Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Prospective Evaluation of the Safety and Compression Performance of Novel Compression Denim Jeans in Healthy Volunteers and Patients With Lymphedema e80971 EN Daiki Ousaka Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Yamada Departments of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Sakano Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Miyake Department of Rehabilitation, Lymphedema Treatment Center, Kousei Hospital Takumi Takahashi Division of Business Management, Matsuoka Corporation Akihiro Matsuoka Division of Production Engineering, Matsuoka Corporation Shintaro Yamada Division of Sales, Kaihara Corporation Akira Shinaoka Department of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Oozawa Department of Clinical Safety, Okayama University Hospital Objectives: The treatment of lower-extremity lymphedema, whether congenital or acquired, remains challenging. Long-term management aimed at reducing complications and maximizing quality of life is essential. Compression stockings are crucial in this management; however, their application is limited by patient experience (ease of wear, texture, breathability, and appearance). This highlights the need to evaluate alternative compression garments that maintain therapeutic efficacy while improving patient adherence.<br> Methods: We developed a novel compression denim product (Flow plus Jeans®) using advanced sewing technology. Its baseline performance (compression ability) was evaluated by measuring pressure gradients at three points (ankle, calf, and thigh) using a mannequin-based compression testing system and compared with those of existing stockings. Thereafter, a safety assessment was conducted on healthy volunteers to evaluate potential adverse effects, including changes in lower limb circumference, signs of deep vein thrombosis (DVT) via ultrasound, and skin complications. A clinical trial in patients with lymphedema was then performed to compare its efficacy with that of conventional compression stockings.<br> Results: Baseline performance testing with a mannequin revealed that Flow plus Jeans demonstrated compression levels and pressure gradients at three calf points comparable to those of standard compression stockings. A safety study involving nine healthy volunteers confirmed that Flow plus Jeans caused no significant changes in lower-limb circumferences after three days of wear, with no cases of DVT or skin complications. In a subsequent clinical trial involving nine female patients with lymphedema, the jeans showed non-inferiority to existing stockings concerning lower-limb circumference measurements at six points (pre-use vs. six months post-use), with patient-reported experiences assessed via questionnaires. Notably, patients reported enhanced satisfaction regarding the jeans' fashionability, which could serve as an incentive for long-term adherence.<br> Conclusion: Our findings suggest that Flow plus Jeans represent a promising novel option for the long-term management of lymphedema, offering an alternative that balances medical efficiency with improved patient satisfaction and demonstrates safety in healthy individuals. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Craniofacial Fibrous Dysplasia to Affect or Not the Optic Nerve in Long-Term Follow-Up of Three Cases e91072 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuhiro Okano Department of Otorhinolaryngology, School of Medicine, International University of Health and Welfare Fibrous dysplasia of the bone is characterized by immature fibrous bones of trabeculae and fibrovascular proliferation in the medulla. In this study, we report three consecutive patients with craniofacial fibrous dysplasia with or without optic nerve involvement. In Case 1, a 43-year-old man with blurred vision in the right eye at the first visit was well until the age of 54 years, when he came back with symptoms suggestive of paranasal sinusitis. Computed tomography scans disclosed a mucocele in the right sphenoid sinus and thickened bilateral ethmoid, sphenoid, and frontal bones. He underwent an emergency nasal endoscopic surgery to make a drainage opening to the sphenoid and ethmoid sinuses on the right side with incomplete success. The pathology of the resected tissue confirmed fibrous dysplasia. With intravenous antibiotics, he recovered from blepharoptosis, complete ophthalmoplegia, and visual acuity decrease on the right side. He was well until the age of 71 years when he had a self-limiting episode of visual field cloudiness caused by the right sphenoid sinus mucocele. At the age of 75 years, he developed abrupt vision loss to no light perception in the right eye. He underwent an open skull surgery to extirpate the sphenoid mucocele on the right side and died of an unknown cause two years later. In Case 2, a 29-year-old man had a two-week-long headache, and computed tomography scans revealed fibrous dysplasia in the bilateral sphenoid bones. Nasal biopsy at the spheno-ethmoid recess proved a pathological diagnosis of fibrous dysplasia. Goldmann perimetry showed normal visual fields in both eyes. He was followed every year by magnetic resonance imaging to maintain normal visual fields until the latest visit at the age of 41 years. In Case 3, a 12-year-old girl was referred to an ophthalmologist to check her vision. She had been diagnosed with fibrous dysplasia of the left maxillary bone at the age of six years by a dentist. She had a gingival resection on the left maxilla at the age of 15 years and had a left maxillary bone resection at 18 years at another hospital. One month after the resection, Goldmann perimetry showed superior peripheral field depression in the left eye, in contrast with the normal visual field in the right eye. She maintained the visual acuity of 1.5 in both eyes until the last visit at the age of 21 years. In fibrous dysplasia as a rare disease, functional and cosmetic problems, including vision problems, should be considered in a case-based approach. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 1 2025 Eyelid Spindle Cell Lipoma: Case Report and Review of Three Patients in Literature e70097 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kiyoshi Yamada Plastic and Reconstructive Surgery, Kousei Hospital Yasumasa Monobe Department of Pathology, General Medical Center, Kawasaki Medical School Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University A 39-year-old woman presented a saucer-shaped mass in the left upper eyelid and underwent the extirpation at local anesthesia. Pathologically, collagen fibers, capillaries, small vessels, and CD34-positive spindle cells were dispersed among mature adipose tissues, indicative of spindle cell lipoma. Long-lasting cyst-like eyelid masses would be usually dermoid cysts, and spindle cell lipoma would be listed as a rare pathological diagnosis in differential diagnoses of cyst-like lesions in the upper and lower eyelid. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2415 24 1 2024 Pathological findings in enucleated eyes of patients with neurofibromatosis type 1: report of a case with 15-year follow-up and review of 14 patients in the literature 341 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kenji Nishida Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takaya Seno Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shigeki Ono Department of Neurological Surgery, General Medical Center, Kawasaki Medical School Backgrounds Iris nodules are frequently noted as clinical manifestations of neurofibromatosis type 1 but the other intraocular manifestations are rare. The purpose of this study is to present a patient with a phthisic eye who underwent enucleation for a cosmetic reason after 15-year follow-up and also to review 14 patients with enucleation described in the literature.<br> Case presentation A 17-year-old man with neurofibromatosis type 1 from infancy underwent the enucleation of phthisic left eye and also had the resection of eyelid subcutaneous mass lesions on the left side for a cosmetic reason. He had undergone four-time preceding surgeries for eyelid and orbital mass reduction on the left side in childhood and had developed total retinal detachment 10 years previously. Pathologically, the enucleated eye showed massive retinal gliosis positive for both S-100 and glial fibrillary acidic protein (GFAP) in the area with involvement of the detached retinal neuronal layer, together with a more fibrotic lesion along the choroid which were, in contrast, negative for both S-100 and GFAP. The choroid, ciliary body, and iris did not show apparent neurofibroma while episcleral neurofibroma was present.<br> Literature review In review of enucleated eyes of 14 patients in the literature, buphthalmic eyes with early-onset glaucoma on the unilateral side was clinically diagnosed in 9 patients who frequently showed varying extent of hemifacial neurofibromatosis which involved the eyelid and orbit on the same side. Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. The phthisic eye in another patient showed massive retinal gliosis similar to the present patient.<br> Conclusions In summary of the 15 patients with neurofibromatosis type 1, including the present patient, buphthalmic or phthisic eyes with no vision were enucleated for cosmetic reasons and showed choroidal neurofibroma in most patients and massive retinal gliosis in two patients including the present patient. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 11 12 2023 Nontuberculous mycobacterial abscess of lacrimal sac and eyelid debridement: Case report e8364 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Okayama University Hospital Motoko Nose Department of Clinical Laboratory, Okayama University Hospital Yasushi Tanimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital A 56-year-old otherwise healthy woman developed abscess from dacryocystitis in the right lower eyelid. The smear of puncture fluid showed acid-fast bacilli and Mycobacterium abscessus was identified after a month. The early start of clarithromycin/ethambutol was switched to clarithromycin/levofloxacin. Debridement specimen after 7-month treatment showed granulomatous tissue with no bacilli. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 12 1 2022 A new severity classification of lower limb secondary lymphedema based on lymphatic pathway defects in an indocyanine green fluorescent lymphography study 309 EN Akira Shinaoka Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuyo Kamiyama Department of Nursing, Kagawa Prefectural Central Hospital Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Most protocols for lymphatic imaging of the lower limb conventionally inject tracer materials only into the interdigital space; however, recent studies indicate that there are four independent lymphatic vessel groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limb. Thus, three additional injection sites are needed for lymphatic imaging of the entire lower limb. We aimed to validate a multiple injection designed protocol and demonstrate its clinical benefits. Overall, 206 lower limbs undergoing indocyanine green fluorescent lymphography with the new injection protocol were registered retrospectively. To assess the influence of predictor variables on the degree of severity, multivariable logistic regression models were used with individual known risk factors. Using a generalized linear model, the area under the curve (AUC) of the conventional clinical model, comprising known severity risk factors, was compared with that of the modified model that included defects in the posterolateral and posteromedial groups. Multivariable logistic regression models showed a significant difference for the posteromedial and posterolateral groups. The AUC of the modified model was significantly improved compared to that of the conventional clinical model. Finding defects in the posteromedial and posterolateral groups is a significant criterion for judging lymphedema severity and introducing a new lymphedema severity classification. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 59 16 2020 Multiple Deep-seated Dentofacial Abscesses Caused by Multidrug-resistant Viridans Group Streptococci 2067 2070 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Mizuta Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kayo Okamoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Hayashi Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Odontogenic infections, generally caused by dental caries and periodontal disease, can result in fatal illness. We herein report a 71-year-old Japanese woman with type 2 diabetes and hemodialysis who suffered from multiple dentofacial abscesses mainly caused by multidrug-resistant Streptococcus oralis. She complained of pain and swelling of her face, with an extraoral fistula from the left cheek. Following 3 surgical debridement procedures and partial mandibulectomy, in addition to 12 weeks of antimicrobial therapy, the multiple dentofacial abscesses were ameliorated. A combination of surgical and antimicrobial treatments following an early diagnosis is essential for reducing further complications. No potential conflict of interest relevant to this article was reported.

Lippincott, Williams & Wilkins Acta Medica Okayama 2169-7574 8 4 2020 Utilization of a Simple Surgical Guide for Multidirectional Cranial Distraction Osteogenesis in Craniosynostosis e2797 EN Chihiro Matsui Department of Plastic and Reconstructive Surgery,Okayama University Hospital Eijiro Tokuyama Department of Plastic and Reconstructive Surgery,Okayama University Hospital Takaya Senoo Department of Plastic and Reconstructive Surgery,Okayama University Hospital Kiyoshi Yamada Department of Plastic and Reconstructive Surgery,Okayama University Hospital Masahiro Kameda Department of Neurological Surgery, Okayama University Hospital Tetsuo Takeuchi Department of Occlusal and Oral Functional Rehabilitation, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery,Okayama University Hospital Background: Multidirectional cranial distraction osteogenesis (MCDO) can achieve a desired shape for deformities of the cranium. In the past, visual estimation was used to reflect on the actual skull, but it was time-consuming and inaccurate. Here we demonstrate an effective osteotomy navigation method using surgical guides made from a dental impression silicone. <br/> Methods: Seven patients who underwent MCDO between August 2013 and September 2016 were included in the study. Five cases involved utilization of the surgical guide for osteotomy. Three-dimensional (3D) printed cranium models were made using 3D computed tomography (3DCT) imaging data and dental impression silicone sheets were molded using the printed cranium models. These surgical guides were sterilized and used for intraoperative osteotomy design. Vertical distance between nasion/porion and osteotomy lines were calculated using 3D printed cranial models and postoperative 3DCT images to assess reproducibility. <br/> Results: The average surgical time/design time was 535/37.0 minutes for the nonsurgical guide group and 486.8/11.8 minutes for the surgical guide group (SG). Treatment using the surgical guide was significantly shorter in terms of operative time and time required for design. For the vertical distance comparison, the average distance was 5.7mm (SD = 0.3) in the non-SG and 2.5mm (SD = 0.44) in the SG, and SG was more accurate. <br/> Conclusions: Shorter operative times and higher reproducibility rates could be achieved by using the proposed surgical guide, which is accurate, low-cost, and easily accessible. No potential conflict of interest relevant to this article was reported.

Lippincott Williams & Wilkins Acta Medica Okayama 00321052 137 1 2016 Histologic Evaluation of Lymphaticovenular Anastomosis Outcomes in the Rat Experimental Model: Comparison of Cases with Patency and Obstruction 83e 91e EN Satoshi Onoda Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, University of Okayama Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, University of Okayama Kumiko Matsumoto Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, University of Okayama Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, University of Okayama BACKGROUND: Lymphaticovenular anastomosis plays an important role in the surgical treatment of lymphedema. The outcomes of lymphaticovenular anastomosis are evaluated based on changes in edema; however, isolated assessment of the anastomosis itself is difficult. The authors used an animal experimental model to conduct a detailed examination of histologic changes associated with lymphaticovenular anastomosis and determined the factors important for success. METHODS: The experimental lymphaticovenular anastomosis model was created using lumbar lymph ducts and iliolumbar veins of Wistar rats. The authors performed anastomosis under a microscope and reviewed postoperative histologic changes using optical and electron microscopy. In addition, electron microscopy and histology were used for detailed examination of the area in the vicinity of the anastomotic region in cases with patency and obstruction. RESULTS: The patency rates immediately after, 1 week after, and 1 month after lymphaticovenular anastomosis were 100 percent (20 of 20), 70 percent (14 of 20), and 65 percent, respectively. A detailed examination of the anastomotic region with electron microscopy revealed that, in cases with patency, there was no notable transformation of the endothelial cells, which formed a smooth layer. In contrast, in obstruction cases, the corresponding region of the endothelium was irregular in structure. CONCLUSIONS: Vessel obstruction after lymphaticovenular anastomosis may be associated with irregular arrangement of the endothelial layer, leading to exposure of subendothelial tissues and platelet formation. One part of the postoperative changes after anastomosis and a cause of obstruction were elucidated in this study. The authors' results may enable improvements in lymphaticovenular anastomosis by translating back to real clinical operations. No potential conflict of interest relevant to this article was reported.

Wiley-Liss Acta Medica Okayama 00224790 114 8 2016 Relationship of the number and size of superficial groin lymph nodes with the stage of secondary lymphatic edema 940 946 EN Satoshi Onoda Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, University of Okayama Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, University of Okayama Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, University of Okayama Noriko Seki Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, University of Okayama Yuji Hiramatsu Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, University of Okayama PURPOSE: This study evaluated the relationships of the size and number of superficial groin lymph nodes with the lower limb lymphedema stage and thus examined the role of superficial lymphatic lymph nodes in secondary lymphedema development. METHODS: We determined the number and size of superficial groin lymph nodes using horizontal plane computed tomography (CT) and the lymphedema stage in the lower limbs of 25 patients with gynecologic cancer. RESULTS: The patients had an average of 2.92 (range, 1-7) superficial groin lymph nodes; the mean size of the 146 evaluated lymph nodes was 7.55 mm (range, 5-15 mm). In 19 of 25 patients (76%), the side with major edema contained fewer superficial groin lymph nodes. In total, 22 patients (88%) had fewer superficial groin lymph nodes or a smaller total lymph node size on the edematous dominant side. CONCLUSIONS: In this evaluation of the link between superficial groin lymph node laterality and secondary lymphedema staging, we found that patients with large lymph node numbers and sizes tended to present with a relatively earlier stage of lymphedema. Our results therefore suggest that the size and number of superficial groin lymph nodes affect the lymphedema stage. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 2 2017 Three-Dimensional Imaging of Lymphatic System in Lymphedema Legs Using Interstitial Computed Tomography-lymphography 171 177 EN Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Akira Shinaoka Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Original Article 10.18926/AMO/54986 As a new trial, we used interstitial computed tomography-lymphography (CT-LG) in 10 patients with lower extremity lymphedema (n=20 limbs) at stage 0, 1, 2, or 3 under the International Society of Lymphology (ISL) classification. In all cases, CT-LG, lymphoscintigraphy, and indocyanine green fluorescence-lymphography (ICG-LG) were performed. In the examination of the ascending level of depicted lymphatic vessels, we measured the diameters of lymphatic vessels detected with CT-LG and conducted an image analysis of dermal backflow of lymph (DB). CT-LG had better resolution than lymphoscintigraphy and enabled the clear visualization of lymphatic vessels with a minimum lumen size of 0.7 mm. CT-LG also showed the three-dimensional architecture of the DB, which originated from deep lymphatic collectors via branched small lymphatic vessels. Our findings are quite valuable not only for detailed examinations of lymphedematous sites and for the lymphedema surgery, but also for investigations of the pathogenesis of lymphedema which has not yet been established. We observed that lymphoscintigraphy could show the lymphatic vessels up to the thigh level in all cases, whereas CT-LG enabled the vesselsf visualization up to the leg level at maximum. In conclusion, CT-LG provided adequate and detailed three-dimensional imaging of the lymphatic system in lymphedema patients. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0959-4965 24 10 2013 Vascularized peripheral nerve grafting promotes myelination of regrowing optic nerve 566 571 EN Seiji Komatsu Taketoshi Wakabayashi Kiyoshi Yamada Kumiko Matsumoto Yoshihiro Kimata Jun Kosaka We investigated whether the use of vascularized peripheral nerve grafts on the optic nerve stump enhances axonal regeneration of retinal ganglion cells compared with isolated nonvascularized grafts. The rat median nerve was microsurgically sutured with its supplying artery and vein to the optic nerve stump. The number of retinal ganglion cells with regenerating axons was evaluated by retrograde labeling into the grafted peripheral nerve, and the myelination of the regenerating axon fibers was examined by electron microscopy. The number of retinal ganglion cells with regenerating axons was significantly higher in the vascularized graft than in the nonvascularized graft. The ratio of myelinated axon fibers was also increased in vascularized grafts. Thus, grafting with their supplying arteries and veins to an injured nerve stump represents a promising strategy to accelerate axonal regeneration from neurons of the central nervous system. No potential conflict of interest relevant to this article was reported.