Yusuke Uchiyama

Factors contributing to blood-brain barrier disruption following intracarotid injection of nonionic iodinated contrast medium for cerebral angiography : experimental study in rabbits

PurposeThis study was performed to investigate the role of injection methods and conditions under a fixed dose of radiographic contrast medium (CM) in respect to promoting blood–brain barrier (BBB) disruption.Materials and methodsA total of 44 white rabbits (average body weight 2.7 ± 0.4 kg) were used, and their carotid injection was performed with nonionic CM. The variables assessed for the carotid injections included the following: iodine content (300 or 150 mg I/ml), liquid temperature (37° or 24°C), and the injection time duration (1 or 30 s). The rabbits were divided into five groups. To evaluate BBB disruption, pre- and post-contrast-enhanced magnetic resonance (MR) studies were performed.ResultsAbnormal enhancement of the brain parenchyma in MRI was noted in only one group, which consisted of high-iodine concentration CM injected at a low temperature over a short injection interval. Statistically significant increased values for the percentage of relative enhancement (RE%) were demonstrated (P < 0.05) in comparison with the saline-injected control group.ConclusionThis result suggests variables that may need to be carefully considered to prevent BBB injury induced by nonionic CM for cerebral angiography, especially in the setting of a neurointerventional procedure.

Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14

Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1-3, 6-8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.

Cerebral Micro bleeds in Coronary Artery Disease Patients during Antiplatelet Therapy

Background: Brain hemorrhage is a serious complication of antiplatelet therapy, particularly dual antiplatelet therapy (DAPT), in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention (PCI). It has been suggested that cerebral micro bleeds (CMBs) detected on magnetic resonance imaging (MRI) are a risk factor for future cerebral haemorrhage. However, little is known about CMBs in CAD patients during antiplatelet therapy. We investigated the temporal changes of CMBs and determined the risk factors for CMBs in patients with CAD on antiplatelet therapy. Methods: This study prospectively enrolled 14 CAD patients who underwent antiplatelet therapy (DAPT in 13 patients) and had no history of symptomatic stroke. Brain MRI was performed at baseline and after 8-month follow-up. Results: Baseline MRI revealed CMBs in two patients (14%). New CMBs were detected by follow-up MRI in two other patients (14%). CMB-positive patients had a greater number of coronary artery lesions (p=0.04) and a tendency to have a higher SYNTAX score at baseline (p=0.06) than CMB-negative patients. Although blood pressure (BP) at baseline did not differ between the CMB-positive and CMB-negative patients, BP after 8 months was significantly higher in CMB-positive than in CMB-negative patients (systolic BP: p=0.03, diastolic BP: p=0.02). Conclusions: CAD patients with severe coronary artery lesions and poor BP control appear to be at higher risk for CMBs during antiplatelet therapy. Accordingly, strict coronary risk control, especially BP control, is necessary to prevent new CMBs in CAD patients receiving long-term antiplatelet therapy

The Successful Treatment of Myeloperoxidase Antineutrophil Cytoplasmic Antibody-positive Hypertrophic Pachymeningitis in Patients with the Limited Form of Granulomatosis with Polyangiitis Using Methotrexate: Two Case Reports

Recent findings have indicated a close relationship between myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive hypertrophic pachymeningitis and the limited form of granulomatosis with polyangiitis (GPA). In Japan, MPO-ANCA-positive hypertrophic pachymeningitis predominantly occurs in elderly individuals. We herein describe the cases of two patients with MPO-ANCA-positive hypertrophic pachymeningitis associated with the limited form of GPA who were successfully treated with a combination of corticosteroids and methotrexate. Although methotrexate has been shown to be less effective than cyclophosphamide for inducing the remission of GPA in patients with organ-threatening diseases, its safety and efficacy may make it a useful alternative treatment modality for patients with the limited form of GPA who show meningeal involvement.