Publications by authors named "Keisuke Suzuki"

410 Publications

Current Update on Clinically Relevant Sleep Issues in Parkinson's Disease: A Narrative Review.

Authors:
Keisuke Suzuki

J Parkinsons Dis 2021 Apr 21. Epub 2021 Apr 21.

Department of Neurology, Dokkyo Medical University, Shimotsuga, Tochigi, Japan.

Sleep disturbances are among the common nonmotor symptoms in patients with Parkinson's disease (PD). Sleep can be disrupted by nocturnal motor and nonmotor symptoms and other comorbid sleep disorders. Rapid eye movement sleep behavior disorder (RBD) causes sleep-related injury, has important clinical implications as a harbinger of PD and predicts a progressive clinical phenotype. Restless legs syndrome (RLS) and its related symptoms can impair sleep initiation. Excessive daytime sleepiness (EDS) is a refractory problem affecting patients' daytime activities. In particular, during the COVID-19 era, special attention should be paid to monitoring sleep problems, as infection-prevention procedures for COVID-19 can affect patients' motor symptoms, psychiatric symptoms and sleep. Therefore, screening for and managing sleep problems is important in clinical practice, and the maintenance of good sleep conditions may improve the quality of life of PD patients. This narrative review focused on the literature published in the past 10 years, providing a current update of various sleep disturbances in PD patients and their management, including RBD, RLS, EDS, sleep apnea and circadian abnormalities.
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http://dx.doi.org/10.3233/JPD-202425DOI Listing
April 2021

Adult-onset Alexander disease mimicking multiple system atrophy predominant cerebellar ataxia.

J Clin Neurosci 2021 May 23;87:150-152. Epub 2021 Mar 23.

Department of Neurology, Dokkyo Medical University, Tochigi, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jocn.2021.03.001DOI Listing
May 2021

A novel mouse model of heatstroke accounting for ambient temperature and relative humidity.

J Intensive Care 2021 Apr 16;9(1):35. Epub 2021 Apr 16.

Department of Emergency, Critical Care and Disaster Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

Background: Heatstroke is associated with exposure to high ambient temperature (AT) and relative humidity (RH), and an increased risk of organ damage or death. Previously proposed animal models of heatstroke disregard the impact of RH. Therefore, we aimed to establish and validate an animal model of heatstroke considering RH. To validate our model, we also examined the effect of hydration and investigated gene expression of cotransporter proteins in the intestinal membranes after heat exposure.

Methods: Mildly dehydrated adult male C57/BL6J mice were subjected to three AT conditions (37 °C, 41 °C, or 43 °C) at RH > 99% and monitored with WetBulb globe temperature (WBGT) for 1 h. The survival rate, body weight, core body temperature, blood parameters, and histologically confirmed tissue damage were evaluated to establish a mouse heatstroke model. Then, the mice received no treatment, water, or oral rehydration solution (ORS) before and after heat exposure; subsequent organ damage was compared using our model. Thereafter, we investigated cotransporter protein gene expressions in the intestinal membranes of mice that received no treatment, water, or ORS.

Results: The survival rates of mice exposed to ATs of 37 °C, 41 °C, and 43 °C were 100%, 83.3%, and 0%, respectively. From this result, we excluded AT43. Mice in the AT 41 °C group appeared to be more dehydrated than those in the AT 37 °C group. WBGT in the AT 41 °C group was > 44 °C; core body temperature in this group reached 41.3 ± 0.08 °C during heat exposure and decreased to 34.0 ± 0.18 °C, returning to baseline after 8 h which showed a biphasic thermal dysregulation response. The AT 41 °C group presented with greater hepatic, renal, and musculoskeletal damage than did the other groups. The impact of ORS on recovery was greater than that of water or no treatment. The administration of ORS with heat exposure increased cotransporter gene expression in the intestines and reduced heatstroke-related damage.

Conclusions: We developed a novel mouse heatstroke model that considered AT and RH. We found that ORS administration improved inadequate circulation and reduced tissue injury by increasing cotransporter gene expression in the intestines.
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http://dx.doi.org/10.1186/s40560-021-00546-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052643PMC
April 2021

A new method of primary engineering of esophagus using orthotopic in-body tissue architecture.

J Pediatr Surg 2021 Mar 26. Epub 2021 Mar 26.

Biotube Co., Ltd, Osaka, Japan.

Purpose: Tissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect.

Method: The cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis.

Results: Postoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin.

Conclusion: Orthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.03.025DOI Listing
March 2021

Hypovolemic shock induced by a large chest wall hematoma caused by a single rib fracture in an elderly patient.

Trauma Case Rep 2021 Apr 17;32:100459. Epub 2021 Mar 17.

Department of Emergency and Disaster Medicine, Showa University.

Displaced rib fractures can injure intercostal vessels leading to chest wall hematomas. As the bleeding occurs within the vessel, compression of the vessel wall helps in preventing further bleeding. Therefore, chest wall hematomas rarely result in shock. A thin 78-year-old man transferred to the emergency department with complaints of left dorsal pain due to an injury. He had a history of hypertension and aorta dissection. He arrived at the ED in a state of shock and presented with a large left dorsal wall mass. Subsequent imaging using computed tomography angiography revealed a large hyperdense hematoma at the left dorsal-flank wall along with rib fracture (11th intercostal artery). Moreover, a large fusiform aneurysm was detected from the abdominal aorta to the iliac arteries. Extravasation of the contrast agent was detected at the branch of the 11th intercostal artery, and hence, embolization was performed. The dermis, which comprises collagen and elastin fibers, plays an important role in vessel compression to prevent bleeding. The aortic media also comprises collagen and elastin fibers. Cell turnover, loss of collagen, and excessive elastolysis are associated with the formation of abdominal aortic aneurysms. The systemic degeneration of connecting tissue (collagen and elastin fiber) appears to be progress in patients with an aortic aneurysms and history of aortic dissection compared with other healthy older individuals. Physicians should be cognizant of the potential unexpected large hematoma complications if a risk of systemic connecting tissue degradation exists, as seen in patients with aortic aneurysm or aortic dissection.
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http://dx.doi.org/10.1016/j.tcr.2021.100459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010857PMC
April 2021

The relationship between changes in deoxy Hb and body composition before and after cycling exercise during unilateral lower extremity occlusion.

J Phys Ther Sci 2021 Mar 17;33(3):199-202. Epub 2021 Mar 17.

Department of Physical Therapy, School of Health Sciences at Odawara, International University of Health and Welfare: 1-2-25 Shiroyama, Odawara-city, Kanagawa 250-8588, Japan.

[Purpose] To clarify the relationship between changes in deoxygenated hemoglobin level due to cycling exercise and body composition in healthy participants with unilateral lower-limb obstruction. [Participants and Methods] The height, weight, body mass index, and body composition (skeletal muscle mass, body water content, and body fat percentage) of nine healthy males were measured along with the anaerobic threshold. The protocol consisted of 7 minutes of rest followed by 4 minutes of cycling exercise (anaerobic threshold level) with unilateral lower extremity occlusion. After exercise, ischemia was released, and the participants was allowed rest for 5 minutes. Deoxygenated hemoglobin levels before and after the exercise and the relationship between the level of variation and each index were examined. [Results] Body water content and skeletal muscle mass showed a significant negative correlation with changes in deoxygenated hemoglobin level; however, no correlation was found for the other indices. Body water content and skeletal muscle mass were found to be significantly positively correlated. they showed a significant positive correlation with deoxygenated hemoglobin levels. [Conclusion] Our study indicates that body water content and skeletal muscle mass play a significant role in the recovery of blood flow following exercise.
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http://dx.doi.org/10.1589/jpts.33.199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012192PMC
March 2021

Impact of the COVID-19 Pandemic on the Quality of Life of Patients with Parkinson's Disease and Their Caregivers: A Single-Center Survey in Tochigi Prefecture.

J Parkinsons Dis 2021 Mar 22. Epub 2021 Mar 22.

Department of Neurology, Dokkyo Medical University, Tochigi, Japan.

Background: The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the mental health of the general population.

Objective: We investigated the determinants of quality of life (QOL) in Parkinson's disease (PD) patients during the COVID-19 pandemic.

Methods: Impacts of lifestyle changes due to the COVID-19 pandemic on 100 patients with PD and their caregivers/spouses were assessed. The Hospital Anxiety and Depression Scale was used to assess anxiety and depression. The physical component summary (PCS) and mental component summary (MCS) scores of the short form (SF)-8 were used to evaluate health-related QOL.

Results: Regarding health-related QOL, physical function, role physical, general health, vitality and the PCS score were significantly worse in PD patients than in caregivers. Worsening of PD-related symptoms, increased stress, and decreased physical activity were observed in 29.0%, 37.0% and 44.0% of PD patients, respectively. Sixteen patients (16.0%) experienced problems with hospital access, but none reported medication shortages. Strong concerns about COVID-19 were reported by 47.0% of caregivers and 50.0% of PD patients. In PD patients, increased gait disturbance and rigidity, disease severity, smoking, the levodopa equivalent dose and decreased body weight predicted a worse PCS score; anxiety, depression, female sex, stress and long disease duration predicted a worse MCS score. In caregivers, age and smoking contributed to a worse PCS score; depression, stress and worsening patient mood contributed to a worse MCS score.

Conclusion: We report the negative impacts of the COVID-19 pandemic on health-related QOL and its determinants in PD patients and their caregivers.
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http://dx.doi.org/10.3233/JPD-212560DOI Listing
March 2021

Parkinson's Disease and Headache: Is there a Relevant Relationship?

Headache 2020 07;60(7):1440-1441

Department of Neurology, Dokkyo Medical University, Mibu, Japan.

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http://dx.doi.org/10.1111/head.13867DOI Listing
July 2020

Central Sensitization in Neurological, Psychiatric, and Pain Disorders: A Multicenter Case-Controlled Study.

Pain Res Manag 2021 15;2021:6656917. Epub 2021 Feb 15.

Department of Neurology, Dokkyo Medical University, Mibu, Japan.

Background: The role of central sensitization in refractory pain-related diseases has not yet been clarified.

Methods: We performed a multicenter case-controlled study including 551 patients with various neurological, psychological, and pain disorders and 5,188 healthy controls to investigate the impact of central sensitization in these patients. Symptoms related to central sensitization syndrome (CSS) were assessed by the Central Sensitization Inventory (CSI) parts A and B. Patients were categorized into 5 groups based on CSI-A scores from subclinical to extreme. The Brief Pain Inventory (BPI), addressing pain severity and pain interference with daily activities, and the Patient Health Questionnaire (PHQ)-9, assessing depressive symptoms, were also administered.

Results: CSI-A scores and CSI-B disease numbers were significantly greater in patients than in controls ( < 0.001). Medium effect sizes ( = 0.37) for CSI-A scores and large effect sizes ( = 0.64) for CSI-B disease numbers were found between patients and control groups. Compared with the CSI-A subclinical group, the CSI-A mild, moderate, severe, and extreme groups had significantly higher BPI pain interference and severity scores, PHQ-9 scores, and CSS-related disease numbers based on ANCOVA. Greater CSI-B numbers resulted in higher CSI-A scores ( < 0.001) and a higher odds ratio ( for trend <0.001). CSS-related symptoms were associated with pain severity, pain interference with daily activities, and depressive symptoms in various pain-related diseases.

Conclusions: Our findings suggest that CSS may participate in these conditions as common pathophysiology.
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http://dx.doi.org/10.1155/2021/6656917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902126PMC
February 2021

Associations between probable REM sleep behavior disorder, olfactory disturbance, and clinical symptoms in Parkinson's disease: A multicenter cross-sectional study.

PLoS One 2021 19;16(2):e0247443. Epub 2021 Feb 19.

Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.

Background: Rapid eye movement sleep behavior disorder (RBD) and olfactory dysfunction are useful for early diagnosis of Parkinson's disease (PD). RBD and severe olfactory dysfunction are also regarded as risk factors for cognitive impairment in PD. This study aimed to assess the associations between RBD, olfactory function, and clinical symptoms in patients with PD.

Methods: The participants were 404 patients with non-demented PD. Probable RBD (pRBD) was determined using the Japanese version of the RBD screening questionnaire (RBDSQ-J) and the RBD Single-Question Screen (RBD1Q). Olfactory function was evaluated using the odor identification test for Japanese. Clinical symptoms were evaluated using the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I-IV.

Results: In total, 134 (33.2%) patients indicated a history of pRBD as determined by the RBD1Q and 136 (33.7%) by the RBDSQ-J based on a cutoff value of 6 points. Moreover, 101 patients were diagnosed as pRBD by both questionnaires, 35 by the RBDSQ-J only, and 33 by the RBD1Q only. The MDS-UPDRS parts I-III scores were significantly higher and disease duration significantly longer in the pRBD group. pRBD was significantly associated with male gender and the MDS-UPDRS part I score. The olfactory identification function was significantly reduced in the pRBD group.

Conclusions: About 33% of the patients with PD had pRBD based on the questionnaires, and both motor and non-motor functions were significantly decreased in these patients. These results suggest that more extensive degeneration occurred in patients with non-demented PD with RBD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247443PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894886PMC
February 2021

Relationship between electrical gaps after Maze procedure and atrial tachyarrhythmias and ablation outcomes after cardiac surgery and concomitant Maze procedure.

Heart Vessels 2021 May 13;36(5):675-685. Epub 2021 Feb 13.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Atrial tachycardia (AT) and atrial fibrillation (AF) commonly occur after cardiac surgeries (CSs). This study investigated the mechanisms and long-term outcomes of AT and AF ablation after various Maze procedures, particularly whether atrial tachyarrhythmias after the Maze procedure occur due to gaps in the Maze lines. We analyzed 37 consecutive cases with atrial tachyarrhythmias after the Maze procedures and concomitant CSs between 2007 and 2019. Fifty-nine atrial tachyarrhythmias were induced in 37 consecutive cases, and 49 of those atrial tachyarrhythmias were mappable ATs. Forty ATs were related to the Maze procedures in the 49 mappable ATs (81.6%). All 37 consecutive cases had residual electrical conductions (gaps) in the Maze lines (88 gaps; 2.4 ± 1.2 gaps/patient). Forty of 88 gaps (45.5%) were associated with gap-related ATs. The common ATs in this study were 1. peri-mitral atrial flutter due to gaps at pulmonary vein isolation (PVI) line to mitral valve annulus (MVA) (20 cases), and 2. peri-tricuspid atrial flutter due to gaps at right atrial incision to the tricuspid valve annulus (TVA) (10 cases). Forty-seven of 49 ATs (95.9%) were successfully ablated at the first session, and there were no complications. The mean follow-up period after ablation was 3.6 ± 3.2 (median, 2.1; interquartile range, 0.89-6.84) years. The Kaplan-Meier analysis of freedom from recurrent atrial tachyarrhythmias after Maze procedure was 82.7% at 1-year follow-up and 75.5% at 4-year follow-up after a single procedure. Reentry was the main mechanism of ATs after Maze procedures and concomitant CSs, and ATs were largely related to the gaps on the Maze lines between the PVI line and the MVA or those on the lines between right atrial incision to the TVA. Long-term follow-up data suggest that catheter ablation of atrial tachyarrhythmias after various Maze procedures is effective and safe.
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http://dx.doi.org/10.1007/s00380-020-01737-3DOI Listing
May 2021

Vertebral osteomyelitis as a hidden cause of persistent meningeal irritation in a patient with pneumococcal meningitis: A case report.

Medicine (Baltimore) 2021 Feb;100(6):e24705

Department of Neurology, Dokkyo Medical University, Japan.

Rationale: Pneumococcal meningitis generally develops from bacteremia and is often complicated by multiple organ infection.

Patient Concerns: A 62-year-old man with no previous medical history developed progressive disturbance of consciousness preceded by high-grade fever and headache for a few days.

Diagnosis: The patient was diagnosed with pneumococcal meningitis based on meningeal irritation, polymorphonuclear cell-predominant pleocytosis of the cerebrospinal fluid (CSF) and a positive pneumococcal urinary antigen test at a different hospital. Despite the administration of meropenem and vancomycin, his consciousness worsened, and the patient was transferred to our hospital. Marked nuchal stiffness was noted. The patient showed a disturbance of consciousness, with a Glasgow Coma Scale score of E3V2M5. No significant cranial nerve palsy, motor weakness or sensory impairment was observed. CSF examination showed polynuclear cell-predominant pleocytosis of 755/μL. Transthoracic echocardiography revealed infectious endocarditis.

Interventions: After the detection of penicillin-susceptible Streptococcus pneumoniae, the antibiotic regimen was changed to aminobenzylpenicillin 12 g/d and ceftriaxone 4 g/d, which improved the patient's consciousness and CSF findings. However, marked neck stiffness and neck pain persisted; we performed a systemic investigation that revealed cervical vertebral osteomyelitis and aortic aneurysm.

Outcomes: After surgical treatment, the patient achieved complete remission of both conditions.

Lessons: We should consider vertebral osteomyelitis as a potential complication of meningitis when nuchal stiffness persists despite an improvement in meningitis.
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http://dx.doi.org/10.1097/MD.0000000000024705DOI Listing
February 2021

V180I genetic Creutzfeldt-Jakob disease with cardiac sympathetic nerve denervation masquerading as Parkinson's disease: A case report.

Medicine (Baltimore) 2021 Jan;100(2):e24294

Department of Neurology, Dokkyo Medical University, Japan.

Rationale: Creutzfeldt-Jakob disease (CJD) with a point mutation of valine to isoleucine at codon 180 of the prion protein gene (V180I) is the most frequent form of genetic CJD in Japan. However, peripheral nerve involvement, especially cardiac sympathetic denervation, has not been investigated in cases with V180I genetic CJD.We herein report a genetically confirmed case of V180I genetic CJD presenting with parkinsonism and cardiac sympathetic nerve denervation.

Patient Concerns: The patient was a 79-year-old Japanese woman who presented with subacute progressive gait disturbance and cognitive impairment. Clinical diagnosis of Parkinson's disease (PD) with mild cognitive impairment was initially suspected based on parkinsonism, such as bradykinesia, rigidity and tremor, and reduced accumulation of cardiac meta-iodobenzylguanidine (MIBG) scintigraphy.

Interventions: Based on parkinsonism and impaired cardiac MIBG findings, levodopa/decarboxylase inhibitor was administered up to 300 mg/day; however, her symptoms were not improved.

Outcomes: Her motor and cognitive function progressively deteriorated.

Diagnosis: Although the patient had no family history of CJD, genetic CJD was diagnosed according to extensive hyperintensities in the bilateral cortices on diffusion-weighted magnetic resonance images, positive tau protein and 14-3-3 protein in the cerebrospinal fluid and a V180I mutation with methionine homozygosity at codon 129 by prion protein gene analysis.

Lessons: We should be aware that reduced uptake of cardiac MIBG scintigraphy in patients presenting with parkinsonism cannot confirm a diagnosis of PD. CJD should be considered when patients show a rapid progressive clinical course with atypical manifestations of PD.
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http://dx.doi.org/10.1097/MD.0000000000024294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808525PMC
January 2021

Predictive factors for dental inflammation with exacerbation during cancer therapy with FDG-PET/CT imaging.

Support Care Cancer 2021 Jan 7. Epub 2021 Jan 7.

Department of Oral and Maxillofacial Surgery, and Plastic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma, 371-8511, Japan.

Purpose: Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation.

Methods: We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system.

Results: Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8-19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2-41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT.

Conclusion: Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.
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http://dx.doi.org/10.1007/s00520-020-05909-9DOI Listing
January 2021

Zonisamide effects on sleep problems and depressive symptoms in Parkinson's disease.

Brain Behav 2021 Mar 5;11(3):e02026. Epub 2021 Jan 5.

Department of Neurology, Dokkyo Medical University, Mibu, Japan.

Background: We aimed to evaluate the effect of zonisamide (ZNS) on motor symptoms and nonmotor symptoms such as depressive symptoms and sleep problems in Parkinson's disease (PD) patients with or without tremor.

Methods: We conducted a 3-month, open-label study to assess the effects of ZNS on motor symptoms, depressive symptoms and sleep problems. Twenty levodopa-treated PD patients with motor fluctuation completed the study. Patients received 25-50 mg/day of ZNS and were assessed for the Japanese version of the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I, III, and IV, PD Sleep Scale (PDSS)-2, Beck depression inventory-2 (BDI-II), and PD Questionnaire (PDQ-8) at baseline and after 1, 2 and 3 months of treatment. Patients were categorized into the tremor group and nontremor group to assess changes in clinical parameters.

Results: At 3 months, the scores on the MDS-UPDRS parts I, III and IV significantly improved and off-time reduced compared to baseline. Additionally, the PDSS-2 total score significantly decreased at 3 months. Although there were no significant differences in changes in UPDRS part I, III, or IV between the groups after ZNS treatment, the tremor group had significant improvements in PDSS-2 at 3 months and BDI-II at 1, 2 and 3 months compared with the nontremor group.

Conclusion: We showed the beneficial effects of ZNS on motor symptoms and sleep problems in levodopa-treated PD patients with motor fluctuation. ZNS may be more effective for several nonmotor symptoms in PD patients with tremor compared with those without tremor.
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http://dx.doi.org/10.1002/brb3.2026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994695PMC
March 2021

Current status and management of pancreatic trauma with main pancreatic duct injury: A multicenter nationwide survey in Japan.

J Hepatobiliary Pancreat Sci 2021 Feb 19;28(2):183-191. Epub 2021 Jan 19.

Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Japan.

Background: Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment.

Methods: As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board-certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated.

Results: Sixty-four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0).

Conclusions: Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics.
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http://dx.doi.org/10.1002/jhbp.877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986433PMC
February 2021

A case of macroreentrant atrial tachycardia between a persistent left superior vena cava and the left atrium with a decremental property.

HeartRhythm Case Rep 2020 Nov 17;6(11):836-840. Epub 2020 Aug 17.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

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http://dx.doi.org/10.1016/j.hrcr.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653479PMC
November 2020

Central sensitization in migraine is related to restless legs syndrome.

J Neurol 2021 Apr 4;268(4):1395-1401. Epub 2020 Nov 4.

Department of Neurology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan.

Objective: We hypothesized that, in migraine patients, central sensitization (CS) could be associated with comorbid restless legs syndrome (RLS).

Methods: We conducted a case-control study including 186 migraine patients and 186 age- and sex-matched healthy controls. Symptoms related to CS syndrome were assessed by the Central Sensitization Inventory (CSI). Individuals with CSI Part A (CSI-A) scores ≥ 40 were defined as having CS. For patients with migraine, the Brief Pain Inventory (BPI) and Patient Health Questionnaire (PHQ)-9 were administered. In the patient group, RLS and migraine were diagnosed through face-to-face interviews.

Results: Among migraine patients, 26 (14.0%) suffered from chronic migraine. The mean disease duration was 23.7 ± 11.8 years. Migraine patients showed a higher rate of CS (21.0% vs. 8.6%) than healthy controls, with an adjusted odds ratio (AOR) of 3.039 (95% confidence interval (CI) 1.560-5.992; p = 0.001). Migraine patients in the CS group had higher rates of smoking, chronic migraine and RLS and higher BPI and PHQ-9 scores than migraine patients in the non-CS group. The use of acute and preventive treatment for migraine did not significantly differ between the CS and non-CS groups. Multivariable analysis identified the presence of RLS (AOR, 28.471; 95% CI 6.438-125.918; p < 0.001) and the BPI pain interference score (AOR, 1.398; 95% CI 1.061-1.843; p = 0.017) as the significant determinants of CS among migraine patients.

Conclusion: Migraine patients were 3 times more likely to have CS than healthy controls. Our study results showed an association between RLS and CS in migraine patients.
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http://dx.doi.org/10.1007/s00415-020-10295-7DOI Listing
April 2021

More than meets the heart: systolic amplification of different emotional faces is task dependent.

Cogn Emot 2021 Mar 19;35(2):400-408. Epub 2020 Oct 19.

Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ, USA.

Interoceptive processes emanating from baroreceptor signals support emotional functioning. Previous research suggests a unique link to fear: fearful faces, presented in synchrony with systolic baroreceptor firing draw more attention and are rated as more intense than those presented at diastole. This study examines whether this effect is unique to fearful faces or can be observed in other emotional faces. Participants ( = 71) completed an emotional visual search task (VST) in which fearful, happy, disgust and sad faces were presented during systolic and diastolic phases of the cardiac cycle. Visual search accuracy and emotion detection accuracy and latency were recorded, followed by a subjective intensity task. A series of interactions between emotion and cardiac phase were observed. Visual search accuracy for happy and disgust faces was greater at systole than diastole; the opposite was found for fearful faces. Fearful and happy faces were perceived as more intense at systole. Previous research proposed that cardiac signalling has specific effects on the attention and intensity ratings for fearful faces. Results from the present tasks suggest these effects are more generalised and raise the possibility that interoceptive signals amplify emotional superiority effects dependent on the task employed.
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http://dx.doi.org/10.1080/02699931.2020.1832050DOI Listing
March 2021

[NPPV Treatment for Neuromuscular Diseases during the COVID-19 Pandemic].

Brain Nerve 2020 Oct;72(10):1085-1089

Department of Neurology, Dokkyo Medical University.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from Wuhan in December 2019 and resulted in a severe outbreak of pneumonia (COVID-19). SARS-CoV-2 is transmitted through respiratory droplets produced by coughs or sneezes, as well as aerosols containing viral particles. Noninvasive positive pressure ventilation (NPPV) is widely used to support respiration in patients with neuromuscular diseases. However, NPPV is also an aerosol-generating procedure. Without appropriate precautions, the risk of spreading the virus is high in NPPV users infected with SARS-CoV-2. At home, self-quarantine is effective in protecting caregivers of patients using NPPV, whereas in hospitals, using a negative pressure room is preferred. As SARS-CoV-2 can survive on surfaces for several days, disinfecting the NPPV machine and the items frequently touched in the room is essential. Setting viral filters is useful for preventing virus transmission and keeping the inside of the NPPV machine clean. Caregivers must wear appropriate personal protective equipment. Furthermore, it should be paid attention to the potential transmission from asymptomatic SARS-CoV-2 carriers. During the current pandemic, it is necessary to minimize the risk of transmission among patients using NPPV.
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http://dx.doi.org/10.11477/mf.1416201653DOI Listing
October 2020

Postcentral gyrus infarction with spared proprioceptive sensation.

eNeurologicalSci 2020 Dec 28;21:100267. Epub 2020 Aug 28.

Department of Neurology, Dokkyo Medical University, Tochigi, Japan.

We here report a patient with postcentral gyrus infarction whose touch and pain sensations in the right forearm and hand were impaired but proprioceptive sensation was spared. We observed the clinicoradiological correlation between sensory impairment of tactile and pain sensation with spared proprioceptive sensation and the posterior postcentral gyrus lesion, which may be important in understanding the function of human primary sensory cortex.
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http://dx.doi.org/10.1016/j.ensci.2020.100267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479268PMC
December 2020

Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure.

Acta Neuropathol Commun 2020 08 27;8(1):148. Epub 2020 Aug 27.

Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.

We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respiratory failure with CO narcosis. She died of respiratory failure at the age of 62, 14 months after disease onset. Her brother also showed parkinsonism at the age of 58 and suddenly died 6 months later. Postmortem examination revealed 4R-tau aggregation, which was characterized by neuronal globose-type tangles or pretangles, bush-like or miscellaneous astrocytic inclusions, and coiled bodies. The temporal tip, the striatum, the substantia nigra, the tegmentum of the midbrain, the medullary reticular formation, and the spinal cord were severely involved with tau aggregation. Argyrophilic grains and ballooned neurons were also found in the medial temporal structures, however, extensions of the 4R-aggregations in the case were clearly broader than those of the argyrophilic grains. Western blot analysis of sarkosyl-insoluble fractions from brain lysates revealed prominent bands of tau at both 33 kDa and 37 kDa. Genetic examinations did not reveal any known pathogenic mutations in MAPT, DCTN-1, PSEN-1, or familial or young-onset parkinsonism-related genes. The clinical manifestations, pathologic findings, and biochemical properties of aggregated tau in our patient cannot be explained by argyrophilic grain disease or other known 4R-tauopathies alone. Our results further extend the clinical and neuropathologic spectra of 4R-tauopathy.
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http://dx.doi.org/10.1186/s40478-020-01025-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450700PMC
August 2020

[Coronavirus disease 2019 (COVID-19) and headaches].

Authors:
Keisuke Suzuki

Rinsho Shinkeigaku 2020 Sep 8;60(9):589-596. Epub 2020 Aug 8.

Department of Neurology, Dokkyo Medical University.

Over the course of the new coronavirus infectious disease (coronavirus disease 2019; COVID-19) pandemic, our social situation has been changing dramatically, in addition to the substantial efforts made for the early and appropriate management of COVID-19 and preventing this infection spreading. Recently, neurological symptoms associated with COVID-19 have been shown to be not uncommon, with headaches receiving attention as one of the main neurological symptoms. The frequency of headaches associated with COVID-19 ranged from 5.6% to 70.3%, based on 21 clinical studies and 8 meta-analyses. However, headaches were observed in 11.1% to 81.0% of non-COVID-19 individuals, including healthcare workers caring for COVID-19 patients. Although detailed descriptions of headaches were rarely provided in the literature obtained, in this article, I wil discuss the frequency and characteristics of headaches, and the pathophysiology of headaches as it relateds to COVID-19.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001490DOI Listing
September 2020

[Bilateral Medial Medulla Infarction Mimicking Guillain-Barré Syndrome and its Variants].

Brain Nerve 2020 Aug;72(8):901-905

Department of Neurology, Dokkyo Medical University.

A 70-year-old man presented with dizziness and unsteadiness when standing and was hospitalized in another hospital. Magnetic resonance imaging (MRI) of the brain on Day 1 showed no abnormalities. The patient developed respiratory failure on Day 1and flaccid tetraplegia on Day 3, and was transferred to our hospital. Progressive upper and lower limb weakness and bulbar symptoms suggested Guillain-Barré syndrome or its variant. Diffusion-weighted MRI on Day 6 disclosed high signal intensities in the bilateral medial portion of the medulla, and the patient was diagnosed with bilateral medial medulla infarction. Bilateral medial medulla infarction should be considered when a patient shows progressive tetraplegia, and bulbar palsy and follow-up MRI is important to confirm the diagnosis. (Received January 23, 2020; Accepted April 21, 2020; Published August 1, 2020).
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http://dx.doi.org/10.11477/mf.1416201617DOI Listing
August 2020

Does good sleep reduce early-morning off periods in patients with Parkinson's disease?

Sleep 2020 08;43(8)

Department of Neurology, Dokkyo Medical University, Tochigi, Japan.

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http://dx.doi.org/10.1093/sleep/zsaa020DOI Listing
August 2020

The novel multi-cytokine inhibitor TO-207 specifically inhibits pro-inflammatory cytokine secretion in monocytes without affecting the killing ability of CAR T cells.

PLoS One 2020 22;15(4):e0231896. Epub 2020 Apr 22.

Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Cancer immunotherapy using chimeric antigen receptor-armed T (CAR T) cells have been shown to improve outcomes significantly in patients with hematological malignancies. However, cytokine release syndrome (CRS) remains a risk. CRS is characterized by the excessive activation of CAR T cells and macrophages. Signs and symptoms of CRS are usually resolved after steroid administration, but steroids abrogate the expansion and persistence of CAR T cell populations. Tocilizumab is a humanized monoclonal antibody (mAb) that attenuates CRS without significant loss of CAR T cell activity. However, interleukin-6 (IL-6)/IL-6 receptor (IL-6R) blockade alone cannot relieve CRS symptoms fully, and novel treatments are needed to prevent or cure CRS. TO-207 is an N-benzoyl-L-phenylalanine derivative that significantly inhibits inflammatory cytokine production in human monocyte and macrophage-specific manner. We investigated whether TO-207 could inhibit cytokine production without impairing CAR T cell function in a CRS-simulating co-culture system.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231896PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176125PMC
July 2020

[A patient with neurosarcoidosis presenting with easy falling and dysphagia].

Rinsho Shinkeigaku 2020 May 18;60(5):346-350. Epub 2020 Apr 18.

Department of Neurology, Dokkyo Medical University.

A 68-year-old woman was referred to our hospital for progressive dizziness, gait disturbances and weight loss for 18 months. The patient was alert and showed dysphagia and a marked tendency to fall backward. Electronystagmography showed bilateral vestibular dysfunction and audiometry showed right sensorineural hearing disturbance. Cerebrospinal fluid exam showed mononuclear pleocytosis and elevated protein levels. On F-FDG PET/CT, abnormal uptake was observed in the mediastinal lymph nodes, from which biopsy specimens were obtained. Histological findings showed non-caseous granuloma and a diagnosis of bilateral vestibulocochlear, glossopharyngeal and vagal nerve palsies due to neurosarcoidosis was made. Steroid therapy resulted in improvement in her clinical symptoms. Neurosarcoidosis should be included in the differential diagnosis of patients showing progressive easy falling and dysphagia.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001404DOI Listing
May 2020

Diagnosis of neurofibromatosis type 1 after rupture of aneurysm and consequent fatal hemothorax.

Am J Emerg Med 2020 07 7;38(7):1543.e3-1543.e5. Epub 2020 Apr 7.

Department of Emergency and Disaster Medicine, Showa University, Fujigaoka Hospital, 1-30 Fujigaoka Aoba-ku, Yokohama 227-8501, Japan; Department of Emergency and Disaster Medicine, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8666, Japan.

Patients with neurofibromatosis type 1 (NF1) can develop both benign and malignant tumors throughout their lives. A 49-year-old man was transferred to the emergency department with complaints of sudden right dorsal pain and respiratory discomfort. He was in shock on arrival. On finding significantly decreased permeability of the left lung field in chest X-ray, drainage was immediately performed. Subsequent computed tomography (CT; Lammert et al., 2005) angiography revealed the extravasation of contrast media from the deep carotid artery, a branch of subclavian artery. It suggested rupture of an aneurysm located at a rare site; the ruptured aneurysm penetrated the pleura, causing shock. The patient was resuscitated. Transcatheter arterial embolization (TAE; Evans et al., 2010) was successfully performed. Immediate drainage, resuscitation, and TAE 2 improved his condition. Most NF1 patients have café-au-lait macules; café-au-lait macules tend to fade with age. Importantly, café-au-lait macules, neurofibromas, and Lisch nodules were noticed at admission. NF1 patients are likely to have a malignant neoplasm when they are young. The patient had been diagnosed with thyroid cancer when he was young. As his deceased mother was an NF1 patient, we diagnosed him with NF1. Detailed patient history and early-stage examination led to the early diagnosis. NF1 should be considered as an early differential diagnosis to improve the outcome of patients in such cases.
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http://dx.doi.org/10.1016/j.ajem.2020.04.004DOI Listing
July 2020

Intramolecular Benzyne-Phenolate [4+2] Cycloadditions.

Angew Chem Int Ed Engl 2020 Jul 8;59(30):12440-12444. Epub 2020 May 8.

Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo, 152-8551, Japan.

An intramolecular benzyne-phenolate [4+2] cycloaddition is reported. Benzyne precursors, having vicinal halogen-sulfonate functionalities, linked with a phenol(ate) by various tether groups undergo efficient intramolecular [4+2] cycloaddition by treatment with either Ph MgLi or nBuLi for halogen-metal exchange to form various benzobarrelenes.
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http://dx.doi.org/10.1002/anie.202003131DOI Listing
July 2020

A case report of cryptococcal meningitis associated with ruxolitinib.

Medicine (Baltimore) 2020 Mar;99(13):e19587

Department of Neurology, Dokkyo Medical University, Mibu, Tochigi, Japan.

We herein report a 76-year-old Japanese man with myelofibrosis who developed cryptococcal meningitis. After treatment for 5 months with ruxolitinib, the patient presented with fever and disturbance of consciousness. Marked nuchal stiffness was noted. The magnetic resonance imaging results of the brain were normal. Lumbar puncture showed an opening cerebrospinal fluid (CSF) pressure of 110 mm H2O, pleocytosis (85 mononuclear cells and 222 polymorphonuclear cells/μL), decreased CSF/serum glucose ratio (43%), and elevated protein (194 mg/dL). Blood and CSF cultures grew no bacteria or fungi. However, cryptococcal antigen was detected in the blood and CSF samples. We discontinued ruxolitinib and started administration of amphotericin B. His condition improved gradually 1 week after initiation of treatment. There have been only a few reports on cryptococcal meningitis associated with ruxolitinib. Physicians should consider the possibility of cryptococcal meningitis in patients receiving ruxolitinib.
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http://dx.doi.org/10.1097/MD.0000000000019587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220082PMC
March 2020