Effects of dual antiplatelet therapy (DAPT) compared to single antiplatelet therapy (SAPT) in patients with traumatic brain injury.

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.

Importance of repeated computed tomography on pediatric traumatic acute posterior fossa subdural hematoma: A case study.

Traumatic acute posterior fossa subdural hematoma (PFSDH) is a rare and potentially fatal condition in which the progressed hematoma compresses the brainstem or causes secondary hydrocephalus. Hence, vigilant monitoring of clinical and radiological findings is crucial to detect the typical sudden deterioration, which can occur in the early stages. However, managing pediatric PFSDHs poses additional challenges due to risks associated with radiation exposure from repeat computed tomography (CT) examinations, potentially impeding crucial diagnostic insights. Here, we present a rare pediatric case of fatal acute traumatic PFSDH. Despite undergoing a timely initial CT scan that indicated the presence of PFSDH, the patient experienced sudden deterioration 15 h later and eventually died. No follow-up CT examinations were conducted during this critical period. This case underscores the challenges in managing pediatric PFSDHs, particularly concerning the benefits of repeated CT examinations in initially stable patients.

Routine screening serum tests to detect underlying thyroid and autoimmune diseases in patients with moyamoya disease.

BACKGROUND: Recent studies have revealed that thyroid and autoimmune diseases may be associated with sporadic moyamoya disease. However, whether routine screening serum tests to detect these underlying diseases are useful or not remains unclear. METHODS: We retrospectively evaluated 459 patients with moyamoya disease but without previous history of thyroid or autoimmune diseases who underwent the screening serum tests targeting thyroid and autoimmune diseases from 2016 to 2023 in our institute. The number of patients who were diagnosed as thyroid or autoimmune diseases after these tests were investigated. RESULTS: Among the patients who were screened, 237 (42.6 %) patients had abnormal results for some factors, such as thyroid hormones or autoantibodies. After consultation with endocrinologists or rheumatologists, 27 (5.9 %) patients were newly diagnosed with thyroid diseases, including six (1.3 %) patients with Graves' disease, 19 (4.1 %) patients with Hashimoto thyroiditis and two (0.4 %) patients with other thyroid diseases; however, none of the patients were diagnosed with nonthyroidal autoimmune diseases, such as Sjogren's syndrome, antiphospholipid syndrome, or rheumatoid arthritis, listed as moyamoya-related diseases and targeted by our screening serum tests. Patients with newly diagnosed underlying diseases were more likely to be female compared to patients without new diagnosis (96.3 % vs. 72.2 %, p = 0.03). CONCLUSION: Routine thyroid-related serum screening may be clinically meaningful in patients with moyamoya disease to detect occult thyroid diseases, especially in female patients. However, routine serum screening tests targeting other autoimmune diseases are not recommended unless the patients have equivalent symptoms.

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.

Intracranial residual lesions following early intensification in a patient with T-cell acute lymphoblastic leukemia: a case report.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) tends to involve central nervous system (CNS) infiltration at diagnosis. However, cases of residual CNS lesions detected at the end of induction and post early intensification have not been recorded in patients with T-ALL. Also, the ratio and prognosis of patients with residual intracranial lesions have not been defined. CASE PRESENTATION: A 9-year-old boy with T-ALL had multiple intracranial tumors, which were still detected post early intensification. To investigate residual CNS lesions, we used 11C-methionine (MET)-positron emission tomography. Negative MET uptake in CNS lesions and excellent MRD status in bone marrow allowed continuing therapies without hematopoietic cell transplantation. CONCLUSIONS: In cases with residual lesions on imaging studies, treatment strategies should be considered by the systemic response, direct assessment of spinal fluid, along with further development of noninvasive imaging methods in CNS. Further retrospective or prospective studies are required to determine the prognosis and frequency of cases with residual intracranial lesions after induction therapy.

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.

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.

Impact of [11C]methionine PET with Bayesian penalized likelihood reconstruction on glioma grades based on new WHO 2021 classification.

OBJECTIVE: The uptake of [11C]methionine in positron emission tomography (PET) imaging overlapped in earlier images of tumors. Bayesian penalized likelihood (BPL) reconstruction increases the quantitative values of tumors compared with conventional ordered subset-expectation maximization (OSEM). The present study aimed to grade glioma malignancy based on the new WHO 2021 classification using [11C]methionine PET images reconstructed using BPL. METHODS: We categorized 32 gliomas in 28 patients as grades 2/3 (n = 15) and 4 (n = 17) based on the WHO 2021 classification. All [11C]methionine images were reconstructed using OSEM + time-of-flight (TOF) and BPL + TOF (ß = 200). Maximum standardized uptake value (SUVmax) and tumor-to-normal tissue ratio (T/Nmax) were measured at each lesion. RESULTS: The mean SUVmax was 4.65 and 4.93 in grade 2/3 and 6.38 and 7.11 in grade 4, and the mean T/Nmax was 7.08 and 7.22 in grade 2/3 and 9.30 and 10.19 in grade 4 for OSEM and BPL, respectively. The BPL significantly increased these values in grade 4 gliomas. The area under the receiver operator characteristic (ROC) curve (AUC) for SUVmax was the highest (0.792) using BPL. CONCLUSIONS: The BPL increased mean SUVmax and mean T/Nmax in lesions with higher contrast such as grade 4 glioma. The discrimination power between grades 2/3 and 4 in SUVmax was also increased using [11C]methionine PET images reconstructed with BPL.

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.

The current status of reversal therapy in Japan for elderly patients with head injury treated with antithrombotic agents: A prospective multicenter observational study.

Background: Acute exacerbation of head injury in elderly patients due to use of antithrombotic agents has become a concern in countries with aging populations. Reversal agents are recommended for treatment, but its usage is unclear. Therefore, we conducted a prospective observational study in this patient population to monitor usage of reversal therapy. Methods: The subjects were 721 elderly patients aged ≥65 years old who were hospitalized in 15 centers from December 2019 to May 2021. Patients were divided into groups who did not receive antithrombotic agents (Group A), who received antithrombotic agents, but did not receive reversal therapy (Group B), and were treated with antithrombotic agents and reversal therapy (Group C). Age, gender, mechanism of injury, neurologic and imaging findings on admission, clinical course after admission and surgery, outcomes and complications were compared among these groups. Time from injury to reversal therapy was examined based on outcomes to investigate trends in the timing of administration of the reversal agent. Results: Acute exacerbation during the clinical course occurred in 9.8 %, 15.8 % and 31.0 % of cases in Groups A, B and C, respectively, and differed significantly among the groups. On head CT, the incidences of hematoma were 35.7 %, 36.5 % and 60.4 %, respectively, with this incidence being significantly higher in Group C; and the respective rates of craniotomy were 18.8 %, 14.0 % and 50.9 %, again with this rate being significantly higher in Group C. The good outcome and mortality rates were 57.1 %, 52.5 % and 35.8 %, and 14.5 %, 18.0 % and 24.5 %, respectively, and both were poorest in Group C. Times from injury to treatment with a reversal agent were significantly shorter in patients without compared to those with acute exacerbation (405.9 vs. 880.8 min) and in patients with favorable outcomes compared to those with unfavorable outcomes (261.9 vs. 543.4 min). Conclusion: Similarly to previous studies, the incidence of acute exacerbation was increased by use of antithrombotic agents. These results suggest that patients in Japan who require hematoma evacuation due to symptom exacerbation tend to be treated with reversal agents. Although it is difficult to assess the efficacy of reversal therapy from this study, earlier treatment with reversal agents before the occurrence of acute exacerbation may be useful to improve outcomes.

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.

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.

Case report: Fatal ischemic stroke induced by unruptured traumatic intracranial vertebral artery dissection.

Intracranial vertebral artery dissection (IVAD) is rare and potentially fatal due to the risk of secondary subarachnoid hemorrhage once ruptured. Unruptured traumatic IVAD is even rarer and can result in ischemic stroke, yet mostly benign when timely diagnosed. Herein, we present an uncommon case of a patient who underwent a fatal ischemic stroke induced by unruptured traumatic IVAD. The patient was symptomatic soon after being physically assaulted but left untreated until acute deterioration for multiple brain infarctions occurred, secondary to IVAD-induced cerebellar stroke. Fifteen days later, he died, regardless of an urgently performed thrombectomy. Multiple serial histologic examinations revealed an unruptured dissection of the intracranial vertebral artery with a slit-like tear of the intimal and medial layers, considered to be the culprit lesion. The 15-day prolonged onset of stroke was rare in traumatic IVADs. Furthermore, the slit-like tear of the intimal layer in our case may support the initial intimal laceration hypothesis for VAD pathogenesis. Since limited pathohistological information is available regarding ischemic IVAD, we believe this rare case will be beneficial in understanding the pathophysiology of ischemic IVAD.

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.

Seizure-related stress and arousal responses mediate a relationship between anxiety trait and state in epilepsy.

BACKGROUND: Epilepsy causes substantial psychological distress and anxiety, primarily due to seizures. However, the impact of stress responses and changes in arousal and their association with anxiety patterns in patients with epilepsy (PWE) remains unclear. This study aimed to investigate the relationships among seizures, stress and arousal characteristics, and trait and state anxiety characteristics in PWE. METHODS: Our sample consisted of 159 outpatients with epilepsy recruited from five institutions in Japan in 2020. Participants completed the State-Trait Anxiety Inventory-Form JYZ (STAI) and the Japanese-Stress Arousal Check List (J-SACL). We analyzed the correlations between inventory scores and clinical information. Using principal component analysis (PCA), we derived epilepsy-specific stress/arousal characteristics, which accounted for high arousal and low-stress levels, termed epilepsy-specific stress or arousal response (ESAR), from the J-SACL scores. We conducted a mediation analysis to assess the mediating role of ESAR in the relationship between traits and state anxiety. RESULTS: We found significant correlations between J-SACL stress and arousal factors (r = -0.845, p < 0.001), ESAR and seizure frequency (r = -0.29, p < 0.001), ESAR and trait anxiety scores on the STAI (r = -0.77, p < 0.0001), and ESAR and state anxiety scores on the STAI (r = -0.60, p < 0.0001). Mediation analysis supported by the Monte Carlo method revealed that ESAR significantly mediated the association between trait and state anxiety. CONCLUSIONS: These findings elucidate the epilepsy-specific stress and arousal characteristics and their roles in mediating traits and state anxiety. These results may reflect the long-term clinical course and unique emotion recognition tendencies in epilepsy.

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.

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.

Increased Parenchymal Free Water May Be Decreased by Revascularization Surgery in Patients with Moyamoya Disease.

PURPOSE: Moyamoya disease (MMD) is a cerebrovascular disease associated with steno-occlusive changes in the arteries of the circle of Willis and with hemodynamic impairment. Previous studies have reported that parenchymal extracellular free water levels may be increased and the number of neurites may be decreased in patients with MMD. The aim of the present study was to investigate the postoperative changes in parenchymal free water and neurites and their relationship with cognitive improvement. METHODS: Multi-shell diffusion MRI (neurite orientation dispersion and density imaging and free water imaging using a bi-tensor model) was performed in 15 hemispheres of 13 adult patients with MMD (11 female, mean age 37.9 years) who had undergone revascularization surgery as well as age- and sex-matched normal controls. Parameter maps of free water and free-water-eliminated neurites were created, and the regional parameter values were compared among controls, patients before surgery, and patients after surgery. RESULTS: The anterior and middle cerebral artery territories of patients showed higher preoperative free water levels (P ≤ 0.007) and lower postoperative free water levels (P ≤ 0.001) than those of normal controls. The change in the dispersion of the white matter in the anterior cerebral artery territory correlated with cognitive improvement (r = -0.75; P = 0.004). CONCLUSION: Our study suggests that increased parenchymal free water levels decreased after surgery and that postoperative changes in neurite parameters are related to postoperative cognitive improvement in adult patients with MMD. Diffusion analytical methods separately calculating free water and neurites may be useful for unraveling the pathophysiology of chronic ischemia and the postoperative changes that occur after revascularization surgery in this disease population.