Proteinuria is a key to suspect autoimmune nodopathies.

BACKGROUND AND PURPOSE: Reports of patients who have autoimmune nodopathies concurrent with nephrotic syndrome are increasing. We investigated whether proteinuria could be a biomarker of autoimmune nodopathies. METHODS: Qualitative urinalysis results were retrospectively obtained from 69 patients who were diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) at a hospital in Japan. Proteinuria was graded as mild to severe (i.e., mild, 30-99; moderate, 100-299; severe, 300 mg/dL or more) according to the results of the urine dipstick test. Autoantibodies against the paranodal proteins contactin 1 (CNTN1), neurofascin 155 (NF155), and contactin-associated protein 1 (Caspr1) and the nodal protein neurofascin 186 (NF186) were measured, and the predominant IgG subclass was determined by enzyme-linked immunosorbent assay in sera from the 69 patients. RESULTS: Four patients (6%), five patients (7%), and one (1%) patient were positive for anti-CNTN1, anti-NF155, and anti-Caspr1 IgG4 antibodies, respectively. No patients had IgG4 antibodies against NF186. Proteinuria of mild or greater levels was found in three patients with anti-CNTN1 IgG4 and two patients with anti-NF155 IgG4 antibodies. The autoantibody-positive patients more frequently had proteinuria of mild or greater levels than the seronegative patients (p = 0.01). CONCLUSIONS: Proteinuria is a possible biomarker of autoimmune nodopathies associated with autoantibodies targeting CNTN1 or NF155. Urinalysis results should be carefully checked for quick differentiation of autoimmune nodopathies from CIDP. Patients who present with nephrotic syndrome should be tested for anti-CNTN1 IgG4 antibodies, and patients who exhibit mild proteinuria should be tested for anti-NF155 IgG4 antibodies.

Reply to Maxwell, A. Comment on "Miyamoto et al. Laryngopharyngeal Mucosal Injury Due to Nasogastric Tube Insertion during Cardiopulmonary Resuscitation: A Retrospective Cohort Study. J. Clin. Med. 2024, 13, 261".

We are grateful for the insightful comments provided by the author [...].

A well-managed case of discontinuous anorectal injury caused by a personal watercraft treated by combining surgery and colonoscopy.

Background: Anorectal injury caused by personal watercraft (PWC)-related trauma is rare. However, PWC accidents have increased recently, and since patients tend to be younger, treatment strategies should consider anal function preservation in addition to saving lives. Case Presentation: A 30-year-old female patient who fell into the water when a PWC suddenly accelerated and injured her perineum with a forceful water jet was transported to our hospital. On examination, she was diagnosed with a traumatic rectal perforation with intraperitoneal findings and an anorectal injury. Emergency surgery, which involved direct suturing, temporary colostomy with intraoperative endoscopy for the rectal perforation, and anorectal reconstruction, was performed. The patient was discharged on postoperative day 19 without complications, and the colostomy was closed 5 months postoperatively. Conclusion: We encountered a case of multiple noncontinuous anorectal injuries due to a PWC accident that was successfully treated using a combination of surgery and intraoperative endoscopy.

Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for trauma and its performance in Japan over the past 18 years: a nationwide descriptive study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed. METHODS: This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score. RESULTS: Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival. CONCLUSIONS: While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care.

A Combined Index Using the Mini-Mental State Examination and Lawton Index to Discriminate Between Clinical Dementia Rating Scores of 0.5 and 1: A Development and Validation Study.

Objective: To develop a combined index using cognitive function and instrumental activities of daily living (IADL) to discriminate between Clinical Dementia Rating (CDR) scores of 0.5 and 1 in the clinical setting, and to investigate its optimal cutoff values and internal and external validities.Methods: We included outpatients aged 65-89 years with CDR scores of 0.5 or 1. The optimal cutoff values and internal validity were verified using Japanese memory clinic-based datasets between September 2010 and October 2021 [National Center for Geriatrics and Gerontology (NCGG) datasets]. Cognitive function and IADL were assessed using the Mini-Mental State Examination (MMSE) and Lawton Index (LI), respectively. The optimal cutoff values were defined using the Youden Index. To verify internal validity, sensitivity and specificity were calculated using stratified 5-fold cross-validation. To verify external validity, sensitivity and specificity of the optimal cutoff values were assessed in the Organized Registration for the Assessment of dementia on Nationwide General consortium toward Effective treatment (ORANGE) Registry dataset between July 2015 and March 2022, which has multicenter clinical data.Results: A total of 800 (mean age, 77.53 years; men, 50.1%) and 1494 (mean age, 77.97 years; men, 43.3%) participants comprised the NCGG and ORANGE Registry datasets, respectively. The optimum cutoff values for men and women were determined as MMSE < 25 and LI < 5 and MMSE < 25 and LI < 8, respectively; such a combined index showed good discriminative performance in internal (sensitivity/specificity: men, 92.50/73.52; women, 88.57/65.65) and external validities (men, 81.43/77.62; women, 77.64/74.67).Conclusion: The index developed is useful in discriminating between CDR scores of 0.5 and 1 and should be applicable to various settings, such as memory clinics and clinical research.

A case of coronary artery compression syndrome resulting from peri-valvular regurgitation and long-standing atrial fibrillation.

A man in his 70s with a history of mitral valve replacement (MVR) and long-standing persistent atrial fibrillation (AF) presented with effort angina. Coronary angiography revealed severe stenosis of the left main coronary artery (LMCA). As it was an emergent case, PCI (percutaneous coronary intervention) was selected for treatment. Intravascular ultrasonography revealed no atherosclerotic lesions in the LMCA. The LMCA was effectively dilated by the drug-eluting stent. No elevation in intracardiac pressure was observed in cardiac catheterization after PCI. Computed tomography scan indicated potential compression of the LMCA by the surrounding structures. In cases of long-standing persistent AF and an enlarged atrium after MVR, the possibility of LMCA stenosis due to anatomical changes should be considered. Learning Objectives: ◾Peri-valvular regurgitation and long-standing persistent atrial fibrillation can potentially cause atrial enlargement.◾Coronary artery stenosis without atherosclerosis can occur due to compression from surrounding structures or shifting of the coronary artery.◾Stent therapy provides a temporary solution and coronary artery bypass grafting or switching should be considered if re-stenosis occurs.

Associations between the burdens of comorbid sleep problems, central sensitization, and headache-related disability in patients with migraine.

Objective: Sleep disturbances are common in migraine patients and affect quality of life. Central sensitization (CS) is likely to play a role in the increased severity and chronicity of migraine. We hypothesized that the number of comorbid sleep problems would affect headache-related disability through the effects of central sensitization (CS). Methods: We performed a cross-sectional study including 215 consecutive patients with migraine. Insomnia was defined as a Pittsburgh Sleep Quality Index (PSQI) global score greater than 5. Probable REM sleep behavior disorder (pRBD) was defined as an RBD screening score of 5 or greater. Excessive daytime sleepiness (EDS) was defined as an Epworth Sleepiness Scale score of 10 or higher. Suspected sleep apnea (SA) was defined as patients with snoring or sleep apnea witnessed 3 or more nights a week. CS was assessed by the Central Sensitization Inventory (CSI). Results: Restless legs syndrome, insomnia, EDS, SA and pRBD were observed in 25.6%, 71.6%, 34.4%, 10.2%, and 21.4%, respectively, of the patients. At least one sleep problem was present in 87.0% of the patients. According to the results of the multinomial logistic regression analysis with no sleep problems as a reference, after we corrected for adjustment factors, the Migraine Disability Assessment (MIDAS) score significantly increased when three or more comorbid sleep problems were present. According to our mediation analysis, an increased number of sleep problems had a direct effect on the MIDAS score after we adjusted for other variables, and the CSI score was indirectly involved in this association. Conclusion: The present study showed an association between migraine-related disability and the burden of multiple sleep problems, which was partially mediated by CS.

Can calcitonin gene-related peptide monoclonal antibodies ameliorate writer's cramp and migraine?

Recently, calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have become available as a prophylactic treatment for migraine and have shown high efficacy and safety in clinical practice. CGRP mAbs have been reported to be effective not only for migraine but also for other comorbidities, such as psychiatric complications in patients with migraine. However, there are no reports examining the effect of CGRP mAbs on dystonia. We treated a patient with comorbid migraine and focal task-specific dystonia (writer's cramp) with a CGRP mAb (erenumab) because of an increase in monthly migraine days despite the addition of migraine prophylaxis. In this patient, erenumab treatment for 3 months led to improvements in symptoms of both focal dystonia and migraine, suggesting a role for CGRP in the pathophysiology of both conditions.

Usefulness of "AcT ratio" in diagnosis of internal carotid artery stenosis: a multicenter, retrospective, observational study.

PURPOSE: The ratio of the internal carotid artery (ICA) to the common carotid artery (CCA), especially the "AcT ratio," which is a modified measurement method of acceleration time, is useful for diagnosing ICA-origin stenosis. However, previous studies were single-center studies. Therefore, this multicenter, retrospective, cross-sectional study aimed to determine whether a method using the AcT ratio is useful for estimating stenosis rates. METHODS: This study included 461 vessels subjected to carotid artery ultrasonography and evaluation for ICA-origin stenosis via NASCET at four hospitals. The duration from the steep rise point to the inflection point or the first peak was defined as AcT on pulsed wave Doppler. The AcT ratio was calculated as AcT of ICA/AcT of ipsilateral CCA. The AcT ratio and rate of ICA-origin stenosis were analyzed using Pearson's correlation coefficient, simple regression analysis, and ROC curve. RESULTS: A significant positive correlation was observed between the AcT ratio and NASCET stenosis. NASCET stenosis of ≥ 50% had a sensitivity, specificity, and negative predictive value (NPV) of 70.2%, 71.6%, and 91.5%, respectively, when the cut-off value of the AcT ratio was 1.17. NASCET stenosis of ≥ 70% had a sensitivity, specificity, and NPV of 70.5%, 72.1%, and 95.9%, respectively, when the cut-off value of the AcT ratio was 1.22. CONCLUSIONS: The findings of this multicenter, retrospective, cross-sectional study suggest that the AcT ratio is useful for diagnosing ICA-origin stenosis, especially for diagnosis by exclusion. NASCET stenosis of ≥ 50% was considered unlikely if the Act ratio was ≤ 1.17, whereas NASCET stenosis of ≥ 70% was considered unlikely if it was ≤ 1.22.

Gait instability, ophthalmoplegia, and chorea with orofacial dyskinesia in a man with anti-Ri antibodies: a case report.

A 79-year-old man was admitted for 2 weeks of dizziness, followed by diplopia, involuntary movement and progressive gait disturbances. Neurologic examination revealed horizontal and vertical gaze paresis, bilateral choreiform movement with orofacial dyskinesia, and limb/truncal ataxia. MRI revealed fluid-attenuated inversion recovery image-hyperintense signal abnormalities in the dorsal midbrain, pontine and medulla. Within another few days, the patient developed type II acute respiratory failure requiring artificial invasive ventilation. Because autoimmune encephalitis was suspected, he received intravenous immunoglobulin therapy followed by intravenous methylprednisolone, but only his ophthalmoplegia improved minimally. Serological tests were positive for anti-Ri onconeural antibodies. CT-guided mediastinal lymph node biopsy was performed and revealed small cell lung carcinoma. We report the rare manifestation of anti-Ri antibody-associated paraneoplastic neurological syndrome (PNS), and this case can alert us to the importance of respiratory management in this diverse neurologic disease. Furthermore, PNSs positive for anti-Ri antibodies should be added to the list of differential diagnoses of chorea with orofacial dyskinesia.

CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society.

BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. METHODS: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. RESULTS: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). CONCLUSIONS: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

Real-world effectiveness of erenumab in Japanese patients with migraine.

Background: Real-world evidence of erenumab effectiveness in migraine patients in Asia with various comorbidities and multiple previous medication failures is still limited. Methods: A 6-month single-center cohort study of 45 patients with episodic or chronic migraine (CM) treated with erenumab was conducted. In the cohort, 60.0% were switching from other calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs), and 66.7% had ≥4 prophylaxis failures. The change in monthly migraine days (MMDs) from baseline and percentages of responders after treatment were calculated. Weekly migraine days (WMDs) were obtained at baseline and at months 1, 2 and 3 and were compared between weeks 2 and 4. Results: In total, 36%, 47%, and 63% of patients had a ≥30% response at 1, 3, and 6 months, respectively. The cumulative percentage of patients achieving a ≥30% response over 6 months was 85%. Early responders (average ≥ 30% response at 1-3 months) accounted for 37.8%, 55.6%, and 25.9% of the total, CGRP mAb-naïve, and CGRP mAb-switching groups, respectively. Late responders (average < 30% response at 1-3 months and average ≥ 30% response at 4-6 months) accounted for 46.4%, 37.5%, and 58.8% of nonearly responders in the total, CGRP mAb-naïve, and CGRP mAb-switching groups, respectively. Mild adverse reactions were observed in 5 patients (11.1%). Wearing-off, defined as an increase in the number of WMDs ≥2 between week 2 and week 4, was observed in 2.4-12.5% at months 1-3. Conclusion: Erenumab was effective in migraine patients. At least 4-6 months may be preferable for efficacy evaluation in patients switching to erenumab from other CGRP mAbs.

Prostaglandin E-major urinary metabolites as a new biomarker for acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is an emergent vascular disease caused by cessation of the blood supply to the small intestine. Despite advances in the diagnosis, intervention, and surgical procedures, AMI remains a life-threatening condition. Prostaglandin E2 major urinary metabolite (PGE-MUM), the urinary metabolite of prostaglandin E2, is known to be stable in urine and has been suggested to be a valuable biomarker for intestinal mucosal inflammation, such as ulcerative colitis. We therefore investigated whether or not PGE-MUM levels reflect the degree of ischemia in an intestinal ischemia-reperfusion model. METHODS: Male rats were used to establish a superior mesenteric artery occlusion (SMAO) group, in which the superior mesenteric artery was clamped, and a sham group. The clamping times in the SMAO group were either 30 minutes or 60 minutes, and reperfusion times were either 3 hours or 6 hours, after which PGE-MUM values were measured. RESULTS: The histological injury score of the SMAO (30-minute ischemia and 6-hour reperfusion group, 1.8 ± 0.4; 60-minute ischemia and 6-hour reperfusion group, 4.7 ± 0.5) and were significantly greater than that of the sham group (0.4 ± 0.7, p < 0.05). The PGE-MUM levels in the SMAO group (30-minutes ischemia and 6-hour reperfusion group, 483 ± 256; 60-minutes ischemia and 6-hour reperfusion group, 889 ± 402 ng/mL) were significantly higher than in the sham group (30-minute and 6-hour observation group, 51 ± 20; 60-minute and 6-hour observation group, 73 ± 32 ng/mL; p < 0.05). Furthermore, the PGE-MUM value was corrected by the concentration of urinary creatinine (Cr). The PGE-MUM/urinary Cr levels in the SMAO group were also significantly higher than in the sham group ( p < 0.05). CONCLUSION: We found that intestinal ischemia-reperfusion increased urinary PGE-MUM levels depending on the ischemic time. This suggests the potential utility of PGE-MUM as a noninvasive marker of intestinal ischemia.

Impact of autonomic symptoms on the clinical course of Parkinson's disease.

PURPOSE: Patients with Parkinson's disease (PD) exhibit various degrees of autonomic symptoms, which may be associated with Lewy body pathology distributed extensively in the autonomic nervous system. We hypothesized that the severity of autonomic symptoms reflects the severity of PD-related pathology, resulting in poor outcomes. The purpose of this study was to evaluate the impact of autonomic symptoms on PD progression. METHODS: We conducted a follow-up study among consecutive patients with PD at Dokkyo Medical University Hospital. Patients underwent comprehensive baseline evaluations and were classified into high and low autonomic symptom groups using the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT). The Kaplan‒Meier survival curves were used to analyze the time to discontinuation of their visits because of PD-related endpoints and to evaluate the association with high SCOPA-AUT scores. RESULTS: Of the 101 patients, 74 (73%) met the inclusion criteria. During the follow-up period (mean 1654 days), 22/74 patients reached PD-related endpoints (death, 4; hospitalization, 9; nursing home institutionalization, 9). PD patients with high SCOPA-AUT scores reached the endpoints faster than those with low SCOPA-AUT scores. A high SCOPA-AUT score, including gastrointestinal, urinary, and thermoregulation domains; high motor symptom scores; and low specific binding ratios (SBRs) on 123I FP-CIT-SPECT (DAT-SPECT) were associated with reaching PD-related endpoints. A high SCOPA-AUT score was associated with reaching the endpoints even after adjustment for covariates. CONCLUSIONS: Patients with high autonomic symptom scores had a greater risk of reaching PD-related endpoints than patients with low autonomic symptom scores.

Evaluation of bone marrow invasion on the machine learning of 18 F-FDG PET texture analysis in lower gingival squamous cell carcinoma.

OBJECTIVES: Lower gingival squamous cell carcinoma (LGSCC) has the potential to invade the alveolar bone. Traditionally, the diagnosis of LGSCC relied on morphological imaging, but inconsistencies between these assessments and surgical findings have been observed. This study aimed to assess the correlation between LGSCC bone marrow invasion and PET texture features and to enhance diagnostic accuracy by using machine learning. METHODS: A retrospective analysis of 159 LGSCC patients with pretreatment 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) examination from 2009 to 2017 was performed. We extracted radiomic features from the PET images, focusing on pathologic bone marrow invasion detection. Extracted features underwent the least absolute shrinkage and selection operator algorithm-based selection and were then used for machine learning via the XGBoost package to distinguish bone marrow invasion presence. Receiver operating characteristic curve analysis was performed. RESULTS: From the 159 patients, 88 qualified for further analysis (59 men; average age, 69.2 years), and pathologic bone marrow invasion was identified in 69 (78%) of these patients. Three significant radiological features were identified: Gray level co-occurrence matrix_Correlation, INTENSITY-BASED_IntensityInterquartileRange, and MORPHOLOGICAL_SurfaceToVolumeRatio. An XGBoost machine-learning model, using PET radiomic features to detect bone marrow invasion, yielded an area under the curve value of 0.83. CONCLUSION: Our findings highlighted the potential of 18 F-FDG PET radiomic features, combined with machine learning, as a promising avenue for improving LGSCC diagnosis and treatment. Using 18 F-FDG PET texture features may provide a robust and accurate method for determining the presence or absence of bone marrow invasion in LGSCC patients.

Systematic observation-based diagnosis of atrioventricular nodal reentrant tachycardia with a bystander concealed nodoventricular pathway.

Background: This study aimed to establish a systematic method for diagnosing atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed nodoventricular pathway (cNVP). Methods: We analyzed 13 cases of AVNRT with a bystander cNVP, 11 connected to the slow pathway (cNVP-SP) and two to the fast pathway (cNVP-FP), along with two cases of cNVP-related orthodromic reciprocating tachycardia (ORT). Results: The diagnostic process was summarized in three steps. Step 1 was identification of the presence of an accessory pathway by resetting the tachycardia with delay (n = 9) and termination without atrial capture (n = 4) immediately after delivery of a His-refractory premature ventricular contraction (PVC). Step 2 was exclusion of ORT by atrio-His block during the tachycardia (n = 4), disappearance of the reset phenomenon after the early PVC (n = 7), or dissociation of His from the tachycardia during ventricular overdrive pacing (n = 1). Moreover, tachycardia reset/termination without the atrial capture (n = 2/2) 1 cycle after the His-refractory PVC was specifically diagnostic. Exceptionally, the disappearance of the reset phenomenon was also observed in the two cNVP-ORTs. Step 3 was verification of the AVN as the cNVP insertion site, evidenced by an atrial reset/block preceding the His reset/block in fast-slow AVNRT with a cNVP-SP and slow-fast AVNRT with a cNVP-FP or His reset preceding the atrial reset in slow-fast AVNRT with a cNVP-SP. Conclusion: AVNRT with a bystander cNVP can be diagnosed in the three steps with few exceptions. Notably, tachycardia reset/termination without atrial capture one cycle after delivery of a His-refractory PVC is specifically diagnostic.

Impact of Istradefylline on Levodopa Dose Escalation in Parkinson's Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study.

INTRODUCTION: A higher levodopa dose is a risk factor for motor complications in Parkinson's disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off. METHODS: This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300-400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes. RESULTS: The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p < 0.0001). The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I and device-evaluated motor activities improved significantly from baseline to 36 weeks in the IST group only (all p < 0.05). Other secondary endpoints were comparable between the groups. Adverse drug reactions (ADRs) occurred in 28.8% and 13.2% of patients in the IST and control groups, respectively, with no serious ADRs in either group. CONCLUSION: IST treatment reduced levodopa dose escalation in PD patients, resulting in less cumulative levodopa use. Adjunctive IST may improve motor function more objectively than increased levodopa dose in patients with PD. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180248.