Publications by authors named "Yasushi Takagi"

243 Publications

Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source.

J Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.

Background: In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission.

Methods: Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF.

Results: We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05).

Conclusions: LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF.
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http://dx.doi.org/10.1016/j.jjcc.2021.05.005DOI Listing
June 2021

Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia.

Life (Basel) 2021 May 24;11(6). Epub 2021 May 24.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% ( < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.
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http://dx.doi.org/10.3390/life11060477DOI Listing
May 2021

Subarachnoid Hemorrhage Due to Rupture of Vertebral Artery Dissecting Aneurysms: Treatments, Outcomes, and Prognostic Factors.

World Neurosurg 2021 May 26. Epub 2021 May 26.

Department of Neurosurgery, Tokushima University, Tokushima, Japan.

Background: Mortality rate after subarachnoid hemorrhage due to rupture of vertebral artery dissecting aneurysms (VADAs) is high; endovascular coil trapping is the first-line therapy to prevent rerupture. To select optimal treatments, the positional relationship between the VADA and posterior inferior cerebellar artery (PICA) and the morphology of the contralateral vertebral artery must be considered, and outcome predictors of different treatment methods and their possible complications must be identified.

Methods: We retrospectively studied 44 patients with ruptured VADAs who had undergone endovascular or surgical treatment. VADA morphology was assessed on conventional preoperative angiograms, and VADAs were categorized based on their site in relation to the PICA. VADA site, treatment method, and complications were used to identify prognostic factors.

Results: The sites of the 44 VADAs were PICA-proximal (n = 3), PICA-distal (n = 22), PICA-absent (n = 7), and PICA-involved (n = 12). Treatments included internal coil trapping (n = 30), proximal coil occlusion (n = 5), and stent placement (n = 3); surgical flow alteration via an occipital artery-PICA bypass and ligation at the proximal vertebral artery and the PICA origin was performed in 6 patients. Periprocedural rebleeding was associated with a poor outcome. Internal coil trapping prevented the rerupture of PICA-proximal and PICA-absent VADAs, and flow alteration prevented rerupture of PICA-involved VADAs; there were no complications directly attributable to these procedures.

Conclusions: Periprocedural rebleeding was a poor prognostic factor. Internal trapping of PICA-proximal and PICA-absent VADAs and flow alteration in PICA-involved VADAs prevented rerupture.
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http://dx.doi.org/10.1016/j.wneu.2021.05.018DOI Listing
May 2021

Reversible Hearing Impairment Due to Inferior Colliculi Compression by a Pineal Glial Cyst.

NMC Case Rep J 2021 Apr 2;8(1):79-84. Epub 2021 Apr 2.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Tokushima, Japan.

Pineal glial cysts associated with bilateral hearing impairment are very rare. Here, we present the case of a 13-year-old boy with a pineal cyst, which caused severe bilateral hearing impairment persisting from 6 years of age. When the patient was 6 years old, the bilateral hearing acuity was about 40 dB on audiometry. Upon admission to our otolaryngology department, his audiogram revealed a bilateral worsening of the hearing acuity (80 dB). Magnetic resonance imaging (MRI) revealed an abnormal pineal cyst with tectal compression from the left with hardly normal bilateral brainstem auditory evoked potentials (BAEPs). We obtained informed consent for exploratory surgery and employed the right occipital transtentorial approach for pineal cyst removal. Based on histological examination, we diagnosed a glial cyst of the pineal gland. At 12 months postoperatively, the patient's hearing improved, showing a bilateral hearing acuity of 40 dB on audiometry. Since the auditory pathway has both crossed and uncrossed fibers at the upper pons and midbrain level, compression at the lateral lemniscus or inferior colliculus level can cause bilateral hearing impairment. In the present case, there was a possible slow pineal cyst growth that eventually compressed the upper pons to the midbrain, lateral lemniscuses, or inferior colliculi from the left side, this eventually led to bilateral hearing impairment. These findings indicate that surgery can improve hearing acuity in patients with a pineal cyst associated with progressive hearing impairment.
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http://dx.doi.org/10.2176/nmccrj.cr.2020-0123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116931PMC
April 2021

A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma.

Hum Genome Var 2021 May 14;8(1):18. Epub 2021 May 14.

Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.
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http://dx.doi.org/10.1038/s41439-021-00150-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121905PMC
May 2021

Preoperative obliteration of choroidal arteries in the treatment of large hypervascular tumors in the lateral ventricle.

BMC Neurol 2021 Mar 12;21(1):113. Epub 2021 Mar 12.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, ShogoinKawahara-cho, Sakyo-ku, 606-8507, Kyoto, Japan.

Background: Removal of large hypervascular tumors in the lateral ventricle still poses a surgical challenge. These tumors are usually fed from choroidal arteries, and vascular control is typically performed late during the removal. We aimed to evaluate the clinical efficacy of our strategy for persistent preoperative obliteration of feeders from the choroidal arteries to manage large hypervascular tumors in the lateral ventricle.

Methods: We retrospectively analyzed six patients with hypervascular tumors in the lateral ventricle. We first attempted to obstruct feeders using endovascular treatment, and, if unavailable, performed initial microsurgical occlusion through the temporal horn for the staged tumor removal.

Results: In all patients, feeder obliteration was successfully performed; the anterior choroidal arteries were occluded by the endovascular treatment and microsurgical occlusion in one and five patients, respectively, while the lateral posterior choroidal arteries were occluded via endovascular treatment in four patients. No patients had permanent symptoms due to feeder obliteration, and tumor devascularization was achieved at the mean rate of 69.9%. During the tumor removal, the mean blood loss volume was 253 ml. No postoperative hemorrhage had occurred, and all patients scored ≤ 2 on the modified Rankin Scale at six months post-removal.

Conclusions: Although further studies are warranted, persistent feeder obliteration of choroidal arteries could be an effective treatment strategy against large hypervascular tumors in the lateral ventricle.
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http://dx.doi.org/10.1186/s12883-021-02129-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953562PMC
March 2021

Relationship between fractional flow reserve and graft patency after coronary artery bypass grafting.

Gen Thorac Cardiovasc Surg 2021 Mar 8. Epub 2021 Mar 8.

Department of Cardiovascular Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.

Background: Bypass for moderately stenosed coronary arteries may cause graft failure (string phenomenon or occlusion). We examined the effects of fractional flow reserve (FFR) on the efficacy of coronary artery bypass grafting (CABG) in preventing graft failure.

Methods: Between January 2013 and December 2017, 48 patients underwent CABG after FFR was measured. Twenty-five grafts in 23 patients were evaluated for graft patency after the procedure. We studied stenosis of native coronary arteries, FFR, graft flow, graft patency, and the presence of pre-procedure and post-procedure myocardial ischemia.

Results: Three internal thoracic arteries showed the string sign, and two saphenous vein grafts showed occlusion. All target coronary arteries for these grafts had moderate (50-75%) stenosis. Of the 25 grafts, five failed, and 20 were successful. All grafts with the string sign had been bypassed for target coronary arteries with the gray-zone FFR value (0.75-0.80). No difference in graft flow was observed between the failed and successful grafts. Patients with graft failure had no postoperative myocardial ischemia in target areas despite graft condition.

Conclusion: Internal thoracic artery graft for coronary arteries with the gray-zone FFR value may exhibit the string phenomenon. We believe that graft failure occurred because the target area had no ischemia before CABG. FFR is useful in pre-operative ischemic evaluation including scintigraphy and will influence the success of revascularization, including the selection of grafts.
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http://dx.doi.org/10.1007/s11748-021-01608-2DOI Listing
March 2021

Prophylactic use of vacuum-assisted closure system for cannula sites: A case of extracorporeal biventricular assist devices for 295 days.

Int J Artif Organs 2021 Feb 2:391398821991156. Epub 2021 Feb 2.

Department of Cardiovascular Surgery, Fujita Health University School of Medicine, Toyoake, Japan.

We report wound management using a vacuum-assisted closure (VAC) system for the cannula sites of extracorporeal biventricular assist devices (BiVADs) for 295 days in a 23-year old Chinese female patient with fulminant giant cell myocarditis, who finally underwent heart transplantation. When the cannula sites appeared necrotic 3 months after BiVADs placement, she received negative pressure wound therapy prophylactically for four cannula sites, using a VAC system for 3 months, followed by no infections. Such prophylactic VAC therapy, using the skin barrier paste usually used for the ostomy pouching system to create a flatter surface and airtightness, may be useful to avoid cannula site infections, which is still a fatal complication causing sepsis, especially in patients with extracorporeal BiVADs.
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http://dx.doi.org/10.1177/0391398821991156DOI Listing
February 2021

Elevated Urinary Titin and its Associated Clinical Outcomes after Acute Stroke.

J Stroke Cerebrovasc Dis 2021 Mar 24;30(3):105561. Epub 2020 Dec 24.

Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University, 2-50-1 Kuramoto, Tokushima 770-8503, Japan.

Introduction: Urinary titin is a biomarker of muscle atrophy, which is a serious complication after stroke. However, there are currently no clinical data regarding urinary titin in stroke patients.

Methods: Consecutive stroke patients admitted to the stroke care unit were included. Spot urine samples were collected immediately after admission, and on days 3, 5, and 7. The primary outcome was the trend of urinary titin in patients after acute stroke. The secondary outcomes included the association between the peak urinary titin level and the modified Rankin Scale (mRS) score, the National Institutes of Health Stroke Scale (NIHSS) score, and the Barthel index (BI) upon hospital discharge. Multivariate analysis was adjusted for age, sex, NIHSS at admission, and the peak urinary titin to predict poor outcome (mRS 3-6).

Results: Forty-one patients were included (29 male; age, 68 ± 15 years), 29 had ischemic stroke, 8 had intracerebral hemorrhage, and 4 had subarachnoid hemorrhage. The levels of urinary titin on days 1, 3, 5, and 7 were 9.9 (4.7-21.1), 16.2 (8.6-22.0), 8.9 (4.8-15.2), and 8.7 (3.6-16.2) pmol/mg Cr, respectively. The peak urinary titin level was associated with the mRS score (r = 0.55, p < 0.01), the NIHSS score (r = 0.72, p < 0.01), and the BI (r = -0.59, p < 0.01) upon hospital discharge. In multivariate analysis, the peak urinary titin was associated with poor outcome (p = 0.03).

Conclusions: Urinary titin rapidly increased after stroke and was associated with impaired functional outcomes at hospital discharge.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105561DOI Listing
March 2021

Factors associated with DWI-ASPECTS score in patients with acute ischemic stroke due to cerebral large vessel occlusion.

Clin Neurol Neurosurg 2020 12 16;199:106316. Epub 2020 Oct 16.

Department of Neurosurgery, Tokushima University, Tokushima, Japan; Department of Advanced Brain Research, Tokushima University, Tokushima, Japan. Electronic address:

Background: The Alberta Stroke Program Early CT score (ASPECTS) of patients with acute ischemic stroke at the time of admission varies. It is crucial to select appropriate methods of treatment, such as recombinant tissue-plasminogen activator, and/or endovascular thrombectomy. According to the recent guidelines, endovascular thrombectomy for patients with large vessel occlusion (LVO) and lesion of ischemic tissue that was not yet infarcted is effective. This result demonstrates the importance of patient selection based on neuroradiological imaging. However, there are many patients who are judged as ineligibility for recanalization therapy because of presence of large ischemic core, indicating unfavorable ASPECTS, at the time of admission. We investigated the factors associated with favorable diffusion-weighted image (DWI)-ASPECTS score at the time of admission.

Methods: We studies patients with LVO within 24 h from onset who were admitted into our hospital. We divided them into two groups, with favorable DWI-ASPECTS (≥6), and unfavorable DWI-ASPECTS (<6) at the time of admission. We investigated factors associated with favorable DWI-ASPECTS by evaluation of our patients' severity of clinical symptom, etiology, and radiological findings.

Results: This study showed that mild white matter lesion (Fazekas scale ≤1), absence of internal carotid artery (ICA) occlusion and cardioembolic stroke were independent factor of favorable DWI-ASPECTS at the time of admission. (odds ratio 12.92, p <  0.001, odds ratio 0.31, p =  0.001, odds ratio 0.16, p = 0.001, respectively) CONCLUSIONS: Absence of severe white matter lesion, cardioembolic stroke, and ICA occlusion might be associated with favorable DWI-ASPECTS at the time of admission.
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http://dx.doi.org/10.1016/j.clineuro.2020.106316DOI Listing
December 2020

Changes in treatment strategy over time for arteriovenous malformation in a Japanese high-volume center.

BMC Neurol 2020 Nov 5;20(1):404. Epub 2020 Nov 5.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Despite rapid developments in devices used to treat arteriovenous malformation (AVM), a randomised trial of Unruptured Brain Arteriovenous malformations published in 2014 recommended conservative treatment for nonhemorrhagic AVM. The purpose of the current retrospective study was to confirm how AVM treatment in Japan has changed and to assess the safety of treatment for hemorrhagic and nonhemorrhagic AVMs.

Methods: We enrolled 242 consecutive patients with AVM; each patient's treatment was selected and performed at our hospital. The type of onset, Spetzler-Martin (S-M) grade, age, sex, selected treatment, mortality, and morbidity were compared between the first and second periods of our study.

Results: In patients with grade I-III AVM, the selected treatment changed between the first and second periods; however, in grade IV and V patients, the selected treatment did not change. Overall, interventions by microsurgery alone decreased (p < 0.001), the proportion of total treatments including microsurgery decreased (p = 0.005), interventions using stereotactic radiosurgery (SRS) alone increased (p = 0.009), and interventions including SRS increased (p = 0.002). Morbidity associated with intervention was 0.92% in the first period and 0% in the second period, and mortality was 0.92% in the first period and 1.67% in the second.

Conclusions: With the development of new devices, the selected treatment was changed in patients with S-M grade I-III AVM, but was not changed in patients with grade IV and V. The complication rate was low and did not change throughout the periods. These findings suggest that the safety of treatment depends on a full understanding of device development and the selection of proper treatment, not on hemorrhagic onset. Further treatment innovations are expected to change the treatment for grade IV and V AVMs.
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http://dx.doi.org/10.1186/s12883-020-01987-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643271PMC
November 2020

Cardiogenic cerebral embolism caused by a severe hypoglycemic attack : a case report.

J Med Invest 2020 ;67(3.4):362-364

Department of Neurosurgery, Kawasaki medical school hopsptal, Okayama, Japan.

The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 : 362-364, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.362DOI Listing
January 2020

Basic research and surgical techniques for brain arteriovenous malformations.

J Med Invest 2020 ;67(3.4):222-228

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler-Martin grade AVMs with low morbidity. J. Med. Invest. 67 : 222-228, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.222DOI Listing
January 2020

Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma.

Sci Rep 2020 09 17;10(1):15286. Epub 2020 Sep 17.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.

Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin stem cells, CD16 or CD163 macrophages and Iba-1 microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects.
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http://dx.doi.org/10.1038/s41598-020-71857-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499211PMC
September 2020

Can Pallidal Deep Brain Stimulation Rescue Borderline Dystonia? Possible Coexistence of Functional (Psychogenic) and Organic Components.

Brain Sci 2020 Sep 15;10(9). Epub 2020 Sep 15.

Parkinson's Disease and Dystonia Research Center, Tokushima University Hospital, Tokushima 770-8503, Japan.

The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.
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http://dx.doi.org/10.3390/brainsci10090636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563555PMC
September 2020

Clinical Outcome and Intraoperative Neurophysiology of the Lance-Adams Syndrome Treated with Bilateral Deep Brain Stimulation of the Globus Pallidus Internus: A Case Report and Review of the Literature.

Stereotact Funct Neurosurg 2020 7;98(6):399-403. Epub 2020 Sep 7.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Background: The Lance-Adams syndrome (LAS) is a myoclonus syndrome caused by hypoxic-ischemic encephalopathy. LAS cases could be refractory to first-line medications, and the neuronal mechanism underlying LAS pathology remains unknown.

Objectives: To describe a patient with LAS who underwent bilateral globus pallidus internus (GPi) stimulation and discuss the pathophysiology of LAS with intraoperative electrophysiological findings.

Patients: A 79-year-old woman presented with a history of cardiopulmonary arrest due to internal carotid artery rupture following carotid endarterectomy after successful cardiopulmonary resuscitation. However, within 1 month, the patient developed sensory stimulation-induced myoclonus in her face and extremities. Because her myoclonic symptoms were refractory to pharmacotherapy, deep brain stimulation of the GPi was performed 1 year after the hypoxic attack.

Results: Continuous bilateral GPi stimulation with optimal parameter settings remarkably improved the patient's myoclonic symptoms. At the 2-year follow-up, her Unified Myoclonus Rating Scale score decreased from 90 to 24. In addition, we observed burst firing and interburst pause patterns on intraoperative microelectrode recordings of the bilateral GPi and stimulated this area as the therapeutic target.

Conclusion: Our results show that impairment in the basal ganglion circuitry might be involved in the pathogenesis of myoclonus in patients with LAS.
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http://dx.doi.org/10.1159/000509318DOI Listing
May 2021

Downregulation of PD-L1 via FKBP5 by celecoxib augments antitumor effects of PD-1 blockade in a malignant glioma model.

Neurooncol Adv 2020 Jan-Dec;2(1):vdz058. Epub 2019 Dec 26.

Department of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Background: Antitumor therapies targeting programmed cell death-1 (PD-1) or its ligand-1 (PD-L1) are used in various cancers. However, in glioblastoma (GBM), the expression of PD-L1 varies between patients, and the relationship between this variation and the efficacy of anti-PD-1 antibody therapy remains unclear. High expression levels of PD-L1 affect the proliferation and invasiveness of GBM cells. As COX-2 modulates PD-L1 expression in cancer cells, we tested the hypothesis that the COX-2 inhibitor celecoxib potentiates anti-PD-1 antibody treatment via the downregulation of PD-L1.

Methods: Six-week-old male C57BL/6 mice injected with murine glioma stem cells (GSCs) were randomly divided into four groups treated with vehicle, celecoxib, anti-PD-1 antibody, or celecoxib plus anti-PD-1 antibody and the antitumor effects of these treatments were assessed. To verify the mechanisms underlying these effects, murine GSCs and human GBM cells were studied in vitro.

Results: Compared with that with each single treatment, the combination of celecoxib and anti-PD-1 antibody treatment significantly decreased tumor volume and prolonged survival. The high expression of PD-L1 was decreased by celecoxib in the glioma model injected with murine GSCs, cultured murine GSCs, and cultured human GBM cells. This reduction was associated with post-transcriptional regulation of the co-chaperone FK506-binding protein 5 (FKBP5).

Conclusions: Combination therapy with anti-PD-1 antibody plus celecoxib might be a promising therapeutic strategy to target PD-L1 in glioblastoma. The downregulation of highly-expressed PD-L1 via FKBP5, induced by celecoxib, could play a role in its antitumor effects.
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http://dx.doi.org/10.1093/noajnl/vdz058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212915PMC
December 2019

High White Blood Cell Count Is a Risk Factor for Contrast-Induced Nephropathy following Mechanical Thrombectomy for Acute Ischemic Stroke.

Cerebrovasc Dis Extra 2020 1;10(2):59-65. Epub 2020 Jul 1.

Department of Neurology, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Background: Although mechanical thrombectomy is a standard endovascular therapy for patients with acute ischemic stroke (AIS), the incidence of and risk factors for contrast-induced nephropathy (CIN) following mechanical thrombectomy are infrequently reported.

Objectives: The aim of this study was to investigate the incidence and risk factors for CIN following mechanical thrombectomy for AIS, and whether the incidence of CIN is related to a poor prognosis.

Methods: We examined consecutive patients who underwent a mechanical thrombectomy in the period from January 2014 to March 2018. The patients' clinical backgrounds, treatments, and clinical prognoses were analyzed. CIN was defined as an increase in the serum creatinine level of ≥44.2 μmol/L (0.5 mg/dL) or 25% above baseline within 72 h after exposure to the contrast medium.

Results: In total, 80 patients (46 men and 34 women aged 74.5 ± 11.5 years) who met our inclusion criteria were analyzed. CIN occurred in 8.8% (7/80) of the patients following mechanical thrombectomy. Although no patients needed permanent dialysis, 1 required temporary dialysis. The median amount of contrast medium was 109 mL. A comparison between the groups with and without CIN showed a significant difference in white blood cell (WBC) count at the time of admission (11.6 ± 2.7 × 103/μL and 8.1 ± 2.7 × 103/μL; p < 0.01) and the cut-off value was 9.70 × 103/μL. In multivariate analysis, contrast volume/estimated glomerular filtration rate by creatinine and WBC count were significantly associated with the incidence of CIN, with odds ratios of 1.64 (95% CI 1.02-2.65; p = 0.04) and 1.61 (95% CI 1.15-2.25; p < 0.01), respectively.

Conclusions: This study found that CIN occurred in 8.8% of patients with AIS following mechanical thrombectomy. High WBC count was associated with an increased risk of CIN and may be helpful for predicting CIN.
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http://dx.doi.org/10.1159/000507918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383160PMC
September 2020

Relation of Fractional Flow Reserve With Transit Time Coronary Artery Bypass Graft Flow Measurement.

Ann Thorac Surg 2021 01 10;111(1):134-140. Epub 2020 Jun 10.

Department of Cardiovascular Surgery, Fujita Health University School of Medicine Toyoake, Aichi, Japan.

Background: Transit-time flow measurement (TTFM) is frequently used for intraoperative graft flow analysis during coronary artery bypass grafting (CABG). Although the TTFM results may be influenced by fractional flow reserve (FFR) of the target coronary artery as a determinant of coronary lesion-specific ischemia, the data have been limited.

Methods: We retrospectively investigated the relationships between the intraoperative TTFM variables and preoperative FFR values of the target coronary arteries in 40 in situ left internal thoracic artery (LITA) grafts to the left anterior descending artery (LAD), which were revealed to be patent on postoperative computed tomographic angiography.

Results: The Spearman correlation coefficients of the TTFM variables with FFR were maximum flow, -0.12 (P = .301); minimum flow (Qmin), -0.43 (P = .004); mean flow (Qm), -0.30 (P = .036); pulsatility index, 0.37 (P = .012); diastolic filling, -0.36 (P = .012); percentage insufficiency, 0.45 (P = .002); and fast Fourier transform (FFT) ratio, -0.07 (P = .329). While Min and Qm showed significant negative correlation, the pulsatility index and percentage insufficiency showed significant positive correlation with FFR.

Conclusions: Most TTFM variables, including Qm, of the LITA graft to the LAD during CABG are strongly affected by preoperative FFR values. Because the FFT ratio is not influenced by FFR, FFT analysis of the TTFM may be recommend in the case of the in situ LITA graft to the LAD with moderate stenosis with a higher FFR exceeding 0.75.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.100DOI Listing
January 2021

Efficacy of intraarterial superselective indocyanine green videoangiography in cerebral arteriovenous malformation surgery in a hybrid operating room.

J Neurosurg 2020 May 22:1-9. Epub 2020 May 22.

1Department of Neurosurgery, Tokushima University Hospital, Tokushima.

Objective: Although intravenous indocyanine green (ICG) videoangiography has been reported to be useful when applied to cerebral arteriovenous malformation (AVM) surgery, the ICG that remains after the procedure makes it difficult to understand the anatomy, to evaluate nidus blood flow changes, and to repeat ICG videoangiography within a short time. Intraarterial ICG videoangiography has emerged as a way to overcome these limitations. The current study presents the results of intraarterial ICG videoangiography undertaken in patients with cerebral AVMs.

Methods: Intraarterial ICG videoangiography was performed in 13 patients with cerebral AVMs. Routine intraoperative digital subtraction angiography at the authors' institution is performed in a hybrid operating room during AVM surgery and includes the added step of injecting ICG to the contrast medium that is administered through a catheter.

Results: Predissection studies were able to visualize the feeder in 12 of 13 cases. The nidus was visualized in 12 of 13 cases, while the drainer was visualized in all cases. After total dissection of the nidus, there was no ICG filling in the drainers found in any of the cases. Washout of the ICG took 4.4 ± 1.3 seconds in the feeders, 9.2 ± 3.5 seconds in the drainers, and 20.9 ± 3.4 seconds in all of the vessels. Nidus flow reduction was confirmed during dissection in 9 of 9 cases. Flow reduction was easy to recognize due to each span being very short. Color-encoded visualization and objective data obtained by Flow 800 analysis reinforced these findings.

Conclusions: The results showed that intraarterial ICG videoangiography was more useful than intravenous ICG videoangiography in cerebral AVM surgery. This was especially effective in the identification of the feeder, nidus, and drainer and in the assessment of the flow dynamics of the nidus. Use of Flow 800 made it simpler and easier to evaluate these findings.
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http://dx.doi.org/10.3171/2020.3.JNS20319DOI Listing
May 2020

Temporal crescent syndrome caused by a lateral ventricular glioependymal cyst: case report.

J Neurosurg Pediatr 2020 May 15:1-5. Epub 2020 May 15.

1Department of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima.

Temporal crescent syndrome is a monocular visual field defect involving the temporal crescent of one eye caused by a retrochiasmal lesion. The most anterior portion of the striate cortex is the only area where the retrochiasmal lesion produces a monocular visual field defect. The authors present the case of a 9-year-old boy who presented with mild headache. MRI revealed a cyst with cerebrospinal fluid signal intensity, occupying the body and trigone of the right lateral ventricle. Conservative treatment with regular clinical and radiological follow-up was chosen because neurological examination findings were normal. Three years later, the patient experienced blurred vision with a temporal crescent defect in the left eye. Endoscopic cyst fenestration was performed, and the pathological findings indicated a glioependymal cyst. After surgery, the monocular temporal crescent disorder was resolved. MRI indicated shrinkage of the cyst and improvement in the narrowing of the anterior calcarine sulcus. These findings suggested that the temporal crescent syndrome was caused by a lateral ventricular glioependymal cyst. This is the first known report of temporal crescent syndrome caused by a lateral ventricular glioependymal cyst. In patients with monocular temporal crescent disorder without intraocular disease, a retrochiasmal lesion in the most anterior portion of the striate cortex should be considered.
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http://dx.doi.org/10.3171/2020.3.PEDS2021DOI Listing
May 2020

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Stroke 2020 05 6;51(5):1530-1538. Epub 2020 Apr 6.

Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya (S. Yoshimura).

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; >0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.
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http://dx.doi.org/10.1161/STROKEAHA.119.028127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185058PMC
May 2020

Cerebral Venous Thrombosis: An Unexpected Complication with Cerebrospinal Fluid Leaks after a Fall in a Patient with Spinocerebellar Ataxia Type 6.

Intern Med 2020 Jul 2;59(14):1749-1753. Epub 2020 Apr 2.

Department of Neurology, University of Tokushima Graduate School of Biomedical Sciences, Japan.

A 65-year-old woman with spinocerebellar ataxia presented with generalized seizures due to subcortical hemorrhaging. Magnetic resonance imaging (MRI) revealed obstruction of the superior sagittal sinus. Despite treatment, she became comatose. MRI newly revealed subdural fluid collection and descent of the brainstem. Her history indicated a recent fall, prompting additional studies, which revealed lumbar fracture and cerebrospinal fluid (CSF) leaks. We performed an epidural blood patch, and her consciousness was fully restored in one month. This is the first report of cerebral venous thrombosis with CSF leaks in the lumbar region due to a fall injury.
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http://dx.doi.org/10.2169/internalmedicine.4388-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434543PMC
July 2020

Action observation treatment improves gait ability in subacute to convalescent stroke patients.

J Clin Neurosci 2020 May 28;75:55-61. Epub 2020 Mar 28.

Yoshinogawa Hospital, Itano-gun, Japan.

The aim of this study was to investigate the effects of action observation treatment (AOT) on gait ability in patients with subacute to convalescent stroke. Sixteen patients with subacute stroke were divided into a control group (n = 8) and AOT group (n = 8) when admitted to the convalescent ward. The control group received a conventional rehabilitation only. In addition to conventional rehabilitation, the AOT received AOT for 3 months (30 min per day 5 times per week). The AOT involved observing the action of another subject in a comfortable gait situation from the front, sides, and back via video and conducting the actual action. All participants were assessed during the main-assessment period, which included a baseline (i.e., when admitted to the convalescent ward) and 1, 2, and 3 months after baseline. The sub-assessment period at 2 and 3 months after baseline was conducted with participants who could walk independently. The main outcomes of the main-assessment and sub-assessment periods were Functional Ambulation Classification (FAC) and the 10-m walk test (10MWT), respectively. With respect to the FAC, we used a split plot design analysis of covariance to test the interaction between assessment time and group. There was no significant interaction between assessment time and group in FAC. However, a significant improvement of the 10MWT in the sub-assessment period was observed in the AOT group, but not the control group. Our results indicate that AOT may be an effective therapy for patients with subacute to convalescent stroke who can walk independently.
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http://dx.doi.org/10.1016/j.jocn.2020.03.031DOI Listing
May 2020

A Juvenile Case of Bow Hunter's Syndrome Caused by Atlantoaxial Dislocation with Vertebral Artery Dissecting Aneurysm.

World Neurosurg 2020 05 14;137:393-397. Epub 2020 Feb 14.

Department of Neurosurgery, Tokushima University, Tokushima, Japan.

Background: Bow hunter's syndrome (BHS) is caused by posterior circulation insufficiency that results from the occlusion or compression of the vertebral artery (VA) during neck rotation. Owing to its rarity, there is no guideline to support the decision of selecting a conservative or a surgical approach. Management of BHS is dependent on each patient.

Case Description: A 13-year-old girl presented with transient visual disturbance, hypoesthesia, and paralysis of the left side of the body. Magnetic resonance imaging revealed an acute cerebral infarction in the right thalamus, and magnetic resonance angiography demonstrated occlusion of the right posterior cerebral artery and dilation of V3 of the left VA. Digital subtraction angiography revealed a left VA dissecting aneurysm at V3 and left VA occlusion at the level of C1-C2 during neck rotation to the right. A dynamic x-ray suggested atlantoaxial joint instability, and three-dimensional computed tomography revealed aplasia of C1 lamina and atlantoaxial rotatory dislocation. BHS with left VA dissecting aneurysm caused by atlantoaxial rotatory dislocation was diagnosed. We performed C1-C2 posterior fusion by the Goel-Harms technique. Stroke did not recur, and computed tomography angiography obtained 8 months postoperatively demonstrated a decrease in the dissecting aneurysm.

Conclusions: To our knowledge, this is the first case of BHS with VA dissecting aneurysm and aplasia of C1 lamina. Based on this case, we suggest that C1-C2 posterior fusion is effective for BHS with VA dissecting aneurysm.
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http://dx.doi.org/10.1016/j.wneu.2020.02.041DOI Listing
May 2020

Clostridium septicum-infected Stanford type A acute aortic dissection: a case report.

Surg Case Rep 2020 Jan 16;6(1):23. Epub 2020 Jan 16.

Department of Cardiovascular Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Toyoake, 470-1192, Japan.

Background: Thoracic aortitis caused by Clostridium septicum is a rare infection with a strong association with malignancy and high mortality rate when left untreated. We report a case of surgical treatment for Stanford type A acute aortic dissection in a patient with C. septicum sepsis and thoracic aortitis.

Case Presentation: A 63-year-old hypertensive man with rheumatoid arthritis presented with general malaise and diagnosed with C. septicum-infected aortitis with sepsis. On the 5th day of hospitalization, Stanford type A acute aortic dissection developed with severe aortic regurgitation. The patient underwent emergent surgical treatment successfully with excision of the infected ascending aorta and aortic root followed by replacement using a composite graft, followed by diagnosis of sigmoid colon cancer 7 months after aortic surgery. He was scheduled to undergo elective colon surgery.

Conclusions: C. septicum aortitis can progress quickly, causing aneurysm or dissection. Therefore, in a patient with C. septicum aortitis, prompt surgical in situ graft replacement should be performed to debride the infected vascular lesions. Further investigations for gastrointestinal and hematological malignancies as a source of C. septicum should be also conducted.
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http://dx.doi.org/10.1186/s40792-020-0770-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965561PMC
January 2020

Active Cancer and Elevated D-Dimer Are Risk Factors for In-Hospital Ischemic Stroke.

Cerebrovasc Dis Extra 2019 22;9(3):129-138. Epub 2019 Nov 22.

Department of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Background And Purpose: Little attention has been paid to the pathogenesis of in-hospital stroke, despite poor outcomes and a longer time from stroke onset to treatment. We studied the pathophysiology and biomarkers for detecting patients who progress to in-hospital ischemic stroke (IHS).

Methods: Seventy-nine patients with IHS were sequentially recruited in the period 2011-2017. Their characteristics, care, and outcomes were compared with 933 patients who had an out-of-hospital ischemic stroke (OHS) using a prospectively collected database of the Tokushima University Stroke Registry.

Results: Active cancer and coronary artery disease were more prevalent in patients with IHS than in those with OHS (53.2 and 27.8% vs. 2.0 and 10.9%, respectively; p < 0.001), the median onset-to-evaluation time was longer (300 vs. 240 min; p = 0.015), and the undetermined etiology was significantly higher (36.7 vs. 2.4%; p < 0.001). Although there was no significant difference in stroke severity at onset between the groups, patients with IHS had higher modified Rankin Scale (mRS) scores (3-6) at discharge (67.1 vs. 50.3%; p = 0.004) and rates of death during hospitalization (16.5 vs. 2.9%; p < 0.001). D-dimer (5.8 vs. 0.8 µg/mL; p < 0.001) and fibrinogen (532 vs. 430 mg/dL; p = 0.014) plasma levels at the time of onset were significantly higher in patients with IHS after propensity score matching. Multivariate logistic regression analysis revealed that active cancer (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.26-4.20), prestroke mRS scores 3-5 (OR 6.78; 95% CI 3.96-11.61), female sex (OR 1.57; 95% CI 1.19-2.08), and age ≥75 years (OR 2.36; 95% CI 1.80-3.08) were associated with poor outcomes.

Conclusions: Patients with IHS had poorer outcomes than those with OHS because of a higher prevalence of active cancer and functional dependence before stroke onset. Elevated plasma levels of D-dimer and fibrinogen, especially with active cancer, can help identify patients who are at a higher risk of progression to IHS.
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http://dx.doi.org/10.1159/000504163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940458PMC
May 2020

Metastatic tumor to the orbital cavity from a primary carcinoma of the uterine cervix : a case report.

J Med Invest 2019 ;66(3.4):355-357

Department of Neurosurgery, Institute of Health Biosciences, the University of Tokushima, Japan.

Metastatic tumors to the orbit of the eye, especially from primary carcinomas of the uterine cervix are very rare. A 64-year-old woman with a history of carcinoma of the uterine cervix presented with right eye pain and blepharoptosis for 2 weeks. Magnetic resonance imaging revealed a mass at the right orbital apex. Surgical extirpation was performed due to severe pain. Postoperative pathology demonstrated a poorly differentiated squamous cell carcinoma. The origin was ultimately considered to be the carcinoma of the uterine cervix. In conclusion, this report describes a rare case of a metastatic tumor at the orbital apex derived from the cervix of the uterus. J. Med. Invest. 66 : 355-357, August, 2019.
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http://dx.doi.org/10.2152/jmi.66.355DOI Listing
June 2020

The risk of hemorrhage in stereotactic biopsy for brain tumors.

J Med Invest 2019 ;66(3.4):314-318

Department of Neurosurgery, Institute of Biomedical Sciences Tokushima University Graduate School, Tokushima, Japan.

Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy. J. Med. Invest. 66 : 314-318, August, 2019.
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http://dx.doi.org/10.2152/jmi.66.314DOI Listing
June 2020

Time-dependent and site-dependent morphological changes in rupture-prone arteries: ovariectomized rat intracranial aneurysm model.

J Neurosurg 2019 Sep 13:1-9. Epub 2019 Sep 13.

Objective: The pathogenesis of intracranial aneurysm rupture remains unclear. Because it is difficult to study the time course of human aneurysms and most unruptured aneurysms are stable, animal models are used to investigate the characteristics of intracranial aneurysms. The authors have newly established a rat intracranial aneurysm rupture model that features site-specific ruptured and unruptured aneurysms. In the present study the authors examined the time course of changes in the vascular morphology to clarify the mechanisms leading to rupture.

Methods: Ten-week-old female Sprague-Dawley rats were subjected to hemodynamic changes, hypertension, and ovariectomy. Morphological changes in rupture-prone intracranial arteries were examined under a scanning electron microscope and the association with vascular degradation molecules was investigated.

Results: At 2-6 weeks after aneurysm induction, morphological changes and rupture were mainly observed at the posterior cerebral artery; at 7-12 weeks they were seen at the anterior Willis circle including the anterior communicating artery. No aneurysms at the anterior cerebral artery-olfactory artery bifurcation ruptured, suggesting that the inception of morphological changes is site dependent. On week 6, the messenger RNA level of matrix metalloproteinase-9, interleukin-1β, and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of metalloproteinase-2 was significantly higher at the posterior cerebral artery, but not at the anterior communicating artery, of rats with aneurysms than in sham-operated rats. These findings suggest that aneurysm rupture is attributable to significant morphological changes and an increase in degradation molecules.

Conclusions: Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysms to rupture.
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http://dx.doi.org/10.3171/2019.6.JNS19777DOI Listing
September 2019