Transcriptome-wide analysis of intracranial artery in patients with moyamoya disease showing upregulation of immune response, and downregulation of oxidative phosphorylation and DNA repair.

OBJECTIVE: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive occlusion of the internal carotid artery and the secondary formation of collateral vessels. Patients with MMD have ischemic attacks or intracranial bleeding, but the disease pathophysiology remains unknown. In this study, the authors aimed to identify a gene expression profile specific to the intracranial artery in MMD. METHODS: This was a single-center, prospectively sampled, retrospective cohort study. Microsamples of the middle cerebral artery (MCA) were collected from patients with MMD (n = 11) and from control patients (n = 9). Using microarray techniques, transcriptome-wide analysis was performed. RESULTS: Comparison of MCA gene expression between patients with MMD and control patients detected 62 and 26 genes whose expression was significantly (p < 0.001 and fold change > 2) up- or downregulated, respectively, in the MCA of MMD. Gene set enrichment analysis of genes expressed in the MCA of patients with MMD revealed positive correlations with genes involved in antigen processing and presentation, the dendritic cell pathway, cytokine pathway, and interleukin-12 pathway, and negative correlations with genes involved in oxidative phosphorylation and DNA repair. Microarray analysis was validated by quantitative polymerase chain reaction. CONCLUSIONS: Transcriptome-wide analysis showed upregulation of genes for immune responses and downregulation of genes for DNA repair and oxidative phosphorylation within the intracranial artery of patients with MMD. These findings may represent clues to the pathophysiology of MMD.

Postoperative Outcomes After Transsacral Epiduroscopic Laser Decompression in Japanese Patients: Denervation Therapy for Discogenic Low-Back Pain.

Background: Transsacral epiduroscopic laser decompression (SELD) is a very noninvasive surgery, so it is effective for elderly patients and athletes and is a new and minimally invasive therapeutic technique that may be useful in many patients with discogenic low-back pain (LBP) having high signal intensity zone (HIZ) in magnetic resonance imaging (MRI). We investigated the clinical outcomes of SELD in Japanese patients with discogenic LBP having HIZ as a first trial. Methods: The subjects consisted of 52 patients who underwent SELD and were followed up for at least 6 months. All patients with LBP with HIZ were operative using the SELD technique. Outcomes of the patients were assessed with visual analogue scale (VAS) for LBP, the Oswestry disability index (ODI), and the EuroQol 5 dimension (EQ-5D). Statistical analyses were carried out using a paired t-test. A p-value of <0.05 was considered significant. For statistical analysis, we used the SPSS software program. Results: At 12 months after the procedure, the average VAS score for LBP fell to 1.2 from 5.6 (p-value <0.05). The ODI score also dropped from the preoperative level of 22.3 to 8.8. The EQ-5D score also significantly increased from the preoperative level of 0.865 (SD 0.10) to 0.950 (SD 0.05). Eight cases of intraoperative cervical pain were observed as complications with no cases of hematomas, infections, and postoperative neurosis was observed. Conclusions: SELD provides a novel minimally invasive technique capable of performing multilevel intervertebral surgery. We believe that SELD is an effective method of treating discogenic LBP due to HIZs.

Step-by-Step Sublaminar Approach With a Newly-Designed Spinal Endoscope for Unilateral-Approach Bilateral Decompression in Spinal Stenosis.

OBJECTIVE: Spinal stenosis is increasingly common due to population aging. In elderly patients with lumbar central canal stenosis (LCCS), minimizing muscle damage and bone resection is particularly important. We performed a step-by-step operation with a newly designed spinal endoscope to obtain adequate decompression in patients with spinal stenosis. METHODS: From April 2015 to August 2016, 78 patients (48 males, 30 females) with LCCS (91 segments) underwent endoscopic decompression using a newly designed endoscope system. The inclusion criteria were: (1) neurogenic intermittent claudication with or without radiculopathy, (2) LCCS, and (3) having exhausted conservative treatment (>3 months). The exclusion criteria were: (1) >10° of instability, (2) spondylolisthesis grade II or greater according to the Meyerding criteria, (3) foraminal stenosis, (4) vascular intermittent claudication, (5) infection, and (6) stenosis combined with malignancy. We performed a step-by-step procedure using a newly designed endoscope system for unilateral-approach bilateral decompression. We used the same incision for 2-3 segments, only moving the skin. RESULTS: The mean follow-up was 2.3±1.3 years. Excellent or good results were found according to the MacNab criteria in 85.9% of cases (67 of 78). The visual analogue scale, Japanese Orthopedic Association score, and Oswestry Disability Index showed significant decreases at 1 month, persisting until the 2-year follow-up. Dural tear occurred in 4 cases (5.1%), and patch repair was performed under endoscopy. No patients experienced aggravated instability requiring surgery. CONCLUSION: We obtained good results with endoscopic decompression surgery using a newly designed instrument that minimized muscle and bone damage in elderly patients with spinal stenosis.

Comparative Prospective Study of Microvascular Anastomosis Training by Self-Learning or with Expert Instruction.

BACKGROUND: Young neurosurgeons have little opportunity to receive expert feedback while learning microvascular anastomosis. Our objective was to determine the importance of expert feedback. We compared students who studied anastomosis by self-learning with those who studied it with expert feedback. Our second objective was to determine the efficacy of intensive training by comparing the skills of the students with expert feedback with those of neurosurgeons. METHODS: Twenty-five medical students and 9 neurosurgeons participated. The students were provided with instructional Digital Video Disks (DVDs) and spent 2 weeks practicing gauze fiber microsuturing followed by 6 weeks practicing end-to-side anastomosis using silicone tube. The students assigned to the expert feedback group received weekly feedback through a video call, whereas those in the self-learning group did not. After training, the students completed a final practical examination that was recorded on DVD. The DVDs and procedural products were numbered and distributed to 2 blinded independent expert neurosurgeons for grading. The neurosurgeons completed a similar examination, and their performances were also recorded and compared with those of the medical students. RESULTS: Compared with the self-learning group, the expert feedback group showed significantly higher anastomosis scores (P = 0.0261) and a nonsignificant tendency toward slower anastomosis times (P = 0.4188). The expert feedback group also achieved significantly higher anastomosis scores than did the neurosurgeons (P = 0.0055). CONCLUSIONS: Expert feedback improves mastery of microvascular anastomosis. Intensive training with regular expert feedback enables medical students to achieve microvascular anastomosis skills better than those of neurosurgeons.

Elevation of Proenkephalin 143-183 in Cerebrospinal Fluid in Moyamoya Disease.

BACKGROUND: In moyamoya disease (MMD), the causes of differences in clinical features between children and adults and of the dramatic temporal changes in moyamoya vessels are poorly understood. We previously discovered elevated levels of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid (CSF) in patients with MMD. This study examined the amino acid sequences of these peptides and quantified in specimens. METHODS: The m/z 4588 and m/z 4473 peptides in CSF from patients with MMD were purified and concentrated by high-performance liquid chromatography and ultrafiltration. Liquid chromatography coupled with tandem mass spectrometry analysis was performed to identify the amino acid sequences of these peptides. We quantified these peptides in samples using sandwich enzyme-linked immunosorbent assay, and concentrations in CSF were compared between MMD (n = 40, 19 male; median age, 37 years) and non-MMD intracranial disease (n = 40, 19 male; median age, 39 years) as controls. RESULTS: These peptides were identified as proenkephalin 143-183 (PENK 143-183). The concentration of PENK 143-183 was significantly greater in patients with MMD (median, 8,270 pmol/L) than control patients (median, 3,760 pmol/L; P < 0.001) and decreased in an age-dependent manner in MMD (r = -0.57; P < 0.001). The area under the receiver operating characteristic curve in children (age <18 years) was 0.885 (95% confidence interval 0.741-1). The correlation between proenkephalin concentration and temporal changes in moyamoya vessels was suggested. CONCLUSIONS: Proenkephalin 143-183 in CSF may offer a helpful diagnostic biomarker in pediatric MMD. The effect of enkephalin peptides through opioid growth factor receptor or delta opioid receptor might be associated with the pathophysiology of MMD.

Hands-on Simulation versus Traditional Video-learning in Teaching Microsurgery Technique.

Bench model hands-on learning may be more effective than traditional didactic practice in some surgical fields. However, this has not been reported for microsurgery. Our study objective was to demonstrate the efficacy of bench model hands-on learning in acquiring microsuturing skills. The secondary objective was to evaluate the aptitude for microsurgery based on personality assessment. Eighty-six medical students comprising 62 men and 24 women were randomly assigned to either 20 min of hands-on learning with a bench model simulator or 20 min of video-learning using an instructional video. They then practiced microsuturing for 40 min. Each student then made three knots, and the time to complete the task was recorded. The final products were scored by two independent graders in a blind fashion. All participants then took a personality test, and their microsuture test scores and the time to complete the task were compared. The time to complete the task was significantly shorter in the simulator group than in the video-learning group. The final product scores tended to be higher with simulator-learning than with video-learning, but the difference was not significant. Students with high "extraversion" scores on the personality inventory took a shorter time to complete the suturing test. Simulator-learning was more effective for microsurgery training than video instruction, especially in understanding the procedure. There was a weak association between personality traits and microsurgery skill.