Whole-exome sequencing reveals the genetic causes and modifiers of moyamoya syndrome.

Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.

Morphological analysis of the trigeminal nerve in trigeminal neuralgia using the nerve's centerline and multiple cross-sections of a 3D model.

OBJECTIVE: Morphological changes such as angulation and torsion of the trigeminal nerve have been reported to cause trigeminal neuralgia (TN). The authors sought to quantify and objectively evaluate the morphological changes of the trigeminal nerve and to elucidate the cause of TN. METHODS: The authors retrospectively analyzed the cases of patients with primary TN who had undergone microvascular decompression at a single facility between January 2016 and December 2022 and had both single-artery compression and a good postoperative outcome. The authors performed segmentation of the trigeminal nerve by using the patients' pre- and postoperative high-resolution MR images, and they then created a 3D model. The centerline of the trigeminal nerve was obtained using volume skeletonization, and the authors created multiple cross-sectional images by reslicing the 3D model perpendicular to the centerline. The parameters analyzed were as follows: the 1) centerline length; 2) centerline curvature; 3) centerline torsion; 4) cross-sectional area; 5) cross-sectional flattening ratio; and 6) cross-sectional long-axis angle. Comparisons were made for each parameter between the affected and unaffected side and between preoperative and postoperative trigeminal nerve findings. RESULTS: After exclusions, 70 of the 127 patients who underwent microvascular decompression during the study period were included in the analysis. In the preoperative images, the trigeminal nerve on the affected side had a significantly longer centerline length (p = 0.0003), greater curvature (p = 0.0012), smaller cross-sectional area (p < 0.0001), and greater flattening ratio (p = 0.0059) than the unaffected side. On the affected side, the preoperative trigeminal nerve had a significantly longer centerline length (p < 0.0001), greater curvature (p = 0.0028), and smaller cross-sectional area (p < 0.0001) compared to the postoperative trigeminal nerve. CONCLUSIONS: It is possible to analyze the morphological changes of the trigeminal nerve by using this method. In the preoperative trigeminal nerve on the affected side, the centerline is long and curved, and the cross-sectional area is small and flat. Further analyses may help clarify the pathophysiology, aid in diagnoses, and predict the efficacy of treatment.

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.

Efficacy of endovascular treatment for distal anterior cerebral artery aneurysms: A multicenter observational study.

OBJECTIVES: Distal anterior cerebral artery (DACA) aneurysms account for 1%-9% of all intracranial aneurysms. Microsurgical treatment is generally preferred for DACA aneurysms; however, it presents challenges owing to the anatomical complexities. Advances in neuro-interventional techniques have yielded promising results. This study aims to compare the clinical outcomes of DACA aneurysms treated with microsurgery and endovascular treatment (EVT) to elucidate the efficacy of EVT. MATERIALS AND METHODS: A multicenter observational registry comprising 16 stroke centers was utilized for this study. Data was retrospectively and prospectively analyzed from 166 patients with DACA aneurysms in our database, which included 4,552 consecutive patients with ruptured or unruptured intracranial aneurysms who underwent microsurgical or endovascular treatment between January 2013 and December 2021. RESULTS: Surgical clipping was performed in 115 patients, and 51 underwent coil embolization. The median follow-up duration was 15.3 months. No significant differences were observed in patient characteristics between the two treatment modalities. There were no differences in complication-related morbidity between the microsurgical treatment and EVT groups in either unruptured (10.5% vs. 9.1%, p=1.00) or ruptured aneurysms (5.2% vs. 6.9%, p=0.66). Coil embolization resulted in higher recurrence and retreatment rates than surgical clipping did, especially for ruptured aneurysms (2.6% vs. 27.6%, p<0.01). CONCLUSIONS: Endovascular treatment is an alternative to microsurgery for DACA aneurysms especially in unruptured cases or the patients who have difficulty undergoing craniotomy due to their general condition, albeit with considerations for higher recurrence and retreatment rates, particularly in ruptured cases. Close follow-up is crucial for the effective management of these challenges. Further studies are needed to refine the treatment strategies for DACA aneurysms.

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.

Comparative Analysis of Patients Undergoing Microvascular Decompression for Trigeminal Neuralgia Caused by Solely Arterial or Solely Venous Compression.

OBJECTIVE: Trigeminal neuralgia (TN) due to venous compression is far less common than that due to arterial compression, and its pathogenesis is less clear. We investigated the clinical and imaging features of TN caused by solely venous compression by measuring the morphologies of the posterior cranial fossa (PCF) and the trigeminal nerve. METHODS: We retrospectively reviewed records of TN patients who underwent microvascular decompression at our institution and extracted cases with solely arterial or solely venous compression. Preoperative magnetic resonance imaging was used to find the length (Y), width (X), height (Z), and volume (V) of the PCF, the angle between the trigeminal nerve and pons, and the distance between Meckel's cave and the root entry zone of the trigeminal nerve. RESULTS: Of 152 patients, 24 had TN caused solely by venous compression. The value of Y was significantly smaller in the venous group than the arterial group (P < 0.01). The trigeminal nerve and pons was significantly smaller in the venous group (P < 0.01). We hypothesized that TN patients with solely venous compression had a characteristic PCF morphology with a short anteroposterior diameter (Y), such that age-related changes in brain morphology could alter the course of the trigeminal nerve and cause compression by a vein. CONCLUSIONS: The morphological features of the PCF differed between patients with TN of venous and those with TN of arterial etiology. Age-related changes in brain morphology and changes of course of the trigeminal nerve may also add to the possibility of developing TN, especially of venous etiology.

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.

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.

Decreased diffusivity along the perivascular space and cerebral hemodynamic disturbance in adult moyamoya disease.

Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via 15O-gas positron emission tomography (PET), and all patients underwent cognitive tests. Compared to controls, patients (38.4 (13.2) years old, 35 females) had lower ALPS indices in the left and right hemispheres (1.94 (0.27) vs. 1.65 (0.25) and 1.94 (0.22) vs. 1.65 (0.19), P < 0.001). While the right ALPS index showed no correlation, the left ALPS index was correlated with parenchymal freewater (ρ = -0.47, P < 0.001); perfusion measured with PET (cerebral blood flow, ρ = 0.70, P < 0.001; mean transit time, ρ = -0.60, P = 0.003; and oxygen extraction fraction, ρ = -0.52, P = 0.003); and cognitive tests (trail making test part B for executive function; ρ = -0.37, P = 0.01). Adult patients with MMD may exhibit decreased glymphatic system activity, which is correlated with the degree of hemodynamic disturbance, increased interstitial freewater, and cognitive dysfunction, but further investigation is needed.

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.

Clinical utility and safety of a trapezoid-shaped electrode placement for evaluating the mesio-basal temporal lobe during epilepsy surgery.

A trapezoid-shaped electrode (TSE) is used for detecting epileptogenicity in patients with temporal lobe epilepsy (TLE). However, the utility and safety associated with TSE placement have not been reported. In this study, we evaluated the safety and usefulness of TSE by analyzing the seizure detection, surgical outcomes and complications in patients with TLE who underwent intracranial electrodes (ICE) placement. Between April 2000 and August 2019, 50 patients with TLE who underwent 51 ICE placement procedures were examined. A TSE with eight contacts covering the parahippocampal gyrus and basal temporal lobe was used. Among the 37 patients who underwent TSE placement, 26 and 11 patients were diagnosed with mesial TLE (mTLE) and extra-mTLE, respectively. The 14 remaining patients without TSE placement were diagnosed with extra-mTLE. Seizure freedom was achieved in 73% (19/26) of mTLE patients detected by TSE and 50% (14/24) of extra-mTLE patients.Good seizure outcomes (Engel class I and II) were observed in 81% (21/26) patients with mTLE and 67% (16/24) patients with extra-mTLE. Radiographic complications were observed in 20% (10/50) patients who underwent ICE placement. Although 6% (3/50) patients showed transient neurological deficits, none were permanent. The electrodes responsible for the occurrence of complications included nine grid electrodes and one TSE. The complication rate after TSE placement was 3% (1/37). More than 64 electrode contacts and male sex, not TSE placement, were identified as significant risk factors for developing complications. This study demonstrated the usefulness and safety of TSE for evaluating mTLE in patients undergoing ICE placement.

Long-term efficacy and safety of perampanel as an add-on therapy in patients with epilepsy.

BACKGROUND: Perampanel (PER) is a newly developed amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist that has been globally approved for the treatment of both focal and generalized seizures. The efficacy and safety of PER have only been reported over short periods of treatment so far. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy. METHOD: This retrospective observational study investigated 176 epilepsy patients who received PER as add-on medical therapy in two Japanese epilepsy centers between June 2016 and July 2022. The adherence, seizure frequency, and plasma concentration of PER were evaluated at three time points: 6 months, 12 months, and 24 months or longer after the start of adjunctive PER treatment. RESULTS: 112 patients undergoing PER treatment were evaluated at 6 months, 86 were evaluated at 12 months, and 52 were evaluated at 24 months or longer. Overall, 42.9 % (48/112), 45.4 % (40/86), and 44.2 % (23/52) of the patients were seizure-free at 6, 12, and 24 months or longer, respectively. The rate of PER tolerance was 78.3 %, 69.9 %, and 54.7 % at 6, 12, and 24 months or longer, respectively. At the latest timepoint, the seizure-free group was taking a significantly lower dose of PER than the seizure-remnant group, and the number of anti-seizure medications (ASMs) was associated with seizure outcomes. In addition, the seizure-free rate was significantly higher in patients who received PER as a first add-on than in those who received it as a late add-on. No significant difference was found in the plasma concentration of PER between the seizure-free and seizure-remnant groups at 24 months or longer. Among the patients receiving PER at dose of 2 mg, however, the plasma concentrations were significantly higher in the seizure-free group than in the seizure-remnant group (282.7 ± 109.8 µg/ml vs 94.7 ± 54.9 µg/ml, p = 0.0024). CONCLUSION: This long-term retrospective observational study provides evidence of the efficacy and safety of PER over 2 years treatment period in Japan. Notably, patients who started on PER as the first add-on showed a better seizure outcome than those who received it as a late add-on over the long term. Measured plasma concentrations may provide valuable guidance for the management of patients. Higher plasma concentration at low dose PER may suggest the better seizure control.

[Microvascular Decompression Surgery Using Exoscope(ORBEYE)].

Compared with an operative microscope, the ORBEYE has several advantages, including fatigue reduction for the operator in a relaxed and head-up natural position, infinite access, wide working space, and high educational value owing to the 3D images shared by everyone. Microvascular decompression surgery(MVDS)has similar advantages. Although operators need to learn surgical skills using different visual and surgical axes, in my personal experience, 10 cases of MVDS were practical for acquiring the skill in terms of operation time. Moreover, arranging proper ORBEYE settings in the operating room is essential for the assistants' accurate support.

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.

[Initial Management of Status Epilepticus].

Status epilepticus(SE)is defined as a prolonged seizure and is a common neurological emergency with high morbidity and mortality rates. As uncontrolled SE causes irreversible neurological damage, prompt diagnosis and treatment are required. If anti-seizure medications and benzodiazepines, which are initial treatments for SE, are not effective and SE deteriorates to refractory, anesthetic drugs are needed to suppress seizure activity under electroencephalogram(EEG)monitoring. Continuous EEG monitoring is useful not only for evaluating the control of SE but also for diagnosing non-convulsive SE(NCSE)and psychogenic non-epileptic seizures. New-onset refractory status epilepticus is defined as refractory SE in a patient without active epilepsy and without a clear acute or active structural, toxic, or metabolic cause. Because autoimmune encephalitis is the most frequently identified cause, immunotherapy can be attempted in addition to antiepileptic treatment within 2 weeks. Although NCSE is the major cause of unconsciousness, diagnosis is difficult because of uncertain clinical symptoms. Continuous EEG monitoring over 24 h is crucial for diagnosis, although arterial spin labeling-magnetic resonance imaging is alternatively useful. Finally, the building of a multidisciplinary cooperation system is required for prompt diagnosis and intensive treatment for controlling SE.

[Intracranial Anatomy and Surgical Techniques for Extended Orbital Exenteration for Sinonasal Malignancy with Orbital Apex Extension].

Gross total tumor resection for sinonasal malignancy with orbital apex extension requires orbital exenteration and bony skull base resection around the orbital apex with sufficient margins. With a detailed discussion of the anatomy, we describe our surgical procedure for extended orbital exenteration with orbital apex resection for sinonasal malignancy.

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.

Regression of periventricular anastomosis after indirect revascularization in pediatric patients with moyamoya disease.

OBJECTIVE: The aim of this study was to evaluate whether indirect revascularization in pediatric patients with moyamoya disease leads to periventricular anastomosis (PVA) regression, which is markedly developed in moyamoya vessels and is regarded as a risk factor for hemorrhage. METHODS: Pediatric patients with moyamoya disease treated with indirect revascularization from 2011 to 2021 were included in this study. Magnetic resonance angiography and arterial spin labeling images acquired before and 1 year after surgery were assessed to obtain a visual scale of postoperative collateral artery formation, moyamoya vessels, PVA, and quantitative values of cerebral blood flow (CBF). The relationship between background information (age, sex, RNF213 p.R4810K variant status, and preoperative CBF) and postoperative collateral artery formation, as well as postoperative CBF improvement and regression of moyamoya vessels and PVA, was evaluated. RESULTS: Of 89 hemispheres in 58 patients (34 females; mean [SD] patient age 8.0 [3.4] years), 74.2% showed good postoperative collateral artery formation and a significant increase in CBF (p < 0.001). Postoperative PVA showed significant regression (postoperative score 1.46 [1.06] vs 2.02 [1.69], p = 0.001), especially in those arising from choroidal arteries (postoperative score 0.28 [0.50] vs 0.72 [0.67], p < 0.001). Compared with hemispheres without good collateral artery formation, those with good collateral artery formation were more likely to show a higher increase in CBF (9.74 [12.44] ml/min/100 g vs -4.86 [9.68] ml/min/100 g, p < 0.001) and regression of PVA (54.5% [36/66] vs 30.4% [7/23], p = 0.015). Although not statistically significant, patients with postoperative PVA progression were younger than those with regression (6.75 [3.03] years vs 8.18 [3.17] years, p = 0.188), and patients with the RNF213 p.R4810K variant were more likely to show regression (28/57 [49.1%] hemispheres vs 5/13 [38.5%] hemispheres, p = 0.069). CONCLUSIONS: Indirect revascularization in pediatric patients with moyamoya disease resulted in good collateral extracranial artery formation and an increase in CBF and PVA regression, especially of vessels arising from choroidal arteries. With good postoperative collateral artery development, patients were more likely to show improved CBF and regression of moyamoya vessels, including PVA. Whether postoperative PVA changes reduce future hemorrhage risk requires further investigation.

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors.

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.