Dr. Rhoton’s key philosophies included “Keep working hard.”, “Make surgery more accurate, gentle and safe”, “We want perfect anatomical dissections, because we want perfect surgical operations”, “Competence without compassion is worthless. Compassion without competence is meaningless”, “Neurosurgeons share a great professional gift; our lives have yielded an opportunity to help mankind in a unique and exciting way” and “There is no finish line for this effort”. His words reveal his passion for microneurosurgery and infinite love for humankind. Although his reknown rested on his reputation as a researcher, Dr. Rhoton was also a devoted educator. The principal aim behind the enormous amount of work he performed was that of educating neurosurgeons worldwide, so that they could be better surgeons. His work included: (1) numerous dissection courses, (2) numerous lectures and publications including about 160 original papers (3) the textbook “RHOTON” and Rhoton Collection (4) the education of 119 research fellows. The projects directed in his lab, produced the international dissemination of neuroanatomical knowledge. The ultimate goal of his microsurgical research was to improve the care of patients with neurosurgical diseases around the world. The technical contributions and humble character of Dr. Rhoton should be remembered as we care for patients.
Histone H3 mutations are frequently found in diffuse midline gliomas (DMGs), which include diffuse intrinsic pontine gliomas and thalamic gliomas. These tumors have dismal prognoses. Recent evidence suggests that one reason for the poor prognoses is that O6-methylguanine-DNA methyltransferase (MGMT) promoter frequently lacks methylation in DMGs. This review compares the epigenetic changes brought about by histone mutations to those by isocitrate dehydrogenase-mutant gliomas, which frequently have methylated MGMT promoters and are known to be sensitive to temozolomide.
Glioblastoma (GBM) still carries a poor prognosis due to the refractoriness against antitumor drugs. Temozolomide (TMZ), one of the few standard therapy drugs against GBM worldwide, has only limited effect due to acquired TMZ resistance of GBM. Therefore, development of novel therapeutic methods to overcome the TMZ resistance of GBM is urgent. The brain is the most cholesterol-rich organ in the human body, so modulation of cholesterol in tumor cells originating from the brain including GBM may be a tumor-specific therapeutic strategy including enhancement of TMZ effects. The unique lipid metabolism of glioma has recently been reported, but the involvement of intracellular cholesterol in TMZ therapy is yet to be fully elucidated. This review summarizes the effect of modulation of intracellular cholesterol level on cancer therapy including GBM treatment and the implications for TMZ therapy. Our recent findings about the involvement of intracellular cholesterol in TMZ-induced GBM cell death are described.
Recent clinical research has revealed a significant correlation between atherosclerosis, one of the primary etiologies of ischemic stroke, and the immune system. Assuming that “disease-specific autoantibodies are produced in the sera of patients with ischemic stroke,” we investigated multiple arteriosclerosis-related antibodies using the serological identification of antigens by recombinant cDNA expression cloning (SEREX), an established method for identifying antigenic proteins. We either screened a human aortic endothelial cell cDNA library or conducted protein array screening using the sera from patients with ischemic stroke, such as carotid artery stenosis or transient ischemic attack (TIA). Next, we measured serum antibody levels using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in patient/healthy donor (HD) cohorts and identified several antigens, the antibody levels of which were significantly higher in patients with ischemic stroke than in HDs. This review introduced the method of identifying antigens by the SEREX and protein microarray and summarized antigenic proteins. In particular, it focused on anti-replication protein A2 antibody and anti-programmed cell death 11 antibody, which are significantly related to atherosclerotic plaque and ischemic brain tissue, respectively, and proposed the mechanism of elevated autoantibody levels against them. Furthermore, this review suggests a possibility of clinical application as an atherosclerotic disease diagnostic marker for TIA or cerebral infarction.
This study sought to analyze the incidence of contralateral microembolic infarctions (MIs) on diffusion-weighted imaging (DWI) following protected carotid artery stenting (CAS) and compared the difference of risk factors between ipsilateral and contralateral lesions. From April 2010 to March 2017, 147 CASs in 140 patients were performed. All the patients underwent DWI within 1 week before and 24 hrs after the procedures. CAS was successfully completed in 145 (98.6%) of the 147 procedures. Forty-nine (33.8%) patients with new MIs revealed on postprocedural DWI were enrolled. They were divided into ipsilateral and contralateral groups based on the side of the CAS and MIs. The ipsilateral group indicates patients with MIs exclusively on the side of CAS. The contralateral group includes patients with MIs on the opposite side of the CAS or both sides. Patients with MIs at vertebrobasilar territory were excluded. Patient characteristics, morphology of the carotid artery and aortic arch, and procedural data were retrospectively assessed and compared between the two groups. Twenty-two (15.2%) and 14 (9.7%) patients were assigned to the ipsilateral and contralateral groups, respectively. Advanced age, left-sided stenosis, severe aortic arch calcification (AAC) on chest X-ray and contralateral carotid occlusion significantly increased the occurrence of contralateral MIs. On multivariable logistic regression analysis, severe AAC was statistically more frequent in the contralateral group. In the present study, the incidences of contralateral MIs after CAS is relatively not low. Advanced aortic atherosclerosis is statistically predictive for contralateral MIs. AAC on chest X-ray is a useful finding for estimating aortic atherosclerosis in candidates for CAS.
Superficial peroneal nerve (S-PN) entrapment neuropathy (S-PNEN) is comparatively rare and may be an elusive clinical entity. There is yet no established surgical procedure to treat idiopathic S-PNEN. We report our surgical treatment and clinical outcomes. We surgically treated 5 patients (6 sites) with S-PNEN. The 2 men and 3 women ranged in age from 67 to 91 years; one patient presented with bilateral leg involvement. Mean post-operative follow-up was 25.3 months. We recorded their symptoms before- and at the latest follow-up visit after surgery using a Numerical Rating Scale and the Japan Orthopedic Association score to evaluate the affected area. We microsurgically decompressed the affected S-PN under local anesthesia without a proximal tourniquet. We made a linear skin incision along the S-PN and performed wide S-PN decompression from its insertion point at the peroneal tunnel to the peroneus longus muscle (PLM) to the point where the S-PN penetrated the deep fascia. One patient who had undergone decompression in the area of a Tinel-like sign at the initial surgery suffered symptom recurrence and required re-operation 4 months later. We performed additional extensive decompression to address several sites with a Tinel-like sign. All 5 operated patients reported symptom improvement. In patients with idiopathic S-PNEN, neurolysis under local anesthesia may be curative. Decompression involving only the Tinel area may not be sufficient and it may be necessary to include the area from the PLM to the peroneal nerve exit point along the S-PN.