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Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson’s disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase. In the STN, beta-band oscillations are modulated by external cues, but it is unknown if this relationship holds in the globus pallidus (GP). Here we report LFP data recorded from the left GP, using a Medtronic PC + S device, in a 68-year-old man with PD and FOG during treadmill walking. A “stepping stone” task was used during which stepping was cued using visual targets of constant color or targets that unpredictably changed color, requiring a step length adjustment. Gait performance was quantified using measures of treadmill ground reaction forces and center of pressure and body kinematics from video monitoring. Beta-band power (12–30 Hz) and number of freezing episodes were measured. Cues which unpredictably changed color improved FOG more than conventional cues and were associated with greater modulation of beta-band power in phase with gait. This preliminary finding suggests that cueing-induced improvement of FOG may relate to beta-band modulation.

BackgroundThe preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown.MethodsIn this single-center, retrospective analyses, 66 Parkinson’s disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi’s gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed.ResultsSubthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders.ConclusionDeep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients.

This study investigated the relationship between preoperative cerebral blood flow (CBF) in patients with idiopathic normal pressure hydrocephalus (INPH) and preoperative clinical symptoms and changes of clinical symptoms after shunt surgery. A total of 32 patients with diagnosed INPH and 18 age-matched healthy controls (HCs) were involved in this study. All subjects underwent magnetic resonance imaging (MRI), including 3D pulsed arterial-spin labeling (PASL) for non-invasive perfusion imaging, and clinical symptom evaluation at baseline, and all patients with INPH were reexamined with clinical tests 1 month postoperatively. Patients with INPH had significantly lower whole-brain CBF than HCs, with the most significant differences in the high convexity, temporal lobe, precuneus, and thalamus. At baseline, there was a significant correlation between the CBF in the middle frontal gyrus, calcarine, inferior and middle temporal gyrus, thalamus, and posterior cingulate gyrus and poor gait manifestation. After shunting, improvements were negatively correlated with preoperative perfusion in the inferior parietal gyrus, inferior occipital gyrus, and middle temporal gyrus. Preoperative CBF in the middle frontal gyrus was positively correlated with the severity of preoperative cognitive impairment and negatively correlated with the change of postoperative MMSE score. There was a moderate positive correlation between anterior cingulate hypoperfusion and improved postoperative urination. Our study revealed that widely distributed and intercorrelated cortical and subcortical pathways are involved in the development of INPH symptoms, and preoperative CBF may be correlative to short-term shunt outcomes.

Background: The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown. Methods: In this single-center, retrospective analyses, 66 Parkinson's disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi's gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed. Results: Subthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders. Conclusion: Deep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between preoperative cerebral blood flow (CBF) in patients with idiopathic normal pressure hydrocephalus (INPH) and preoperative clinical symptoms and changes of clinical symptoms after shunt surgery. A total of 32 patients with diagnosed INPH and 18 age-matched healthy controls (HCs) were involved in this study. All subjects underwent magnetic resonance imaging (MRI), including 3D pulsed arterial-spin labeling (PASL) for non-invasive perfusion imaging, and clinical symptom evaluation at baseline, and all patients with INPH were reexamined with clinical tests 1 month postoperatively. Patients with INPH had significantly lower whole-brain CBF than HCs, with the most significant differences in the high convexity, temporal lobe, precuneus, and thalamus. At baseline, there was a significant correlation between the CBF in the middle frontal gyrus, calcarine, inferior and middle temporal gyrus, thalamus, and posterior cingulate gyrus and poor gait manifestation. After shunting, improvements were negatively correlated with preoperative perfusion in the inferior parietal gyrus, inferior occipital gyrus, and middle temporal gyrus. Preoperative CBF in the middle frontal gyrus was positively correlated with the severity of preoperative cognitive impairment and negatively correlated with the change of postoperative MMSE score. There was a moderate positive correlation between anterior cingulate hypoperfusion and improved postoperative urination. Our study revealed that widely distributed and intercorrelated cortical and subcortical pathways are involved in the development of INPH symptoms, and preoperative CBF may be correlative to short-term shunt outcomes. [ABSTRACT FROM AUTHOR]

The issue of aging is a complex social challenge. When elderly people suffer from diseases such as hemiplegia, their quality of life is greatly affected. The only way to reduce the impact of such diseases is to perform long-term rehabilitation, which is extremely time-consuming. Thus, gait information for clinical practice can effectively help subjects with stroke and their occupational therapists. In this study, a pressure-sensor-based gait analysis system is proposed to help occupational therapists evaluate the gait of disabled people. To effectively acquire gait information without affecting the user's activities, the insole of the foot is selected as the pressure-sensing interface. To accurately acquire information of the plantar pressure, force-sensing resistor (FSR) film pressure sensors (FPSs) are used. To greatly reduce the differences between the outputs of FSR FPSs, linear regression is used to normalize the outputs. To correctly detect the steps in the gait cycle, an endpoint detection algorithm is applied. The experimental results showed that the proposed normalization process can greatly reduce the differences between the outputs of FSR FPSs. Moreover, occupational therapists agreed that the proposed system can help them evaluate the gait of users. [ABSTRACT FROM AUTHOR]

This pilot study investigated the feasibility and preliminary effects of an intensive 1-week day camp program for children with Developmental Coordination Disorder (DCD) that focused on vestibular rehabilitation. Ten participants (6-10 years) were assessed twice pre-intervention, post intervention, and at 8-week follow-up. Videonystagmography, Video Head Impulse Tests (vHIT), and Modified Emory Clinical Vestibular Chair Test (m-ECVCT) test were assessed at baseline. Outcomes measures were gaze stability (Dynamic Visual Acuity; DVA), functional gait (Functional Gait Assessment; FGA), balance (Sensory Organization Test), motor function (Bruininks-Oseretsky Test), and participation (Miller Function and Participation). No abnormal results were detected from the videonystagmography, vHIT and m-ECVCT. There was a 100% attendance rate at the camp and assessment sessions. FGA scores significantly improved following intervention and changes were maintained at follow-up. The number of children with abnormal DVA scores decreased from 3 to 1 to 0 between pre-intervention, post-intervention, and follow-up. There were no significant changes in any of the other outcomes following intervention. Intensive vestibular rehabilitation delivered in a day camp format is feasible and show positive preliminary effects on functional gait and dynamic visual acuity in children with DCD. [ABSTRACT FROM AUTHOR]

The study preliminarily explored the sequence and difference of involvement in different neuroanatomical structures in idiopathic normal pressure hydrocephalus (INPH). We retrospectively analyzed the differences in diffusion tensor imaging (DTI) parameters in 15 ROIs [including the bilateral centrum semiovale (CS), corpus callosum (CC) (body, genu, and splenium), head of the caudate nucleus (CN), internal capsule (IC) (anterior and posterior limb), thalamus (TH), and the bilateral frontal horn white matter hyperintensity (FHWMH)] between 27 INPH patients and 11 healthy controls and the correlation between DTI indices and clinical symptoms, as evaluated by the INPH grading scale (INPHGS), the Mini-Mental State Examination (MMSE), and the timed up and go test (TUG-t), before and 1 month after shunt surgery. Significant differences were observed in DTI parameters from the CS (pFA1 = 0.004, pADC1 = 0.005) and the genu (pFA2 = 0.022; pADC2 = 0.001) and body (pFA3 = 0.003; pADC3 = 0.002) of the CC between the groups. The DTI parameters from the CS were strongly correlated with the MMSE score both pre-operatively and post-operatively. There was association between apparent diffusion coefficient (ADC) values of anterior and posterior limbs of the IC and MMSE. The DTI parameters of the head of the CN were correlated with motion, and the ADC value was significantly associated with the MMSE score. The FA value from TH correlated with an improvement in urination after shunt surgery. We considered that different neuroanatomical structures are affected differently by disease due to their positions in neural pathways and characteristics, which is further reflected in clinical symptoms and the prognosis of shunt surgery.

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson’s disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD.Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h/day, 6 days/week) of enriched rehabilitation (ER; n = 20; mean age, 66.14 ± 4.15 years; 45% men) or conventional rehabilitation (CR; n = 20; mean age 65.32 ± 4.23 years; 50% men). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed the general motor function using the Unified PD Rating Scale—Part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI).Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER.Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG).

The study preliminarily explored the sequence and difference of involvement in different neuroanatomical structures in idiopathic normal pressure hydrocephalus (INPH). We retrospectively analyzed the differences in diffusion tensor imaging (DTI) parameters in 15 ROIs [including the bilateral centrum semiovale (CS), corpus callosum (CC) (body, genu, and splenium), head of the caudate nucleus (CN), internal capsule (IC) (anterior and posterior limb), thalamus (TH), and the bilateral frontal horn white matter hyperintensity (FHWMH)] between 27 INPH patients and 11 healthy controls and the correlation between DTI indices and clinical symptoms, as evaluated by the INPH grading scale (INPHGS), the Mini-Mental State Examination (MMSE), and the timed up and go test (TUG-t), before and 1 month after shunt surgery. Significant differences were observed in DTI parameters from the CS (p FA1 = 0.004, p ADC1 = 0.005) and the genu (p FA2 = 0.022; p ADC2 = 0.001) and body (p FA3 = 0.003; p ADC3 = 0.002) of the CC between the groups. The DTI parameters from the CS were strongly correlated with the MMSE score both pre-operatively and post-operatively. There was association between apparent diffusion coefficient (ADC) values of anterior and posterior limbs of the IC and MMSE. The DTI parameters of the head of the CN were correlated with motion, and the ADC value was significantly associated with the MMSE score. The FA value from TH correlated with an improvement in urination after shunt surgery. We considered that different neuroanatomical structures are affected differently by disease due to their positions in neural pathways and characteristics, which is further reflected in clinical symptoms and the prognosis of shunt surgery. [ABSTRACT FROM AUTHOR]

Raymond Garcin, professor of neurology in Paris, France, and his Brazilian assistant, Professor Roberto Melaragno described in 1948 the phenomenon defined as "bégaiement de la mise en route du mouvement" in patients with Parkinson's disease. This was one of the first descriptions of freezing of gait (FOG) in the world. [ABSTRACT FROM AUTHOR]

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson's disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD. Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h/day, 6 days/week) of enriched rehabilitation (ER; n = 20; mean age, 66.14 ± 4.15 years; 45% men) or conventional rehabilitation (CR; n = 20; mean age 65.32 ± 4.23 years; 50% men). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed the general motor function using the Unified PD Rating Scale—Part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI). Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER. Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG). [ABSTRACT FROM AUTHOR]

BACKGROUND: In patients with Parkinson disease (PD), severe postural and gait impairments are rarely observed in early stage of disease and non-motor symptoms (NMS) are often overlooked. OBJECTIVE: This observational study aimed to characterize the impact of non-motor impairments on walking kinematics in early stages PD patients, and to assess the differences of gait parameters and NMS between PD patients with and without mild cognitive impairment (MCI). METHODS: Twenty-six patients with Modified Hoehn and Yahr Scale score≤2 were evaluated for NMS using Kings Parkinson's Pain Scale, Parkinson Fatigue Severity scale, Parkinson Anxiety Scale, Beck Depression Inventory and Epworth Sleepiness Scale, kinematic parameters through an inertial sensor and cognitive performance by a comprehensive neuropsychological battery. RESULTS: Fatigue had a moderate negative correlation with step cadence, and a moderate to strong positive correlation with gait duration, Timed Up and Go (TUG) and TUG Dual Task (p < 0.01). Pain showed positive moderate correlation with gait duration (p < 0.01). Twelve patients resulted affected by MCI and reported significantly worse scores in gait duration, pain and fatigue (p < 0.05). According to cognitive z scores, PD-MCI group showed a moderate negative correlation between visuospatial abilities and fatigue (p < 0.05). CONCLUSIONS: NMS significantly affect walking kinematics whereas a limited role of cognitive status on motor performance occur in the early PD stages. [ABSTRACT FROM AUTHOR]

Introduction: Several systematic reviews and meta-analyses have suggested that physical activity programs combining low impact exercises and resistance exercises help maintaining functional capacity in older adults. Objective: To analyze the effects of an aquatic training program involving both impact and explosive exercises on gait parameters of women aged 60 and above. Materials and methods: 60 physically active women (64.08±3.98 years) were divided into 2 groups: those training in a pool by performing series of jumps, i.e., the experimental group (EG= 35), and the control group (CG=35). EG participants trained 3 times per week during 32 weeks in an hour per session basis. Body composition measurements, explosive strength, and gait parameters (in a 6 meters long track) were assessed using the center of pressure (COP) indicator before and after participating in the training program. Results: When comparing both groups, differences in explosive strength and power (EG vs. CG; p values=from 0.05 to 001) were observed, as well as changes in gait parameters related to the COP (EG vs. CG: p = 0.05-001), in particular EG participants had significant and positive changes. Conclusion: The aquatic training program described here produced an increase in muscle strength and muscle power, thus gait parameters were improved. Bearing this in mind, an improved availability of similar programs for older adults should be considered, since their participation in these programs could help them improve their functional capacity, and, thus, their quality of life.

Background: Gait disturbances and balance remain challenging issues in Parkinsonian patients (PD) with deep brain stimulation (DBS). Short pulse deep brain stimulation (spDBS) increases the therapeutic window in PD patients, yet the effect on gait and postural symptoms remains unknown. Objective: We assessed the efficacy of spDBS compared to conventional DBS (cDBS) within the subthalamic nucleus (STN) on Parkinsonian gait. Methods: The study was a single-centre, randomized, double-blind, clinical short-term trial. 20 PD patients were studied postoperatively in three different conditions (DBS stimulation switched off (off DBS), spDBS with 40μs pulse width, cDBS with 60μs pulse width) on regular medication. The primary endpoint was the relative difference of gait velocity at self-paced speed during quantitative gait analysis between stimulation conditions. Secondary endpoints were changes of further measures of quantitative gait analysis, Ziegler course, Berg balance scale, FOG questionnaire, MDS-UPDRS, PDQ-39, and HADS. Mixed-model analysis and post-hoc t-tests were performed. Results: Both spDBS and cDBS improved gait velocity at self-paced speed compared to off DBS, however, there was no significant difference between both stimulation modes. Still, 40% of the patients preferred spDBS over cDBS subjectively. Both stimulation modes were equally effective in improving secondary endpoints of gait, balance, motor and non-motor performances. Conclusion: The use of spDBS and cDBS is equally effective in improving gait and balance in PD and might be beneficial in specified cohorts of PD patients. [ABSTRACT FROM AUTHOR]

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Niemann-Pick type C (NPC) is a rare but treatable lysosomal disorder with heterogeneous clinical presentations including cognitive impairment, movement disorders and vertical gaze palsy. We illustrate five cases of genetically confirmed NPC and highlight backward leaning during gait as a relevant clinical sign and a useful diagnostic clue. [ABSTRACT FROM AUTHOR]

Background: The rehabilitation of gait disorders in patients with multiple sclerosis (MS) and stroke is often based on conventional treadmill training. Virtual reality (VR)-based treadmill training can increase motivation and improve therapy outcomes. The present study evaluated an immersive virtual reality application (using a head-mounted display, HMD) for gait rehabilitation with patients to (1) demonstrate its feasibility and acceptance and to (2) compare its short-term effects to a semi-immersive presentation (using a monitor) and a conventional treadmill training without VR to assess the usability of both systems and estimate the effects on walking speed and motivation.Methods: In a within-subjects study design, 36 healthy participants and 14 persons with MS or stroke participated in each of the three experimental conditions (VR via HMD, VR via monitor, treadmill training without VR).Results: For both groups, the walking speed in the HMD condition was higher than in treadmill training without VR and in the monitor condition. Healthy participants reported a higher motivation after the HMD condition as compared with the other conditions. Importantly, no side effects in the sense of simulator sickness occurred and usability ratings were high. No increases in heart rate were observed following the VR conditions. Presence ratings were higher for the HMD condition compared with the monitor condition for both user groups. Most of the healthy study participants (89%) and patients (71%) preferred the HMD-based training among the three conditions and most patients could imagine using it more frequently.Conclusions: For the first time, the present study evaluated the usability of an immersive VR system for gait rehabilitation in a direct comparison with a semi-immersive system and a conventional training without VR with healthy participants and patients. The study demonstrated the feasibility of combining a treadmill training with immersive VR. Due to its high usability and low side effects, it might be particularly suited for patients to improve training motivation and training outcome e. g. the walking speed compared with treadmill training using no or only semi-immersive VR. Immersive VR systems still require specific technical setup procedures. This should be taken into account for specific clinical use-cases during a cost-benefit assessment. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Gait disturbances are important clinical features of cerebral small vessel disease (CSVD) that increase the risk of falls and disability. Brain structural alterations and gait disturbances in CSVD patients have been well demonstrated. However, intrinsic resting cerebral function patterns in CSVD patients with gait disorders remain largely unknown. Fifty-eight CSVD patients were enrolled in our studies and categorized into the gait disorder group (CSVD-GD, n = 29) and no-gait disorder group (CSVD-NGD, n = 29) based on a gait examination. Gait was quantitatively assessed with the Timed Up and Go test and the intelligent device for energy expenditure and activity (IDEEA). Functional MRI and fractional amplitude of low-frequency fluctuation (fALFF) analyses were employed to explore local intrinsic neural oscillation alterations. Functional connectivity based on fALFF results was calculated to detect the potential changes in remote connectivity. Compared with the CSVD-NGD group, the CSVD-GD group showed decreased fALFF in regions mainly located in the sensorimotor network and frontoparietal network, such as the left supplementary motor area (SMA.L) and the left superior parietal gyrus, and increased fALFF in the right inferior frontal gyrus (orbital part), the left caudate, and the left precuneus. Moreover, the CSVD-GD patients exhibited lower connectivity between the SMA.L and temporal lobe, which was related to gait speed. The fALFF value of the SMA.L was associated with cadence. This study highlights the regional and network interaction abnormalities of the SMA in CSVD patients with gait disturbances. These findings could provide further insight into the neural mechanisms of gait disturbances in CSVD.

脑小血管病的影像改变包括脑白质高信号、腔隙性脑梗死、血管周围间隙、脑微出血、脑 萎缩等。步态障碍是脑小血管病的重要临床特征，进一步导致跌倒风险增加。脑小血管病破坏脊髓 运动系统和皮层、基底节纤维联系的完整性，同时存在视空间和执行功能障碍、抑郁状态等多种认 知或精神心理障碍，均与步态异常显著相关。在步态障碍的上述产生机制中，侧脑室周围、额叶深部 白质疏松与运动协调和认知损伤相关；腔隙性脑梗死常见于运动-认知风险人群；血管周围间隙、一 定数量的脑微出血、脑萎缩或脑灌注异常等均会导致认知损伤相关步态障碍。本文根据近期研究进 展，以不同的临床或影像特征为基础，对脑小血管病导致步态障碍的发病机制进行详细综述。 Abstract: Gait disorder is an important clinical feature of cerebral small vessel disease (CSVD), and can lead to accidental tumble. Imaging features of CSVD include white matter hyperintensities, lacunar infarction, perivascular spaces, cerebral microbleeds, brain atrophy, abnormal cerebral perfusion, and so on. Broken integrality of spinal cord connection with cortex and basal ganglia, visuospatial and execution function dysfunction, together with cognitive impairment or depression in CSVD were all related to gait disorders. White matter hyperintensities in periventricular and deep frontal lobe can lead to motor coordination and cognitive impairment. Lacunar infarction are often found in those with high risk of motor and cognitive impairment. Perivascular spaces, a degree of cerebral microbleeds, brain atrophy and abnormal cerebral perfusion all can bring about gait disorders related to cognitive impairment. Based on clinical and imaging characteristics, this article reviewed the pathogenesis of gait disorders in CSVD.

Introduction: This Perspective reassesses the consensus opinion that statin-associated muscle symptoms (SAMS) occur in <1% of users and associated myopathic proximal muscle weakness is even more rare. Areas covered: Of the over 180,000 participants in clinical trials and large registries of statin users, only a few studies have included a standard manual muscle test (MMT), dynamometry or a focused questionnaire to assess for proximal weakness and related disability in daily and recreational activities. Formal strength testing suggests, however, that weakness can be demonstrated in at least 10% of users. Expert opinion: Reporting inaccuracies about SAMS, confirmation bias among experts and physicians, absence of a standard questionnaire regarding the potential consequences of weakness on physical capacity, and the failure to routinely perform an objective assessment of strength may have led to under-diagnosis of statin-induced myopathy. A brief MMT before cholesterol-lowering agents are started and at follow-up visits, a 12-week withdrawal of the statin in the presence of new paresis without an alternative cause, and the exam finding that strength recovers off the statin are necessary to assess the incidence of drug-induced proximal weakness and inform alternative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: To uncover possible impairments of walking and dynamic postural stability in patients with primary orthostatic tremor (OT). Methods: Spatiotemporal gait characteristics were quantified in 18 patients with primary OT (mean age 70.5 ± 5.9 years, 10 females) and 18 age-matched healthy controls. One-third of patients reported disease-related fall events. Walking performance was assessed on a pressure-sensitive carpet under seven conditions: walking at preferred, slow, and maximal speed, with head reclination or eyes closed, and while performing a cognitive or motor dual-task paradigm. Results: Patients exhibited a significant gait impairment characterized by a broadened base of support (p = 0.018) with increased spatiotemporal gait variability (p = 0.010). Walking speed was moderately reduced (p = 0.026) with shortened stride length (p = 0.001) and increased periods of double support (p = 0.001). Gait dysfunction became more pronounced during slow walking (p < 0.001); this was not present during fast walking. Walking with eyes closed aggravated gait disability as did walking during cognitive dual task (p < 0.001). Conclusion: OT is associated with a specific gait disorder with a staggering wide-based walking pattern indicative of a sensory and/or a cerebellar ataxic gait. The aggravation of gait instability during visual withdrawal and the normalization of walking with faster speeds further suggest a proprioceptive or vestibulo-cerebellar deficit as the primary source of gait disturbance in OT. In addition, the gait decline during cognitive dual task may imply cognitive processing deficits. In the end, OT is presumably a complex network disorder resulting in a specific spino-cerebello-frontocortical gait disorder that goes beyond mere tremor networks. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish a comprehensive and yet parsimonious model of daily mobility activity in patients with neurological gait disorders. Patients (N = 240) with early-stage neurological (peripheral vestibular, cerebellar, hypokinetic, vascular or functional) gait disorders and healthy controls (N = 35) were clinically assessed with standardized scores related to functional mobility, balance confidence, quality of life, cognitive function, and fall history. Subsequently, daily mobility was recorded for 14 days by means of a body-worn inertial sensor (ActivPAL®). Fourteen mobility measures derived from ActivPAL recordings were submitted to principle component analysis (PCA). Group differences within each factor obtained from PCA were analyzed and hierarchical regression analysis was performed to identify predictive characteristics from clinical assessment for each factor. PCA yielded five significant orthogonal factors (i.e., mobility domains) accounting for 92.3% of the total variance from inertial-sensor-recordings: ambulatory volume (38.7%), ambulatory pattern (22.3%), postural transitions (13.3%), sedentary volume (10.8%), and sedentary pattern (7.2%). Patients' mobility performance only exhibited reduced scores in the ambulatory volume domain but near-to-normal scores in all remaining domains. Demographic characteristics, clinical scores, and fall history were differentially associated with each domain explaining 19.2–10.2% of their total variance. This study supports a low-dimensional five-domain model for daily mobility behavior in patients with neurological gait disorders that may facilitate monitoring the course of disease or therapeutic intervention effects in ecologically valid and clinically relevant contexts. Further studies are required to explore the determinants that may explain performance differences of patients within each of these domains and to examine the consequences of altered mobility behavior with respect to patients' risk of falling and quality of life. [ABSTRACT FROM AUTHOR]

Gait disorder appears in the whole process of Parkinson's disease (PD), which causes disability and serious affects in PD patients. The mechanism of gait disorder in PD is still unclear. Functional brain - neuroimaging can be used to analyse the characteristics and rules of brain functional activity related to gait disorder in PD, and has important clinical significance in revealing the neural physiopathologia mechanism of gait disorder, guiding the treatment and evaluating the curative effect. This paper briefly summarizes the research progress of fMRI and functional near-infrared spectroscopy (fNIRS) in gait disorder of PD, to provide reference for future research. [ABSTRACT FROM AUTHOR]

Gait disturbances are important clinical features of cerebral small vessel disease (CSVD) that increase the risk of falls and disability. Brain structural alterations and gait disturbances in CSVD patients have been well demonstrated. However, intrinsic resting cerebral function patterns in CSVD patients with gait disorders remain largely unknown. Fifty-eight CSVD patients were enrolled in our studies and categorized into the gait disorder group (CSVD-GD, n = 29) and no-gait disorder group (CSVD-NGD, n = 29) based on a gait examination. Gait was quantitatively assessed with the Timed Up and Go test and the intelligent device for energy expenditure and activity (IDEEA). Functional MRI and fractional amplitude of low-frequency fluctuation (fALFF) analyses were employed to explore local intrinsic neural oscillation alterations. Functional connectivity based on fALFF results was calculated to detect the potential changes in remote connectivity. Compared with the CSVD-NGD group, the CSVD-GD group showed decreased fALFF in regions mainly located in the sensorimotor network and frontoparietal network, such as the left supplementary motor area (SMA.L) and the left superior parietal gyrus, and increased fALFF in the right inferior frontal gyrus (orbital part), the left caudate, and the left precuneus. Moreover, the CSVD-GD patients exhibited lower connectivity between the SMA.L and temporal lobe, which was related to gait speed. The fALFF value of the SMA.L was associated with cadence. This study highlights the regional and network interaction abnormalities of the SMA in CSVD patients with gait disturbances. These findings could provide further insight into the neural mechanisms of gait disturbances in CSVD. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegia is a heterogeneous group of clinically and genetically neurodegenerative diseases characterized by progressive gait disorder. Hereditary spastic paraplegia can be inherited in various ways, and all modes of inheritance are associated with multiple genes or loci. At present, more than 76 disease-causing loci have been identified in hereditary spastic paraplegia patients. Here, we report a novel mutation in SPAST gene associated with hereditary spastic paraplegia in a Chinese family, further enriching the hereditary spastic paraplegia spectrum. Methods: Whole genomic DNA was extracted from peripheral blood of the 15 subjects from a Chinese family using DNA Isolation Kit. The Whole Exome Sequencing of the proband was analyzed and the result was identified in the rest individuals. RaptorX prediction tool and Protein Variation Effect Analyzer were used to predict the effects of the mutation on protein tertiary structure and function. Results: Spastic paraplegia has been inherited across at least four generations in this family, during which only four HSP patients were alive. The results obtained by analyzing the Whole Exome Sequencing of the proband exhibited a novel disease-associated in-frame deletion in the SPAST gene, and this mutation also existed in the rest three HSP patients in this family. This in-frame deletion consists of three nucleotides deletion (c.1710_1712delGAA) within the exon 16, resulting in lysine deficiency at the position 570 of the protein (p.K570del). This novel mutation was also predicted to result in the synthesis of misfolded SPAST protein and have the deleterious effect on the function of SPAST protein. Conclusion: In this case, we reported a novel mutation in the known SPAST gene that segregated with HSP disease, which can be inherited in each generation. Simultaneously, this novel discovery significantly enriches the mutation spectrum, which provides an opportunity for further investigation of genetic pathogenesis of HSP. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between serum uric acid (UA) level and gait disorders in patients with cerebellar small vessel disease (CSVD). Methods: 172 patients with CSVD admitted to our hospital from January 2018 to January 2019 were divided into the study group (87 cases) and the control group (85 cases) according to the serum uric acid level. The clinical data of the two groups were collected and compared, and Logistic regression analysis of the correlation between paraventricular, deep white matter high signal and gait disorder in patients with serum uric acid and CSBD. Results: There was no significant difference in age, sex, body mass index, blood glucose index, blood lipid index, hypertension, diabetes mellitus and smoking status between the two groups (P>0.05). The serumuric acid level and the proportion of drinking patients in the study group was significantly higher than that in the control group (P<0.05). The high ratio of ventricular high signal and deep white matter high signal were significantly higher than the control group (P<0.05). The gait disorder, high paraventricular signal and deep white matter high signal were taken as the influencing factors. The results showed that there was a positive correlation between serum uric acid level and gait disorder, high paraventricular signal and deep white matter high signal (P<0.05). Conclusion: The serum hyperuricemia of CSVD patients is positively correlated with the severity of high signal lesions in paraventricular and deep white matter, which is also a risk factor for gait disorder. [ABSTRACT FROM AUTHOR]

Background: X‐linked dystonia parkinsonism (XDP) is a rare disorder characterized by adult‐onset, progressive dystonia that, over time, is combined with or replaced by features of parkinsonism. Gait impairment is common. Methods: Case series of 4 XDP patients with a unique gait disorder. Results: The patients displayed a characteristic gait disorder with combined dystonic and parkinsonian gait features, with phasic knee bending. Of these patients, all had parkinsonism and three‐quarters had prominent dystonic features, but 1 had predominant parkinsonism and subtle dystonic features. Conclusion: Although XDP is a classic form of dystonia parkinsonism, some cases can mimic idiopathic Parkinson's disease. We describe a gait disorder which appears unique to XDP, involving phasic dystonic knee bending superimposed on parkinsonian shuffling, and may help clinically differentiate one of our parkinsonian‐predominant patients from more‐common forms of parkinsonism. The gait is distinct from other complex dystonic disorders with gait involvement. View Supplementary Video [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a common neurodegenerative disease, one of the symptoms of which is a gait disorder, which decreases gait speed and cadence. Recently, augmented feedback training has been considered to achieve effective physical rehabilitation. Therefore, we have devised a numerical modeling process and algorithm for gait detection and classification (GDC) that actively utilizes augmented feedback training. The numerical model converted each joint angle into a magnitude of acceleration (MoA) and a Z-axis angular velocity (ZAV) parameter. Subsequently, we confirmed the validity of both the GDC numerical modeling and algorithm. As a result, a higher gait detection and classification rate (GDCR) could be observed at a higher gait speed and lower acceleration threshold (AT) and gyroscopic threshold (GT). However, the pattern of the GDCR was ambiguous if the patient was affected by a gait disorder compared to a normal user. To utilize the relationships between the GDCR, AT, GT, and gait speed, we controlled the GDCR by using AT and GT as inputs, which we found to be a reasonable methodology. Moreover, the GDC algorithm could distinguish between normal people and people who suffered from gait disorders. Consequently, the GDC method could be used for rehabilitation and gait evaluation.

Gait disturbance is a common sequela of stroke. Conventional gait analysis has limitations in simultaneously assessing multiple joints. Therefore, we investigated the gait characteristics in stroke patients using hip-knee cyclograms, which have the advantage of simultaneously visualizing the gait kinematics of multiple joints. Stroke patients (n = 47) were categorized into two groups according to stroke severity, and healthy controls (n = 32) were recruited. An inertial measurement unit sensor-based gait analysis system, which requires placing seven sensors on the dorsum of both feet, the shafts of both tibias, the middle of both femurs, and the lower abdomen, was used for the gait analysis. Then, the hip-knee cyclogram parameters (range of motion, perimeter, and area) were obtained from the collected data. The coefficient of variance of the cyclogram parameters was obtained to evaluate gait variability. The cyclogram parameters differed between the stroke patients and healthy controls, and differences according to stroke severity were also observed. The gait variability parameters mainly differed in patients with more severe stroke, and specific visualized gait patterns of stroke patients were obtained through cyclograms. In conclusion, the hip-knee cyclograms, which show inter-joint coordination and visualized gait cycle in stroke patients, are clinically significant.

Introduction: Little is published on the prognosis of small fiber neuropathy (SFN).Methods: A retrospective analysis of 101 patients with biopsy proven SFN.Results: Study participants included 87 patients with length-dependent SFN and 14 patients with non-length-dependent SFN. The average duration of symptoms was 3.2 years prior to SFN diagnosis, and the average follow-up duration after diagnosis was 6.2 years. Neuropathic pain was present in 98% of patients and in 84.2% of patients at the final visit. The average total number of pain medications ever used was 4.4 per patient. Signs of autonomic dysfunction were initially present in 24.8% of patients, but improved in most. Large fiber involvement was seen in 11.9% of patients. Small fiber neuropathy affected employment and ambulation status in 5.3% and 6.3% of patients, respectively.Discussion: Small fiber neuropathy tends to be stable and rarely affects ambulation and employment status. Effective pain control remains a challenge. [ABSTRACT FROM AUTHOR]

Copyright of Revista Facultad de Medicina de la Universidad Nacional de Colombia is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: A cerebral ischemic stroke involves mitochondrial dysfunction, motor deficits, and paralysis; and Danhong injection (DHI) might possess mitochondrial protection and functional recovery in a stroke subject through promoting expression of parkin, a ubiquitin ligase playing a key role in the regulation of proteins and mitochondria quality control. Objective: To investigate the therapeutic effects of DHI on the histological, cellular, and functional recovery of Wistar rats after middle cerebral artery occlusion/reperfusion (MCAO/R). Methods: One hundred and twenty healthy male Wistar rats (250–300 g), were randomly assigned to six groups (twenty rats/group). Rats were subjected to 1 h MCAO/R and subsequently administered the intravenous doses of DHI (0.75, 1.5, and 3 mL/kg) to the respective groups (twice a day for 14 days). Unlike the other groups, the sham group received surgery without vessel occlusion. All the animals were tested for gait behavior using the CatWalk system. The body weight/survival rates were recorded daily for 14 days. The parkin protein expression of the brain tissue was quantified by immunohistochemistry analysis. Additionally, cultured cortical neurons were incubation with DHI or minocycline (MC) and then deprived of oxygen and glucose for 2 h (to resemble ischemic/reperfusion), followed by 4 h reoxygenation. Cellular and mitochondrial phenotypes were assayed by high content analysis. Results: Neurological integrity and paw parameters of the animals were altered in the model group but significantly ameliorated by DHI administration. Also, the infarct volume and survival rate were significantly improved in DHI groups. DHI enhanced the expression of parkin protein in the brain and improved the relative mitochondrial reductase activity of the cultured neurons. Conclusions: The overall result shows that daily intervention with DHI provides neuroprotection and survival to improve gait motion in Wistar rats. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Gerontologie und Geriatrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Stiff person syndrome (SPS) is a rare neurological disease resulting in stiffness and spasm of muscles. It initially affects the axial muscles and then spread to limb muscles. Emotional stress exacerbated the symptoms and signs of the disease. The pathophysiology of the disease is caused by the decreased level of the glutamic acid decarboxylase (GAD) activity due to an autoantibody against GAD that decreases the level of gamma-aminobutyric acid (GABA). In this paper, we present a case of atypical presentation of SPS with lower limb stiffness misdiagnosed as conversion disorder. Case presentation: We report a patient with atypical presentation of SPS with lower limb stiffness and gait disorder misdiagnosed as conversion disorder for a year. Her antithyroid peroxidase antibody (anti-TPO Ab) level was 75 IU (normal value: 0–34 IU). Intravenous immunoglobulin (IVIG) was administered (2gr/kg, 5 days) for the patient that showed significant improvement in the follow-up visit. Conclusion: It is essential that in any patient with bizarre gait disorder and suspicious to conversion disorder due to the reversibility of symptoms, SPS and other movement disorder should be considered.

Abstract: Background: Acquired copper deficiency (ACD) is a rare condition usually diagnosed from haematological changes. Aims: To characterise the diagnosis features and the evolution of patients with ACD revealed by neurological symptoms. Methods: Clinical, biological and magnetic resonance imaging (MRI) data were prospectively analysed at diagnosis and during follow up under copper supplementation. Results: Seven patients were studied over a 5‐year period. Time to diagnosis ranged from 2.5 to 15 months. Subacute ascending paraesthesias and gait disorder were the first symptoms. All patients had a posterior cord syndrome (PCS) with sensory ataxic gait associated with superficial hypoesthesia of the feet; 50% had also lateral cord signs. Electrodiagnostic tests diagnosed a lower limb sensory neuropathy in four patients. Spinal cord MRI was normal in three of seven patients. Anaemia and lymphopenia were diagnosed in six of seven patients. Serum copper was always low, and urinary copper was low or normal. Serum and urinary zinc were high in four patients. Decreased copper intake (stoma/parenteral nutrition, malnutrition, malabsorption with lack of vitamin supplementation after bariatric or other digestive surgeries) was found in four patients, and the chronic use of denture adhesive paste containing zinc was discovered in four patients. One patient had both the causes recorded. After copper supplementation, copper balance and then haematological disturbances were the first features to normalise gradually in 2 months. Radiological myelitis disappeared in 10 months, whereas neurological symptoms improved in six of seven patients after a mean follow up of 2 years. Conclusions: Progressive PCS with anaemia and lymphopenia must raise the possibility of an ACD. Early copper supplementation could increase the neurological prognosis. [ABSTRACT FROM AUTHOR]

We describe an elderly woman meeting criteria for vascular parkinsonism/dementia associated with a likely pathogenic variant in the COL22A1 gene, supported by functional experiments in a zebrafish model. We suggest that white matter hyperintensities may not represent small-vessel ischemic disease and that, if confirmed by further observations, COL22A1 may be included among the adult-onset leukoencephalopathies mislabeled as "vascular parkinsonism." [ABSTRACT FROM AUTHOR]