cho, Won-Sang,Chung, Young Seob,Kim, Jeong Eun,Jeon, Jin Pyeong,Son, Young Je,Bang, Jae Seung,Kang, Hyun-Seung,Sohn, Chul-Ho,Oh, Chang Wan American Association of Neurological Surgeons 2015 Journal of Neurosurgery Vol.122 No.1

<B>OBJECT</B><P>Moyamoya disease (MMD) is a rare cerebrovascular disease and its natural history is still unclear. The authors aimed to investigate the natural course of hemodynamically stable cases of adult MMD, with the analysis of stroke risk factors.</P><B>METHODS</B><P>Two hundred forty-one patients were included in this retrospective study. One hundred sixty-six (68.9%) were female, and mean age (± SD) at first visit was 41.3 ± 12.0 years (range 18-69 years). Unilateral involvement was identified in 33 patients, and 19 patients (7.9%) had a family history of MMD. According to the clinical presentations, patients were classified into hemorrhagic (n = 62, 25.7%), ischemic (n = 144, 59.8%), and asymptomatic (n = 35, 14.5%) groups. The mean duration of follow-up was 82.5 ± 62.9 months (range 7.3-347.0 months).</P><B>RESULTS</B><P>The annual stroke risk was 4.5%, and the annual risks of rebleeding in the hemorrhagic group and recurrent ischemic events in the ischemic group were 4.3% and 3.0%, respectively. There was no significant difference in cumulative stroke risk between the 3 groups (p = 0.461). Risk factors included thyroid disease for overall strokes (HR 2.56, 95% CI 1.16-5.67), initial hemorrhagic presentation for hemorrhagic strokes (HR 2.53, 95% CI 1.24-5.17), and initial ischemic presentation for ischemic strokes (HR 2.69, 95% CI 1.15-6.27). Familial MMD was a common risk factor for all types of stroke. Among the 3 clinical groups, the hemorrhagic group showed the worst clinical status at discharge and at most recent follow-up. Twenty-three patients (9.5%) eventually underwent revascularization surgery.</P><B>CONCLUSIONS</B><P>There was no statistically significant difference in the incidence of stroke in the different clinical groups; clinical status, however, was most severe in patients with hemorrhagic presentation. In patients who experienced stroke during the follow-up period, the stroke type tended to correspond to their initial presentation. Close follow-up is needed in patients with thyroid disease and a family history of MMD.</P>

Gamma Knife surgery for intracranial chordoma and chondrosarcoma: radiosurgical perspectives and treatment outcomes

Kim, Ji Hee,Jung, Hyun Ho,Chang, Jong Hee,Chang, Jin Woo,Park, Yong Gou,Chang, Won Seok American Association of Neurological Surgeons 2014 Journal of Neurosurgery Vol.121 No.suppl

<B>Object</B><P>Intracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that are reported to be similar in terms of anatomical location, clinical presentation, and radiological findings but different in terms of behavior and outcomes. The purpose of this study was to investigate and compare clinical outcomes after Gamma Knife surgery (GKS) for the treatment of intracranial chordoma and chondrosarcoma.</P><B>Methods</B><P>The authors conducted a retrospective review of the results of radiosurgical treatment of intracranial chordomas and chondrosarcomas. They enrolled patients who had undergone GKS for intracranial chordoma or chondrosarcoma at the Yonsei Gamma Knife Center, Yonsei University College of Medicine, from October 2000 through June 2007. Analyses included only patients for whom the disease was pathologically diagnosed before GKS and for whom more than 5 years of follow-up data after GKS were available. Rates of progression-free survival and overall survival were analyzed and compared according to tumor pathology. Moreover, the association between tumor control and the margin radiation dose to the tumor was analyzed, and the rate of tumor volume change after GKS was quantified.</P><B>Results</B><P>A total of 10 patients were enrolled in this study. Of these, 5 patients underwent a total of 8 sessions of GKS for chordoma, and the other 5 patients underwent a total of 7 sessions of GKS for chondrosarcoma. The 2- and 5-year progression-free survival rates for patients in the chordoma group were 70% and 35%, respectively, and rates for patients in the chondrosarcoma group were 100% and 80%, respectively (log-rank test, p = 0.04). The 2- and 5-year overall survival rates after GKS for patients in the chordoma group were 87.5% and 72.9%, respectively, and rates for patients in the chondrosarcoma group were 100% and 100%, respectively (log-rank test, p = 0.03). The mean rates of tumor volume change 2 years after radiosurgery were 79.64% and 39.91% for chordoma and chondrosarcoma, respectively (p = 0.05). No tumor progression was observed when margin doses greater than 16 Gy for chordoma and 14 Gy for chondrosarcoma were prescribed.</P><B>Conclusions</B><P>Outcomes after GKS were more favorable for patients with chondrosarcoma than for those with chordoma. The data also indicated that at 2 years after GKS, the rate of volume change is significantly higher for chordomas than for chondrosarcomas. The authors conclude that radiosurgery with a margin dose of more than 16 Gy for chordomas and more than 14 Gy for chondrosarcomas seems to enhance local tumor control with relatively few complications. Further studies are needed to determine the optimal dose of GKS for patients with intracranial chordoma or chondrosarcoma.</P>

Brain involvement by leprosy presenting as a frontal cystic lesion

Lee, Kyung-Hwa,Moon, Kyung-Sub,Yun, Sook Jung,Won, Young Ho,Lee, Jae-Hyuk,Lee, Min-Cheol,Jung, Shin American Association of Neurological Surgeons 2014 Journal of Neurosurgery Vol.121 No.1

<P>Leprosy has a predilection for peripheral nerves and is not considered to involve the CNS. The idea that the CNS is exempt from <I>Mycobacterium leprae</I> bacilli has been suspected from a clinical perspective or CSF study in leprosy patients. However, there has been no direct evidence for CNS involvement by leprosy in a living patient. To the best of the authors' knowledge, the present case is the first report providing histopathological and molecular evidence for CNS involvement by leprosy in a living patient. Brain MRI revealed a 2-cm cystic lesion in the right frontal lobe of the patient. The medical history revealed that the patient had been receiving multidrug therapy for borderline lepromatous leprosy. Neuronavigation-guided craniotomy and lesion removal were performed due to a presumptive diagnosis of low-grade glioma. The brain specimen demonstrated variably thickened blood vessels and densely scattered foamy macrophages in the perivascular spaces and parenchymal stroma. Fite acid-fast stain displayed red granular inclusions that were suggestive for fragmented <I>M. leprae. M. leprae</I>-specific nested polymerase chain reaction amplification showed positive bands, and DNA sequencing also demonstrated homology with the <I>M. leprae</I> genome. This case supports the notion that <I>M. leprae</I> can involve the cerebral cortex regardless of cranial nerve engagement.</P>

Recurrence rates after neuroendoscopic fenestration and Gamma Knife surgery in comparison with subtotal resection and Gamma Knife surgery for the treatment of cystic craniopharyngiomas. Clinical article

Park, Y.S.,Chang, J.H.,Park, Y.G.,Kim, D.-S. American Association of Neurological Surgeons 2011 Journal of neurosurgery Vol.114 No.5

PDIA6 regulation of ADAM17 shedding activity and EGFR-mediated migration and invasion of glioblastoma cells

Kim, Tae-Wan,Ryu, Hyang-Hwa,Li, Song-Yuan,Li, Chun-Hao,Lim, Sa-Hoe,Jang, Woo-Youl,Jung, Shin American Association of Neurological Surgeons 2017 Journal of Neurosurgery Vol. No.

<B>OBJECTIVE</B><P>In patients with glioblastoma, local invasion of tumor cells causes recurrence and shortens survival. The goal of this study was to determine whether protein disulfide isomerase (PDI) A6 regulates migration and invasion of glioblastoma cells and the associated factors.</P><B>METHODS</B><P>U87MG cells were treated with either PDIA6 or ADAM17 small interfering RNA (siRNA) fragments or with both types of siRNA fragments, and expression was confirmed by reverse transcription-polymerase chain reaction and Western blot. Migration and invasion were assessed using a wound-healing assay, a Matrigel assay, and an organotypic culture system. After the U87MG cells were treated with siRNAs and epidermal growth factor receptor (EGFR) inhibitors, the expression of matrix metalloproteinase-2 (MMP-2), membrane Type 1-matrix metalloproteinase (MT1-MMP), integrin, phosphorylated focal adhesion kinase (pFAK), and phosphorylated EGFR (pEGFR) was detected by Western blotting and zymography.</P><B>RESULTS</B><P>U87MG cell migration and invasion increased significantly after inhibition of <I>PDIA6</I>. The MMP-2 activation ratio and ADAM17 activity (as a sheddase of the proligand) increased, and expression of pEGFR, pFAK, integrin α5β3, and MT1-MMP was induced, compared with control levels. Furthermore, heparin-binding epidermal growth factor (EGFR signaling ligand) was highly expressed in <I>PDIA6</I>-knockdown cells. After siPDIA6-transfected U87MG cells were treated with EGFR signaling inhibitors, expression of pFAK, MMP-2, and MT1-MMP decreased and invasion decreased significantly. Simultaneous double-knockdown of <I>PDIA6</I> and <I>ADAM17</I> reduced pEGFR and pFAK expression, compared with control levels.</P><B>CONCLUSIONS</B><P>The authors propose that inhibiting <I>PDIA6</I> could transduce EGFR signaling by activating and inducing <I>ADAM17</I> during migration and invasion of U87MG glioblastoma cells. The results of this study suggest that PDIA6 is an important component of EGFR-mediated migration and invasion of U87MG cells. This is the first report of the effects of PDIA6 on migration and invasion in glioblastoma.</P>

Outcomes of Gamma Knife surgery for trigeminal neuralgia secondary to vertebrobasilar ectasia

Park, Kyung-Jae,Kondziolka, Douglas,Kano, Hideyuki,Berkowitz, Oren,Ahmed, Safee Faraz,Liu, Xiaomin,Niranjan, Ajay,Flickinger, John C.,Lunsford, L. Dade American Association of Neurological Surgeons 2012 Journal of Neurosurgery Vol.116 No.1

<B>Object</B><P>Vertebrobasilar ectasia (VBE) is an unusual cause of trigeminal neuralgia (TN). The surgical options for patients with medically refractory pain include percutaneous or microsurgical rhizotomy and microvascular decompression (MVD). All such procedures can be technically challenging. This report evaluates the response to a minimally invasive procedure, Gamma Knife surgery (GKS), in patients with TN associated with severe vascular compression caused by VBE.</P><B>Methods</B><P>Twenty patients underwent GKS for medically refractory TN associated with VBE. The median patient age was 74 years (range 48-95 years). Prior surgical procedures had failed in 11 patients (55%). In 9 patients (45%), GKS was the first procedure they had undergone. The median target dose for GKS was 80 Gy (range 75-85 Gy). The median follow-up was 29 months (range 8-123 months) after GKS. The treatment outcomes were compared with 80 case-matched controls who underwent GKS for TN not associated with VBE.</P><B>Results</B><P>Intraoperative MR imaging or CT scanning revealed VBE that deformed the brainstem in 50% of patients. The trigeminal nerve was displaced in cephalad or lateral planes in 60%. In 4 patients (20%), the authors could identify only the distal cisternal component of the trigeminal nerve as it entered into the Meckel cave.</P><P>After GKS, 15 patients (75%) achieved initial pain relief that was adequate or better, with or without medication (Barrow Neurological Institute [BNI] pain scale, Grades I-IIIb). The median time until pain relief was 5 weeks (range 1 day-6 months). Twelve patients (60%) with initial pain relief reported recurrent pain between 3 and 43 months after GKS (median 12 months). Pain relief was maintained in 53% at 1 year, 38% at 2 years, and 10% at 5 years. Some degree of facial sensory dysfunction occurred in 10% of patients. Eventually, 14 (70%) of the 20 patients underwent an additional surgical procedure including repeat GKS, percutaneous procedure, or MVD at a median of 14 months (range 5-50 months) after the initial GKS. At the last follow-up, 15 patients (75%) had satisfactory pain control (BNI Grades I-IIIb), but 5 patients (25%) continued to have unsatisfactory pain control (BNI Grade IV or V). Compared with patients without VBE, patients with VBE were much less likely to have initial (p = 0.025) or lasting (p = 0.006) pain relief.</P><B>Conclusions</B><P>Pain control rates of GKS in patients with TN associated with VBE were inferior to those of patients without VBE. Multimodality surgical or medical management strategies were required in most patients with VBE.</P>

Endoscopic endonasal approach for craniopharyngioma: the importance of the relationship between pituitary stalk and tumor

Dho, Yun-Sik,Kim, Yong Hwy,Se, Young-Bem,Han, Doo Hee,Kim, Jung Hee,Park, Chul-Kee,Wang, Kyu-Chang,Kim, Dong Gyu American Association of Neurological Surgeons 2018 Journal of Neurosurgery Vol.129 No.3

<B>OBJECTIVE</B><P>The endoscopic endonasal approach (EEA) is commonly used for the treatment of craniopharyngioma; therefore, it is essential to analyze outcomes in order to understand the benefits and drawbacks. The goal of this paper was to evaluate the clinical features and outcomes associated with this treatment approach.</P><B>METHODS</B><P>From July 2010 to March 2016, 82 adult craniopharyngioma patients underwent an EEA at the authors’ institution. Of these cases, intraoperative records and immediate postoperative MR images were available for 68 patients. The patients underwent systemized endocrinological evaluation. Eighteen of 68 patients who underwent EEA for recurrence or regrowth of residual lesions after previous surgical management were excluded in the analysis of the anatomical tumor classification. The authors retrospectively analyzed preoperative clinical features and previous anatomical classifications, focusing on the relationship of the pituitary stalk and tumor, to determine predictive factors for the clinical outcome, such as the extent of resection, visual function, endocrinological function, recurrence rate, and complications.</P><B>RESULTS</B><P>The mean tumor size was 2.5 cm (3.1 cm for primary tumors and 1.9 cm for recurrent lesions). Gross-total resection (GTR) was achieved in 62 (91.1%) patients (48 [96.0%] patients with primary tumors and 14 [77.8%] patients with recurrent tumors). The rate of GTR was higher in the primary group than in the group with recurrence (p = 0.038). The overall pre- and postoperative visual impairment scale (VIS) scores were 40.8 and 22.1, respectively (50.9 and 14.3 in the primary group and 30.7 and 29.9 in patients with recurrence, respectively). The improvement rate in VIS score was higher in the primary group than in the recurrent group (p = 0.001). Endocrinological function was improved in 4 patients (5.9%) and deteriorated in 32 of 68 patients (47.1%). Tumor invasion into the center of the pituitary stalk affected the postoperative outcomes most significantly. Cognitive dysfunction was observed in 22 patients before surgery and improved in 20 patients (90.9%) after surgery. Hydrocephalus was found in 7 patients and resolved after surgery in all cases. CSF leakage occurred in 2 (2.9%) of 68 patients and was repaired by revision surgery in both patients. Ten patients without CSF leakage also received antibiotics for the treatment of meningitis. The infection rate was higher in the recurrent group. Postoperative endocrinological evaluation showed no deficits in 12 patients and panhypopituitarism in 55 patients. The remaining patient had growth hormone deficiency. Forty-three patients had new-onset diabetes insipidus, and 1 patient had persistent diabetes insipidus after surgery. There were 2 (2.9%) cases of recurrence during the mean 30.7-month follow-up period; one patient underwent radiosurgery and the other underwent reoperation.</P><B>CONCLUSIONS</B><P>The EEA resulted in excellent surgical outcomes and acceptable morbidity rates, regardless of the anatomical location of the tumor. Invasion of the craniopharyngioma into the center of the pituitary stalk has strong predictive power for postoperative endocrinological outcome.</P>

Tetraarsenic oxide-induced inhibition of malignant glioma cell invasion in vitro via a decrease in matrix metalloproteinase secretion and protein kinase B phosphorylation.

Gwak, Ho-Shin,Park, Myung-Jin,Park, In-Chul,Woo, Sang Hyeok,Jin, Hyeon-Ok,Rhee, Chang Hun,Jung, Hee-Won American Association of Neurological Surgeons 2014 Journal of Neurosurgery Vol.121 No.6

<P>Local invasiveness of malignant glioma is a major reason for the failure of current treatments including surgery and radiation therapy. Tetraarsenic oxide (As4O6 [TAO]) is a trivalent arsenic compound that has potential anticancer and antiangiogenic effects in selected cancer cell lines at a lower concentration than arsenic trioxide (As2O3 [ATO]), which has been more widely tested in vitro and in vivo. The authors tried to determine the cytotoxic concentration of TAO in malignant glioma cell lines and whether TAO would show anti-invasive effects under conditions independent of cell death or apoptosis.</P>

Biomechanical head impact characteristics during sparring practice sessions in high school taekwondo ahtletes

데이빗오설리반 American Association of Neurological Surgeons 2017 Journal of Neurosurgery: Pediatrics Vol.1 No.1