Cholinergic nucleus degeneration and its association with gait impairment in Parkinson's disease.

BACKGROUND: The contribution of cholinergic degeneration to gait disturbance in Parkinson's disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD. METHODS: This cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association. RESULTS: PD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1-2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side. CONCLUSIONS: Our study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei's impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

The impact of anxiety on gait impairments in Parkinson's disease: insights from sensor-based gait analysis.

BACKGROUND: Sensor-based gait analysis provides a robust quantitative tool for assessing gait impairments and their associated factors in Parkinson's disease (PD). Anxiety is observed to interfere with gait clinically, but this has been poorly investigated. Our purpose is to utilize gait analysis to uncover the effect of anxiety on gait in patients with PD. METHODS: We enrolled 38 and 106 PD patients with and without anxiety, respectively. Gait parameters were quantitively examined and compared between two groups both in single-task (ST) and dual-task (DT) walking tests. Multiple linear regression was applied to evaluate whether anxiety independently contributed to gait impairments. RESULTS: During ST, PD patients with anxiety presented significantly shorter stride length, lower gait velocity, longer stride time and stance time, longer stance phase, smaller toe-off (TO) and heel-strike (HS) angles than those without anxiety. While under DT status, the differences were diminished. Multiple linear regression analysis demonstrated that anxiety was an independent factor to a serials of gait parameters, particularly ST-TO (B = -2.599, (-4.82, -0.38)), ST-HS (B = -2.532, (-4.71, -0.35)), ST-TO-CV (B = 4.627, (1.71, 7.64)), ST-HS-CV(B = 4.597, (1.66, 7.53)), ST stance phase (B = 1.4, (0.22, 2.58)), and DT stance phase (B = 1.749, (0.56, 2.94)). CONCLUSION: Our study discovered that anxiety has a significant impact on gait impairments in PD patients, especially exacerbating shuffling steps and prolonging stance phase. These findings highlight the importance of addressing anxiety in PD precision therapy to achieve better treatment outcomes.

A retrospective analysis on 1901 women with high grade cervical intraepithelial neoplasia by colposcopic biopsy.

OBJECTIVE: Clinically, an unbefitting management for high grade squamous intraepithelial lesion (HSIL) may result from an inaccurate diagnosis by colposcopy bioposy.The study aimed to assess the diagnostic accuracy by colposcopic biopsy and evaluate the associated factors in diagnosing HSIL. STUDY DESIGN: Clinical data of 1901 women who were primarily diagnosed as HSIL by colposcopic biopsy and then underwent definitive surgery within six-month interval in Women's Hospital, School of Medicine, Zhejiang University during 2009-2015, were retrospectively collected. The diagnostic accuracy of HSIL by colposcopic biopsy was assessed and the correlations between diagnostic accuracy and clinic-pathological variables were calculated by univariate and multivariate analysis using the pathological diagnosis by definitive surgery as a reference standard. RESULTS: The accordance rate of HSIL diagnosis between colposcopic biopsy and definitive surgery was 80.6%, with an under-diagnosis rate of 5.8% and an over-diagnosis rate of 13.6%. Cytology≤low grade squamous intraepithelial lesion(LSIL) (OR:1.599;95%CI:1.185-2.160), colposcopy≤LSIL (OR:2.083;95%CI:1.537-2.824), endocervical curettage (ECC)≤LSIL(OR:2.813;95%CI:2.051-3.857), and lesion without gland involved (OR:1.751;95%CI:1.299-2.361) were independent risk factors for over-diagnosis of HSIL. Women with≥3 risk factors had a 5.078-flod higher risk for over-diagnosis of HSIL compared to those with≤1 risk factor. Irregular vaginal bleeding (OR:2.570,95%CI:1.668-3.960), colposcopy=HSIL (OR:1.699,95%CI:1.022-2.824), ECC=HSIL (OR:2.666, 95%CI:1.728-4.113), and multiple biopsies (OR:1.818, 95%CI:1.153-2.868) were independent risk factors for under-diagnosis of HSIL. Women with ≥3 risk factors had a 5.710-flod higher risk for under-diagnosis of HSIL compared to those with ≤1 risk factor. CONCLUSIONS: The diagnostic accuracy of HSIL by colposcopic biopsy is about 80% and associated with some factors including symptom, cytology result, colposcopy diagnosis, and biopsy number. These variables may be predictors for over-diagnosis or under-diagnosis of HSIL by colposcopic biopsy.