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.

Case report: Chronic inflammatory demyelinating polyneuropathy superimposed on Charcot-Marie-tooth type 1A disease after SARS-CoV-2 vaccination and COVID-19 infection.

Background: There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of immune mediated neuropathies like chronic inflammatory demyelinating polyneuropathy (CIDP), but the impact of SARS-CoV-2 vaccination and COVID-19 infection on genetic disorders such as Charcot-MarieTooth (CMT) remains unclear. Case presentation: A 42-year-old male with occulted CMT neuropathy type lA (CMT1A) who developed limb numbness and weakness after the second SARS-CoV-2-vaccination was confirmed by identifying characteristic repeats in the p11.2 region of chromosome 17. Due to the progressive deterioration of muscle strength over 8 weeks, limb atrophy, moderately elevated protein counts in the cerebrospinal fluid, and significant improvement with intravenous human immunoglobulin, which were characteristic of acquired inflammatory neuropathies, he was eventually diagnosed with CIDP superimposed on CMT1A. However, after a three-month plateau, the patient contracted COVID-19, which led to repeated and worsening symptoms of limb weakness and atrophy, thus was diagnosed with a recurrence of CIDP and treated with Intravenous immunoglobulin and methylprednisolone 500 mg/d for 5 consecutive days, followed by oral prednisone and mycophenolate mofetil tablets. On 2 month follow-up, he exhibited remarkable clinical improvement and could walk independently with rocking gait. After 1 year of follow-up, the patient's condition was stable without further change. Conclusion: Our case indicates that CMT1A can deteriorate after SARS-CoV-2 vaccination. Thus, SARS-CoV-2 vaccination should be considered a potential predisposing factor for CMT1A worsening. The possible superposition of CMTIA and CIDP in the context of SARS-CoV-2 infection or immunity suggests that any clinical exacerbation in patients with CMT1A should be carefully evaluated to rule out treatable superposition inflammation. In addition, electrophysiological and imaging examination of the proximal nerves, such as the axillary nerve, is helpful for the diagnosis of CIDP.

Effects of rhythmic visual cues on cortical activation and functional connectivity features during stepping: an fNIRS study.

Introduction: Rhythmic visual cues (RVCs) may influence gait initiation by modulating cognition resources. However, it is unknown how RVCs modulate cognitive resources allocation during gait movements. This study focused on investigating the effects of RVCs on cortical hemodynamic response features during stepping to evaluate the changes of cognitive resources. Methods: We recorded cerebral hemoglobin concentration changes of 14 channels in 17 healthy subjects using functional near-infrared spectroscopy (fNIRS) during stepping tasks under exposure to RVCs and non-rhythmic visual cues (NRVCs). We reported mean oxygenated hemoglobin (HbO) concentration changes, ß-values, and functional connectivity (FC) between channels. Results: The results showed that, the RVC conditions revealed lower HbO responses compared to the NRVC conditions during the preparation and early stepping. Correspondingly, the ß-values reflected that RVCs elicited lower hemodynamic responses than NRVCs, and there was a decreasing trend in stimulus-evoked cortical activation as the task progressed. However, the FC between channels were stronger under RVCs than under NRVCs during the stepping progress, and there were more significant differences in FC during the early stepping. Discussion: In conclusion, there were lower cognitive demand and stronger FC under RVC conditions than NRVC conditions, which indicated higher efficiency of cognitive resources allocation during stepping tasks. This study may provide a new insight for further understanding the mechanism on how RVCs alleviate freezing of gait.

Short Step Length Estimation for Parkinson's Disease Patients by Using Fusion Data from Camera-IMU in Smart Glasses.

Shortened step length is a prominent motor abnormality in Parkinson's disease (PD) patients. Current methods for estimating short step length have the limitation of relying on laboratory scenarios, wearing multiple sensors, and inaccurate estimation results from a single sensor. In this paper, we proposed a novel method for estimating short step length for PD patients by fusing data from camera and inertial measurement units in smart glasses. A simultaneous localization and mapping technique and acceleration thresholding-based step detection technique were combined to realize the step length estimation. Two sets of experiments were conducted to demonstrate the performance of our method. In the first set of experiments with 12 healthy subjects, the proposed method demonstrated an average error of 8.44% across all experiments including six fixed step lengths below 30 cm. The second set of straightly walking experiments were implemented with 12 PD patients, the proposed method exhibited an average error of 4.27% compared to a standard gait evaluation technique in total walking distance. Notably, among the results of step lengths below 40 cm, our method agreed with the standard technique (R 2=0.8659). This study offers a promising approach for estimating short step length for PD patients during smart glasses-based gait training.

Serum Olink Proteomics-Based Identification of Protein Biomarkers Associated with the Immune Response in Ischemic Stroke.

The immune response is considered essential for pathology of ischemic stroke (IS), but it remains unclear which immune response-related proteins exhibit altered expression in IS patients. Here, we used Olink proteomics to examine the expression levels of 92 immune response-related proteins in the sera of IS patients (n = 88) and controls (n = 88), and we found that 59 of these proteins were differentially expressed. Feature variables were screened from the differentially expressed proteins by the least absolute shrinkage and selection operator (LASSO) and the random forest and by determining whether their proteins had an area under the curve (AUC) greater than 0.8. Ultimately, we identified six potential protein biomarkers of IS, namely, MASP1, STC1, HCLS1, CLEC4D, PTH1R, and PIK3AP1, and established a logistic regression model that used these proteins to diagnose IS. The AUCs of the models in the internal validation and the test set were 0.962 (95% confidence interval (CI): 0.895-1.000) and 0.954 (95% CI: 0.884-1.000), respectively, and the same protein detection method was performed in an external independent validation set (AUC: 0.857 (95% CI: 0.801-0.913)). These proteins may play a role in immune regulation via the C-type lectin receptor signaling pathway, the PI3K-AKT signaling pathway, and the B-cell receptor signaling pathway.

Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.

Corrigendum: Single- and dual-task gait performance and their diagnostic value in early-stage Parkinson's disease.

[This corrects the article DOI: 10.3389/fneur.2022.974985.].

Neuropsychiatric disturbance detecting polycythemia vera myelofibrosis: a case report and literature review.

Background: Neuropsychiatric disturbances and chorea are less recognized consequences of polycythemia vera (PV), and their role in post-PV myelofibrosis (MF) has not been reported. Clinical features that predict post-PV MF lack specificity. Case presentation: We describe an elderly patient with PV who developed acute-onset reversible neuropsychiatric disturbances accompanied by generalized chorea and was finally diagnosed with post-PV MF after a bone marrow examination. We also reviewed four cases of late PV associated with neuropsychiatric symptoms since 1966 and analyzed their clinical characteristics and therapeutic effects. Conclusion: Our case indicates that Janus kinase 2 (JAK2)-related PV is a treatable cause of late-onset chorea and that chorea may herald the deterioration of hematological parameters. Our case provides a clinically specific representation of post-PV MF. Patients with a long course of PV are recommended to undergo bone marrow re-examinations when they present with neuropsychiatric symptoms to achieve an early diagnosis of post-PV MF.

Single- and dual-task gait performance and their diagnostic value in early-stage Parkinson's disease.

Background: Gait parameters are considered potential diagnostic markers of Parkinson's disease (PD). We aimed to 1) assess the gait impairment in early-stage PD and its related factors in the single-task (ST) and dual-task (DT) walking tests and 2) evaluate and compare the diagnostic value of gait parameters for early-stage PD under ST and DT conditions. Methods: A total of 97 early-stage PD patients and 41 healthy controls (HC) were enrolled at Hwa Mei hospital. Gait parameters were gathered and compared between the two groups in the ST and DT walking test, controlling for covariates. Utilizing the receiver operating characteristic curve, diagnostic parameters were investigated. Results: In the ST walking test, significantly altered gait patterns could be observed in early-stage PD patients in all domains of gait, except for asymmetry (P < 0.05). Compared to the ST walking test, the early-stage PD group performed poorly in the DT walking test in the pace, rhythm, variability and postural control domain (P < 0.05). Older, heavier subjects, as well as those with lower height, lower level of education and lower gait velocity, were found to have a poorer gait performance (P < 0.05). Stride length (AUC = 0.823, sensitivity, 68.0%; specificity, 85.4%; P < 0.001) and heel strike angle (AUC = 0.796, sensitivity, 71.1%; specificity, 80.5%; P < 0.001) could distinguish early-stage PD patients from HCs with moderate accuracy, independent of covariates. The diagnostic accuracy of gait parameters under ST conditions were statistically noninferior to those under DT conditions(P>0.05). Combining all gait parameters with diagnostic values under ST and DT walking test, the predictive power significantly increased with an AUC of 0.924 (sensitivity, 85.4%; specificity, 92.7%; P < 0.001). Conclusion: Gait patterns altered in patients with early-stage PD but the gait symmetry remained preserved. Stride length and heel strike angle were the two most prominent gait parameters of altered gait in early-stage of PD that could serve as diagnostic markers of early-stage PD. Our findings are helpful to understand the gait pattern of early-stage PD and its related factors and can be conducive to the development of new diagnostic tools for early-stage PD.

Vestibulo-ocular reflex abnormality in Parkinson's disease detected by video head impulse test.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease characterized by dopaminergic neuronal loss. The underlying cause of PD is unknown. OBJECTIVE: To assess the clinical relevance of vestibular-ocular reflex (VOR) gain in patients with PD, especially those in the early stages. METHODS: Sixty-three PD patients and 56 control healthy individuals were enrolled in this study between Mar 2015 and Aug 2015. VOR gains were determined by video head impulse test (vHIT) device. Statistical analysis was performed to assess the difference in VOR gains between PD patients and normal people. The relationship of VOR gain with age, duration and severity of disease was also assessed. RESULTS: In the control group, average VOR gain was 0.98±0.09 on the left side and 0.99±0.16 on the right side. No statistically significant difference was observed between the two sides in the control group (P>0.05). In the PD group, average VOR gain was 1.20±0.22 on the left side and 1.23±0.23 on the right side. No statistically significant difference was observed between the two sides in the PD group (P>0.05). There was a significant difference in VOR gain between the PD (both in early and mid-late stages) and the control group (P<0.05). A weak correlation was observed between VOR gain and the motor Unified Parkinson Disease Rating Scale score. No correlation of VOR gain with age, duration of disease or the Hoehn and Yahr Scale score was observed. VOR gains in PD patients were found to be higher than normal, especially in the early stages of the disease. CONCLUSION: vHIT is a potential tool to determine the VOR gain in PD patients and may help detect PD at an early stage.

Isolated Medial Rectus Palsy: Rare Presentation of Mesencephalon Infarction.

Isolated medial rectus palsy due to mesencephalon lesion is extremely rare. We here describe a patient of midbrain infarction involving the medial rectus subnuclei presenting as isolated medial rectus palsy. Axial diffusion-weighted and coronal T2-weighted magnetic resonance imaging showed acute ischemic lesion in mesencephalon.

IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.

This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P < 0.05). In addition, IL-15 is proved to increase cell migration and nucleus expression of NF-kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels.

Cervical spinal epidural abscess following acupuncture and wet-cupping therapy: A case report.

OBJECTIVE: Report of an uncommon complication of acupuncture and wet cupping. METHODS: A 54-year-old man presented with neck pain and fever. Magnetic resonance imaging of the cervical spine revealed an epidural abscess at C4 to T2. RESULTS: The symptoms related to epidural abscess resolved partially after treatment with antibiotics. CONCLUSION: Acupuncture and wet-cupping therapy should be taken into consideration as a cause of spinal epidural abscesses in patients who present with neck pain and fever. Furthermore, acupuncture and wet-cupping practitioners should pay attention to hygienic measures.