Reliability and benefit of estimated continuous cardiac output measurement using shunt-side SpO2 monitor in hemodialysis.

INTRODUCTION: Estimated continuous cardiac output (esCCO) is a novel technology that enables non-invasive and continuous monitoring of cardiac output. We compared the concordance in accuracies among esCCO measurements in the shunt limb and non-shunt limb. METHODS: In this single-center prospective observational study, we include Japanese patients who underwent dialysis at our center between April 27, 2021, and February 28, 2023. Clinical accuracy of esCCO was evaluated in the shunted and non-shunted bilateral digits. Agreement between the measurements was analyzed using Lin's congruent correlation and Bland-Altman analysis. RESULTS: For 43 individuals, Lin's concordance correlation coefficient was 0.9887 (95% confidence interval of 0.9886-0.9887) indicating good agreement. The values of esCCO measured in the shunt and non-shunt limbs were compatible. The percentage errors for the 43 patients with arterio-venous fistula (AVF) or arterio-venous graft (AVG), 32 with AVF, and 11 with AVG were 9.3%, 9.3%, and 8.9%, respectively. CONCLUSION: esCCO could be used in shunt as well as non-shunt limbs during dialysis, allowing continuous and non-invasive hemodynamic monitoring.

Difference in the immediate effect on positional nystagmus for head positions with interval time during Epley maneuver: a randomized trial.

OBJECTIVES: The Epley maneuver (EM) shows immediate effect, wherein disappearance of positional nystagmus occurs soon after the EM. Our previous study showed that setting interval times during the EM reduced the immediate effect. The purpose of this study is to identify the head position for which interval time reduces the immediate effect. METHODS: Fifty-one patients with posterior canal type of benign paroxysmal positional vertigo (BPPV) were randomly assigned to the following three groups: 10 min interval time set at the first head position of the EM in group A, at the third head position in group B, and at the fourth head position in group C. The primary outcome measure (POï¼­) was the ratio of maximum slow-phase eye velocity of positional nystagmus soon after the EM, compared with that measured before the EM. A large ratio value indicates a poor immediate effect of the EM. RESULTS: The POï¼­ in group A (0.07) was smallest (B: 0.36, C: 0.49) (p < 0.001). DISCUSSION: The interval times at the third and fourth head positions reduced the immediate effect of the EM. Our previous study showed that the effect of BPPV fatigue is continued by maintaining the first head position of the EM. BPPV fatigue constitutes fatigability of positional nystagmus with repeated performance of the Dix-Hallpike test. Our findings may be interpreted in accordance with the theory that the immediate effect of the EM is BPPV fatigue itself, because we observed that the effect of BPPV fatigue is strongest in group A.

Efficacy and Tolerability of Ivabradine for Cardiomyopathy in Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an intractable X-linked myopathy caused by dystrophin gene mutations. Patients with DMD suffer from progressive muscle weakness, inevitable cardiomyopathy, increased heart rate (HR), and decreased blood pressure (BP). The aim of this study was to clarify the efficacy and tolerability of ivabradine treatment for DMD cardiomyopathy.A retrospective analysis was performed in 11 patients with DMD, who received ivabradine treatment for more than 1 year. Clinical results were analyzed before (baseline), 6 months after, and 12 months after the ivabradine administration.The initial ivabradine dose was 2.0 ± 1.2 mg/day and the final dose was 5.6 ± 4.0 mg/day. The baseline BP was 95/64 mmHg. A non-significant BP decrease to 90/57 mmHg was observed at 1 month but it recovered to 97/62 mmHg at 12 months after ivabradine administration. The baseline HR was 93 ± 6 bpm and it decreased to 74 ± 12 bpm at 6 months (P = 0.011), and to 77 ± 10 bpm at 12 months (P = 0.008). A linear correlation (y = 2.2x + 5.1) was also observed between the ivabradine dose (x mg/day) and HR decrease (y bpm). The baseline LVEF was 38 ± 12% and it significantly increased to 42 ± 9% at 6 months (P = 0.011) and to 41 ± 11% at 12 months (P = 0.038). Only 1 patient with the lowest BMI of 11.0 kg/m2 and BP of 79/58 mmHg discontinued ivabradine treatment at 6 months, while 1-year administration was well-tolerated in the other 10 patients.Ivabradine decreased HR and increased LVEF without lowering BP, suggesting it can be a treatment option for DMD cardiomyopathy.

Obturator Hernia in a Patient Undergoing Hemodialysis.

Obturator hernia is a rare condition that commonly affects frail older women. A 54-year-old woman presented to our hospital with left hip joint pain. She had suffered a left pubic bone fracture and commenced maintenance hemodialysis. Pelvic computed tomography (CT) showed an incarcerated small intestine through the left obturator foramen, while abdominal CT showed marked intestinal dilatation. She underwent emergency laparotomy, and the incarcerated small intestine was found to be necrotic. Partial small intestinal resection and bilateral obturator hernioplasty were performed. Because obturator hernia is a potentially fatal condition, early detection and treatment are important.

Intraoperative rapid diagnosis of pleural lavage cytology in non-small cell lung cancer.

OBJECTIVE: Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery. METHODS: A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection. RESULTS: The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity. CONCLUSIONS: Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery.

Feasibility and safety study of wearable cyborg Hybrid Assistive Limb for pediatric patients with cerebral palsy and spinal cord disorders.

Introduction: The wearable cyborg Hybrid Assistive Limb (HAL) is the world's first cyborg-type wearable robotic device, and it assists the user's voluntary movements and facilitates muscle activities. However, since the minimum height required for using the HAL is 150 cm, a smaller HAL (2S size) has been newly developed for pediatric use. This study aimed to (1) examine the feasibility and safety of a protocol for treatments with HAL (2S size) in pediatric patients and (2) explore the optimal method for assessing the efficacy of HAL. Methods: This clinical study included seven pediatric patients with postural and motor function disorders, who received 8-12 sessions of smaller HAL (2S size) treatment. The primary outcome was the Gross Motor Function Measure-88 (GMFM-88). The secondary outcomes were GMFM-66, 10-m walk test, 2- and 6-min walking distances, Canadian Occupational Performance Measure (COPM), a post-treatment questionnaire, adverse events, and device failures. Statistical analyses were performed using the paired samples t-test or Wilcoxon signed-rank test. Results: All participants completed the study protocol with no serious adverse events. GMFM-88 improved from 65.51 ± 21.97 to 66.72 ± 22.28 (p = 0.07). The improvements in the secondary outcomes were as follows: GMFM-66, 53.63 ± 11.94 to 54.96 ± 12.31, p = 0.04; step length, 0.32 ± 0.16 to 0.34 ± 0.16, p = 0.25; 2-MWD, 59.1 ± 57.0 to 62.8 ± 63.3, p = 0.54; COPM performance score, 3.7 ± 2.0 to 5.3 ± 1.9, p = 0.06; COPM satisfaction score, 3.3 ± 2.1 to 5.1 ± 2.1, p = 0.04. Discussion: In this exploratory study, we applied a new size of wearable cyborg HAL (2S size), to children with central nervous system disorders. We evaluated its safety, feasibility, and identified an optimal assessment method for multiple treatments. All participants completed the protocol with no serious adverse events. This study suggested that the GMFM would be an optimal assessment tool for validation trials of HAL (2S size) treatment in pediatric patients with posture and motor function disorders.

Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.

PURPOSE: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. METHODS: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. RESULTS: Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). CONCLUSIONS: From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.

Polarity and Dielectric Property Control Triggered by a Coordinated Solvent Molecule Exchange in Luminescent Mononuclear Aluminium(III) Complexes.

The development of molecule-based multifunctional switchable materials that exhibit a switch of polarity and dielectric property are extremely limited. We have demonstrated solvent-vapour-induced reversible molecular rearrangements between nonpolar crystals [Al(sap)(acac)(sol)] (H2 sap=2-salicylideneaminophenol, acac=acetylacetonate, sol=MeOH (1), EtOH (2)) and polar crystal [Al(sap)(acac)(DMSO)] (3). This crystal-to-crystal structural transformation was accompanied by a switch of second harmonic generation (SHG) and dielectric properties, including the formation of ferroelectric domains, thus reflecting the SHG-active polar Cc space group of 3. This is the first reported example of dielectric properties and polarity switching in luminescent mononuclear aluminium(III) complexes, which exhibit strong green emission in the solid state.

Comparison of the efficacy of the Epley maneuver and repeated Dix-Hallpike tests for eliminating positional nystagmus: A multicenter randomized study.

Background and objectives: Patients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix-Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week. Methods: This multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%. Results: Data for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin. Discussion: This study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living. Classification of evidence: This study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week. Registration number: UMIN000016421.

Minimal change nephrotic syndrome diagnosed with acute femoral thromboembolism and successfully salvaged limb: a case report.

A 64-year-old man visited the outpatient department of our hospital for the first time due to bilateral lower limb edema, which he noticed 1 week before the visit. Pain suddenly developed in the left lower limb while the patient was in the waiting room. Nephrotic syndrome was suspected based on blood and urine test results. Acute arterial thromboembolism in the left lower limb associated with hypercoagulation due to nephrotic syndrome was suspected, and a diagnosis was made using computed tomography angiography. Arterial thrombectomy was urgently performed, and the limb was salvaged without sequelae. Based on renal biopsy, minimal change nephrotic syndrome was diagnosed, and the patient underwent remission induction with steroid therapy. Heparin was drip infused and apixaban was orally administered to prevent recurrent thrombosis. Nephrotic syndrome in the acute phase is often complicated by thrombosis. Particularly, arterial thromboembolism requires prompt treatment, and prophylactic anticoagulation therapy needs to be considered.

Effect of cyborg-type robot Hybrid Assistive Limb on patients with severe walking disability in acute stroke: A randomized controlled study.

OBJECTIVES: To investigate whether early gait training using Hybrid Assistive Limb (HAL) is feasible and improves walking and independency compared with conventional physical therapy (CPT) in patients with severe walking disability after stroke. METHODS: We conducted a single-center, randomized controlled study. Patients with first-ever stroke who had severe walking disability were included. All patients started gait training within 10 days post-stroke onset. Twenty-four patients were randomly assigned into HAL or CPT groups. Outcome measures were collected at three time points, at baseline, completion of 20 sessions of gait training (second assessment), and 3 months after the initiation of gait training. The primary outcomes were changes in motor sub-scores of the Functional Independence Measure or Functional Ambulation Category at the completion of the second assessment from baseline. RESULTS: Twenty-two patients (median age, 68 years; 12 patients in the HAL group and 10 patients in the CPT group) completed the study. There were no significant differences in primary outcomes. Apathy scale, one of the secondary outcomes, showed a decreasing trend in the HAL group (mean change of -3.8, 95% CI -8.14 to 0.475), and a slight increasing trend in the CPT group (mean change of 1.2, 95% CI -2.66 to 5.06) at the second assessment. Patients in the HAL group experienced no adverse events. CONCLUSIONS: Early gait training in patients with severe walking disability after stroke using HAL was feasible. Walking ability and independency were not improved at the completion of 20 sessions of gait training.

A Novel Medium for Isolating Two Japanese Species in the Fusarium graminearum Species Complex and a Dipstick DNA Chromatography Assay for Species Identification and Trichothecene Typing.

Members of the Fusarium graminearum species complex (Fg complex) are the primary pathogens that cause Fusarium head blight in wheat and barley. Fg complex members grow poorly on Fusarium oxysporum-selective media, such as Komada and Fo-G2, that have also been used for the isolation of other Fusarium species. Therefore, Komada medium was modified as FG medium for the isolation of Fg complex members. However, the production of pentachloronitrobenzene that is the most effective component of FG medium is discontinued and new media is required for the selective isolation of Fg complex members. In addition, the rapid diagnosis of isolated fungi is useful for the disease control. Novel tools have been developed for isolating and characterizing Fg complex members. FG21, a semi-selective medium for isolating Fg complex members, was developed using potato dextrose agar. Furthermore, a dipstick DNA chromatography assay was developed both to identify Fusarium graminearum sensu stricto and Fusarium asiaticum in the Fg complex and their trichothecene mycotoxin types. The easier isolation and characterization of Fg complex members in Japan was attained by the combined use of FG21 medium and the dipstick DNA chromatography assay.

Investigation of bactericidal effect of a mid-infrared free electron laser on Escherichia coli.

The rapid increase in the number of bacteria that are resistant to many commonly used antimicrobial agents and their global spread have become a major problem worldwide. In particular, for periodontal disease, which is a localized infection, there is a growing need for treatment methods that do not primarily involve antimicrobial agents, and antimicrobial photodynamic therapy (aPDT) is attracting attention. In this study, the bactericidal effects of a mid-infrared free electron laser (MIR-FEL) on E. coli were investigated as a basic study to examine the applicability of MIR-FELs, which can selectively excite molecular vibrations due to their wavelength tunability, to aPDT. The optimal irradiation wavelengths to be examined in this study were determined from the infrared spectrum of the bacteria, which was obtained using Fourier transform infrared spectroscopy. Five irradiation wavelengths (6.62, 6.88, 7.14, 8.09 and 9.26 µm) were selected from the FT-IR spectrum, and we found that the bactericidal effects at a wavelength of 6.62 µm were markedly stronger than those observed at the other wavelengths. At this wavelength corresponding to the Amide II band, the bacterial survival rate decreased significantly as the irradiation time increased. On the contrary, irradiation of a neodymium-doped yttrium aluminum garnet (Nd: YAG) laser at 1.06 µm exhibited no distinct bactericidal effect. No morphological changes were observed after MIR-FEL irradiation, suggesting that a bacterial organelle molecule may be the target of MIR-FEL irradiation, but the exact target was not identified. Furthermore, the temperature change induced in the culture medium by the laser irradiation was ± 1.5 °C at room temperature. These results suggest that the bactericidal effects of MIR-FEL are derived from photochemical reactions involving infrared photons, since E. coli is usually killed by heating it to 75 °C for 1 min or longer.

Artificial Intelligence-Powered Prediction of ALK Gene Rearrangement in Patients With Non-Small-Cell Lung Cancer.

PURPOSE: Several studies reported the possibility of predicting genetic abnormalities in non-small-cell lung cancer by deep learning (DL). However, there are no data of predicting ALK gene rearrangement (ALKr) using DL. We evaluated the ALKr predictability using the DL platform. MATERIALS AND METHODS: We selected 66 ALKr-positive cases and 142 ALKr-negative cases, which were diagnosed by ALKr immunohistochemical staining in our institution from January 2009 to March 2019. We generated virtual slide of 300 slides (150 ALKr-positive slides and 150 ALKr-negative slides) using NanoZoomer. HALO-AI was used to analyze the whole-slide imaging data, and the DenseNet network was used to build the learning model. Of the 300 slides, we randomly assigned 172 slides to the training cohort and 128 slides to the test cohort to ensure no duplication of cases. In four resolutions (16.0/4.0/1.0/0.25 µm/pix), ALKr prediction models were built in the training cohort and ALKr prediction performance was evaluated in the test cohort. We evaluated the diagnostic probability of ALKr by receiver operating characteristic analysis in each ALKr probability threshold (50%, 60%, 70%, 80%, 90%, and 95%). We expected the area under the curve to be 0.64-0.85 in the model of a previous study. Furthermore, in the test cohort data, an expert pathologist also evaluated the presence of ALKr by hematoxylin and eosin staining on whole-slide imaging. RESULTS: The maximum area under the curve was 0.73 (50% threshold: 95% CI, 0.65 to 0.82) in the resolution of 1.0 µm/pix. In this resolution, with an ALKr probability of 50% threshold, the sensitivity and specificity were 73% and 73%, respectively. The expert pathologist's sensitivity and specificity in the same test cohort were 13% and 94%. CONCLUSION: The ALKr prediction by DL was feasible. Further study should be addressed to improve accuracy of ALKr prediction.

A shuttling-based two-qubit logic gate for linking distant silicon quantum processors.

Control of entanglement between qubits at distant quantum processors using a two-qubit gate is an essential function of a scalable, modular implementation of quantum computation. Among the many qubit platforms, spin qubits in silicon quantum dots are promising for large-scale integration along with their nanofabrication capability. However, linking distant silicon quantum processors is challenging as two-qubit gates in spin qubits typically utilize short-range exchange coupling, which is only effective between nearest-neighbor quantum dots. Here we demonstrate a two-qubit gate between spin qubits via coherent spin shuttling, a key technology for linking distant silicon quantum processors. Coherent shuttling of a spin qubit enables efficient switching of the exchange coupling with an on/off ratio exceeding 1000, while preserving the spin coherence by 99.6% for the single shuttling between neighboring dots. With this shuttling-mode exchange control, we demonstrate a two-qubit controlled-phase gate with a fidelity of 93%, assessed via randomized benchmarking. Combination of our technique and a phase coherent shuttling of a qubit across a large quantum dot array will provide feasible path toward a quantum link between distant silicon quantum processors, a key requirement for large-scale quantum computation.

Quantum error correction with silicon spin qubits.

Future large-scale quantum computers will rely on quantum error correction (QEC) to protect the fragile quantum information during computation1,2. Among the possible candidate platforms for realizing quantum computing devices, the compatibility with mature nanofabrication technologies of silicon-based spin qubits offers promise to overcome the challenges in scaling up device sizes from the prototypes of today to large-scale computers3-5. Recent advances in silicon-based qubits have enabled the implementations of high-quality one-qubit and two-qubit systems6-8. However, the demonstration of QEC, which requires three or more coupled qubits1, and involves a three-qubit gate9-11 or measurement-based feedback, remains an open challenge. Here we demonstrate a three-qubit phase-correcting code in silicon, in which an encoded three-qubit state is protected against any phase-flip error on one of the three qubits. The correction to this encoded state is performed by a three-qubit conditional rotation, which we implement by an efficient single-step resonantly driven iToffoli gate. As expected, the error correction mitigates the errors owing to one-qubit phase-flip, as well as the intrinsic dephasing mainly owing to quasi-static phase noise. These results show successful implementation of QEC and the potential of a silicon-based platform for large-scale quantum computing.

The Combined Efficacy of a Two-Year Period of Cybernic Treatment With a Wearable Cyborg Hybrid-Assistive Limb and Leuprorelin Therapy in a Patient With Spinal and Bulbar Muscular Atrophy: A Case Report.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a rare, slowly progressive, incurable, and hereditary neurodegenerative disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. After extensive review, two treatments for SBMA have recently been approved in Japan; this decision was based on the results of randomized controlled trials: First, anti-androgen therapy using leuprorelin acetate (leuprorelin), a disease-modifying drug that can inhibit the progression of dysphagia but has not yet been proved to improve gait function; second, cybernic treatment with a wearable cyborg hybrid assistive limb (HAL®) (Cyberdyne Inc. Tsukuba, Japan). The HAL is an innovative walking exercise system that has been shown to significantly improve gait function in eight neuromuscular diseases without reduction in muscle function, including SBMA. It is possible that the combination of these two approaches might yield better outcomes. However, the long-term effects of such a combined approach have yet to be clinically evaluated. Here, we describe the case of a 39-year-old male with SBMA who commenced anti-androgen therapy with leuprorelin 1 year previously; this was followed by cybernic treatment with HAL. The duration of walking exercise with HAL was 20-30 min a day in one session. Over 2 weeks, the patient underwent nine sessions (one course). The efficacy of HAL was evaluated by gait function tests before and after one course of cybernic treatment. Then, leuprorelin treatment was combined with cybernic sessions every 2 months for 2 years (13 courses in total). Walking ability, as evaluated by the 2-min walk test, improved by 20.3% in the first course and peaked 10 months after the commencement of combined therapy (a 59.0% improvement). Walking function was maintained throughout the period. Generally, SBMA is characterized by moderately increased serum levels of creatine kinase (CK), reflecting neuromuscular damage; interestingly, the patient's CK levels decreased dramatically with combined therapy, indicating remarkable functional improvement. Long-term combined therapy improved the patient's gait function with a steady reduction in CK levels. The combination of leuprorelin with cybernic treatment can, therefore, improve and maintain gait function without damaging the motor unit and may also suppress disease progression.