Gait-combined closed-loop brain stimulation can improve walking dynamics in Parkinsonian gait disturbances: a randomised-control trial

日本発、歩行リハビリテーションの未来への一歩 パーキンソン病に新たな光明. 京都大学プレスリリース. 2023-06-23.[Objective] Gait disturbance lowers activities of daily living in patients with Parkinson’s disease (PD) and related disorders. However, the effectiveness of pharmacological, surgical and rehabilitative treatments is limited. We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation (tES) for healthy volunteers and patients who are post-stroke, and achieved significant entrainment of gait rhythm and an increase in gait speed. Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances. [Methods] Twenty-three patients were randomly assigned to a real intervention group using gait-combined closed-loop oscillatory tES over the cerebellum at the frequency of individualised comfortable gait rhythm, and to a sham control group. [Results] Ten intervention sessions were completed for all patients and showed that the gait speed (F(1, 21)=13.0, p=0.002) and stride length (F(1, 21)=8.9, p=0.007) were significantly increased after tES, but not after sham stimulation. Moreover, gait symmetry measured by swing phase time (F(1, 21)=11.9, p=0.002) and subjective feelings about freezing (F(1, 21)=14.9, p=0.001) were significantly improved during gait. [Conclusions] These findings showed that gait-combined closed-loop tES over the cerebellum improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms. This new non-pharmacological and non-invasive intervention could be a breakthrough in restoring gait function in patients with PD and related disorders

Levodopa‐Carbidopa Intestinal Gel Injection for Patient with Severe Parkinson's Disease Followed by Total Hip Arthroplasty: A Case Report and Literature Review

Background Patients with Parkinson's disease have a high dislocation rate after total hip arthroplasty (THA). This study describes a case with severe Parkinson's disease who developed rapidly destructive coxarthrosis (RDC) and underwent THA using a dual mobility cup after a levodopa‐carbidopa intestinal gel (LCIG) infusion. Case presentation The patient is a 59‐year‐old female with a ten‐year history of Parkinson's disease, which was first treated with oral levodopa. The patient developed RDC of the right hip joint. However, THA was difficult owing to Parkinson's disease and its treatment side effects, such as wearing‐off, dyskinesia, and freezing of the gait, Thus, LCIG was initiated, and improvement in wearing‐off and dyskinesia was observed. Two months after the LCIG therapy, the disease was controlled well. THA was subsequently performed using a dual mobility cup to prevent postoperative dislocation. Postoperatively, LCIG therapy was continuously administered to carefully manage the disease, which was controlled well with no increase in wearing‐off and dyskinesia after surgery. At 1 year after surgery, the walking speed, stride length, and the Harris hip score improved compared to preoperatively. The UPDRS III motor score improved to eight without signs of wearing‐off or dyskinesia. The Hoehn‐Yahr scale was II in the “on” period and remained unchanged 1 year after surgery. The patient could walk without a cane and had satisfactory functional outcomes. Conclusion This case proved that LCIG treatment performed preoperatively, followed by THA using a dual mobility cup, and strict management of Parkinson's disease could result in a satisfactory clinical course without recurrence of wearing‐off and dyskinesia. Similar procedures may benefit other patients with Parkinson's disease who have previously been deemed unsuitable for THA

Evaluation of lower extremity gait analysis using Kinect V2

Introduction: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. Methods: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson’s correlation and overall agreement with a method of meta-analysis of Pearson’s correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. Results: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. Conclusions: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint

Switching Tenofovir/Emtricitabine plus Lopinavir/r to Raltegravir plus Darunavir/r in Patients with Suppressed Viral Load Did Not Result in Improvement of Renal Function but Could Sustain Viral Suppression: A Randomized Multicenter Trial

<div><p>Background</p><p>Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral load.</p> <p>Methods</p><p>This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks calculated with Cockcroft-Gault equation.</p> <p>Results</p><p>58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3 (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026). Per protocol analysis showed that the HIV-RNA was <50 copies/mL at week 48 in all patients of both arms (24 in RAL+DRV and 29 in LPV/r+TVD).</p> <p>Conclusions</p><p>Switching LPV/r+TVD to RAL+DRV/r did not significantly increase the proportion of patients who showed >10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load.</p> <p>Trial Registration</p><p><a href="http://clinicaltrials.gov" target="_blank">ClinicalTrials.gov</a> NCT01294761 <a href="http://clinicaltrials.gov/ct2/show/nct01294761?term=spare&rank=2" target="_blank"><u>http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2</u></a>, Umin Clinical Trials Registry UMIN000005116 <a href="http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=r000006083&language=j" target="_blank"><u>http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J</u></a>)</p> </div

Proportion of patients with HIV RNA <50 copies/ml at 24 and 48 weeks.

<p>(A) Per protocol analysis. (B) Intention-to-treat analysis. VL, viral load; RAL, raltegravir; DRV/r, ritonavir-boosted darunavir; LPV/r, ritonavir-boosted lopinavir; TVD, fixed dose of tenofovir/emtricitabine.</p

Median changes in markers of renal tubular function between baseline and 48 weeks.

<p>(A) Urinary β2 microglobulin, (B) Urinary albumin, (C) Percent tubular resorption of phosphate, (D) Urinary N-acetyl-β-D-glucosaminidase. RAL, raltegravir; DRV/r, ritonavir-boosted darunavir; LPV/r, ritonavir-boosted lopinavir; TVD, fixed dose of tenofovir/emtricitabine.</p