Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

PURPOSE: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. METHODS: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. RESULTS: Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). CONCLUSION: Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

Spatial coefficient of variation of arterial spin labeling magnetic resonance imaging can predict decreased cerebrovascular reactivity measured by acetazolamide challenge single-photon emission tomography.

PURPOSE: The aim of this study was to investigate whether the spatial coefficient of variation of arterial spin labeling (ASL-CoV) acquired in clinical settings can be used to estimate decreased cerebrovascular reactivity (CVR) measured with single-photon emission computed tomography (SPECT) and acetazolamide challenge in patients with atherosclerotic stenosis of intra- or extracranial arteries. METHODS: We evaluated the data of 27 atherosclerotic stenosis patients who underwent pseudocontinuous ASL and SPECT. After spatial normalization, regional values were measured using the distributed middle cerebral artery territorial atlas of each patient. We performed comparisons, correlations, and receiver operating characteristic (ROC) curve analyses between ASL-cerebral blood blow (CBF), ASL-CoV, SPECT-CBF and SPECT-CVR. RESULTS: Although the ASL-CBF values were positively correlated with SPECT-CBF values (r = 0.48, 95% confidence interval (CI) = 0.28-0.64), no significant difference in ASL-CBF values was detected between regions with and without decreased CVR. However, regions with decreased CVR had significantly greater ASL-CoV values than regions without decreased CVR. SPECT-CVR was negatively correlated with ASL-CoV (ρ = -0.29, 95% CI = -0.49 - -0.06). The area under the ROC curve of ASL-CoV in predicting decreased CVR (0.66, 95% CI = 0.51-0.81) was greater than that of ASL-CBF (0.51, 95% CI = 0.34-0.68). An ASL-CoV threshold value of 42% achieved a high specificity of 0.93 (sensitivity = 0.42, positive predictive value = 0.77, and negative predictive value = 0.75). CONCLUSION: ASL-CoV acquired by single postlabeling delay without an acetazolamide challenge may aid in the identification of patients with decreased CVR on SPECT.

Spontaneous occlusion of ruptured microaneurysm formed on postoperative transosseous anastomosis after indirect revascularization in a patient with moyamoya disease.

A 40-year-old female with a history of ischemic moyamoya disease treated with indirect revascularization at ages 12 and 25 years presented with a sudden severe headache. Imaging studies revealed focal parenchymal hemorrhage and acute subdural hematoma, confirming a microaneurysm formed on the postoperative transosseous vascular network as the source of bleeding. Conservative management was performed, and no hemorrhage recurred during the 6-month follow-up period. Interestingly, follow-up imaging revealed spontaneous occlusion of the microaneurysm. However, due to the rarity of this presentation, the efficacy of conservative treatment remains unclear. Further research on similar cases is warranted.

T2-FLAIR mismatch sign correlates with 11C-methionine uptake in lower-grade diffuse gliomas.

PURPOSE: The T2-FLAIR mismatch sign is recognized as an imaging finding highly suggestive of IDH-mutant astrocytomas. This study was designed to determine whether the T2-FLAIR mismatch sign correlates with uptake of 11C-methionine in lower-grade gliomas. METHODS: We included 78 histopathologically verified lower-grade gliomas (grade 2: 31 cases, grade 3: 47 cases) in this study. 78 patients underwent 11C-methionine positron emission tomography (MET-PET) scans and magnetic resonance (MR) imaging scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. MR imaging scans were evaluated for the presence of the T2-FLAIR mismatch sign by three independent reviewers. We compared molecular status, the T2-FLAIR mismatch sign and 11C-methionine uptake among patients with different lower-grade glioma molecular types. RESULTS: The 78 lower-grade gliomas were assigned to one of three molecular groups: Group A (IDH-mutant and 1p/19q non-codeleted, n = 22), Group O (IDH-mutant and 1p/19q codeleted, n = 20), and Group W (IDH wildtype, n = 36). T2-FLAIR mismatch was found in 16 cases (20.5%) that were comprised of 8 (36.4%), 0 (0%), 8 (22.2%) cases in the molecular group A, O and W, respectively. The median T/N ratio of MET-PET in tumors with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.83, p < 0.001, Mann-Whitney U test). In the Groups A and W (excluding Group O), the median T/N ratio on MET-PET in groups A and W (but not group O) with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.81, p = 0.002, Mann-Whitney U test). CONCLUSION: The T2-FLAIR mismatch sign correlated with lower 11C-methionine uptake in lower grade gliomas.

Changes in the clinical spectrum of pediatric moyamoya disease over 40 years.

OBJECTIVE: To investigate the chronological changes in the clinical presentation and long-term prognosis of pediatric-onset moyamoya disease in our institute over 40 years. METHODS: We evaluated 282 pediatric-onset (≤ 15 years old) moyamoya disease patients who visited our institute from 1981 to 2020 (divided into the former period, 1981-2000, and the latter period, 2001-2020). Differences in the clinical presentation and the long-term outcome were compared between the periods. Multivariate analysis was also performed to reveal the risk factors for poor long-term outcomes. RESULTS: Compared to the former period, the total number of patients, the onset age and both the number of patients with family history and relatively older patients without symptoms or with headache were greater in the latter period (p < 0.05). The number of patients with poor long-term outcomes was significantly lower in the latter period (24.9% vs. 6.7%, p < 0.01). Multivariate analysis revealed that stroke onset, late cerebrovascular events and postoperative complications were independent risk factors for poor long-term outcomes (odds ratio = 31.4, 40.8 and 5.4, respectively). CONCLUSIONS: Over the last 40 years, the number of pediatric moyamoya disease patients has increased, especially in relatively older patients with mild presentation and favorable long-term outcomes. In clinical studies, these chronological changes and the inclusion period of the participants need to be accounted for. Whether the increased diagnostic rate in the recent era has led to a decrease in late cerebrovascular events and favorable outcomes throughout life remains unknown and should be evaluated in the future.

Differences in cerebral blood flow measurement using arterial spin labeling MRI between patients with moyamoya disease and patients with arteriosclerotic cerebrovascular disease.

BACKGROUND: It is unclear whether the accuracy of arterial spin labeling (ASL) magnetic resonance imaging (MRI) is the same between moyamoya disease (MMD), which is known to have markedly elevated cerebral blood volume (CBV), and atherosclerotic intracranial arterial stenosis (AS), which has relatively less elevated CBV. PURPOSE: To investigate how the differences in hemodynamics affect measurement of ASL-cerebral blood flow (CBF) using ASL for patients with MMD and AS. MATERIAL AND METHODS: Fourteen MMD and ten AS patients were evaluated with ASL-MRI, magnetic resonance angiography (MRA), and 15O-gas positron emission computed tomography (PET). The regional CBF values of ASL using two post-labeling delays (PLDs; 1525 ms and 2525 ms) were compared with the PET-derived CBF, CBV, and mean transit time (MTT). Corresponding anterior circulation results were evaluated by flow territory map-based analysis. RESULTS: The correlation between the ASL-CBF values (2525 ms) and PET-CBF declined in the MMD group (r = 0.28; P < 0.01), while the AS group showed good correlation (r = 0.77; P < 0.01). In the MMD group, the ASL-CBF values (2525 ms) overestimated the PET-CBF values as the regional CBV values increased (r = 0.35; P < 0.01). When the regions of interest were divided into two subgroups according to the degree of arterial stenosis by MRA, the correlation coefficient between the ASL-CBF (2525 ms) and PET-CBF values improved (mild stenosis: r = 0.36; P = 0.06; severe stenosis: r = 0.51; P < 0.01). CONCLUSION: The accuracy of CBF measurements using ASL-MRI differed between patients with MMD and AS. The prominent increase of CBV and the degree of arterial stenosis may have affected the accuracy of ASL-CBF in patients with MMD.

Long-term prognosis of 452 moyamoya disease patients with and without revascularization under perfusion-based indications.

OBJECTIVES: To evaluate the long-term outcomes of patients treated under our perfusion-based strategy and assess whether conservative treatment without surgical treatment under our strategy is acceptable. MATERIALS AND METHODS: A total of 315 adult and 137 pediatric MMD patients (follow-up period ≥ 3 years from 2001 to 2020) were included. Follow-up events in each patient group (pediatric or adult, surgically treated or conservatively treated) were evaluated and compared to each other using a log-rank test. Risk factors for stroke and nonstroke events were also investigated using a multivariate Cox proportional hazard model. RESULTS: In adult-onset patients, the stroke event rates (person-year %) were not different between surgically treated patients and conservatively treated patients (2.00 % vs. 1.59 %, p = 0.558); however, conservative patients showed a higher stroke rate than surgically treated hemispheres (0.34 %; p = 0.025) and hemorrhagic stroke was the major type (18/26, 69.2 %). Hemorrhagic onset was associated with increased risk of stroke in adults (hazard ratio (95 % confidence interval) = 2.43 (1.10-5.36)). In pediatric-onset patients, no conservatively treated patients experienced stroke; however, nonstroke events occurred more frequently than in surgically treated hemispheres (4.86 % vs. 1.71 %, p = 0.020 for transient ischemic attack; and 7.91 % vs. 1.31 %, p < 0.001 for asymptomatic progression on magnetic resonance angiography). CONCLUSIONS: In adult patients, conservatively treated patients experienced stroke more frequently, especially hemorrhagic stroke. An additive strategy to prevent stroke in hemorrhagic-onset patients without hemodynamic disturbance seems to be needed. Pediatric patients with mild hemodynamic disturbance can be safely observed without initial surgical intervention, but close follow-up for disease progression is necessary.

Spatial coefficient of variation of arterial spin labeling MRI for detecting hemodynamic disturbances measured with 15O-gas PET in patients with moyamoya disease.

PURPOSE: The aim of this study was to investigate whether the spatial coefficient of variation of arterial spin labeling (ASL-CoV) acquired in clinical settings can be used to estimate the hemodynamic disturbances measured with 15O-gas positron emission tomography (PET), especially an increased oxygen extraction fraction (OEF), in patients with moyamoya disease. METHODS: We evaluated 68 adult patients with moyamoya disease who underwent ASL (postlabeling delay (PLD) = 1525 ms and 2525 ms) and PET. Regional values were measured using the middle cerebral artery territorial atlas divided into proximal, middle, and distal regions based on the arterial transit time, and correlations of ASL-CoV with cerebral blood flow, cerebral blood volume, mean transit time, and OEF, as well as the relationship between increased OEF and ASL-CoV, were evaluated. RESULTS: Regardless of the choice of region and PLD, ASL-CoV was significantly correlated with PET-measured parameters, including OEF (|ρ|= 0.30-0.80, P < 0.001). Regions with an increased OEF showed a significantly higher ASL-CoV than regions with a nonincreased OEF (P ≤ 0.03) regardless of the choice of region and PLD. The accuracy of identification of an increased OEF was highest when using a PLD of 1525 ms and the middle region (area under the curve = 0.750; using a cutoff value of 31.27, sensitivity = 97.4%, specificity = 41.7%, negative predictive value = 92.6%, and positive predictive value = 67.9%). CONCLUSION: ASL-CoV may help identify patients with increased OEF.

[Indirect Revascularization Surgery for Chronic Ischemia in Moyamoya Disease].

Indirect revascularization is a surgical procedure to reduce cerebral ischemia, using subcutaneous tissues or dura mater supplied by extracranial arteries as grafts. The perfusion pressure gradient between the cortex and the graft, if present, induces arteriogenesis and develops extracranial-intracranial anastomoses to supply blood flow to the cerebral cortex underneath the graft. Therefore, it is essential to perform the craniotomy over the site of the cerebral ischemia to induce functional anastomoses. The details of the indirect revascularization procedure vary among institutes in terms of the grafts used(skin arteries, such as the superficial temporal artery; temporal muscle, galea, or pericranium), dura mater incisions(removal and replacement with the grafts, linear incision, or multiple small incisions), and the location and size of the craniotomy. Indirect revascularization is especially effective in patients with moyamoya disease because the pathophysiology of the disease itself is related to intracranial to extracranial carotid system conversion. Generally, indirect revascularization was considered ineffective in patients with atherosclerotic steno-occlusive cerebrovascular disease; however, recent clinical trials suggested that it may also be effective in these patients. If a future clinical trial demonstrates a positive outcome, indirect revascularization may become a possible treatment for atherosclerotic patients.

De Novo Renal Artery Stenosis Developed in Initially Normal Renal Arteries during the Long-Term Follow-Up of Patients with Moyamoya Disease.

BACKGROUND: The de novo occurrence of renal artery stenosis in renal arteries that were angiographically confirmed to be normal in the past has never been reported before in patients with moyamoya disease. CASE DESCRIPTION: During the long-term follow-up of pediatric patients with moyamoya disease, we observed 3 patients who developed de novo renal artery stenosis in arteries that had been angiographically confirmed to be normal 1 year after the surgery (7 years on average, ranging from 4 to 11 years). All of these patients were neurologically stable after successful indirect bypass surgery during childhood. However, more than 10 years after the surgery (15 years on average, ranging from 14 to 23 years), they developed hypertension and were found to have de novo renal artery stenosis, which was ameliorated by endovascular angioplasty. During the follow-up after angioplasty, 1 patient experienced a recurrence of hypertension and required a second and third angioplasty for restenosis. Another patient died of intracranial hemorrhage 2 years after angioplasty. In the 2 surviving patients, gene analysis of the ring finger protein 213 (RNF213; p.R4810K) point mutation, the susceptibility gene for moyamoya disease in the Asian population, was positive for the heterozygous variant. CONCLUSIONS: De novo renal artery stenosis might develop in initially normal arteries during long-term follow-up, particularly among pediatric patients with moyamoya disease. Considering the extracranial manifestations of moyamoya disease, clinicians should keep in mind that de novo renal artery stenosis could emerge later in their life. Thus, it is crucial to continue to follow these patients for decades, even if the patients are neurologically stable after bypass surgery. Monitoring for blood pressure and the de novo occurrence of renal artery stenosis is important to prevent hypertension-related morbidity and mortality, such as intracranial hemorrhage, in this disease population.

Unraveling Specific Brain Microstructural Damage in Moyamoya Disease Using Diffusion Magnetic Resonance Imaging and Positron Emission Tomography.

BACKGROUND AND PURPOSE: Chronic ischemia may induce brain microstructural damage and lead to neurocognitive dysfunction in patients with Moyamoya disease (MMD). We applied neurite orientation dispersion and density imaging (NODDI) and 15O-gas positron emission tomography (PET) to elucidate the specific ischemic brain microstructural damage of MMD in the cortex and the white matter. MATERIALS AND METHODS: Thirty-one patients (16-63years old, 9 males) and 20 age- and sex-matched normal controls were enrolled in this study. NODDI evaluates quantitative parameters reflecting neurite and axonal density, network complexity and the interstitial fluid in all participants. Of 31 patients, 12 newly diagnosed patients were evaluated with PET, also. We evaluated correlations between the microstructural parameters of NODDI and the hemodynamic and metabolic parameters of PET, the relationship between NODDI and clinical severity of each hemisphere (Normal, Asymtpomatic, Symptomatic, and Infarcted) as well as neurocognitive performance. RESULTS: All NODDI parameters significantly correlated with PET parameters (absolute r = 0.46-0.83, P ≤ .048) and clinical severity (P < .001), suggesting that neurite and axonal density and network complexity decreased, and the interstitial fluid increased, as the ischemic burden became severe. NODDI parameters reflecting neurite and axonal density and network complexity significantly correlated with neurocognitive profiles (r = 0.36-0.64, P ≤ .048), but the interstitial fluid component did not. CONCLUSIONS: Chronic ischemia in patients with MMD may induce decreased neurite and axonal density, simplified network complexity, and may lead to neurocognitive dysfunction. The increased interstitial fluid accompanying hemodynamic impairment may not be identical to the decreased neurite density and might be driven by another mechanism.

Microstructural Damage in Normal-Appearing Brain Parenchyma and Neurocognitive Dysfunction in Adult Moyamoya Disease.

Background and Purpose -Microstructural damage in the brain induced by chronic ischemia is suggested to play a pivotal role in the neurocognitive dysfunction of adults with Moyamoya disease (MMD). We investigated specific changes in the brain microstructure and their correlations with neurocognitive dysfunction in patients with MMD using a multishell diffusion magnetic resonance imaging technique called neurite orientation dispersion and density imaging. Methods- We evaluated 26 patients with MMD (16-63 years old, 20 females) and 20 age- and sex-matched normal volunteers using neurite orientation dispersion and density imaging and neuropsychological batteries. Neurite orientation dispersion and density imaging calculates 2 parameters: the intracellular volume fraction (Vic), which reflects the axon density in the white matter and dendrite density in the cortex, and the orientation dispersion index (OD), which reflects the network complexity. The microstructural damage and its correlation with neurocognitive performance were evaluated by performing a whole-brain analysis using SPM12 and correlation analysis with regional values. Results- Patients with MMD had significantly lower Vic in the white matter and a lower OD mainly in the cortex than those of the controls ( P<0.001, family-wise error corrected). Of all neuropsychological scores, Processing Speed Index (PS) exhibited the strongest correlation with Vic in the white matter ( P<0.001, family-wise error corrected). The Vic and OD values for regions with group differences, including both temporoparietal and frontal areas, correlated with neurocognitive performance (absolute r=0.37-0.64; P<0.01). Conclusions- Chronic ischemia in MMD may decrease the axon density in the white matter and dendrite density in the cortex (Vic) and simplify network complexity (OD), leading to neurocognitive dysfunction. Processing Speed Index may be the most sensitive index used to evaluate the ischemic burden, and the posterior part of the brain may play an important role in neurocognitive function. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000023082.

Isolation of Nabscessin C from Nocardia abscessus IFM 10029T and a Study on Biosynthetic Pathway for Nabscessins.

A new aminocyclitol derivative, designated nabscessin C (1), was isolated from Nocardia abscessus IFM 10029T. Nabcessin C is an isomer of nabscessins A (2) and B (3) with different positioning of the acyl group. Absolute configuration of nabscessin A was determined by conversion into the 2-deoxy-scyllo-inosamine pentaacetyl derivative (4) by hydrolysis and acetylation of 2. The biosynthetic pathway of nabscessins is proposed based on gene expression analysis.

Unique Angiographic Appearances of Moyamoya Disease Detected with 3-Dimensional Rotational Digital Subtraction Angiography Imaging Showing the Hemodynamic Status.

BACKGROUND: The aim of this study was to identify the unique morphological arterial features in patients with moyamoya disease on 3-dimensional rotational digital subtraction angiography. MATERIALS AND METHODS: One hundred seven hemispheres of 58 consecutive patients with moyamoya disease that were analyzed with fused 3-dimensional images of internal carotid angiograms and vertebral angiograms that were marked with different colors were reviewed. Angiographic findings in the posterior watershed area were classified, and the utility of the classification was analyzed by comparing it with clinical presentations and quantitative hemodynamic parameters obtained with positron emission tomography. RESULTS: Two unique angiographic appearances were identified. A vacant vessel appearance (no arterial inflow despite absence of cortical infarction) was observed mostly in transient ischemic attack hemispheres. In hemispheres with a vacant vessel appearance, cerebral blood flow was decreased, cerebral blood volume was increased, and mean transit time was prolonged significantly (P = .00017, P = .0061, and P = .00026, respectively). A cocktail vessel appearance (mixture of carotid and vertebral arterial flow) was most commonly observed in asymptomatic cases, as well as in ischemic hemispheres. Cerebral blood volume increased and mean transit time was prolonged significantly (P = .036 and P = .014, respectively) in hemispheres with a cocktail vessel appearance. The trend of progression in hemodynamic severity in the order of normal appearance, cocktail vessel appearance, and vacant vessel appearance in the watershed area was statistically significant. CONCLUSION: Fused 3-dimensional digital subtraction angiography demonstrated unique angiographic features in the watershed area, and this represented the degree of cerebral hemodynamic impairment in moyamoya disease.

Nabscessins A and B, Aminocyclitol Derivatives from Nocardia abscessus IFM 10029T.

Two new aminocyclitol amide derivatives, nabscessins A (1) and B (2), were isolated from the culture broth of a pathogenic actinomycete species, Nocardia abscessus IFM 10029T. The structures of nabscessins A and B were elucidated by spectral studies, and the compounds showed antifungal activity against Cryptococcus neoformans, with IC50 values of 32 and 16 µg/mL, respectively.

Correlation between Clinical Presentations and Hemodynamic Parameters Measured by Dynamic Susceptibility Contrast Magnetic Resonance Imaging in Adult Patients with Moyamoya Disease.

BACKGROUND: The examination of cerebral hemodynamics is indispensable for the clinical management of patients with moyamoya disease (MMD). In this study, we examined the correlation between clinical presentations and hemodynamic parameters measured by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in adult patients with MMD. METHODS: One hundred fifty-seven hemispheres in 122 adult patients with MMD were examined by DSC-MRI to measure the regional relative cerebral blood volume (CBV) and relative mean transit time (MTT). The patients were divided into 4 groups based on their clinical presentations: a nonsymptomatic (NS), hemorrhagic (H), infarction (I), and transient ischemic attack (T) group. The regional CBV and MTT values were compared among the 4 groups. RESULTS: The relative value of CBV was significantly higher in groups T and I than in the NS group (P < .01). The CBV of group H was higher than that of the NS group only in the frontal lobe cortex. There were no significant statistical differences among the 3 symptomatic groups. Prolongation of the MTT in comparison with the cerebellum (MTT delay) was significantly higher in groups T and I than in the NS group in all regions of the cerebral cortex (P < .05). The MTT delay was significantly lower in group H than in group T in the frontal lobe and the Rolandic area (P < .05). CONCLUSIONS: Hemodynamic factors measured by DSC-MRI reflected the variable clinical presentations of patients with MMD. DSC-MRI is a useful modality for evaluating the clinical conditions of individual adult patients with MMD.

Intraoperative Telestration System in Endoscopic Transsphenoidal Surgery Contributes to Improved Surgical Safety and Efficient Surgical Education.

OBJECTIVE: To evaluate the effectiveness of a "telestration" system in which the mentor annotates the view of the surgical field, for endoscopic transsphenoidal surgery (ETS). METHODS: The use of telestration was evaluated for sellar floor-opening during ETS and for a task performed using ETS simulation training. During ETS, the mentor outlined the opening area of the sella turcica on the monitor and then the trainee surgeon opened the sella, either with the telestration displayed (telestration (+) group, n = 8) or without (telestration (-) group, n = 7). In the task using an ETS training model, 18 subjects were asked to touch the indicated targets with the forceps, once with the instructions given via telestration and once with verbal instructions only. RESULTS: During ETS, the telestration (+) group had a significantly higher concordance rate between the planned bone window and actual bone window than the telestration (-) group (92.97 ± 4.16% vs. 77.57 ± 10.51%, P = 0.014). In the ETS model, the time required to finish the task was significantly less with telestration than with verbal instructions alone (P = 0.002). None of the subjects had errors when telestration was used, while subjects made an average of 0.33 ± 0.59 errors and had to re-listen to the instructions 0.27 ± 0.46 times when only verbal instructions were given. CONCLUSIONS: The use of the telestration system during ETS facilitated the communication of the mentor's intentions to the trainee surgeon and contributed to safer, more accurate surgery. The system was also thought to be useful in reducing operative time.

Stroke and Disease Progression During Long-Term Follow-Up of Patients with Moyamoya Disease Older Than 50 Years.

OBJECTIVE: The long-term prognosis of elderly patients with moyamoya disease (MMD) is not fully understood and needs to be elucidated. METHODS: MMD patients who first visited our institute between 1999 and 2019, were ≥ 50 years of age, and were followed for ≥1 year were retrospectively included. Follow-up data such as stroke and disease progression on magnetic resonance angiography (MRA) were collected from medical records. The surgical outcomes of ischemic patients treated with indirect revascularization were assessed. RESULTS: Of the 60 patients included (mean (standard deviation) = 57.0 (5.5) years, 38 females), 9 patients initially received indirect revascularization, 3 patients received direct revascularization, and 49 patients were treated conservatively. During the 57.4 (53.7) month follow-up, the symptomatic stroke rate (person-year %) was 2.79%, and MRA progression was 3.14%. Symptomatic patients had a greater rate of symptomatic stroke than asymptomatic patients did (1.46%-5.74% vs. 0.94%, P = 0.15), while MRA progression was more common in asymptomatic patients (0%-3.83% vs. 5.64%, P = 0.22). Among the 14 hemispheres of 11 patients who underwent indirect revascularization, 13/14 (92.9%) demonstrated good neovascularization and no ischemic stroke occurred after surgery. CONCLUSIONS: In elderly patients with MMD, MRA progression was not uncommon, especially in asymptomatic patients. Symptomatic patients exhibited a high symptomatic stroke rate, and indirect revascularization seems to be effective at reducing future ischemic stroke in ischemic patients with misery perfusion. Because follow-up events were not uncommon, lifelong follow-up seems necessary for elderly MMD patients, as well as for younger patients.

Synergistic Interaction of Thyroid Autoantibodies and Ring Finger Protein 213 Variant in Moyamoya Disease.

Recently, thyroid autoantibodies were found to be associated with moyamoya disease (MMD). The ring finger protein 213 (RNF213) p.R4810K variant represents the most important susceptibility genotype of this disease, but its relationship with thyroid autoantibodies remains to be elucidated. Thus, in this study, we aimed to evaluate the clinical relevance of thyroid autoantibodies in each RNF213 genotype in patients with MMD. Included in this study were patients with MMD without a thyroid disease history and in euthyroid status; they were then classified into the mutated or nonmutated based on the RNF213 p.R4810K genotype and positive or negative based on thyroid autoantibody (thyroperoxidase and thyroglobulin) levels. Clinical data of each group were thereafter evaluated. Among the 209 patients, the mutated RNF213 p.R4810K variant and positive thyroid autoantibodies were detected in 155 and 41 patients, respectively. Positive thyroid autoantibodies were found to be more common in the nonmutated patients than in the mutated patients (31.5% vs. 15.5%; P = 0.011). In the mutated patients, as compared to autoantibody-negative patients, autoantibody-positive patients were determined to be more likely to have advanced disease with posterior cerebral artery involvement (54.2% vs. 29.0%; P = 0.017), white matter infarction (58.3% vs. 37.6%; P = 0.046), and a higher modified Rankin Scale at last visit (16.7% vs. 3.1%; P = 0.021). These results suggest that thyroid autoantibodies can act as an immunity inducer in patients with MMD lacking the susceptibility gene RNF213 p.R4810K variant. Moreover, the simultaneous presence of thyroid autoantibodies and the variant seems to aggravate the disease, which indicates synergy between thyroid autoantibodies and the variant.

Is initial unilateral revascularization acceptable in pediatric patients with bilateral moyamoya disease with mild contralateral hemodynamic disturbance?

OBJECTIVE: Although asymmetrical vascular involvement between hemispheres is common in pediatric patients with bilateral moyamoya disease, whether hemispheres with mild vascular changes and hemodynamic impairment require immediate surgical revascularization or whether they can be observed until disease progression remains unclear. The authors evaluated the long-term outcomes of their strategy to initially perform unilateral surgery and withhold surgery to the contralateral hemispheres with mild vascular changes and hemodynamic impairment. METHODS: The authors retrospectively evaluated Japanese pediatric patients (onset age ≤ 15 years) diagnosed with bilateral sporadic moyamoya disease who underwent unilateral revascularization. The authors investigated whether the patient underwent additional collateral surgery and the incidence of ischemic events during follow-up. They also compared visual assessments of arterial spin labeling (ASL) images obtained before initial surgery, before additional contralateral surgery, and at last follow-up. RESULTS: Overall, 30/47 patients (63.8%) experienced progression of hemodynamic impairment in the contralateral hemisphere and underwent additional surgery. The age at initial surgery of the patients who needed additional contralateral surgery was significantly younger than that of the patients who did not require contralateral surgery (mean [SD] 7.0 [3.0] years vs 9.8 [2.6] years, p = 0.002). One patient (age 4 years) developed ischemic stroke before admission for preoperative evaluation 2 months after novel symptom onset, and another patient (age 6 years) experienced ischemic stroke in the contralateral hemisphere while discontinuing antiplatelet agents before surgery; both patients fully recovered from the neurological deficits. In contralateral hemispheres that required additional surgery, the ASL visual assessment scores significantly decreased before the additional contralateral surgery compared to those obtained before the initial surgery (p = 0.008). CONCLUSIONS: In pediatric patients with bilateral moyamoya disease, withholding surgery for hemispheres with mild vascular changes and hemodynamic impairment is generally safe. Younger patients were more likely to experience contralateral progression and require additional surgery, so close follow-up is needed. ASL imaging is useful for detecting and following the progression of hemodynamic impairment in conservatively treated hemispheres.