樋口 佳則

BACKGROUND: The best surgical approach for resecting bilateral parafalcine meningioma, as well as the optimal anesthesia and airway management for craniotomy in patients with interstitial pneumonia (IP) for preventing postsurgical exacerbation, remains unclear. OBSERVATIONS: A 66-year-old female with a history of multiple relapses of IP underwent craniotomy for resection of a 4.5-cm bilateral parafalcine meningioma located just beneath the inferior sagittal sinus. To avoid mechanical ventilation or high-concentration oxygenation, the entire procedure was performed under nonintubated spontaneous breathing conditions with a supraglottic airway/laryngeal mask airway (SGA/LMA) device. Half of the tumor was resected using the ipsilateral interhemispheric approach, while the remaining half was resected using the contralateral transfalcine approach (CTA). No brain retractors were required. Preoperative embolization contributed toward reducing blood loss and surgery duration. During most of the operation, additional oxygen administration was not required. The postoperative course was uneventful, without exacerbation of the IP. LESSONS: This case demonstrated the utility and feasibility of a unilateral interhemispheric approach combined with CTA for resection of a bilateral parafalcine meningioma. Additionally, this case provides an alternative method of airway and anesthesia management with an SGA/LMA device and nonintubated spontaneous breathing for the prevention of postoperative acute exacerbation of IP.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

INTRODUCTION: Historical reservations regarding radiosurgery (SRS) for small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for short-interval/diffuse CNS-progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small-cell-lung-cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000-2022 were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the prospective JLGK0901 SRS trial were analyzed as a comparison cohort (N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable (MV) adjustment (including age/sex/performance-status/year/extracranial disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC, mutation-negative-NSCLC, and SCLC. RESULTS: OS was superior with NSCLC over SCLC in the retrospective dataset (median-OS, 10.5 vs 8.6 months, MV-p<0.001) and JLGK0901. Hazard estimates for first CNS-progression favoring NSCLC were similar in both datasets but reached significance in the retrospective dataset only (MV-HR:0.82 [95%-CI:0.73-0.92], p=0.001). In the PSM cohorts, there were continued OS advantages for NSCLC (median-OS, 23.7 [EGFR/ALK-positive-NSCLC] vs 13.6 [mutation-negative-NSCLC] vs 10.4 months [SCLC], pairwise-p-values<0.001), but no significant differences in CNS-progression. Neurological mortality and number of lesions at CNS-progression were similar for NSCLC and SCLC patients. Leptomeningeal-progression was increased in NSCLC patients in the retrospective dataset only (MV-HR:1.61 [95%-CI:1.14-2.26], p=0.007). CONCLUSION: After SRS, SCLC was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC overall but was similar in patients matched on baseline characteristics. Neurological mortality, lesions at CNS-progression, and leptomeningeal-progression were comparable. These findings may better inform clinical decision-making for SCLC patients.

【目的】痙性対麻痺に伴う歩行障害の改善を期待したバクロフェン髄注療法(Intrathecal Baclofen;ITB)の手術適応基準は未だ明確でない。バクロフェンスクリーニングを行った30症例のうち手術に至らなかった症例での,スクリーニング時の特徴を見いだすため検討を行った。【方法】独歩が可能でバクロフェンスクリーニングを試行した痙性対麻痺症例30例を対象とした。6.25～50μgのバクロフェン髄注を行い4時間後に痙性(modified Ashworth score;mAS),筋力(manual muscle test;MMT)の評価を行った。スクリーニング後15例が手術を希望され手術を行った。手術非施行例15例,手術施行例15例とし,両群間のスクリーニング時のmAS,MMTに関し解析を行った。【結果】全症例での解析では下肢の有意なmAS低下を認め,MMTでは有意な変化を示さなかった。10m歩行,timed up and goではバクロフェン投与で有意な変化を認めなかった。手術施行例と非施行例の比較を行うと,mASでは両群間に有意差を認めないものの,下肢MMTでは手術非施行例で有意な低下を認め,特に股関節屈曲・伸展でのMMTの低下が認められた。【結語】バクロフェンによる痙性が改善したとしても,股関節屈曲・伸展筋力低下がより手術適応に関わる因子と考えられる。(著者抄録)

OBJECTIVE Due to the heterogeneous definitions of tumor regrowth and various tumor volume distributions, the nature of small remnants after vestibular schwannoma (VS) surgery and the appropriate timing of adjuvant stereotactic radiosurgery for these remnants remain unclear. In this study, the growth potential of small remnants (&lt; 1 cm³) after VS surgery was compared with that of treatment-naïve (TN) small VSs. METHODS This retrospective single-center study included 44 patients with VS remnants following subtotal resection (STR) of a large VS (remnant group) and 75 patients with TN VS (&lt; 1 cm³; TN group). A 20% change in tumor volume over the imaging interval indicated radiographic progression or regression. Tumor progression-free survival (TPFS) rates were estimated using the Kaplan-Meier method. RESULTS In the remnant group, the mean preoperative tumor volume was 13.8 ± 9.0 cm³ and the mean tumor resection rate was 95% ± 5%. The mean tumor volume at the start of the observation period did not differ significantly between the two groups (remnant vs TN: 0.41 ± 0.29 vs 0.34 ± 0.28 cm³, p = 0.171). The median periods until tumor progression was detected were 15.1 (range 4.9–76.2) months and 44.7 (range 12.6–93.2) months in the TN and remnant groups, respectively. In the remnant group, the TPFS rates were 74% and 70% at 3 and 5 years after the surgery, respectively, compared with 59% and 47% in the TN group. The log-rank test demonstrated a significant difference (p = 0.008) in the TPFS rates between the two groups. Furthermore, 42 patients each from the remnant and TN groups were matched based on tumor volume. TPFS was significantly longer in the remnant group than in the TN group (3-year rates, 77% vs 62%; 5-year rates, 73% vs 51%; p = 0.02). In the remnant group, 18% of the tumor remnants demonstrated regression during follow-up, compared with 9% in the TN group, but this intergroup difference was not significant (p = 0.25). CONCLUSIONS This study demonstrated that the growth potential of small VS remnants was lower than that of TN tumors. Observing for small remnants may be appropriate after STR of a large VS. Given the risk of tumor regrowth, careful observation using MRI should be mandatory during follow-up.

BACKGROUND AND IMPORTANCE: Cholesterol granuloma (CG) is the most common petrous apex (PA) cystic lesion. Posterolateral expansion of a PA CG (PACG) compresses the internal auditory canal (IAC), leading to vestibulocochlear (VC) and facial nerve dysfunction. Even small, symptomatic PACGs are managed surgically. The preferred strategy is not complete removal, but drainage and aeration. PACG with anteromedial expansion using an endoscopic endonasal approach provides natural drainage into the nasal sinus without risking VC and facial dysfunction. Endoscopic endonasal approach is inappropriate for small PACGs without anteromedial expansion because of potential damage to the petrous internal carotid artery. Small PACGs without anteromedial expansion are managed using extradural middle fossa (EMF) approach, which lacks a natural drainage pathway, thus necessitating an artificial drainage pathway for PACG aeration to prevent recurrence. We introduced EMF approach for CG decompression and cyst-to-mastoid antrum (MA) diversion for managing small, symptomatic PACGs without anteromedial expansion. CLINICAL PRESENTATION: A 48-year-old woman presented with headache, vertigo, tinnitus, and left hemifacial spasm with preserved hearing because of IAC compression caused by a small PACG without anteromedial expansion. Using the EMF approach, the CG and IAC were safely decompressed. Effective and long-standing artificial drainage for CG aeration was established by anterior petrosectomy and silicone tubing from the CG into the MA. Surgery resolved the symptoms, which have not recurred in 3 years. CONCLUSION: Granuloma decompression and cyst-to-MA diversion using silicone tubing using the EMF approach is a safe and effective surgical management for small, symptomatic PACG without anteromedial expansion.

刺激装置 (IPG) 交換術中に偶発的に発見された乳がん症例を経験したため, 文献的考察も含め報告する. 60歳代女性. 進行期パーキンソン病に対して両側視床下核脳深部刺激療法 (DBS) が施行された. 3.5年後, IPGの電池消耗のため交換術を施行. 術中, 右胸部のIPG留置部内に約1cmの硬結を触れたため, 生検を行い病理検査に提出し新しいIPGを留置した. 病理検査の結果, 浸潤型乳管癌の診断となり, 後日, 右乳房全摘出およびセンチネルリンパ節生検を行い, 同時にIPGを左側へ再留置した. 術後分子標的薬による治療と化学療法を行い経過観察中である. 乳がん好発年齢のDBS後の患者では乳がん発症の可能性を考慮し, 乳がんに対する適切な検診方法を考慮する必要がある.

BACKGROUND: The Movement Disorders Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) is increasingly used to assess motor dysfunction before and after subthalamic nucleus deep brain stimulation (STN-DBS). OBJECTIVES: We, therefore, investigated whether the MDS-UPDRS can detect longitudinal changes in motor function after STN-DBS in the same way as UPDRS. METHODS: We examined 21 patients with Parkinson's disease (PD) (mean age 59.2 ± 10.6 years, mean disease duration 12.0 ± 3.0 years) who underwent STN-DBS and whose motor functions were assessed by the UPDRS and MDS-UPDRS before, 3 months after, and 1 year after STN-DBS. We then evaluated the consistency between the scores of Parts II and III of the UPDRS and MDS-UPDRS during the off phase using Lin's concordance coefficient (LCC) and a Bland-Altman plot. RESULTS: The scores of Parts II and III of both the UPDRS and MDS-UPDRS were significantly decreased 3 months and 1 year after STN-DBS during the off phase. Scores of the UPDRS and MDS-UPDRS showed significant positive correlations before and after STN-DBS. We calculated estimated MDS-UPDRS scores from the UPDRS scores using a regression line and calculated the LCC between the MDS-UPDRS and the estimated MDS-UPDRS scores. The LCC value was 0.59-0.91, which suggests a relatively high consistency between the UPDRS and MDS-UPDRS. The Bland-Altman plot showed that differences between both scores were basically within ±1.96 standard deviations of the difference. CONCLUSION: The present preliminary study indicated that the utility of the MDS-UPDRS in evaluating motor function before and after STN-DBS demonstrates its potential equivalency to the UPDRS.

BACKGROUND AND PURPOSE: The Renal Graded Prognostic Assessment (GPA) is relatively new and has not been sufficiently validated using a different dataset. We thus developed a new grading index, the Renal Brain Metastasis Score (Renal-BMS). MATERIALS AND METHODS: Using our dataset including 262 renal cancer patients with brain metastases (BMs) undergoing stereotactic radiosurgery (SRS) (test series), we validity tested the Renal-GPA. Next, we applied clinical factor-survival analysis to the test series and thereby developed the Renal-BMS. This system was then validated using another series of 352 patients independently undergoing SRS at nine gamma knife facilities in Japan (verification series). RESULTS: Using the test series, with the Renal-GPA, 95% confidence intervals (CIs) of the post-SRS median survival times (MSTs) overlapped between pairs of neighboring subgroups. Among various pre-SRS clinical factors of the test series, six were highly associated with overall survival. Therefore, we assigned scores for six factors, i.e., "KPS ≥ 80%/<80% (0/3)", "tumor numbers 1-4/≥5 (score; 0/2)", "controlled primary cancer/not (0/2)", "existing extra-cerebral metastases/not (0/3)", "blood hemoglobin ≥ 11.0/<11.0 g/dl (0/1)" and "interval from primary cancer to SRS ≥ 5/<5 years (0/1)". Patients were categorized into three subgroups according to the sum of scores, i.e., 0-4, 5-8 and 9-12. In the test and verification series, post-SRS MSTs differed significantly (p < 0.0001) with no overlaps of 95% CIs among the three subgroups. CONCLUSIONS: The Renal BMS has the potential to be very useful to physicians selecting among aggressive treatment modalities for renal cancer patients with BMs.

<sec> <title>BACKGROUND</title> Anatomical variations, such as high jugular bulbs and air cell development in the petrosal bone, should be evaluated before surgery. Most bone defects in the internal auditory canal (IAC) posterior wall are observed in the perilabyrinthine cells. An aberrant vascular structure passing through the petrous bone is rare. </sec> <sec> <title>OBSERVATIONS</title> A 48-year-old man presented with a right ear hearing disturbance. Magnetic resonance imaging revealed a 23-mm contrast-enhancing mass in the right cerebellopontine angle extending into the IAC, consistent with a right vestibular schwannoma. Preoperative bone window computed tomographic scans showed bone defects in the IAC posterior wall, which ran farther posteroinferiorly in the petrous bone, reaching the medial part of the jugular bulb. The tumor was accessed via a lateral suboccipital approach. There was no other major vein in the cerebellomedullary cistern, except for the vein running from the brain stem to the IAC posterior wall. To avoid complications due to venous congestion, the authors did not drill out the IAC posterior wall or remove the tumor in the IAC. </sec> <sec> <title>LESSONS</title> Several aberrant veins in the petrous bone are primitive head sinus remnants. Although rare, their surgical implication is critical in patients with vestibular schwannomas. </sec>

OBJECTIVE: The relationship between quantitative posturography results and growth of vestibular schwannomas (VSs) during conservative management has not been studied. We aimed to clarify the relationship between the presence of disequilibrium based on posturographic measurement and VS growth. METHODS: This retrospective, single-center study included 53 patients with VSs (Koos stage I or II) managed conservatively after initial diagnosis. Radiographic progression was considered present if 20% volumetric growth was observed over the imaging interval. Posturography was performed at initial diagnosis, and sway velocity (SV) and sway area were calculated. Tumor growth-free survival was estimated using the Kaplan-Meier method. RESULTS: Mean follow-up period was 2.87 ± 2.58 years, up to tumor growth detection or last follow-up magnetic resonance imaging. Tumor growth incidence was 40.8% and 61.2% at 2 and 5 years, respectively. Cerebellopontine angle extension and SV with eyes open were related to tumor growth. Tumor growth-free survival of patients with cerebellopontine angle extension and patients with intracanalicular tumor at 2 years was 37.3% and 76.4%, respectively. Tumor growth-free survival of patients with SV >2.06 cm/second and patients with SV ≤2.06 cm/second at 2 years was 30.8% and 68.9%, respectively. The Cox hazard model demonstrated a significant risk for future tumor growth with SV >2.06 cm/second (relative risk, 2.475; 95% confidence interval, 1.11-5.37, P = 0.027). CONCLUSIONS: We demonstrated a positive correlation between SV with eyes open and future tumor growth. Posturographic data are objective and quantitative; thus, SV may be a potential predictor of future growth of VSs.

BACKGROUND AND PURPOSE: As more cancer patients with brain metastases (BMs) are surviving longer due to recent advancements in various treatment modalities, we developed a grading system for stereotactic radiosurgery (SRS)-treated BM patients with long survival. This is a Graded Prognostic Model for Patients Surviving 3 Years or More (GPM ≥ 3Ys). MATERIALS AND METHODS: First, using clinical factor-survival time analysis of 3237 patients in whom gamma knife (GK) SRS was performed by the second author (test cohort), we developed the GPM ≥ 3Ys based on survival ≥3 years as the objective variable. The validity of this model was then tested using another series of 3317 patients independently undergoing GK SRS performed by the third author (verification cohort). Number of patients surviving 3 years or more were 289 (8.9%) and 348 (10.5%), respectively. RESULTS: Using the test series, among various pre-SRS clinical factors, noted below, five were shown to be highly correlated with survival of ≥3 years. Therefore, we assigned scores for these five factors, i.e., "tumor numbers 1/2-4/≥5 (score; 6/1/0)", "female/male (5/0)", "KPS ≥80%/<80% (5/0)", "primary cancers of breast/lung/gastrointestinal tract/other (score; 1/0/3/0)", "controlled primary cancer/not (8/0)" and "existing extra-cerebral metastases/not (5/0). Patients were categorized into four grades according to the sum of scores, i.e., 0-9, 10-19, 20-29 and 30-36. Post-SRS mean survival times (MSTs) differed significantly (p < 0.0001) with no overlapping of 95% confidence intervals (CIs) among the four grades. Also, in the verification series, MSTs differed significantly (p < 0.0001) with no overlapping of 95% CI among the four grades of the GPM ≥ 3Ys system. CONCLUSION: Although this was a retrospective study, the GPM ≥ 3Ys system was shown to be very useful to physicians selecting among more aggressive treatment modalities for patients in whom longer survival can be expected.

OBJECTIVE: Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) is a standard surgical treatment option in patients with advanced Parkinson's disease. Adverse effects on cognitive function have been reported, impacting the quality of life of patients and caregivers. We aimed to investigate a quantitative predictive preexisting cognitive factor for predicting postoperative cognitive changes. METHODS: Thirty-five patients underwent STN-DBS. A battery of neuropsychological tests were used to examine executive function, processing speed, and visuospatial function both preoperatively and 1 year postoperatively. A multiple logistic regression analysis was performed to investigate the relationships between preoperative factors and cognitive outcomes. The predictive value of the preoperative factors for global cognitive decline during long-term follow-up were evaluated. RESULTS: The patients exhibited significant changes in processing speed and visuospatial function after surgery. Using reliable change index values, lower preoperative scores on the Similarities and Object Assembly subtests of the Wechsler Adult Intelligence Scale III were associated with decreases in visuospatial function at 1 year after DBS. The odds ratios were 10.2 for Similarities and 9.53 for Object Assembly. The proportion of Mini Mental State Examination-maintained patients with low scores on the Similarities subtest was significantly lower than that of patients with high scores at 3 and 5 years. No factors were found to be related to decreases in processing speed. CONCLUSIONS: Preoperative evaluation of the Similarities and Object Assembly subtests may be useful to identify patients who are at a greater risk of experiencing decreases in visuospatial functioning after STN-DBS. Furthermore, a low score on the Similarities subtest may predict future global cognitive deterioration.

OBJECTIVE: The treatment of patients with ≥11 brain metastases (BMs) with stereotactic radiosurgery (SRS) alone has yet to be established. The aim of this study was to compare results of SRS alone in patients with 5-10 BMs versus 11-20 BMs. METHODS: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 1515 patients with 5-10 tumors and 804 patients with 11-20 tumors treated with Gamma Knife SRS by 2 experienced neurosurgeons between 1998 and 2018. The Kaplan-Meier method was applied to determine post-SRS survival times, and competing risk analyses were used to estimate cumulative incidences of the secondary end points. RESULTS: The post-SRS median survival time was slightly longer in the group with 5-10 tumors (7.7 months) than in the group with 11-20 tumors (6.5 months) (P < 0.0001). Median survival time differences were statistically significant for patients with lung cancers but not for patients with breast, gastrointestinal tract, kidney, and other cancers. Multivariable analysis revealed female sex, better Karnofsky performance scale score, controlled primary cancer, and absence of extracerebral metastases to be statistically significant predictors of longer survival in the 2 patient cohorts. Crude and cumulative incidences of local recurrences were significantly lower in the group with 11-20 tumors than in the group with 5-10 tumors, while those of other secondary end points were similar to or lower in the group with 11-20 tumors than in the group with 5-10 tumors. Post-SRS outcomes were relatively poor in patients with 11-20 tumors from kidney or other cancers. CONCLUSIONS: Carefully selected patients with 11-20 BMs are not unfavorable candidates for SRS alone.

von Hippel-Lindau (VHL) disease is characterized by neoplastic and cystic lesions, such as central nervous system (CNS) hemangioblastoma and clear cell renal cell carcinoma (RCC), arising in multiple organs. Here, we report a case of an RCC that metastasized to a spinal hemangioblastoma in a patient diagnosed with VHL disease. This is a unique case study because visceral neoplasms rarely metastasize to the CNS. The patient had undergone posterior fossa surgery for the removal of hemangioblastomas in the right cerebellar hemisphere as a child. He was diagnosed with RCC at the age of 20 years, and he underwent partial nephrectomy at the age of 35 years. The patient underwent surgical removal of a spinal tumor from Th8, which was also diagnosed as a hemangioblastoma at the age of 40. However, the residual spinal tumor rapidly regrew within 1.5 years. A second surgery was performed due to progressive leg motor weakness. The resected tumor from the second surgery had two distinct components between the tumor center and the margin. Immunohistochemistry of CD10, PAX 8, and inhibin A demonstrated the predominant region of the tumor was RCC. Pathological findings confirmed tumor-to-tumor metastasis of the RCC migrating into residual spinal hemangioblastoma. It can be challenging to distinguish hemangioblastoma from RCC in neuroimaging. We suggest that tumor-to-tumor metastasis should be considered as a differential diagnosis if benign tumors grow rapidly, even if the pathological diagnosis does not initially confirm malignancy. The biological mechanisms of RCC migrating into residual hemangioblastoma are discussed.

聴神経腫瘍(VS)の自然歴、術後残存腫瘍に関する知見をまとめる。VSの腫瘍成長の頻度は定義により多様で、成長リスクとして初診時の腫瘍サイズ、平衡異常、嚢胞性腫瘍などが報告されている。自然歴での聴力低下のリスクは、腫瘍成長、診断時聴力、腫瘍体積などが報告されており、診断時に将来の聴力低下のリスクを考慮した治療方針も検討する必要がある。手術・定位放射線治療(SRS)での聴力温存は39〜87%で、治療前の良好な聴力が術後聴力温存の予後因子となる。自然歴と手術・SRSにおけるリスク・予後を考慮した治療選択が不可欠である。術後残存腫瘍増大リスクとして残存腫瘍体積が報告されており、残存腫瘍の大きさに応じ早期のSRS施行は妥当である。(著者抄録)

Background: Indications for subthalamic nucleus deep brain stimulation (STN-DBS) surgery are determined basically by preoperative motor function; however, postoperative quality of life (QOL) is not necessarily associated with improvements in motor symptoms, suggesting that neuropsychiatric symptoms might be related to QOL after surgery in patients with Parkinson's disease. Objectives: We aimed to examine temporal changes in neuropsychiatric symptoms and their associations with QOL after STN-DBS. Materials and Methods: We prospectively enrolled a total of 61 patients with Parkinson's disease (mean age = 65.3 ± 0.9 years, mean disease duration = 11.9 ± 0.4 years). Motor function, cognitive function, and neuropsychiatric symptoms were evaluated before and after DBS surgery. Postoperative evaluation was performed at 3 months, 1 year, and 3 years after surgery. Results: Of the 61 participants, 54 completed postoperative clinical evaluation after 3 months, 47 after 1 year, and 23 after 3 years. Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. Non-motor symptoms such as impulsivity and the Unified PD Rating Scale (UPDRS) part I score were associated with QOL after STN-DBS. Conclusions: Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. The UPDRS part I score and higher impulsivity might be associated with QOL after STN-DBS.

INTRODUCTION: Brain metastasis (BM) is one of the most important issues in the management of breast cancer (BC), since BMs are associated with neurological deficits. However, the importance of BC subtypes remains unclear for BM treated with Gamma Knife radiosurgery (GKS). Thus, we conducted a multicenter retrospective study to compare clinical outcomes based on BC subtypes, with the aim of developing an optimal treatment strategy. METHODS: We studied 439 patients with breast cancer and 1-10 BM from 16 GKS facilities in Japan. Overall survival (OS) was analyzed by the Kaplan-Meier method, and cumulative incidences of systemic death (SD), neurologic death (ND), and tumor progression were estimated by competing risk analysis. RESULTS: OS differed among subtypes. The median OS time (months) after GKS was 10.4 in triple-negative (TN), 13.7 in Luminal, 31.4 in HER2, and 35.8 in Luminal-HER2 subtype BC (p < 0.0001). On multivariate analysis, poor control of the primary disease (hazard ratio [HR] = 1.84, p < 0.0001), active extracranial disease (HR = 2.76, p < 0.0001), neurological symptoms (HR 1.44, p = 0.01), and HER2 negativity (HR = 2.66, p < 0.0001) were significantly associated with worse OS. HER2 positivity was an independent risk factor for local recurrence (p = 0.03) but associated with lower rates of ND (p = 0.03). TN histology was associated with higher rates of distant brain failure (p = 0.03). CONCLUSIONS: HER2 positivity is related to the longer OS after SRS; however, we should pay attention to preventing recurrence in Luminal-HER2 patients. Also, TN patients require meticulous follow-up observation to detect distant metastases and/or LMD.

BACKGROUND: There is little information on stereotactic radiosurgery (SRS) results for brain metastases (BMs) in lung cancer patients ≥75 years of age. We aimed to reappraise whether SRS results for patients ≥75 (very elderly) differ from those of patients with 65-74 years old (elderly). METHODS: This IRB-approved retrospective cohort study was based on our prospectively-accumulated database including 7351 consecutive patients undergoing gamma knife (GK) SRS performed for BMs by two highly experienced neurosurgeons during the 1998-2018 period. We selected a total of 2915 elderly patients (age ≥65 years, 39.7 % of the 7351) with lung cancers (902 females, 2013 males, median age; 72 [maximum; 96] years, 2441 NSCLCs, 474 SCLCs) for this study. RESULTS: Post-SRS median survival times (MSTs, months) differed significantly between the two lung cancer types, NSCLC (9.0) and SCLC (7.2, p < 0.0001). In NSCLC patients, post-SRS MSTs were significantly shorter in the very elderly (9.7) than those in the elderly (7.8) group (p < 0.0001). However, in SCLC patients, there were no significant MST differences (7.3 vs 6.9, p = 0.52) between the two age groups. In both NSCLC and SCLC patients, neither crude nor cumulative incidences of secondary endpoints in the very elderly group, i.e., neurological death, neurological deterioration, local recurrence, repeat SRS, salvage whole brain radiotherapy and SRS-related complications, were shown to be unfavorable to those in the elderly group. CONCLUSIONS: Our results suggest that carefully-selected patients ≥75 years of age are not poor candidates for SRS as compared to those 65-74 years old.

Epstein-Barr virus-associated smooth muscle tumour (EBV-SMT) is a rare disease occurring in immunosuppressed patients, such as those with AIDS, post-transplantation immunodeficiency and congenital immunodeficiency. Intracranial EBV-SMT after solid organ transplantation has been reported. However, intracranial lesions after bone marrow transplantation are extremely rare. We report the case of a 47-year-old man with a history of acute myeloid leukaemia and bone marrow transplantation. He had symptoms of trigeminal neuralgia, and MRI revealed a left cavernous sinus tumour. He started taking oral gabapentin, but his symptoms did not improve. We performed transnasal endoscopic surgery. Postoperative MRI showed complete removal of the cavernous sinus lesion. Pathological examination showed spindle-shaped cells positive for smooth muscle markers and EBV-encoded small RNA in situ hybridisation. EBV-SMT was pathologically diagnosed. His symptoms improved after surgery. No tumour recurrence was noted on follow-up MRI after 15 months without adjuvant radiation or chemotherapy.

Isolated hypoglossal nerve palsy (IHP), or hypoglossal nerve palsy without any other neurological signs, is rare. We report a woman with atlantoaxial dislocation (AAD) who presented with IHP due to hypoglossal nerve compression by an osteophyte at the hypoglossal canal. A 77-year-old woman presented with speech difficulties and the feeling of a swollen tongue on the left side for 3 days. Her only neurological feature was left hypoglossal nerve palsy. She had been diagnosed with AAD 2 years before. Computed tomography (CT) and high-resolution magnetic resonance imaging (MRI) revealed the compression of the basicranial hypoglossal nerve at the external orifice of the hypoglossal canal by an AAD osteophyte which was causing IHP. IHP can develop due to hypoglossal nerve compression by an osteophyte from AAD. CT and high-resolution MRI revealed this rare mechanism of IHP.

This video case presents techniques of retrosigmoid curative removal of small vestibular schwannoma (VS) with functional preservation. A 49-year-old woman with right intrameatal VS presented with sudden hearing loss. Preoperative hearing was American Academy of Otolaryngology-Head and Neck Surgery (AAO) class A (pure tone audiometry: 18 dB). Magnetic resonance imaging showed VS filling the right internal auditory canal (IAC). She underwent retrosigmoid suboccipital VS removal in lateral position using auditory brainstem response monitoring, resulting in total tumor removal with preservation of auditory brainstem response. No facial palsy occurred, and AAO class A (pure tone audiometry: 26 dB) hearing was preserved postoperatively. Techniques for curative tumor removal with functional preservation are as follows: 1) wide and deep IAC exposure with preservation of the meatal dura: though covered by the preserved meatal dura, meatal tumor bulges out after appropriate canal exposure, which also comprises petrous dura flap preparation and canal skeletonization; 2) sharp tumor debulking and dissection: tumor debulking is always mandatory to avoid damage to nerve function; 3) IAC reconstruction: after completion of tumor removal, the IAC roof is reconstructed using the petrous dura flap and muscle graft to restore the cerebrospinal fluid space in the canal and preserve long-term nerve function. Magnetic resonance imaging with gadolinium administration at 1 year and 5 years after surgery showed total tumor removal with no recurrence (i.e., curative tumor removal) and restored cerebrospinal fluid space in the canal by IAC reconstruction.

Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited. Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT. Design, Setting, and Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019. Interventions: SRS and WBRT for small cell lung cancer brain metastases. Main Outcomes and Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses. Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results. Conclusions and Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.

Purpose: The role of stereotactic radiosurgery (SRS) alone for patients with >= 5 brain metastases is not fully understood. The objective of the study was to compare SRS-alone treatment results for 2 to 4 versus 5 to 15 tumors.Methods and Materials: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 1150 patients with 2 to 4 tumors and 939 with 5 to 15 tumors who underwent Gamma Knife SRS during a 20-year period (1998-2018). The Kaplan-Meier method was used to determine post-SRS survival times, and competing risk analyses were applied to estimate cumulative incidences of the secondary endpoints.Results: The post-SRS median survival time was slightly longer in the group with 2 to 4 tumors (8.1 months) than in that with 5 to 15 tumors (7.2 months, P = .0010). Median survival time differences were statistically significant for non-small cell lung cancer, gastrointestinal tract cancer, and others but not for small cell lung cancer, breast cancer, and kidney cancer. Multivariable analysis demonstrated female sex, better Karnofsky Performance Status score, non-small cell lung cancer (vs gastrointestinal tract cancer), younger age, controlled primary cancer, and no extracerebral metastases to be significant predictors of a longer survival period in both tumor number groups. Crude and cumulative incidences of salvage whole brain radiation therapy were significantly higher in the group with 5 to 15 tumors than in that with 2 to 4 tumors, although those of other secondary endpoints were similar to or lower in the 5 to 15 tumor number group than those in the group with 2 to 4 tumors.Conclusions: We conclude that carefully selected patients with >= 5 to 15 tumors are not unfavorable candidates for SRS alone. (C) 2019 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.

PURPOSE: This study aimed to validate whether the recently-proposed prognostic grading system, initial brain metastasis velocity (iBMV), is applicable to breast cancer patients receiving stereotactic radiosurgery (SRS). We focused particularly on whether this grading system is useful for patients with all molecular types, i.e., positive versus negative for EsR, PgR and HER2. METHODS AND MATERIALS: This was an institutional review board-approved, retrospective cohort study using our database, prospectively accumulated at three gamma knife institutes, during the 20-year-period since 1998. We excluded patients for whom the day of primary cancer diagnosis was not available, had synchronous presentation, lacked information regarding molecular types, and/or had received pre-SRS radiotherapy and/or surgery. We ultimately studied 511 patients categorized into two classes by iBMV scores, i.e., < 2.00 and ≥ 2.00. RESULTS: The median iBMV score for the entire cohort was 0.97 (IQR 0.39-2.84). Median survival time (MST) in patients with iBMV < 2.00, 15.9 (95% CI 13.0-18.6, IQR 7.5-35.5) months, was significantly longer than that in patients with iBMV ≥ 2.00, 8.2 (95% CI 6.8-9.9, IQR 3.9-19.4) months (HR 1.582, 95% CI: 1.308-1.915, p < 0.0001). The same results were obtained in patients with EsR (-), PgR (-), HER2 (+) and HER2 (-) cancers, while MSTs did not differ significantly between iBMV < 2.00 vs ≥ 2.00 in patients with EsR (+) and PgR (+) cancers. CONCLUSIONS: This system was clearly shown to be applicable to breast cancer patients with SRS-treated BMs. However, this system is not applicable to patients with hormone receptor (+) breast cancer.

PURPOSE: Stereotactic radiosurgery (SRS) is typically considered for patients who cannot undergo surgical resection for large (> 10 cm3) brain metastases (BMs). Staged SRS requires adaptive planning during each stage of the irradiation period for improved tumor control and reduced radiation damage. However, there has been no study on the tumor reduction rates of this method. We evaluated the outcomes of two-stage SRS across multiple primary cancer types. METHODS: We analyzed 178 patients with 182 large BMs initially treated with two-stage SRS. The primary cancers included breast (BC), non-small cell lung (NSCLC), and gastrointestinal tract cancers (GIC). We analyzed the overall survival (OS), neurological death, systemic death (SD), tumor progression (TP), tumor recurrence (TR), radiation necrosis (RN), and the tumor reduction rate during both stages. RESULTS: The median survival time after the first Gamma Knife surgery (GKS) procedure was 6.6 months. Compared with patients with BC and NSCLC, patients with GIC had shorter OS and a higher incidence of SD. Compared with patients with NSCLC and GIC, patients with BC had significantly higher tumor reduction rates in both sessions. TP rates were similar among primary cancer types. There was no association of the tumor reduction rate with tumor control. The overall cumulative incidence of RN was 4.2%; further, the RN rates were similar among primary cancer types. CONCLUSIONS: Two-stage SRS should be considered for BC and NSCLC if surgical resection is not indicated. For BMs from GIC, staged SRS should be carefully considered and adapted to each unique case given its lower tumor reduction rate and shorter OS.

乳癌脳転移に対するガンマナイフ治療(GKS)後のサブタイプ別の治療成績について検討した。脳転移に対する初回治療としてGKSを施行したサブタイプ既知の乳癌脳転移症例439例を対象とした。原発巣の組織から得られたHER2、エストロゲン受容体(ER)およびプロゲステロン受容体(PR)の情報に基づき、サブタイプをTriple negative(TN、HER2/ER/PRともに陰性)、Luminal(HER2陰性、ERまたはPR陽性)、Luminal-HER2(HER2陽性、ERまたはPR陽性)、HER2(HER2陽性、ER/PRともに陰性)に分類した。その結果、Luminalが154例、Luminal-HER2が111例、HER2が105例、TNが69例であった。観察期間中央値は16.4ヵ月で、症例登録終了時に292例(66.5%)の死亡を確認した。全生存期間中央値(MST)はTN 10.4ヵ月、Luminal 13.7ヵ月、HER2 31.4ヵ月、Luminal-HER2 35.8ヵ月で4群間に有意差を認めた。また、全身死および神経死の累積発生頻度に関して、いずれもHER2陽性群が有意に低値を示しており、局所再発の発生頻度はHER2陽性群で高かった。GKS後の追加GKSの頻度は1年でLuminal 42.9%、Luminal-HER2 52.4%、HER2 52.4%、TN 69.4%であり、TNで最も頻度が高かった。全脳照射の追加の頻度もGKS後1年でLuminal 5.3%、Luminal-HER2 3.8%、HER2 3.4%、TN 24.1%であり、TNが最も頻度が高かった。脳転移に対するGKS施行後の全生存、ND、SDおよび腫瘍制御は乳癌サブタイプにより異なることが示された。

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery. METHODS: Western aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[123I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients, before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected. RESULTS: Although motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery. CONCLUSION: Present results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.

PURPOSE: Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma. METHODS: We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events. RESULTS: Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0 months, HR 0.60, 95% CI 0.48-0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12-1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups. CONCLUSIONS: Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.

BACKGROUND: The surgical resection of large supracerebellar hemangioblastomas (SHBs) is exceptionally challenging due to their vascularity and deep anatomic location and is associated with a high risk of postoperative complications and mortality. Access to the posterior incisural space can be achieved by either an infratentorial supracerebellar approach or occipital transtentorial approach (OTA). However, the optimal surgical strategy has not yet been established. Here, we report 2 cases of large SHBs that were successfully and safely resected via a unilateral OTA with multimodal assistance. CASE DESCRIPTION: Two patients presented to our hospital with ataxia due to large, solid SHBs. After preoperative embolization, gross total resection of the SHBs was achieved via an OTA. Furthermore, endoscopic assistance was used to resect the remnant portion of the tumor in the second patient. Both patients experienced transient ataxia but were discharged from the hospital without serious complications. CONCLUSIONS: The combination of an OTA with preoperative embolization and endoscopic assistance may reduce the intraoperative risk and contribute to improved outcome in patients with such clinically challenging tumors.

PURPOSE: Stereotactic radiosurgery (SRS) has been increasingly used for elderly patients with brain metastases (BMs). However, no studies based on a large sample size have been reported. To compare SRS treatment results between elderly and non-elderly patients, we performed a subset study of elderly patients using our prospectively-accumulated multi-institution study database (JLGK0901 Study, Lancet Oncol 15:387-395, 2014). METHODS: During the 2009-2011 period, 1194 eligible patients undergoing gamma knife SRS alone for newly diagnosed BMs were enrolled in this study from 23 gamma knife facilities in Japan. Observation was discontinued at the end of 2013. The 1194 patients were divided into the two age groups, 693 elderly ( ≥ 65 years) and 501 non-elderly ( < 65 years) patients. Our study protocol neither set an upper age limit nor required dose de-escalation. RESULTS: Median post-SRS survival time was significantly shorter in the elderly than in the non-elderly patient group (10.3 vs 14.3 months, HR 1.380, 95% CI 1.218-1.563, p < 0.0001). However, regarding all secondary endpoints including neurological death, neurological deterioration, SRS-related complications, leukoencephalopathy, local recurrence, newly-developed tumors, meningeal dissemination, salvage SRS, whole brain radiotherapy and surgery and decreased mini-mental state examination scores, the elderly patient group was not inferior to the non-elderly patient group. In the 693 elderly patients, there was no post-SRS median survival time difference between those with 5-10 versus 2-4 tumors (10.8 vs 8.9 months, HR 0.936, 95% CI 0.744-1.167, p = 0.5601). CONCLUSIONS: We conclude that elderly BM patients are not unfavorable candidates for SRS alone treatment.