Predicting slight freezing of gait in Parkinson's disease with anticipatory postural adjustments and limits of stability.

INTRODUCTION: Gait initiation (GI) includes automatic and voluntary movements. However, research on their impact on the first step in patients with Parkinson's disease (PD) and their relationship to freezing of gait (FOG) is lacking. We examined the effects of automatic movements (anticipatory postural adjustments [APAs]) and voluntary movements (limits of stability [LOS]) on the first step (first-step duration and first-step range of motion), along with their early recognition and prediction of slight FOG. METHODS: Twenty-three patients with PD and slight freezing (PD + FOG) and 25 non-freezing patients with PD (PD-FOG) were tested while off medications and compared with 24 healthy controls (HC). All participants completed a 7-m Stand and Walk Test (7 m SAW) and wore inertial sensors to quantify the APAs and first step. LOS was quantified by dynamic posturography in different directions using a pressure platform. We compared differences among all three groups, analysed correlations, and evaluated their predictive value for slight FOG. RESULTS: In PD + FOG, APAs and LOS were worse than those in the PD-FOG and HC groups (p < 0.001), and the first step was worse than that in HC (p < 0.001). APAs were correlated mainly with the first-step duration. APAs and LOS were correlated with the first-step range of motion. APAs have been recognized as independent predictors of FOG, and their combination with LOS enhances predictive sensitivity. CONCLUSION: APAs and LOS in patients with PD directly affect the first step during GI. In addition, the combination of APAs and LOS helped predict slight FOG.

Brain Temporal-Spectral Functional Variability Reveals Neural Improvements of DBS Treatment for Disorders of Consciousness.

Deep brain stimulation (DBS) is establishing itself as a promising treatment for disorders of consciousness (DOC). Measuring consciousness changes is crucial in the optimization of DBS therapy for DOC patients. However, conventional measures use subjective metrics that limit the investigations of treatment-induced neural improvements. The focus of this study is to analyze the regulatory effects of DBS and explain the regulatory mechanism at the brain functional level for DOC patients. Specifically, this paper proposed a dynamic brain temporal-spectral analysis method to quantify DBS-induced brain functional variations in DOC patients. Functional near-infrared spectroscopy (fNIRS) that promised to evaluate consciousness levels was used to monitor brain variations of DOC patients. Specifically, a fNIRS-based experimental procedure with auditory stimuli was developed, and the brain activities during the procedure from thirteen DOC patients before and after the DBS treatment were recorded. Then, dynamic brain functional networks were formulated with a sliding-window correlation analysis of phase lag index. Afterwards, with respect to the temporal variations of global and regional networks, the variability of global efficiency, local efficiency, and clustering coefficient were extracted. Further, dynamic networks were converted into spectral representations by graph Fourier transform, and graph energy and diversity were formulated to assess the spectral global and regional variability. The results showed that DOC patients under DBS treatment exhibited increased global and regional functional variability that was significantly associated with consciousness improvements. Moreover, the functional variability in the right brain regions had a stronger correlation with consciousness enhancements than that in the left brain regions. Therefore, the proposed method well signifies DBS-induced brain functional variations in DOC patients, and the functional variability may serve as promising biomarkers for consciousness evaluations in DOC patients.

Effective DBS treatment improves neural information transmission of patients with disorders of consciousness: an fNIRS study.

Objective.Deep brain stimulation (DBS) is a potential treatment that promotes the recovery of patients with disorders of consciousness (DOC). This study quantified the changes in consciousness and the neuromodulation effect of DBS on patients with DOC.Approach.Eleven patients were recruited for this study which consists of three conditions: 'Pre' (two days before DBS surgery), 'Post-On' (one month after surgery with stimulation), and 'Post-Off' (one month after surgery without stimulation). Functional near-infrared spectroscopy (fNIRS) was recorded from the frontal lobe, parietal lobe, and occipital lobe of patients during the experiment of auditory stimuli paradigm, in parallel with the coma recovery scale-revised (CRS-R) assessment. The brain hemodynamic states were defined and state transition acceleration was taken to quantify the information transmission strength of the brain network. Linear regression analysis was conducted between the changes in regional and global indicators and the changes in the CRS-R index.Main results.Significant correlation was observed between the changes in the global transition acceleration indicator and the changes in the CRS-R index (slope = 55.910,p< 0.001,R2= 0.732). For the regional indicators, similar correlations were found between the changes in the frontal lobe and parietal lobe indicators and the changes in the CRS-R index (slope = 46.612,p< 0.01,R2= 0.694; slope = 47.491,p< 0.01,R2= 0.676).Significance.Our study suggests that fNIRS-based brain hemodynamics transition analysis can signify the neuromodulation effect of DBS treatment on patients with DOC, and the transition acceleration indicator is a promising brain functional marker for DOC.

fNIRS-based functional connectivity signifies recovery in patients with disorders of consciousness after DBS treatment.

OBJECTIVE: While deep brain stimulation (DBS) has proved effective for certain patients with disorders of consciousness (DOC), the working neural mechanism is not clear, the response varies for patients, and the assessment is inadequate. This paper aims to quantify the DBS-induced changes of consciousness in DOC patients at the neural functional level. METHODS: Ten DOC patients were included for DBS surgery. The DBS target was the right centromedian-parafascicular (CM-pf) nuclei for four patients and the bilateral CM-pf nuclei for six patients. Functional near-infrared spectroscopy (fNIRS) was taken to measure the neural activation of patients, in parallel with Coma Recovery Scale-Revised (CRS-R), before the DBS surgery and one month after. The fNIRS signals were recorded from the frontal, parietal, and occipital lobes. Functional connectivity analysis quantified the communication between brain regions, area communication strength, and global communication efficiency. Linear regression analysis was conducted between the changes of indices based on functional connectivity analysis and the changes of the CRS-R index. RESULTS: Patients with trauma (n = 4) exhibited a greater increase of CRS-R scores after DBS treatment compared with patients with hemorrhage (n = 4) and brainstem infarction (n = 2). Global communication efficiency changed consistently with the CRS-R index (slope = 57.384, p < 0.05, R2=0.483). No significant relationship was found between the changes of area communication strength of six brain lobes and the changes of the CRS-R index. CONCLUSIONS: The cause of DOC is essential for the outcome of DBS treatment, and brain communication efficiency is a promising functional marker for DOC recovery. SIGNIFICANCE: fNIRS-based functional connectivity analysis on brain network signifies changes of consciousness in DOC patients after DBS treatment.

A non-contact system for intraoperative quantitative assessment of bradykinesia in deep brain stimulation surgery.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for a number of neurological diseases, especially for the advanced stage of Parkinson's disease (PD). Objective assessment of patients' motor symptoms is crucial for accurate electrode targeting and treatment. Existing approaches suffer from subjective variability or interference with voluntary motion. This work is aimed to establish an objective assessment system to quantify bradykinesia in DBS surgery. METHODS: Based on the analysis of the requirements for intraoperative assessment, we developed a system with non-contact measurement, online movement feature extraction, and interactive data analysis and visualization. An optical sensor, Leap Motion Controller (LMC), was taken to detect hand movement in three clinical tasks. A graphic user interface was designed to process, compare and visualize the collected data and assessment results online. Quantified movement features include amplitude, frequency, velocity, their decrement and variability, etc. Technical validation of the system was performed with a motion capture system (Mocap), with respect to data-level and feature-level accuracy and reliability. Clinical validation was conducted with 20 PD patients for intraoperative assessments in DBS surgery. Treatment responses with respect to the bradykinesia movement features were analyzed. Single case analysis and group statistical analysis were performed to examine the differences between preoperative and intraoperative performance, and the correlation between the clinical ratings and the quantified assessment was analyzed. RESULTS: For the movements measured by LMC and Mocap, the average Pearson's correlation coefficient was 0.986, and the mean amplitude difference was 2.11 mm. No significant difference was found for all movement features quantified by LMC and Mocap. For the clinical tests, key movement features showed significant differences between the preoperative baseline and intraoperative performance when the brain stimulation was ON. The assessment results were significantly correlated with the MDS-UPDRS clinical ratings. CONCLUSIONS: The proposed non-contact system has established itself as an objective intraoperative assessment, analysis, and visualization tool for DBS treatment of Parkinson's disease.

Plantar pressure-based temporal analysis of gait disturbance in idiopathic normal pressure hydrocephalus: Indications from a pilot longitudinal study.

BACKGROUND AND OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is a common yet potentially reversible neurodegenerative disease, and gait disturbance is a major symptom. Lots of methodological and clinical work has been conducted on gait disturbance analysis for differential diagnosis, presurgical test, and postsurgery assessment of iNPH. Nevertheless, the verification analysis was mostly lacking for surgery response, and the temporal characteristics of ground reaction force has been rarely investigated. METHODS: In this work, we propose that plantar pressure features fundamentally signifies iNPH gait disturbance and improvement after cerebrospinal fluid (CSF) drainage by lumbar puncture tap test as well as surgical shunt implantation. The plantar pressure signals of six iNPH patients and eight healthy controls were collected, and an online database of sixteen healthy controls were used. For patients, data were collected in five periods, which are the baseline before the tap test, 8, 24, and 72 hours after the tap test, and one month after the shunt implantation surgery, respectively. Fast dynamic time warping (DTW) with an improved DTW barycenter averaging (DBA) method was proposed for temporal analysis with the measured and online plantar pressure data. An plantar-pressure variation index (PPVI) was formulated to characterize the temporal dynamic stability of walking. RESULTS: The PPVI based on temporal analysis of plantar pressure well discriminated the impaired gait (baseline, 24 and 72 hours after tap test) with the improved gait (8 hours after tap test and follow up after surgery) of the patients. Further, the PPVI was close for the improved gait of the patients and the healthy gait measured in our study as well as in the online database. CONCLUSIONS: Plantar pressure-based temporal features are promisingly effective for clinical examination and treatment of iNPH.

Quantified assessment of deep brain stimulation on Parkinson's patients with task fNIRS measurements and functional connectivity analysis: a pilot study.

BACKGROUND: Deep brain stimulation (DBS) has proved effective for Parkinson's disease (PD), but the identification of stimulation parameters relies on doctors' subjective judgment on patient behavior. METHODS: Five PD patients performed 10-meter walking tasks under different brain stimulation frequencies. During walking tests, a wearable functional near-infrared spectroscopy (fNIRS) system was used to measure the concentration change of oxygenated hemoglobin (△HbO2) in prefrontal cortex, parietal lobe and occipital lobe. Brain functional connectivity and global efficiency were calculated to quantify the brain activities. RESULTS: We discovered that both the global and regional brain efficiency of all patients varied with stimulation parameters, and the DBS pattern enabling the highest brain efficiency was optimal for each patient, in accordance with the clinical assessments and DBS treatment decision made by the doctors. CONCLUSIONS: Task fNIRS assessments and brain functional connectivity analysis promise a quantified and objective solution for patient-specific optimization of DBS treatment. TRIAL REGISTRATION: Name: Accurate treatment under the multidisciplinary cooperative diagnosis and treatment model of Parkinson's disease. Registration number is ChiCTR1900022715. Date of registration is April 23, 2019.

Intraoperative Quantitative Measurements for Bradykinesia Evaluation during Deep Brain Stimulation Surgery Using Leap Motion Controller: A Pilot Study.

Deep brain stimulation (DBS) has shown a remarkably high effectiveness for Parkinson's disease (PD). In many PD patients during DBS surgery, the therapeutic effects of the stimulation test are estimated by assessing changes in bradykinesia as the stimulation voltage is increased. In this study, we evaluated the potential of the leap motion controller (LMC) to quantify the motor component of bradykinesia in PD during DBS surgery, as this could make the intraoperative assessment of bradykinesia more accurate. Seven participants with idiopathic PD receiving chronic bilateral subthalamic nucleus deep brain stimulation (DBS) therapy were recruited. The motor tasks of finger tapping (FT), hand opening and closing (OC), and hand pronation and supination (PS) were selected pre- and intraoperatively in accordance with the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale. During the test, participants performed these tasks in sequence while being simultaneously monitored by the LMC and two professional clinicians. Key kinematic parameters differed between the preoperative and intraoperative conditions. We suggest that the average velocity ( V ¯ ) and average amplitude ( A ¯ ) of PS isolate the bradykinetic feature from that movement to provide a measure of the intraoperative state of the motor system. The LMC achieved promising results in evaluating PD patients' hand and finger bradykinesia during DBS surgery.

Quantitative Analysis of Postural Instability in Patients with Parkinson's Disease.

INTRODUCTION: Postural instability is commonly observed in Parkinson's disease, leading to an increasing risk of falling and worsening as the disease progresses. We found that limit of stability can be applied to reflect the dynamic evolution of postural instability in patients with Parkinson's disease. METHODS: Forty-three patients (9 of Hoehn and Yahr stage I, 12 of stage II, 14 of stage III, and 8 of stage IV) met the criteria for the diagnosis of idiopathic Parkinson's disease and could stand independently for at least 10 minutes. Twelve healthy controls with no sign of parkinsonism were also recruited. Postural instability was assessed by posturography in different directions (forward, backward, right, left, forward-right, forward-left, backward-right, and backward-left). This study trial was registered with the Chinese Clinical Trial Registry (no. ChiCTR1900022715). RESULTS: All participants were able to complete the limit of stability tasks without any complications. Patients in stages II to IV exhibited smaller end point excursion and slower time to complete than controls, suggesting an impaired limit of stability. The patients in stage II exhibited a remarkable decline in most directions compared to controls, except for right and left, and forward and backward decline occurred the earliest. For patients in stage III, right was the only direction with no significant difference from controls. In stage IV patients, the limit of stability declined significantly in all directions (p < 0.05). CONCLUSIONS: The postural abnormalities of Parkinson's disease can occur at early stages, and the pattern of decline is more severe in the forward-backward direction. This trial is registered with ChiCTR1900022715.

Effect of Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) on balance performance in Parkinson's disease.

PURPOSE: To study the effect of STN-DBS on balance performance of Parkinson's disease. METHOD: 16 idiopathic PD patients treated with bilateral STN-DBS (DBS Group) and 20 PD patients treated with Levodopa (Medicine group) were included in the study. Clinical material including Levodopa Equivalent Daily Dose (LEDD, mg/day), life quality (PDQ-39) were collected. For DBS group and Medicine group, The motor disability (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale Ⅲ, MDS-UPDRSIII) and balance performance (MDS-UPDRS 3.12, Berg Balance Scale BBS) and the Limits of Stability (LoS) (target acquisition percentage, trunk swing angle standard deviation, time) in state of Med-Off/Med-On at preoperation, postoperation, 6 months postoperation and 12 months postoperation were evaluated. Repeated ANOVA was used to analyze the effect of STN-DBS on balance performance. RESULT: The Clinical material (age, gender, duration, LEDD preoperation, PDQ39), motor disability (Med-on/Med-Off), balance performance (Med-on/Med-Off) and LoS preoperation had no differences in DBS-group and Medical-group (P>0.05). During the follow up, LEDD, PDQ39, Motor disability (MDS-UPDRSIII), balance performance (MDS-UPDRS 3.12, BBS) in Medicine-group had no significant changes in both Med-Off and Med-On. For DBS-group, immediately improvement of motor disability (MDS-UPDRSIII), LoS (target acquisition percentage, trunk swing angle standard deviation, time) and LEDD were observed postoperation (P<0.05); PDQ39, balance performance (MDS-UPDRS 3.12, BBS) began to improve at 6 months and 12 months postoperation. Repeated ANOVA showed that DBS could significantly improve the motor disability, balance performance and LoS in PD. CONCLUSION: STN-DBS could improve the balance performance of PD patients in H&Y3.

Clinical experience of comprehensive treatment on the balance function of Parkinson's disease.

To investigate the effect of multi-disciplinary teamwork on balance performance of Parkinson's disease (PD).Sixteen primary Parkinson's disease patients (8 male, 8 female) treated with bilateral subthalamic nucleus deep brain stimulation (STN-DBS) were included in the study. The median age of patients was 60.5 years; all patients were in the Hoehn&Yahr (H&Y) 3 stage; the median PD duration of the disease was 9 years. For each patient, multi-disciplinary teamwork treatment including DBS, medication, physical therapy and psychotherapy proceeded. levodopa equivalent daily dose (LEDD, mg/day), life quality (PDQ-39), Motor disability (MDS-UPDRSIII) and balance performance (MDS-UPDRS 3.12, Berg Balance Scale BBS, Limits of Stability LoS) were assessed in different time and status respectively: preoperation (Med-off, Med-on), postoperation (Stim-Off/Med-Off, Stim-On/Med-Off, Stim-On/Med-On), 6 months postoperation (Stim-On/ Med-Off, Stim-On/Med-On) and 12 months postoperation (Stim-On/Med-Off, Stim-On/Med-On).The LEDD, life quality (PDQ-39) continued to improve during the follow-up, statistical difference were found in both 6 months postoperation and 12 months postoperation compared with preoperation. The Motor disability (MDS-UPDRSIII), balance performance (MDS-UPDRS 3.12, BBS) and the LoS (target acquisition percentage, trunk swing angle standard deviation, time) showed significant improvement in Stim-On/med-Off 6 months postoperation and 12 months postoperation separately compared with Med-Off preoperation.Multi-disciplinary teamwork for PD patients with STN-DBS could improve balance performance.

The Study of Subthalamic Deep Brain Stimulation for Parkinson Disease-Associated Camptocormia.

BACKGROUND Camptocormia is an axis symptom of Parkinson disease. It remains uncertain whether treatment with medications and surgery are effective. In this study, we assessed the efficacy of subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson disease-associated camptocormia and explored some of its mechanisms. MATERIAL AND METHODS Parkinson disease-associated camptocormia was diagnosed by the following procedures. All patients underwent bilateral STN DBS. The patents' camptocormia was rated by degree and MDS Unified Parkinson's Disease Rating Scale (UPDRS) item 3.13 before and after DBS surgery. Rehabilitation and psychological interventions were used after surgery, in addition to adjustments of medication and stimulus parameters. The treatment effects on camptocormia were assessed comparing medication-off (presurgery) versus stimulation-on (post-surgery). Ethical approval for this study was provided through the Center of Human Research Ethics Committee (No. 2019-35). This study trial was registered in Chinese Clinical Trial Registry (No. ChiCTR1900022655). All the participants provided written informed consent. RESULTS After DBS surgery, all of study patients' symptoms were improved, with different levels of improvement. The minimum and maximum improvement rates were 20% and 100% respectively. The score of item 3.13 of the MDS-UPDRS III and the degree of camptocormia were found to be obviously improved (P<0.05). CONCLUSIONS STN DBS can improve Parkinson disease-associated camptocormia; STN DBS assisted with rehabilitation and psychological intervention appears to be more effective.

The experimental study of miRNA in pituitary adenomas.

AIM: We investigated the differential miRNA expression in pituitary adenomas (both non-functioning and gonadotropin-secreting) and normal pituitaries. MATERIAL AND METHODS: RNA was extracted and purified from pituitary adenomas (10 non-functioning and 10 gonadotropin-secreting) and from two normal pituitary tissue samples. The samples were analyzed by miRNA microarray. Gene expression was measured using realtime RT-PCR with SYBR GREEN I. RESULTS: In non-functioning pituitary adenomas, 25 miRNA genes were up-regulated (six by over 5-fold) and 15 were down-regulated (six by more than 10-fold). miR-124a was the most up-regulated gene (38.58-fold), and miR-31 the most down-regulated gene (21.5-fold). In gonadotropin-secreting pituitary adenomas, 16 miRNA genes were up-regulated (six by over 4-fold) and 13 were down-regulated (seven by more than 10-fold). miR-10b was the most up-regulated gene (48.73-fold), and miR-503 the most down-regulated gene (39.8-fold). Five genes were up-regulated in both subtypes: miR-523, miR-10b, miR-520b, miR-422a, and miR-422b. The RT-PCR results were consistent with those of the gene chips. CONCLUSION: We established miRNA expression maps of non-functioning and gonadotropin-secreting pituitary adenomas. The most strongly differentially expressed genes were miR-124a and miR-31 in non-functioning pituitary adenomas, and miR-10b and miR-503 in gonadotropin-secreting pituitary adenomas.

[Value of intraoperative ultrasound in precise glioma resection].

OBJECTIVE: To explore the application value of real-time intraoperative ultrasound in glioma surgery. METHODS: A total of 80 cases of glioma were localized by intraoperative ultrasound, and their resection degree was evaluated postoperatively by magnetic resonance imaging (MRI). RESULTS: All gliomas were located precisely by real-time intraoperative ultrasound under the guidance of preoperative MRI. Among them, 72 cases underwent total resection, 2 cases had residual tumor on post-operative MRI. Subtotal resection was performed in 8 cases. And one of them had larger residual tumor on post-operative MRI. The accuracy rate of resection was 96.2%. There was no complication related with ultrasound. CONCLUSION: Intraoperative ultrasound may help a neurosurgeon to locate lesions, select optimal approaches, guide operative procedures and estimate the extent of resection. Because of its small, flexible and convenient features, it will be widely used in neurosurgery.

[Intraoperative oculomotor nerve monitoring during skull base tumor surgery].

OBJECTIVE: To explore the intraoperative oculomotor nerve monitoring during skull base tumor surgery for injury avoidance. METHODS: The study was conducted from January 2006 to January 2012. Monitoring group:35 skull base tumor operations were monitored by neurophysiology (22 males and 13 females). CONTROL GROUP: 26 skull base tumor operations without intraoperative monitoring were treated with microsurgery alone (16 males and 10 females). The prognoses of different groups were evaluated. RESULTS: Monitoring group:2 cases had injury of oculomotor nerve. One of them suffered mild diplopia and recovered one months later. Another one had blepharoptosis and mydriasis, reaction to light was absent and recovered six months later. CONTROL GROUP: 6 cases had injury of oculomotor nerve. Five of 6 cases recovered six months later. And one showed no recovery after a 1-year follow-up. CONCLUSION: Intraoperative monitoring of oculomotor is essential for the protection of oculomotor nerve during skull base tumor surgery.