Difference in Clinical Phenotype, Mutation Position, and Structural Change of RNF213 Rare Variants Between Pediatric and Adult Japanese Patients with Moyamoya Disease.

It is unclear how rare RNF213 variants, other than the p.R4810K founder variant, affect the clinical phenotype or the function of RNF213 in moyamoya disease (MMD). This study included 151 Japanese patients with MMD. After performing targeted resequencing for all coding exons in RNF213, we investigated the clinical phenotype and statistically analyzed the genotype-phenotype correlation. We mapped RNF213 variants on a three-dimensional (3D) model of human RNF213 and analyzed the structural changes due to variants. The RNF213 p.R4810K homozygous variant, p.R4810K heterozygous variant, and wild type were detected in 10 (6.6%), 111 (73.5%), and 30 (19.9%) MMD patients, respectively. In addition, 15 rare variants were detected in 16 (10.6%) patients. In addition to the influence of the p.R4810K homozygous variant, the frequency of cerebral infarction at disease onset was higher in pediatric patients with other rare variants (3/6, 50.0%, P = 0.006) than in those with only the p.R4810K heterozygous variant or with no variants (2/51, 3.9%). Furthermore, on 3D modelling of RNF213, the majority of rare variants found in pediatric patients were located in the E3 module and associated with salt bridge loss, contrary to the results for adult patients. The clinical phenotype of rare RNF213 variants, mapped mutation position, and their predicted structural change differed between pediatric and adult patients with MMD. Rare RNF213 variants, in addition to the founder p.R4810K homozygous variant, can influence MMD clinical phenotypes or structural change which may contribute to the destabilization of RNF213.

Five-Day Bed Rest Reduces Postoperative Intracerebral Hemorrhage After Direct Bypass for Moyamoya Disease.

OBJECTIVE: Postoperative intracerebral hemorrhage (ICH) after direct bypass surgery for Moyamoya disease could contribute to neurologic deterioration. The aim of this study was to evaluate the effectiveness of 5-day bed rest in reducing the occurrence of postoperative ICH. METHODS: This study included 122 consecutive hemispheres in 87 Japanese adult MMD patients, composed of 80 control hemispheres from historical data and 42 hemispheres after 5-day bed rest. They all underwent direct bypass surgery. The incidence of postoperative ICH and neurologic deterioration assessed via the modified Rankin Scale were investigated and statistically analyzed. RESULTS: Postoperative ICH was observed in 9 out of the 80 (11.3%) control patients, but not in the 42 patients with 5-day bed rest. The incidence of postoperative ICH and neurologic deterioration via the modified Rankin Scale were significantly different between the 2 groups (P = 0.0268 and 0.0078, respectively). Univariate logistic analysis revealed that 5-day bed rest significantly reduced the incidence of postoperative ICH (P = 0.0048). CONCLUSIONS: Five-day bed rest after direct bypass surgery dramatically can reduce the incidence of postoperative ICH and neurologic deterioration after direct bypass surgery.

Pre-Therapeutic Factors Predicting for the Necessity of Rescue Treatments in Mechanical Thrombectomy.

Objective: Mechanical thrombectomy for acute large vessel occlusion (LVO) is currently widely performed. However, rescue treatment (RT), such as percutaneous transluminal angioplasty (PTA) and stenting, is occasionally required, particularly in the case of atherothrombotic brain infarction (ATBI) or dissection. As RT requires higher levels of therapeutic skills and additional devices, early prediction of its performance and preparation are important. We retrospectively investigated the pre-therapeutic factors for predicting the necessity of RT. Methods: We reviewed 149 consecutive patients who underwent mechanical thrombectomy for acute LVO between April 2014 and December 2019. Eight patients were excluded because of missing clinical data. RT was performed when severe stenosis was observed in occluded vessels or proximal to them during mechanical thrombectomy. We investigated pre-therapeutic neurological, laboratory, and radiological findings in the 141 remaining patients, and compared them between RT and non-RT groups. Results: RT was performed on 23 of the 141 patients. We found four pre-therapeutic factors with significantly different rates between RT/non-RT as follows: (1) Atrial fibrillation 8.7%/71.1% (p <0.001), (2) diabetes mellitus 39.1%/19.5% (p = 0.04), (3) susceptibility vessel sign (SVS) by T2-weighted imaging 17.4%/66.1% (p <0.001), and (4) tapered occlusion by magnetic resonance angiography (MRA) 47.8%/11.9% (p <0.001). The plasma level of brain natriuretic peptide (BNP) was also significantly different between the two groups. When the BNP level was less than 70 pg/mL, the sensitivity for being in the RT group was 86.9% and the specificity was 83.5%. Conclusion: Pre-therapeutic findings, such as diabetes mellitus, tapered occlusion, absence of atrial fibrillation, negative SVS, and BNP level less than 70 pg/mL, are predictors of RT in mechanical thrombectomy.

[Advantages and Pitfalls of the Lateral Supraorbital Approach as Less Invasive Surgery for Unruptured Anterior Circulation Aneurysms].

The lateral supraorbital approach(LSOA)is widely accepted as a less invasive surgical technique compared with the conventional pterional approach(PA). However, only a few studies have reported less invasiveness associated with LSOA. To evaluate this issue, we retrospectively investigated the surgical outcomes in 133 patients who underwent LSOA and 28 patients who underwent PA for unruptured anterior circulation aneurysms. We analyzed operation time, postoperative symptoms and complications, and the length of postoperative hospitalization(in days)for each method. All aneurysms were successfully clipped regardless of the approach. The operation time was significantly shorter, the postoperative headache rate was lower, resumption of oral intake was more rapid, and length of hospitalization was shorter in the LSOA group. Statistical significance was not observed in the postoperative complication rates. Compared with conventional PA, LSOA was associated with less invasiveness and better patient satisfaction. LSOA is a safe and effective alternative to conventional PA, following optimal patient selection.

Infantile Aspergillus fumigatus ventriculitis successfully treated with monitoring of plasma and cerebrospinal fluid voriconazole concentration level.

Aspergillosis is a rare fungal infection in newborns, and its morbidity and mortality are high. Voriconazole (VRCZ) is the first-line antifungal agent for invasive Aspergillus infection, but little data is available about its pharmacokinetics in infants. We report a case of a premature infant who developed ventriculitis due to Aspergillus fumigatus and received combination antifungal therapy including VRCZ. ß-D glucan and Aspergillus antigen index were elevated in the cerebrospinal fluid (CSF). We titrated the dose of VRCZ by monitoring plasma and CSF concentrations. The CSF to plasma concentration ratio of VRCZ ranged from 0.47 to 1.36 (median 0.71). While VRCZ adequately penetrates the blood-brain barrier, its concentration is highly variable in infants.

Brainstem pilocytic astrocytoma with H3 K27M mutation: case report.

In this report, the authors present the first case of adult brainstem pilocytic astrocytoma (PA) with the H3 K27M mutation. A 53-year-old man was incidentally found to have a 2.5-cm partially enhanced tumor in the tectum on MRI. The enhancement in the lesion increased over 3 years, and gross-total removal was performed via the occipital transtentorial approach. The resected tissue indicated PA, WHO Grade I, and genetic analysis revealed the H3 K27M mutation. However, although the radiological, surgical, and pathological findings all corresponded to PA, this entity can easily be misdiagnosed as diffuse midline glioma with the H3 K27M mutation, which is classified as a WHO Grade IV tumor according to the updated classification. This case highlights the phenotypic spectrum of PA, as well as the biology of the H3 K27M-mutated gliomas, and may prove to be an exception to the rule that diffuse midline gliomas with the H3 K27M mutation behave in an aggressive manner. Based on the findings of this case, the authors conclude that, in addition to detecting the existence of the H3 K27M mutation, an integrated approach in which a combination of clinical, pathological, and genetic information is used should be applied for accurate diagnosis and determination of the appropriate treatment for diffuse midline gliomas.

Elevated Release of Beta-thromboglobulin and Platelet Factor 4 in Cerebral Infarction Patients with Branch Atheromatous Disease: A Preliminary Report.

This study evaluated the levels of the platelet activation markers beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in patients with branch atheromatous disease (BAD). Patients with newly diagnosed cerebral infarctions were recruited into the study; those with cardiogenic cerebral infarctions were excluded. Beta-TG and PF4 levels were measured before therapeutic intervention and compared between patients with and without BAD; Welch's t-test was used to determine significant differences between the groups. A total of 15 subjects were enrolled in the study, and 8 were diagnosed with BAD. Beta-TG (P = 0.031) and PF4 (P = 0.041) levels were significantly higher in the BAD patients than in the non-BAD patients. Platelet activity is normally elevated in patients with cerebral infarctions, but is elevated to an even greater extent in BAD patients. The evaluation of beta-TG and PF4 levels may be beneficial for the elucidation of BAD.